Kidney Problems Causes and Treatment

The Kidney Disease Solution

The ebook teaches you how to beat kidney disease in a way that no big pharm company wants you to know. The biggest companies make their money when people like you, with kidney disease come in and wonder if there is any way that they can be cured. The medical industry profits off of these sorts of people, because most people do not know that there is a way around the mass-produced medical industry. With the information in this ebook guide you will be able to restore your help without using drugs that end up hurting your kidneys even more. You will be able to avoid surgery, or having to use dialysis just to survive. You can also improve your quality of life if you are already on dialysis or end stage renal failure. This book was born of years of research from Duncan Capicchiano, ND. All of his research, findings, and suggestions are available to you! Read more...

The Kidney Disease Solution Overview

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Chronic Kidney Disease 2007

9th International Conference on Dialysis, January 24-26, 2007, Austin, Texas 7 Finances of the Independent Dialysis Facility 12 Dialysis and Nanotechnology Now, 10 Years, or Never 18 The Basic, Quantifiable Parameter of Dialysis Prescription Is Kt V Urea Treatment Time Is Determined by the Ultrafiltration Requirement All Three Parameters Are of Equal Importance 31 Impact ofthe Change in CMS Billing Rulesfor Erythropoietin on Hemoglobin Outcomes in Dialysis Patients 39 Diabetes Changing the Fate of Diabetics in the Dialysis Unit 48 Major Difficultiesthe US Nephrologist Faces in Providing Adequate Dialysis 53 What Is Needed to Achieve a Hemoglobin of 11.0-13.0 g dl in End-Stage Renal Disease 69 Inflammation and Subclinical Infection in Chronic Kidney Disease A Molecular Approach 77 Managing Complexity at Dialysis Service Centers across Europe 90 Treatment Time and Ultrafiltration Rate Are More Important in Dialysis Prescription than Small Molecule Clearance 99 Increasing AV Fistulae and...

Cachexia in Chronic Kidney Disease

Many reports indicate that in patients with advanced chronic kidney disease (CKD) and those on dialysis there is a high prevalence of PEM, up to 40 or more, and a strong association between malnutrition and greater morbidity and mortality 25 . CKD patients not only have a high prevalence of malnutrition, but also a higher occurrence rate of inflammatory processes. Many conditions leading to malnutrition and wasting may also cause inflammation. Oxidative stress may be a major underlying cause for both conditions 26 . Since both malnutrition and inflammation are strongly associated with each other and can change many nutritional measures and clinical outcomes in the same direction, and because the relative contributions of measures of these two conditions to each other and to poor outcomes in CKD patients are not yet well defined, the term 'malnutrition-inflammation complex syndrome' (MICS) has been suggested to denote the important contribution of both of these conditions to end-stage...

Preparation of Microdialysis Apparatus

A multiwell dialysis apparatus has been designed to facilitate small-scale 6. Cut 20-30 mm squares of dialysis membrane from dialysis tubing (6-8 kDa MWCO, prepared by standard methods) using a clean blade. 7. Soak the squares briefly in the starting buffer for the dialysis. 8. Place the dialysis membrane squares over the bottom of the projecting tubes and seal by fitting rubber O-rings which slide to fix into the grooves on the tubes. Ensure there are no folds in the membrane.

Cardiopulmonary Bypass In Chronic Renal Disease

Cardiopulmonary bypass in chronic renal disease is usually done for procedures involving coronary bypass or valve replacement. Myocardial infarction is the cause of death in one- third of patients on hemodialysis. Chronic anemia in the presence of the AV fistula used for dialysis contributes to ischemic changes. Preoperative cardiac catheterization can be life-threatening in these patients from the fluid shifts and potassium arrhythmias, hence the patient should be dialyzed in the morning prior to catheterization and again the evening prior to surgery. One could consider putting in femoral instead of radial arterial lines in anticipation of future AV fistulas. The perfusion flow should be the standard 2.4 l min m2. Hourly potassium levels are checked and levels greater than 6.0 mEq l are treated with glucose and insulin. One can perform hemodialysis following, or even during, cardiopulmonary bypass. One should at least use an ultrafiltrator to remove volume accumulated during...

Dialysis Prescription

The only widely accepted method to quantify the dose of dialysis is the fractional clearance of urea from body water or Kt VU, where K is dialyzer urea clearance, t is treatment time and V is the urea distribution volume (KDOQI) which is considered to be a dose surrogate for removal of low molecular weight toxins. There have been two prospectively randomized, controlled trials (RCTs) of dialysis therapy 1, 2 and in both these trials the dialysis dose was tightly controlled with urea kinetic modeling (UKM). In contrast there have been no prospectively RCTs on the effect of treatment time on outcome. Over the years large observational studies (OSs) have not shown a consistent effect of treatment time on mortality until recently two fairly large OSs were report- ed which statistically show an association of longer treatment time with lower mortality 3, 4 . However, the validity of OSs, which might be characterized as 'guilt or innocence by association', have recently been seriously...

Types And Aspects Of Renal Failure

Renal failure is classified as either acute or chronic. Acute renal failure occurs suddenly, often secondary to sudden acute illness or to therapy. Acute renal failure is characterized by loss of sodium in blood and increased fraction of sodium excretion in the urine (FENa), especially when compared to creatinine clearance. Loss of sodium is due primarily to decreased tubular function, which helps regulate sodium and other electrolyte levels as well as water balance. Glomerular filtration rate is usually less than 20 mL min. Chronic renal failure occurs over a longer period of time, with renal insufficiency progressing through several clear-cut stages. Chronic renal failure may also be secondary to an underlying illness. Chronic renal failure is often caused by chronic illness with complications that affect the kidney, such as the immunologic damage of systemic lupus erythematosus or the nonimmuno-logic damage of diabetic nephropathy or multiple myeloma. Acute renal failure may be...

Complications of renal failure

Significant problems occur in the presence of postoperative renal failure. The recognition and treatment of these conditions is mandatory. 50 grams in 70 sorbitol solution can be given as a retention enema repeated on a Q1-2 hour basis. Each exchange will reduce the potassium level by approximately 200 mEq. If permanent reduction in the potassium level is required, or if the level becomes uncontrollable with the above modalities, either peritoneal dialysis or hemodialysis must ensue. Pulmonary dysfunction frequently accompanies renal failure. This is caused by a combination of excessive fluid retention and increase susceptibility to pulmonary infections. The treatment of this problem, therefore, is control of excessive total body water in addition to antibiotic treatment of any existing pneumonias. CNS disturbances frequently occur in the presence of ongoing renal failure. Increasing concentration of metabolic poisons produces somnolence and seizures in many patients. Therefore,...

Treatment of renal failure

Acidosis resulting from renal failure should be treated with sodium bicarbonate. In addition, renal injury by agents such as myoglobin or hemoglobin precipitation in the renal tubules has been shown to be markedly improved by alkaliniza-tion of the urine. Indications for Dialysis The absolute indications for either hemo- or peritoneal dialysis in the postoperative cardiac patient are only three in number. A lesser indication for dialysis may be considered significantly elevated blood urea nitrogen. In certain patients where the BUN raises to excessively high levels and evidence of CNS pathology may be occurring, an argument can be voiced for hemodialysis.

Changing the Fate of Diabetics in the Dialysis Unit

In a symposium on diseases of kidney reported in 1971 Williem J. Kolff was quoted as saying in 1938, 'Gradually the idea grew in me that if we could only remove 20 g of urea and other retention products per day we might relieve this man's nausea and that if we did this from day to day, life might still be possible' 8 . Dunea 8 started his article after this statement and wrote, 'Within three decades dialysis has revolutionized the field of nephrology and opened new vistas in the treatment of uremia. Yet, dialysis gradually outgrew its difficult beginnings and became established among the great medical achievements of our age.' In this article there is no mention of the diabetic ESRD patient. A year later in 1972, Ghavamian et al. 9 report on 9 patients with renal failure resulting from DN who were treated by hemodialysis. The average duration of diabetes was 21 years and the average duration of nephropathy was 26 months. One patient survived for more than 3 years. The others survived...

Treatment of ischemic acute renal failure

Many experimental treatments for acute renal failure have been tested in the IPRK, either for efficacy or in the assessment of mechanisms leading to renal cell injury. One example leading to clinical application will be discussed. Lieberthal et al 180 observed that renal vascular resistance was increased during reflow in the isolated erythrocyte- perfused kidney subjected to 25 min of ischemia. Endothelium-independent vasodilators (atrial natriuretic factor, ANF, and sodium nitro-prusside) prevented the increase. Acetylcholine and the calcium ionophore A23187, two vasodilators that act by releasing endothelium-derived relaxing factor, had no effect, while two inhibitors of EDRF, methylene blue and gossypol, increased RVR in nonischemic kidneys by an amount comparable to that found with ischemia alone. The increase in RVR found with the combination of EDRF inhibition and ischemia was the same as that found with ischemia alone. In further studies 93 , they found that ANF, administered...

Mechanisms of drug induced acute renal failure

Another aspect of renal function, which contributes to drug nephrotoxicity, involves the renal enzyme systems that play key roles in maintaining body homeo-stasis. The flame retardant tris, which enters the proximal tubular cell conjugated with glutathione, undergoes bioactivation by glutathione-S-transferase resulting in reactive episulfonium ions that can cause cell death 25 . While the P-450 system of the liver is more abundant, substantial sex-linked renal P-450 activity causing bioactivation of xenobiotics, has been documented in animals 23 . A similar role in human nephrotoxicity has yet to be established. However, medullary prostaglandin synthetase has been assigned a prominent role in analgesic nephropathy where it is hypothesized to co-oxidize acetaminophen to the N-acetyl-p-benzoquinoneimine that then arylates cellular macromolecules to cause cell death 28 . Thus, the unique role of the kidneys in regulating body solute and water content, also make them targets for...

Myeloma cast nephropathy

Myeloma cast nephropathy (MCN) is the most common form of myeloma renal disease and frequently progresses to chronic renal failure. It is often precipitated by dehydration, hypercalcemia, and use of diuretics or nons-teroidal anti-inflammatory drugs, all causing a reduction in glomerular filtration. Renal failure is reversible in about 50 of patients.8-10,46 The physical basis for light-chain nephrotoxicity has not been elucidated. The initial finding that the isoelectric point of light chain was the determinant for its nephrotoxicity has not been con-firmed.45 47 Nevertheless, coprecipitation of light chain and Tamm-Horsfall protein in distal tubules leads to obstructing cast formation, tubular atrophy, disruption of the basement membrane, interstitial inflammation and fibrosis and eventually nephrosclerosis, all features characteristic of myeloma kidney.4648

Water for the Production of Dialysis Fluid

Generally patients undergoing three times weekly dialysis treatments utilise dialysis fluid flow rates of between 500 and 800 ml min, which corresponds to the use of 120-200 litres of fluid over a 4-hour treatment session. In contrast to the normal population, who not only are exposed to significantly lower volumes of water and in whom the gut offers a high degree of protection from impurities that may be present, dialysis patients are not only exposed to higher volumes of water, but during dialysis only the semi-permeable membrane present in the dialyser separates their blood from the dialysis fluid. Thus many of the permitted contaminants in drinking water have the potential to cause problems in dialysis patients (table 1). To minimise risks from such exposure, standards for water quality such as the AAMI RD62 in the United States have been developed and implemented. These define the maximum permitted contaminants with compliance linked to reimbursement. The attainment of the...

Answers To Case 17 Acute Renal Failure

Summary A 54-year-old diabetic male is receiving medical therapy consisting of oral aspirin, beta-blockers. ACE inhibitor, and intravenous nitroglycerin for treatment of his angina and hypertension. He undergoes coronary angiography, which reveals no significant stenosis. He is normotensive. His funduscopic examination shows dot hemorrhages and hard exudates, evidence of diabetic retinopathy. In this setting, the baseline elevated creatinine level on admission likely represents diabetic nephropathy as well. His creatinine level has risen to 2.9 mg dL from 1.6 mg dL on admission. By the next day. he has become oliguric. New clinical problem Acute renal failure (ARF).

The Production of Dialysis Fluid

Historically the production of dialysis fluid was by the manual mixing of concentrated electrolyte solution with water in a large tank, which was then heated and pumped to the dialyser 1 . With the advent of single-patient proportioning systems in the late 1960s, the production of the dialysis fluid moved to the patients bedside and whilst this approach remains the most widely used, alternatives such as a central delivery system or systems that incorporate pre-mixed dialysis fluid continue to be used 2 . Early single-patient proportioning systems used sodium bicarbonate for buffering, but problems arising from the formation of calcium carbonate meant that this approach was abandoned in favour of acetate 3 . Acetate remained the buffer of choice until the early 1980s when, with the increased use of high-efficiency dialysis treatments and the availability of new technology to minimise calcium carbonate formation, bicarbonate re-emerged as the preferred buffer. The preparation of...

Classification of human acute renal failure

When it comes to assessing whether HBOCs decrease the likelihood of acute renal failure or cause acute renal failure, the important question is 'what is acute renal failure ' Simply defined, acute renal failure has occurred when there is an increase in serum creatinine of 8-125 mol l (0.3-0.5 mg dl) above baseline within 48 hours of an intervention however, no one has shown an association of transient changes in serum creatinine with morbidity or with likelihood of long-term recovery (Mehta and Chertow, 2003). Mehta and Chertow (2003) used epidemiological data to classify human acute renal failure under four domains (S) susceptibility (I) insult (R) response and (E) end-organ consequences. Susceptibility relates to the severity of pre-existing chronic kidney disease and risk factors. Risk factors include diabetes mellitus with micro-albuminuria, dehydration, multiple myeloma, congestive heart failure, and decompensated cirrhosis. Insult is rated as known or unknown, and by proximity...

Animal models of acute tubular necrosis renal failure

Animal models of acute tubular necrosis do not correlate well with human acute renal failure (Lieberthal et al., 2000 Rosen and Heyman, 2001 Heyman et al., 2002 Bonventre and Weinberg, 2003). Human acute renal failure may follow transient mild hypotension with blood pressure between 80 and 100 mmHg, but rat kidneys survive a blood pressure of less than 50 mmHg for 2-3 hours (Lieberthal et al., 2000). Blood pressure must be less than 20 mmHg to induce renal failure in rats. In contrast, total renal ischemia for 30-60 minutes is often used to produce acute tubular necrosis in rats, but human kidneys tolerate up to 75 minutes of warm ischemia without acute renal failure after transplantation. Structural and functional changes similar to those observed in human acute renal failure have been produced by the combined effect of high-output heart failure with indomethacin and L-NAME to inhibit prostaglandin and nitric oxide production (Goldfarb et al., 2001), or by combining endo-toxin...

Evolution of Dialysis Duration

In the early 1960s chronic hemodialyses were long procedures, usually 20-40 h week on standard Kiil dia-lyzers in-center 5 or 8-10 h three times weekly at home 6 . The first trials of shorter dialysis duration were at- Dialysis Clinic, Inc. tempted in the late 1960s. Schupak and Merrill 7 indicated that shorter dialysis sessions (total duration of 1216 h week with the use of coil dialyzers) achieved biochemical control similar to that achieved on Kiil dialyzers with longer dialysis durations. The tendency to shorten dialysis duration continued in the 1970s. The major incentive was the need of more intensive utilization of dialysis centers because the number of candidates for chronic dialysis markedly exceeded the availability of treatment facilities 8, 9 . In the late 1970s, an increasing number of centers in Europe and in the US followed this trend. Short dialysis had a tremendous appeal to the patients once they were told that the results were not worse than those with long dialysis.

Problems with Short Dialysis Small t

In the first paper on shorter dialysis duration, Schupak and Merrill 7 reported a markedly higher rate of hypertension problems than in the early reports with longer dialysis 5, 6 , The French Dialysis Registry reported a gradual decrease in hemodialysis duration during the 1970s and a higher rate of hypotensive episodes 25 . In 1983, the European Dialysis and Transplant Association reported 'the proportion of deaths in the Federal Republic of Germany was twice as high in short dialysis' 26 . An early warning that a short duration of dialysis was associated with multiple problems related to water and sodium retention came in the report by Sellars et al. 27 . Exchangeable sodium was significantly increased with short dialysis, and more patients required antihyperten-sive drugs. Another warning came from Germany in the report by Wizemann and Kramer 28 in 1987. They did not observe any significant differences in serum biochemistry between short (2.5 h) and long dialysis (4 h), except for...

Advantages of Long Dialysis Large T

From the above discussion, the advantages of long dialysis to the patients are obvious better tolerance of dialysis, better control of blood pressure, better removal of MMs, better rehabilitation, and longer survival. The average ratio of patients to dialysis personnel is 3-4 to 1 in the US. Because of better tolerance of dialysis with fewer hypotensive episodes, the same ratio in Tassin is 6 to 1 56 . Thus, the financial disadvantage of longer dialysis may be blunted by a reduced staff requirement. Long di Dialysis Quality The acceptance of this index was based on insufficient data and their false interpretation. In the NCDS study the tendency toward lower morbidity with longer dialysis duration was rejected as statistically insignificant because p was 0.06 instead of 0.05 (sic ). However, the power of this study was low because of an insufficient number of patients, short study duration (52 weeks) and disregard of residual renal function, which must have been substantial as many...

Ca Kinetics in Dialysis Therapy

The primary purposes of Ca kinetic modeling during dialysis are (1) to quantitatively assess Ca mass balance during dialysis with current therapy (2) to determine the feasibility of predicting Ca mass balance from key dialysis prescription parameters so that it can be prospective-ly prescribed and controlled in dialysis therapy, and (3) to minimize accumulation and inhibit vascular calcification and mortality. There are no reported studies that we are aware of attempting to develop a model to analyze Ca mass balance during dialysis. A review of this subject in PubMed for the past 30+years indicated the most complete balance data were contained in a paper by Hou et al. 1 published in the American Journal of Kidney Disease in 1991. They reported mean serial blood levels and total net dialysate flux every 30 min in 6 patients on three different concentrations of CdiCa - 3.50, 2.50 and 1.50 mEq l. These mass balance data are extremely useful but the authors did not attempt to formulate a...

Ca Mass Balance over the Complete Dialysis Cycle

Ca mass balance (accumulation in the body) will be determined by the net intake of Ca minus the removal of Ca as schematically depicted in figure 1. The volume of distribution for ionized Ca (VCa2+) is defined as being anatomically equal to the extracellular fluid volume (VECW). The ultrafiltrate during dialysis is considered uniformly removed from VCa, a well-mixed pool of ionized, diffusible Ca 2+. There is virtually no quantitative understanding of the magnitudes of intake, removal and accumulation with current dialysis therapy. We hope that we can learn to predict and control mass balance and the risk of Ca accumulation in the vascular system through use of kinetic modeling of Ca in dialysis therapy.

Hypertension in Hemodialysis Patients

Hypertension occurs in 90 of patients starting hemodialysis and persists in 70-90 of hemodialysis patients in the US 57 . In the large, multicenter Hemodialysis (HEMO) Study more than 70 of patients were hypertensive by JNC VI guidelines, and almost 75 required antihypertensive medications 58 . This is contrary to the situation in the late 1960s, when strict control of true dry body weight was practiced and the majority of patients did not require antihypertensive agents 59 . There is a consensus that most patients on dialysis have volume-dependent hypertension. Only a small proportion of patients have vasoconstrictive hypertension requiring bilateral nephrectomy in the past 59 or blood The possibility of controlling blood pressure in a reno-prival state by drastic reduction in dietary salt intake was first shown by Kempner 60, 61 in the 1940s. It was subsequently shown that the beneficial effect of the 'rice diet' on hypertension was related to the lowering of plasma volume and...

Justification for Short Dialysis

Three factors were necessary for the widespread acceptance of short dialysis economic incentives, technical feasibility, and medical scientific justification 10 . Economic incentives were demonstrated by early proponents of short dialysis. In the meantime, very efficient dialyzers had been designed and their values demonstrated in short-term studies 11, 12 . Nevertheless, short-term studies would not be sufficient for the widespread use of short dialysis. Some scientific support and a mathematical formula were needed to define an adequate dose of dialysis and justify short treatment duration. Square Meter-Hour Hypothesis and Dialysis Index The first such formula was developed in the early 1970s. Uremic peripheral neuropathy was a common complication of hemodialysis and very resistant to treatment. This complication was not dependent on urea and creatinine concentrations, but was rare with 24-27 h weekly hemodialysis on standard Kiil dialyzers and in patients on peritoneal dialysis....

Classification Of Glomerulonephritis Based On Clinical Presentation

Membranoproliferative glomerulonephritis (MPGN, types I and II) Mesangioproliferative glomerulonephritis (MSGN) Crescentic glomerulonephritis Immune deposit (anti-GBM) Pauci-immune (ANCA) Fibrillary glomerulonephritis Proliferative glomerulonephritis (IgA nephropathy) Secondary renal disorders (based on clinical presentation) Lupus nephritis It is difficult to predict the prognosis and outcome of most GNs. Whereas some are self-limiting and largely asymptomatic (e.g IgA-associated), others may progress to end-stage renal failure (ANCA-mediated GN) without treatment. Unfortunately, as is the case with a number of immune-mediated disorders, treatment currently is limited to supportive therapy (hemodialysis for renal failure, antihypertensive medications and diuretics for edema) with or without immunosuppressive drugs. When appropriate, the underlying disease should be treated (infective endocarditis, hepatitis, SLE. or vasculitis). The use of steroids and cyclophosphamide has been...

Reconstitution of Nucleosomes by Salt Step Dialysis

Place the reconstitution mixture into a 6-8 kDa MW cut-off dialysis bag. All subsequent dialysis steps are for 2 h at 4 C against 1 L of dialysis buffers unless specified. The first dialysis buffer is TE containing 1.2 M NaCl. Subsequent dialyses are with fresh TE containing 1.0, 0.8, and then 0.6 M NaCl. The procedure is completed with a final dialysis against TE overnight. Nucleosomes at this stage can be used for gel shift experiments where EDTA does not interfere. 3. For DNA cleavage experiments with EPD, two additional dialysis steps are required. First dialyze the reconstitutes against 10 mM Tris-HCl, pH 8.0 several hours to remove the EDTA. A second dialysis against fresh 10 mM Tris-HCl, pH 8.0 removes trace amounts of EDTA and prepares the samples for chemical mapping with EPD.

Approach To Acute Renal Failure Definitions

Acute renal failure (ARF) Abrupt decline in glomerular filtration rate (GFR). True GFR is difficult to measure, so we rely on increases in serum creatinine levels to indicate a fall in GFR. Because creatinine is Oliguria Less than 400 mL of urine output in 24 hours. Physiologically, it is the lowest amount of urine a person on a normal diet can make if he or she is severely dehydrated and not retain uremic waste products. Oliguria is a poor prognostic sign in ARF. Patients with oliguric renal failure have higher mortality rates and less renal recovery than do patients who are nonoliguric. Uremia Nonspecific symptoms of fatigue, weakness, nausea and early morning vomiting, itchiness, confusion, pericarditis, and coma attributed to the retention of waste products in renal failure but do not always correlate with the BUN level. A highly malnourished patient with renal failure may have a modestly elevated BUN and be uremic. Another patient may have a highly elevated BUN and be...

Enrichment of the Dialysis Fluid

Although dialysis fluid predominantly contains electrolytes, a buffer and glucose, the potential exists for other compounds to be added for specific applications. The first such approach was the addition of urea to the dialysis fluid to minimise dialysis disequilibrium 25 which was also used more recently by Doorenbos et al. 26 . Other compounds that have been added include amino acids to compensate for the loss during dialysis 27, 28 , ethanol for the treatment of ethylene glycol or methanol overdose 29 . Gupta et al. 30 used this approach to transport ferric pyrophosphate complexed with sodium citrate into the blood of patients undergoing haemodialysis to replenish their iron stores. An increase in treatment frequency is gaining popularity. Prolonged daily nocturnal dialysis has been shown to result in hypophosphataemia in patients treated with this modality and in this setting the addition of phosphate to the dialysis fluid may prove to be helpful in normalising plasma phosphate...

Clinical Assessment of Dialysis Quality

One may ask what index of dialysis adequacy should be used instead of Kt Vurea. It is tempting to give a simple formula, easy to implement and easy for bureaucrats to control. If such a formula were really developed, nephrol-ogists would not be needed in dialysis centers - computer programs and dialysis technicians would suffice. I do not believe that such a formula will be developed any time soon as dialysis is a very complex procedure. The use of rigid, quantitative guidelines (e.g., spKt Vurea of 1.3 per dialysis) assumes that all patients behave identically in response to therapeutic maneuvers, like the mean of the group, but this is not true 88 . Medicine is still an art, not exclusively science the individual approach assumes that there are differences among patients which require adjustment of the dialysis prescription for each patient based on clinical symptoms and signs. It is better to use clinical judgment instead of misleading formulae. During the early years of chronic...

Glomerular Nephritis

Glomerular nephritis may be caused by immunologic damage such as systemic lupus erythematosus, poststreptococcal damage, or hypersensitivities to drugs. The cause also may be nonimmunologic in origin, such glomerular nephritis that is produced by diabetic nephropathy. Chronic glomerular nephritis is a slower developing disease and may be idiopathic, and is characterized by gradual uremia and loss of functioning nephrons. diabetic nephropathy - disease of the kidney, including inflammatory, degenerative, and sclerotic conditions, caused by diabetes Acute glomerular nephritis is characterized by a sudden onset of hematuria and proteinuria and a decrease in glomerular filtration rate characterized by a rise in plasma creatinine and a fall in creatinine clearance compared with reference ranges.

Renal Failure

Renal insufficiency (serum creatinine > 2 mg dL) is present in 20-30 of patients at diagnosis.1-7 This may be an underestimation. In a study of more than 1300 newly diagnosed patients, the frequency of renal failure increased from 31 to 49 , when the creatinine clearance was also measured.6 Renal failure affected 24 of patients with IgG, 31 with IgA, 100 with IgD, and 52 with light-chain myeloma. Advanced age, late disease stage, heavy light-chain proteinuria, and hypercalcemia were identified as risk factors.6 Occasionally, severe acute renal failure is the first manifestation of myeloma. This is often precipitated by confounding events, such as dehydration, infection, and hypercalcemia.8-10 Over the course of the disease,

Dialysis

Dialysis is the process of separating substances in solution by means of their unequal diffusion through a semipermeable membrane. The essentials for dialysis are (1) a solution containing the substance to be removed (blood) (2) a semipermeable membrane permeable to the substances to be removed and impermeable to substances to be retained (synthetic membrane in hemodialysis or the peritoneal membrane in peritoneal dialysis), and (3) the solution to which the permeable substances are to be transferred (dialysate). The device containing the semipermeable membrane is called a dialyzer. Hemodialysis is performed on the majority (approximately 85 ) of the patients while peritoneal dialysis is used for the rest.

Peritoneal Dialysis

Peritoneal dialysis is carried out in the peritoneal cavity of the patient. The peritoneum is a thin membrane lining the abdominal cavity and covering the abdominal organs. It forms a closed sac. Through a cannula placed through the skin or a catheter permanently implanted, dialysate solution (about 2 liters in an adult) is infused, allowed to dwell for a designated time period, and drained. This process is repeated according to the needs of the patient. This semipermeable membrane permits transfer of solutes from the blood to the dialysate. The efficiency of the process is strongly dependent upon the blood flow through the peritoneal membrane the permeability of the peritoneal membrane and the dialysate conditions of flow, volume, temperature, and net concentration gradient. Peritoneal dialysis may be performed intermittently or continuously. The low volume of dialysate, the low degree of agitation of the dialysate in the peritoneal cavity, and blood flow dynamics in the peritoneum...

Oregon Health Sciences University Portland Oregon USA 2University of Texas Southwestern Medical Center Dallas Texas USA

Mechanisms of drug induced acute renal failure_5 Drugs are an infrequent cause of community-acquired acute renal failure (ARF). However, drugs share the spotlight with renal hypoxia as the leading etiologic factors for hospital acquired ARF 1, 2 . With the increasing capacity of the medical establishment to treat the most serious life-threatening conditions, the in-hospital exposure to nephrotoxic drugs will increase as will the risk of drug-induced ARF. the patient population surveyed derived from a community wide database or is it restricted to hospitalized patients What definition was adopted to designate acute renal failure (ARF) For in-hospital surveys, were both post-surgical and medical patients enrolled, and if so what was the contribution from ICU patients with multi-organ failure With what precision was the ARF diagnoses established Were multiple centers involved in providing the information These are the questions that complicate meaningful estimates of the incidence of...

Particular features due to specific drugs

Antibiotics, in combination with NSAIDs, ACE inhibitor and contrast media, are responsible for the majority of cases with drug-induced ARF. The antibiotic class most often implicated is the aminoglycosides 4, 5, 8 . Acute renal failure complicating treatment with aminoglycosides occurs in about 10 of therapeutic courses most of these patients receive inappropriate regimens of the drug 7 . Over 30 billion tablets of NSAID were dispensed in the United States in 2000 approximately 16 represent prescriptions for NSAIDs 43 . These compounds enjoy a remarkable benefit risk ratio when used in the treatment of acute self-limited pain syndromes. However, when taken chronically by the elderly or individuals with certain co-morbid conditions, the frequency of adverse reactions rises dramatically. Unfortunately, the real incidence of nephrotoxicity due to NSAIDs is unknown due to a lack of an accurate method of detection. The overall incidence could be very low, considering that up to 40 million...

Monitoring of renal function

Is a demonstrable rise in the serum creatinine concentration. A rise in the serum creatinine concentration that just exceeds the normal range may reflect as much as a 50 decline in the GFR. The failure of the serum creatinine to accurately reflect the degree of renal injury is particularly evident in patients with decreased muscle mass or those with chronic liver failure. Crea-tinine is produced from the metabolism of creatine in skeletal muscle. In turn, creatine is derived from the liver. In the setting of chronic liver disease or malnourished patients with decreased muscle mass creatinine synthesis becomes impaired. As a result more profound decreases in the GFR may occur before the serum crea-tinine concentration begins to rise above normal values 53 . By contrast, the serum creatinine concentration is a sensitive indicator of changing renal function in patients with chronic renal failure. In these patients a small decline in the GFR is associated with a large increase in the...

Architecture Pore Geometry and Steric Hindrance

Existing polymer membranes used in dialysis and ultrafiltration have been extensively studied. The pores in such membranes are formed by extrusion and solvent casting techniques. The geometry and surface chemistry of the pores arise from the chemistry of the polymers and the fluid dynamics of the casting process. In general, the hollow-fiber membranes are fairly thick or employ a multilayer scaffold for mechanical support, and have a distribution of pore sizes rather than a regular array of uniform pores. Pores in conventional polymeric membranes tend to be either roughly cylindrical, have a round orifice terminating a larger channel, or have a structure resembling an open-cell sponge. Extensive description of porous structures used in commercial ultrafiltration and microfiltration may be found in 9, 10 . It is not clear that any of these structures provide optimal geometries for membrane filtration for two reasons.

Genetichereditary susceptibility

Inherited renal disease is an infrequent cause of ESRD, cystic kidney disease being the most prevalent accounting for about 3 of all cases 61 . However, experimentally inbred strains of rats are selected because of their known susceptibility to toxic injury, an example of which is the Fischer 344 rat 63 . This selective animal susceptibility has led to speculation that a similar situation might exist for humans. A possible relationship between occupational exposure and genetic susceptibility comes from a study conducted by the Michigan Renal Registry 64 . The study design was a case-control involving 325 men with ESRD in which an occupational exposure was sought. The results found that the strongest association for ESRD patients was a family history of renal disease (odds ratio 9.30). Patients with ESRD that were excluded from consideration included diabetic nephropathy, polycystic kidney disease, heroin nephropathy, lupus nephropathy, nephropathy due to malignancy, Alport's syndrome,...

Occupationalenvironmental exposure

While there are well-recognized instances of drugs and toxins inducing ARF, the evidence supporting their causality in CRF ESRD is circumstantial and thus less compelling. This is to be expected given the insidious nature of progressive renal failure, an observation that suggests a long latency between exposure and onset of disease. This problem is compounded by the superimposition of associated chronic conditions associated with and leading to renal failure. Additionally, the lack of a uniform system of classifying renal disease (mixture of clinical and pathologic terms) and the distinct possibility of multifactorial causes for renal failure because of the many potential nephrotoxins, which exist in our environment 70 . At the Workshop on Chronic Disease in the Workplace, conducted by the Workplace Health Fund in 1983, it was estimated that nearly 4 million workers were exposed to known or suspected nephrotoxins during the 1971-72 interval 71 . Of interest was the list of...

MEMS and ECF Volume Sensing

Critical to the success of an automated dialysis platform is on-line real-time estimation of ECF volume, a complex engineering problem in its own right. Esopha-geal Doppler monitoring (EDM), pulmonary-artery catheters, and peripheral waveform analysis all provide measures of central hemodynamic parameters. Bioimped-ance and hematocrit monitoring may provide estimates

Individual risk factors

Individuals may be at increased risk for developing nephrotoxicity from various drugs based on unique circumstances. For example, several antibiotics are well recognized as having nephrotoxic potential 121 but it must be appreciated that they are often administered under clinical circumstances in which acute renal insults co-exist, i.e., hypotension, reduced cardiac output, depressed liver function, etc. Rasmussen & Ibels used multivariant analysis to determine the role of acute insults such as hypotension, dehydration, pig-menturia, liver disease, sepsis, aminoglycoside administration and contrast media for patients developing ARF without a prior history of renal disease 4 . In 41 of 121 patients a single insult was considered to be responsible for ARF, 80 of the time this was hypotension. The remaining 80 patients were exposed to 140 insults or 1.75 patient giving support to the concept of the multifactorial basis for inducing nephrotoxic renal injury. This same pattern of...

Reconciliation of RCT Results with OS Results

Many patients had to have a reduction in dose to fit even the higher spKt V 1.40 target for the standard arm of HEMO. This caused concern about inadequate dialysis, especially in patients who did not quite reach the spKt V goal of 1.40. Consequently the HEMO safety committee instructed the Data Coordinating Center (DCC) to stratify the standard arm by quintiles of Kt V and monitor outcome over this range in the standard arm 5 . The results of these analyses are shown in figure 7A where a highly significant decrease in RRM was observed as the stratified spKt V increased in the standard arm. This observation might well have resulted in early termination of the study and a conclusion that the minimum adequate spKt V is 1.6 if the DCC had not done the same analysis in the high dose arm and found exactly the same relationship. This striking dose targeting bias found in both arms of HEMO reveals a serious flaw in OSs - they are in a sense self-fulfilling prophecies in that the optimal dose...

Length with Mortality in Australia and New Zealand

This study was reported simultaneously 4 with the DOPPS study. It was an OS using data from the Australia New Zealand Dialysis Registry (ANZDATA). It is of interest to note that 20 of patients in ANZADATA are on home dialysis which is not a generalizable therapy category with external validity in view of the very low frequency of home dialysis in most countries. Further, the dialyzers most often used are low flux which also raises question about the generalizability of the data. Certainly arguments about time and minimum mortality cannot be compared in low flux compared to high flux therapy.

Induction of a limited set of autoreactive T cells

A chemical may trigger autoimmunity by inducing the expression of an antigen that is normally absent. For example, CdCl2 triggers HSP70 expression in SJL J renal tubular cells since no T-cell tolerance towards this antigen has been acquired during ontogeny, heat shock proteins reactive T-cells are induced and transfer tubulointerstitial nephritis into normal mice 7 . A toxin may also induce, directly or indirectly, the expression of normally cryptic determinants of auto-antigens for which no T-cell tolerance has been achieved. This could trigger immunopathological manifestations. Antigen presenting cells from mice infected with Theiler's virus initially present virus determinants and then auto-antigens from the central nervous system, which is responsible for autoreactive T-cell activation and demyelinating disease 8 . Metals including Au and Hg may induce the presence of cryptic determinants from bovine RNase A 9, 10, 11 but the role of such a phenomenon in the development of...

Tubulointerstitial nephritides

Most often, tubulointerstitial nephritis is the con Drug-induced tubulointerstitial nephritis represents 1-10 of cases of acute renal failure and is characterized by infiltrates of mononuclear cells with tubular cell injury 49 . Most of the patients exhibit enhanced serum IgE levels, hypereosinophilia and or hy-pereosinophiluria, fever and skin rashes. Most often, withdrawal of the drug, with or without concomitant steroid administration, improves the renal functions. Rifampicin-induced tubulointerstitial nephritis is interesting because, at least in some cases, a target might be identified 50 . There is often an association between renal failure and hematological abnormalities (hemolytic anemia and thrombopenia). Patients develop rifampicin-dependent IgG and IgM antibodies against the I antigen of red blood cells, which caused red blood cell lysis through interaction with the antigen on the erythrocyte surface. These antibodies, or a cell-mediated response against this antigen, could...

Morphology of nephrotoxic injury

The changes in renal epithelial morphology that accompany acute renal failure are often subtle. At least four cellular fates can be identified in acute renal failure cells may be necrotic cells may become apop-totic they may replicate and divide or they may appear indifferent to the stress (Figure 1). Frank necrosis, as is often seen experimentally, is not prominent in the vast majority of human cases. Necrosis is usually patchy, involving small clusters of cells, sometimes resulting in small areas of denuded basement membrane. Less obvious injury is more often noted, including loss

Pathophysiology of cell injury

The mechanisms of the changes in cell viability during renal injury are incompletely understood. Most of the experimental data have been derived from the is-chemia-reperfusion model of acute renal failure and have focused on necrotic cell death. Because as many as 50 of patients have ischemia-induced acute renal failure, the observations should be relevant to a large portion of the patients at risk. Also, different stresses initiate common biochemical events, so that understanding the relevant pathways of one stress will most likely be applicable to others. What follows is a detailed analysis of some of the pathways currently thought to execute cell death in a variety of nephro-toxic insults.

Disruption of energy production

Both organelles oxidize short chain, medium chain, and long chain fatty acids to generate ATP 9-11 . Inhibition of fatty acid oxidation may represent a common pathophysiologic response of the kidney, and in particular the proximal tubule, during is-chemia reperfusion and cisplatin-induced acute renal failure. Ischemia reperfusion injury and cisplatin inhibits fatty acid oxidation in mouse kidney and in proximal tubule cells in culture 12, 13 . In each of these insults there is reduced PPAR-a mediated transcription and activity. These DNA binding proteins induce mRNA of key enzymes in fatty acid oxidation. Another transcription factor, the PPAR-Gamma-Coactivator-1 (PGC-1) was also reduced by cisplatin. This latter nuclear protein has been shown to be a transcriptional co-activator of PPAR-a 14 , PPAR-g 15 , RXR 16 , and other transcription factors like Nuclear Respiratory Factors (NRFs) that play critical roles in the regulation of oxidative metabolism, cellular...

Caspases and cell death

Considerable evidence is accumulating to implicate the caspase pathway in the pathophysiology of acute renal failure. Caspases are a family of cell death proteases 33 that play an essential role in the execution phase of apoptosis and act upstream of DNA fragmentation 34-39 . The term 'caspase' for the cell death proteases embodies two distinct catalytic properties of these enzymes such that 'c' refers to the cysteine protease and 'aspase' refers to their specific ability to cleave after an Asp amino acid 33 . The role of caspases in apoptosis was first recognized in 1993 40 when it was discovered that the cell death gene CED3 in Caenorhab-ditis elegans has sequence homology to caspase-1, which was then called interleukin-1 b converting enzyme 40 .

Who Benefits from Guidelines

If patients are not benefiting from guidelines, who is I suppose overworked physicians and physician-extenders perceive a benefit from having things laid out in cookbook form it is a big time saver. This is increasingly important as shrinking Medicare reimbursement has led to higher patient loads and volume of service. But the major beneficiaries are those with large financial stakes the pharmaceutical industry, professional societies, dialysis companies, insurance companies, Centers for Medicare and Medicaide Services (CMS), and the guideline writers all reap considerable financial benefit from the guideline industry. Foundation's KDOQI evidence-based clinical practice guidelines' the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) will award a certificate of excellence for kidney disease management based on fulfillment of certain eligibility criteria. The JCAHO web site states on the certificate award, 'It is the best signal to your community that the quality...

Renal stress engages the cell cycle and is a determinant of cytotoxicity

Shortly after acute renal failure many normally quiescent kidney cells enter the cell cycle. Orderly progression through the cell cycle is regulated by sequential synthesis, activation, compartmentalization and degradation of proteins controlling both entry and exit from each of the four phases of the cycle G1 (gap-1), S (DNA synthesis), G2 (gap-2) and M (mitosis) (Figure 4). Control of the various phases of the growth cycle is exerted by the cyclical activation and repression of the cyclin-dependent kinases. Two important regulators of the cell cycle have been now shown to participate in acute renal failure. One family of proteins, the cyclin-dependent kinase inhibitors, which bind to and inhibit assembled cyclin kinases, and in particular the cyclin-dependent kinase inhibitor protein p21 is expressed in all forms of renal failure studied, including ischemia-reperfusion, cisplatin and obstructive uropathy. This protein binds to and inhibits the CDKs that regulate the G1 S a G2 M...

Knockout mouse models

In the early 1940s, the effect of induced is-chemic myopathy on renal perfusion in the rabbit was studied. It was conclusively demonstrated in this model that there was extreme renal cortical vasoconstriction with preservation of the medullary circulation 7 . This early first demonstration of posttraumatic vasomotor nephropathy was independently confirmed 20 years later in the USA when 'preferential renal cortical ischemia' was demonstrated in acute renal failure in man. Since then, many animals have been used to study

Compensatory responses

The ability to generate mice with a targeted mutation in a desired gene has made them a very attractive model. The first knockout mouse line was generated over 15 years ago. Many hundreds of genes have been targeted. In mice with a targeted mutation, it is possible to determine the function of gene product in various pathological conditions including renal ischemia. However, there may be discrepancies between results of studies in mice with a targeted mutation versus mice treated with an agent to neutralize the specific protein. For example, specific neutralization of interleukin-18 (IL-18) using anti-IL-18 antiserum, results in prolonged survival in lipopolysaccharide (LPS) lethality 8 whereas the IL-18 deficient mouse is often not protected against LPS lethality 9 . Also, neutralizing antibodies against IL-18 reduce disease severity in inflammatory bowel disease 10 . In contrast, IL-18 deficient mice exhibit enhanced disease severity 11 . In general, if neutralizing antibodies are...

Chemicalinduced disregulation of the immune system

Chemicals may also cause an autoimmune kidney disease in the context of B- and or T-cell activation, independent of antigen-specific recognition. This will lead to B-cell polyclonal activation with production of autoantibodies since, normally, autoreactive B-cells exist but are not activated due to a lack of T-cell help. Autoreactive T-cells with a high affinity for auto-pep-tides are eliminated in the thymus or at the periphery while those with a low affinity for auto-peptides escape deletion and emigrate to the periphery (discussed in 13, 14 ). Several mechanisms explain the absence of autoimmunity in normal individuals auto-peptides do not deliver any signal (T-cells are ignorant) or are recognized by a T-cell in the absence of adequate costimu-lation, which induces functional inactivation (T-cells are anergic). Finally, regulatory cells exert a negative control on potentially deleterious autoreactive T-cells. In this respect, some anergic cells could represent a subset of...

Proximal vs distal tubular injury

Mitogen-activated protein (MAP) kinase activation is regionally distributed in the postischemic kidney. It has been demonstrated that ischemia-reperfusion injury induces the activation of the c-Jun N-terminal ki-nases (JNKs) that occurred both in the cortex and inner stripe of the outer medulla 81, 82 . During ischemia, JNK activation has a deleterious effect and inhibition of JNK s ameliorated renal failure 81 . Proximal tubule cells are more sensitive than thick ascending limb (TAL) cells to oxidative stress as assessed by cell counting, light microscopy, propidium iodide uptake and fluorescence-activated cell sorting (FACS) analysis. Immunoprecipitation kinase analysis revealed that JNK activation occurred in both cell types, whereas extracellular regulated kinase (ERK) activation occurred only in TAL cells. In TAL cells, ERK inhibition reduced cell survival nearly fourfold after oxi-dant exposure. In proximal tubule cells, activation of the ERK pathway by insulin-like growth...

An Alternative Hypothesis

The reduced survival in MHD patients with a low BMI has recently been explained by a novel hypothesis 7 . Briefly, both in healthy and MHD subjects, visceral organ mass (i.e. high metabolic rate compartment, HMRC) relative to whole body mass (HMRC BW) is inversely related to weight and urea distribution volume (V). V, as determined by urea kinetic modeling, is closely related to MM (fig. 1), whereas fat mass contributes only marginally. Viscera are the most likely source of uremic toxins, and their mass and metabolic activity may be related to uremic toxin generation. According to this hypothesis the concentration of uremic toxins in V is higher in subjects with a low V (and thus low MM and low BMI), resulting in an under-dialysis in low BMI patients when dosed by Kt V. Dialysis dose is currently pre- in relation to body composition and dialysis vintage are needed. In these studies, the mass of specific organs (especially liver and gut), subcutaneous and visceral fat and MM have to be...

Finding a Safe Path between Scylla and Charybdis

Multiple factors contribute to vitamin C deficiency in dialysis patients dietary restriction, losses during dialysis, and fear of oxalosis. This uncertainty is compounded by difficulties in measurement of plasma vitamin C, which is very unstable in the blood sample 38, 39 . Currently, plasma vitamin C is rarely determined. Standardized clinical methods for measuring plasma vitamin C are urgently needed, which would allow measurement of vitamin C to be done as a routine procedure to assess vitamin C status. The improved Hb response to iron therapy seen in many patients indicates that there is a true Scylla of vitamin C deficiency is there likewise a true Charybdis of oxalosis in hemodialysis patients There has been no evidence for at least 10 years that dialysis patients are harmed by increased doses of vitamin C, but this worry persists among nephrologists. Controlled studies of the impact of vitamin C supplements on the occurrence of oxalate deposits are needed, and then perhaps we...

Endothelin in ischemiareperfusion injury

Many studies of endothelin action have been performed in the IPRK. The potential potent vasoconstrictor role of endothelin in acute renal failure was first noted in the IPRK by Firth 171 , who also observed that endothelin-1 mRNA was upregulated for several days after renal pedicle clamping in vivo 172 . In vivo studies suggest that this upregulation of endothelin is modestly stimulated by hypoxia alone 173, 174 but that rapid and prolonged upregulation occurs after ischemia in renal medullary interstitial cells, damaged tubules at the corticomedullary junction and peritu-bular capillaries surrounding these damaged tubules 175-177 . IPRK studies showed that pretreatment with a selective endothelin (ETA) receptor antagonist), BQ-123, ameliorated the fall in inulin clearance and sodium transport in a renal artery clamp model of ischemic acute renal failure 178 . The benefit of endothelin antagonists in ischemic acute renal failure in vivo and in vitro is complicated by the different...

Role of Th1 and Th2 cells in the development of nephropathies

In humans, crescentic glomerulonephritis is also presumed to be Th1-mediated 25 . It is noteworthy that immunization of the Th2 prone BALB c mice, with heterologous immunoglobulin prior to injection of het-erologous anti-glomerular basement membrane immu-noglobulin induces a glomerulopathy that is different from the one observed in C57BL 6 Th1 prone mice. The role of Th1 cells in a model of tubulointerstitial nephritis induced by immunization with tubular basement membrane antigens has also been documented Table 2. Role of Th1 and Th2 cells in the development of kidney diseases. Thl-dependent nephritides Tubulointerstitial nephritis induced by immunization of SJL with renal tubular antigens.

Vitamin C Effects on Erythropoiesis

The management of anemia utilizes much of the resources dedicated to patients on dialysis hemoglobin, ferritin, transferrin saturation, erythropoietin therapy and the intravenous administration of iron complexes (IV-iron) are reviewed extensively for each patient, with dose adjustments monthly or even at more frequent intervals. Improved vitamin C status may lead to improved anemia management in these patients. The biochemistry of vitamin C and iron are intimately related at the level of the gastrointestinal tract, vitamin C helps maintain iron as Fe2+, which is more soluble than Fe3+ at the alkaline pH of the small intestine, and is more readily absorbed across the intestinal mucosa 12, 13 . However, the iron requirements of dialysis patients are greater than most persons with normal renal function, and several investigations 14, 15 have reported that oral iron supple ments have limited ability to meet the iron needs of these patients. The consensus among dialysis clinicians is...

Electrolyte Composition

Sodium is the main cation of the extracellular fluid and, during dialysis, is removed from the body by both diffusion and convection. As dialysis evolved, there has been considerable interest in adjusting the sodium levels in the dialysis fluid largely to improve patient tolerance to the dialysis procedure. Sodium levels in the dialysis fluid may be considered as 'hyponatraemic' hypernatrae-mic' or 'isonatraemic' 6 , with current technology, the levels no longer need to be constant throughout treatment 7 . In clinical practice the use of hyponatraemic dialysis fluid (sodium concentration 130-135 mmol l) has declined and should be avoided as secondary to the loss of sodium by diffusion, there is a decrease in plasma osmolar-ity resulting in cellular over-hydration which contributes to disequilibrium syndrome (fatigue, 'washed-out' feeling, muscle cramps, headache, neurological symptoms), and intradialytic hypotension. For the majority of patients a hypernatraemic dialysis fluid (sodium...

Microbiological Quality

Febrile reactions were common in the early dialysis procedures. The electrolyte concentrates in use today are manufactured in accordance with internationally recog nised standards such as ISO 13958, Concentrates for Hae-modialysis and Related Therapies. The acid concentrates do not support bacterial growth, however liquid bicarbonate concentrates have been shown to support bacterial growth and there may be a rapid increase in levels after dilution 22 . High levels in the dialysis fluid lead to pyrogen reactions and fever 23, 24 . Intact bacteria cannot cross the dialyser membrane, however bacterial products such as endotoxins, muramyl di-peptides and exotoxins, potent inducers of cytokines and stimulators of the acute phase response, are able to transfer leading to the stimulation of mononuclear cells and contributing to chronic inflammation associated with long-term hae-modialysis therapy. Such transfer is related to the type of dialyser membrane (cellulosic vs. synthetic) and the...

The NCDS Dosing Controversy and HEMO

In addition to the step function in outcome shown in figure 4 , continuous linear and exponential functions relating probability of failure to Kt V could also be written with equivalent p values as described in the mechanistic analysis paper 7 , Subsequently others strongly argued that outcome should be an exponential function as shown in figure 5A because of accumulating OS experiences which indicated continuing improvement in outcome up to spKt V 1.40 8 , The HEMO study 2 was subsequently undertaken to evaluate the benefit of higher dialysis doses in a RCT. The HEMO study design The UKM universe of dialysis dosing The UKM universe of dialysis dosing Fig. 6. Observational studies reported during the pilot phase of HEMO were interpreted to show that spKt V < 1.40 was inadequate dialysis. These studies had a profound effect on HEMO and moved the standard therapy area up to spKt V 1.4. Consequently the domain of NCDS dosing controversy over 25 years was not even studied. Fig. 6....

Materials and Methods

Tients under sterile conditions immediately after needle insertion but before any intravenous fluid was given (mid-week dialysis session) to measure the inflammatory parameters and make microbiological analyses (standard and molecular). Microbiological study controls in phase 1 were internal controls for amplification (DNA from Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, P. aeruginosa ATCC 35218, Candida albicans ATCC 90028) whole blood of 20 healthy blood donors, and dialysis ultrapure water collected from different points of the treatment plant. 200 ml of dialysate collected during dialysis was centrifuged at 2,000 rpm for 10 min in order to pellet bacterial cells. The pellet thus obtained was digested overnight in 10 mM Tris-HCl (pH 8.3) and mM KCl 50 with proteinase K to a final concentration of 0.5 g l and Nonidet P-40 at 55 C. The mixture was then boiled for 10 min and centrifuged to remove debris. The supernatant was used as template for amplifications. In...

A link between proximal and distal tubular injury and recovery

The studies in the IPRK and in vivo outlined in the previous section highlighted that both proximal straight tubules (S3) and MTAL were potential targets for hypoxic injury. The anatomical proximity of these tubular segments emphasizes the location of both segments in a region under constant threat of hypoxia. Outer medullary hyperaemia is a consistent phenomenon following renal artery clamping to induce acute renal failure first described by Mason and others 158, 159 . It was hypothesized that erythrocyte aggregation and stasis in the outer stripe was produced by oxygen-derived free radicals causing extravasation of plasma and local hemoconcentration, however free radical scavengers were of no benefit, whereas hemodilution and raised intraarterial pressure each reduced both medullary hyperaemia and tubular necrosis 158 . The phenomenon of medullary hyperaemia has not been as well described in the IPRK, probably because eryth-rocytes are usually not added to the perfusate and ischemia...

Contribution of established renal cell culture models to the understanding of nephrotoxic mechanisms

The immunosuppressive drug cyclosporine A (CSA) has revolutionized transplant medicine. However, CSA induced-nephrotoxicity still represents a major therapeutic challenge. Chronic CSA nephropathy is characterized by a decrease in glomerular filtration rate (GFR), tubular atrophy, interstitial fibrosis and progressive renal dysfunction. It is difficult to delineate the mechanisms of CSA toxicity from clinical data since the majority of clinical experiences with CSA have been in renal transplant recipients. Animal models of CSA nephropathy have brought some insights, how

Problems with High Small Solute Clearances Large K

Blood Flow and Efficiency of Dialysis Short dialysis with fixed Kt Vurea leads to maximization of dialysis efficiency by using higher efficiency dia-lyzers and high blood and dialysate flows however, the influence of blood flow on the efficiency of dialysis is markedly lower than dialysis time. Removal of MMs (including phosphorus) is only slightly dependent on blood and dialysate flows 13 . so compensating shortened dialysis time by increasing blood flow is not effective. This is not only related to the slow diffusion of these molecules through the membrane, but also to multicompartmental behavior, i.e., slow diffusion from the extravascular space to the plasma 78 . This process may be compared to the poor 'plasma-refilling rate' of water and sodium in high ultrafiltration rate hemodialysis. It is worth realizing that even for removal of small molecules, an increased time of dialysis is more effective than increased blood and dialy-sate flows, because spKt Vurea (single pool) is...

Increasing AV Fistulae

The pathways to increased AV fistula prevalence are now clearly delineated in the K DOQI recommendations and Fistula First change concepts 11, 12 . Patients should be referred for evaluation for access placement approximately 6 months before dialysis initiation. Arterial and venous mapping, typically by ultrasound is performed to identify appropriate vessels for AV fistula creation 13 . This provides visualization of arteries and veins including the approximately 50 of vessels that are not apparent on physical examination. To minimize early AV fistula failure, arteries should be 6 2 mm in diameter, without dampening of the waveform and without a significant pressure differential between the arms. Veins should be

Decreasing Catheter Risk

Dialysis catheters play an important role in the provision of hemodialysis because they can provide immediate access for emergent dialysis and alternatives for patients with inadequate vasculature or medical conditions that preclude alternative access. Ideally catheters function as a short-term bridge to AV fistula or AV graft placement. Unfortunately, catheter use is often prolonged even when not medically necessary. In 2004, 63 of patients maintained on hemodialysis for < 0.5 years, 36 on dialysis 0.5-0.9 years and 26 of patients on hemodialysis for 1-1.9 years were dialyzed via a catheter 17 . This occurred despite the fact that over two thirds of catheter patients have adequate vessels for alternative access placement 18 and that catheter patients have almost double the mortality risk of AV fistula or AV graft patients 1,2 .

Successes Challenges and Opportunities

The combination of national and regional vascular access initiatives supported by new medical technologies has successfully increased national AV fistula prevalence from 26 in December 1998 to 33 in December 2002 and 42.9 in June 2006. Regionally, AV fistula rates range from 37.1 in Virginia and Maryland (ESRD network 5) to 59.5 in the Pacific Northwest (ESRD network 16) 11, 17 , During the same period, catheter use has increase from 19 in December 1998 to 27 in December 2002 and remained at 27 in December 2004 17 , Although programs to increase fistula prevalence do not necessarily increase catheter use, they can unless combined with concerted catheter reduction efforts. Currently, there is no routine coverage for chronic kidney disease (CKD) care and few CKD programs. These programs increase permanent access placement and decrease catheter use surrounding dialysis initiation. In the US, most patients require placement of a central venous catheter for dialysis initiation. Even in...

The Goal Achieving Neutral Phosphate Balance

Neutral phosphorus balance is achieved when total body phosphorus generation (GiP) is balanced by total body phosphorus elimination (JiP). Whole body iP generation is dependent on (i) intestinal iP and protein absorption and (ii) the amount of iP released from or deposited in endogenous tissues, such as bone. Phosphate binders (PBs) are used to decrease GiP by effectively lowering intestinal phosphorus absorption. In the face of lacking renal function, iP elimination in dialysis patients is almost completely dependent on dialytic iP removal. It is therefore clear that a neutral phosphorus balance can only be achieved when the total amount of iP, which has either been intestinally absorbed or released from endogenous tissues during the interdialytic phase, is completely removed by dialysis. Since phosphate removal during dialysis is limited, as delineated below, the only way to achieve neutral balance with current treatment strategies is to lower GiP to a minimum by optimizing the...

Phosphorus Restriction

(2) Since dietary phosphorus ingestion is closely related to protein intake, phosphorus restriction bears the risk of developing protein malnutrition. For dialysis patients a protein intake of 1.0-1.2 g kgbody weight day and maximum phosphorus intake of 1,000 mg day has been recommended, but a much lower mean dietary intake has been reported with 53.7 8 28.6 g for protein and 903 8 468 mg day for phosphorus 21 . Achieving adequate dietary protein intake will, in most cases, be associated with higher phosphorus intake.

Restriction and PB Therapy

From a general viewpoint, it can be stated that it should always be possible to reduce intestinal iP absorption to a level which can be balanced by dialysis phosphorus elimination. That neutral phosphorus balance can be achieved with the combined efforts of today's treatment options has been demonstrated by various studies on the efficacy of PBs. In the treat-to-goal study normophosphatemia was achieved within a couple of weeks after study initiation 24 . The 'secret' of this success lies in repeated and intensive patient counseling and stepwise adjustments of PB dosage to serum phosphate levels. In the treat-to-goal study sevelamer-treated subjects ingested an average of 8 tablets (800 mg), while calcium acetate-treated subjects ingested an average dose of seven tablets (667 mg) day. In both study groups normalization of phosphate levels (5.1 8 1.2 and 5.1 8 1.4 mg dl, respectively) was achieved. The more intense patient care in a study setting may also have contributed to the...

The Ca Model and Ca Buffer Pool

The model is again depicted in figure 2 where another compartment, termed a Ca 'buffer pool', is shown. This buffer pool is defined as a source of very rapid Ca mobilization (M+Ca) into extracellular fluid (ECW) or sequestration (M-Ca) beyond ECW during dialysis when there is a concentration gradient between plasma and dialysate. As shown quantitatively below, such a Ca pool rapidly buffering changes in plasma concentration was found to be required mathematically to close mass balance of clinical data with the model. It must be emphasized that only the intradialytic portion of the dialysis cycle is considered in the following and no attempt has been made here to close mass balance over the complete cycle which will include accumulation or depletion during the interdialytic phase of the cycle. Good estimates of Ca2+ balance between dialyses will be required to optimize prescription writing. Mass balance of Ca2+ during a dialysis treatment is defined as change in Ca content of the...

Reported Clinical Studies

The serial measured and model calculated Cpi Ca and CdiCa values are plotted for the Hou data in figure 3. The calculated values agree very closely with values observed with all three dialysate concentrations when MCa is adjusted with equation 9. The powerful effect of M-Ca can also be seen. The values for CpiCa have nearly reached equilibrium with Cdi Ca when MCa 0 in the calculations. Note that although there is some change in CpCa2+, the plasma concentration is far from equilibrium with CdiCa2+ after 4 h of dialysis with substantial positive and negative Ca concentration gradients. The Ca buffer pool was very effective to minimize change in CpiCa. The properties of this pool will be discussed further below. Koo et al. 3 reported CpCaT with CdiCa 0 values in 7 studies of 6 patients with hypercalcemia and renal failure due to malignancies. They reported CpiCaT values pre-dialysis, at 1 h of dialysis and postdialysis, and Kt VU. VCa was estimated as 11 liters and D Ca was estimated to...

Current Conclusions with Regard to Ca Modeling

(1) A model of Ca balance during dialysis has been developed from review of polished data. (4) Interdialytic Ca mass balance studies will be required to assess mass balance over the complete dialysis cycle and optimization of Ca balance during dialysis. (5) When the model is fully validated it should be possible to reliably prescribe and analyze Ca mass balance during dialysis.

Clinical and Organizational Monitoring

IMS Working with Guidelines (EBPG) and SOPs Orientation towards quality and continual improvement is a fundamental principle within Fresenius Medical Care and a key element of management policy for all business sectors. Within the Patient Care Business Unit, FME aims to set and achieve higher standards of dialysis care supported by both internal, corporate requirements as well as external standards. FME's overall approach to quality assurance is based on the principles of continuous quality improvement (CQI) as presented in the 1990 Institute of Medicine report 'Medicare a strategy for quality assurance' 17 . CQI is a theory it is not a structure for an effective dialysis quality assurance program. In order to manage the practical implementation of these varying requirements the concept of an IMS was selected. Under this framework, the CQI techniques are applied in conjunction with (mainly) internal and (where possible) external benchmarking in a system driven by quality targets....

Coexisting chronic diseases

Conventional wisdom dictates that pre-existing renal insufficiency is a well-established significant risk factor in the ARF of contrast-associated nephropathy 101 . However, a study by Levy et al. 102 questions this wisdom. These authors performed a cohort analytical study involving over 16,000 patients undergoing radiocontrast procedures. One hundred and seventy-four patients diagnosed with contrast-associated nephropathy were paired to a like number of nephr-opathy-free patients matched for age, baseline creati-nine and similar radiocontrast procedures. Mortality in contrast-associated nephropathy patients was 34 compared to 7 in match control group. When the authors considered the contribution of co-morbid conditions, the mortality rate in the ARF group was consistently higher for patients with diabetes, hypertension, cancer, lymphoma, liver disease, heart failure, acute myocardial infarction, sepsis and gastrointestinal bleeding. The authors concluded that the high mortality rate...

Abstract

Medicare pays 80 of the cost of dialysis treatment and associated medications. Congress directed the Centers for Medicare and Medicaid Services (CMS) to develop both a process of regular and more or less 'automatic' updates of composite rate setting and 'bundling' as much of the laboratory and ancillary medications as possible into the composite rate. In response to this mandate, CMS revised the wage indexing process, added an annual update, and removed the limits on the wage index range. CMS has moved the 'margin' from medication acquisition and administration to an annually revised 'drug add-on' to the composite rate and fixed reimbursement of separately billed medication (ancillary) to the average sales price +6 . CMS is funding a demonstration project on near 100 bundling to be completed by 2008 that will include metrics for automatically increasing the base composite rate. Copyright 2007 S. Karger AG, Basel The independent dialysis facility receives its revenue from the provision...

Healthcare Delivery

Dialytic treatment of ESRD is at an awkward stage of development in the early 21st century. The clinical success of dialysis has led to its broad acceptance as standard of care for ESRD. However, as the ESRD population continues to grow, the dollar cost and morbidity of intermittent in-center hemodialysis has drawn increased attention from physicians and the public and driven exploration of new modes of treatment. It is instructive to explore the impact of technology on another treatment, defibrillation, whose history remarkably parallels that of dialysis. Today, defibrillation and dialysis remain standard lifesaving treatments. However, in the last decade, the parallel histories of defibrillation and dialysis have diverged. Hemodialysis remains, for the most part, a bedside treatment requiring the patient to report to a treatment center and be assessed by a health care provider. That provider connects the patient to a large machine, which the provider then continuously monitors and...

Hemofiltration

Trol of extracellular fluid (ECF) volume should ECF regulation go awry, death from pulmonary edema or cardiovascular collapse may shortly ensue. In dialytic practice today, extracellular volume is estimated by patient weight. A patient's true 'dry weight' is quantitated by removing fluid volume during the dialysis session until the patient experiences symptomatic hypovolemia. Total body weight is in fact only a very crude surrogate for effective intravascular volume, a conceptual quantity encompassing blood volume, cardiac output, and systemic vascular resistance. A significant fraction of the human monitoring in hemodialysis is directed towards ECF volume control. Nurses or technicians weigh the patient, adjust the dialysis machine, and remain vigilant for signs and symptoms of volume overload or cardiovascular collapse. Automated ECF volume sensing is a key technology in automated dialysis.

Populations at risk

The changes in renal function of patients experiencing nephrotoxicity can be as dramatic as a sudden, acute deterioration requiring immediate dialysis to an insidious asymptomatic decline. This difference in presentation probably represents the level of exposure, i.e., dose and duration, to a drug or environmental toxin plus a component of genetic susceptibility. This formulation is supported experimentally since it has been shown that the rapidity with which renal failure occurs is dependent on the rate at which a known neph-rotoxin is administered 57 . Similar observations regarding the influence of time-dosage effects have come from our laboratory using an experimental model of aminoglycoside nephrotoxicity 58 . The human counterpart is a study reported by Nicolau et al. 59 involving once daily aminoglycoside dosing in over 2000 patients. They found that in addition to dosing schedule, age and duration of treatment were factors in precipitating aminoglycoside-induced ARF. While...

Gender

In searching for an explanation of the slower rate of progression to ESRD for female patients, Miller et al. 82 have identified a gender dependent difference in the renal hemodynamic effect of angiotensin II. The infusion of angiotensin II in women was associated with a parallel decline in GFR and effective renal plasma flow (ERPF), while in men GFR was maintained despite the angiotensin II-induced fall in ERPF. Thus, for women, the decline in filtration fraction (FF) paralleled the fall in GFR, while in men FF remained unchanged. The authors speculate that the gender difference in progression to ESRD is due to the angiotensin II associated sustained FF in men which is absent in women. It has been recognized for some time that glomerular hypertension, which would be required to sustain FF in the face of a fall in ERPF, is a known contributor to the progression of renal failure 83 .

Nutrition

Glomerular hyperfiltration regularly follows the ingestion of a protein rich diet. Furthermore, experimentally induced hyperfiltration induces glomerulo-sclerosis and chronic renal failure in animals deprived of their renal reserve 86 . In addition, pathologic variations in the body's mineral content has been linked with chronic renal injury in the case of severe hypokalemia induced by eating disorders 87 , and shown to augment toxin induced injury in the case of calcium depletion and lead nephropathy 88 , or salt depletion and analgesic nephropathy 89 . intakes of 2 drinks day or less did not increase the risk of renal failure.

Final OS Anecdote

In 1992 when the data from Charra et al. 11 appeared showing very low mortality with long 6- to 8-hour treatment times, we reported the analysis of our 4-year experience in San Francisco with high flux dialysis 12 and UKM. We examined several of the large international databases and matched each database with respect to age and diabetes to our results with the results shown in figure 15. Certainly the unique data from Charra et al. 11 stand out, but the next lowest mortality rate was in San Francisco with by far the shortest mean treatment time of 2.3 h.

Results

Figure 1 shows the distribution of 3-month average HGB immediately before and after the implementation of the EMP on April 1, 2006. It is not surprising that there is a relatively small difference between the two distributions, given that the lifespan of the red blood cell in dialysis patients averages 64 days 1 . Overall, there was a 0.2 decrease in the percentage of patients with a 3-month average HGB of > 13 g dl. On the other hand, there was a 1.1 increase in the percentage of patients with a 3-month average HGB of < 11 g dl. An HGB of < 11 g dl has previously been shown to be associated with a greater risk of mortality and hospitalization 2, 3 . In summary, 5 months of follow-up data show that the April 2006 EMP rules appear to have reduced the percentage of patients with a HGB of > 13 g dl slightly, but with the side effect of putting a greater percentage of patients into HGB categories of < 11 g dl. Given the observed intra-patient HGB variability, it is unrealistic...

Molecular aspects

Exposure of renal cells to a hostile environment initiates a complex molecular response including the activation of phosphorylation cascades and the expression of many genes. Many of these molecular responses are not confined to areas of regeneration and in fact are localized to nephron segments not undergoing obvious injury or repair. For example, a typical immediate early gene response (IEG), as indicated by c-fos and c-jun activation, occurs most prominently in areas not undergoing an increase in DNA synthesis. Because the sites of increased DNA synthesis are spatially separated from those of IEG expression and many of the responses, including the expression of chemokine genes, resemble the response observed in cells exposed to adverse environmental conditions such as ionizing radiation, oxidants, and hypertonicity, the expression of these genes under these circumstances has been termed the Stress Response. This response is thought to be a major determinant of whether cells survive...

Suggested Reading

1 Rettig RA, Levinksy NG (eds) Kidney Failure and the Federal Government. Washington, National Academy Press, 1991. 5 Thompson TG Report to Congress Toward a Bundled Outpatient Medicare End Stage Renal Disease Prospective Payment System. Washington, Department of Health and Human Services, 2003.

Ischemic

Ischemic ARF may be induced by intrarenal nore-pinephrine injection or by renal artery clamping. There are similarities between these two models of ischemic renal failure. In the norepinephrine model of renal failure, as in the arterial clamping model, there is the same degree of tubular injury except for a slightly greater frequency of tubular casts at 48 hours in ischemic model 18 . In both models, calcium channel blockers improve renal function 19, 20 . The major difference is that in the renal artery clamping model, morphology at 48 hours showed smooth muscle necrosis in half of the resistance vessels, but in less than 10 of those in nore-pinephrine-induced model. There are bilateral and unilateral models of ischemic ARF. The bilateral model is used more often because it is more similar to the pathophysiology of the syndrome of acute renal failure in humans and the most likely to yield clinically relevant information. Moreover, uni-nephrectomy immediately before renal artery...

Histology

Histologic changes remain to be an important marker of kidney injury in ARF both in human and in animals. Histological parameters of ARF include tubular necrosis, loss of proximal tubular brush border, casts in tubular lumens, neutrophil accumulation, Interstitial edema and vascular erythrocyte congestion. To assess the histological changes, a quantitative or semiquantitative approach should always be used. Areas of kidney damage such as cortex, outer or inner

Scurvy

Since dialysis patients can have plasma vitamin C concentrations of < 10 M, the occurrence of scurvy is a possible outcome. Dialysis patients often have gingivitis, which is usually diagnosed as periodontal disease 34 . but vitamin C deficiency should be considered, since bleeding gums are a major scorbutic symptom. Dialysis patients frequently complain of fatigue since fatigue is an early symptom of scurvy 35 , the role of vitamin C deficiency should be further explored 36 . Scurvy is also associated with increased bone resorption 37 , and impaired resistance to infection. Many of the symptoms of scurvy are seen in dialysis patients, and therefore specific diagnosis has been difficult to achieve. To resolve this controversy, a controlled trial of vitamin C supplements in patients with low plasma vitamin C levels is warranted to examine its effect on scurvy-like symptoms.

Radiocontrast

Increased endothelin release, others demonstrated that different contrast agents had varying effects on the renal circulation. For example, pretreatment with BQ123 (a selective endothelin (ETA) receptor antagonist), but not with phosphoramidon (an endothelin-converting enzyme inhibitor), inhibited the sustained fall in renal perfusate flow produced by both iotrolan and diatri-zoate. BQ123 markedly potentiated the renal vasodilatation produced by diatrizoate 185 and the AT1 receptor blocker, bosentan, prevented reduction in crea-tinine clearance after diatrizoate 186 . However, subsequent studies in the IPRK however suggest that NO and endothelin-mediated events are independent and not modulated by these radiocontrast agents. For example, in careful dose response studies in the IPRK, Morcos et al 187 observed that L-NAME did not interfere with the vasodilatation induced by diatrizoate in the presence of BQ123 and concluded that diatri-zoate did not interfere with endothelium derived...

Mercuric chloride

A progressive fall in glomerular capillary plasma flow is observed in mercuric chloride-induced acute renal failure although the site of the main histological lesion is the proximal tubule. Studies in the IPRK showed that intense mercuric chloride-induced vasoconstriction could be inhibited by captopril but not enalapril arguing against renin-angiotensin system involvement, with binding of free Hg by the sulphydryl group of captopril suggesting a simpler explanation and supporting possible attack by Hg to tissue thiol moieties as the mechanism for vasoconstriction 194 . However, vasoconstriction was absent in the non-filtering IPRK, suggesting that intraluminal mechanisms might be involved 169 . Adenosine analogues selective for the A1 subclass of adenosine receptors, such as N6-cyclohexyladenosine (CHA), induce vasoconstriction in the IPRK 195 . However, theophylline failed to reverse mercuric chloride-induced vasoconstriction 196 . More recent studies in vivo suggest that increased...

Other Constituents

Contemporary dialysis fluids can be either glucose-free or contain glucose up to 200 mg l. The use of glucose-free dialysis fluid is associated with significant glucose loss during treatment with a risk of hypoglycaemia and should be avoided. A glucose concentration of 100 mg dl seems reasonable for the majority of patients, such levels may also be helpful in ameliorating post-dialysis fatigue and headache 18 . Whilst 200 mg dl should be used for those patients in whom the nutritional value of supplementation is a priority. The kidney is a key organ of hydrogen ion (H+) handling, and metabolic acidosis is one of the main complications of uraemia. Correction through dialysis occurs through buffer supply, rather than through H + clearance. Diffusive influx of buffer into the patient has been used since the beginning of the dialysis era. Historically acetate was used, although acetate is not a buffer as such, but derives its buffering action through metabolism. Technical issues with the...

Conclusions

The preparation and composition of dialysis fluid is an important element of treatment optimisation since many of the constituents play a role in patient well-being. Whereas historically the composition of the dialysis fluid was matched to that of plasma in respect of electrolytes, today technology permits individualisation of the major components of dialysis fluid, such as the sodium and bicarbonate, to the patients requirements to improve treat- Early dialysis treatments were frequently accompanied by pyrogen reactions arising from bacterial contamination of the dialysis fluid. Today the focus is on the stimulation of mononuclear cells by bacterial fragments contributing to chronic inflammation associated with long-term haemodialysis therapy, which has led to suggestions regarding the desirability of using ultra-pure dialysis fluid to prevent or delay complications associated with their presence 31 .

Discussion

High molecular weight bacterial DNA weighs several billion Daltons 23 , but its confor-mational structure is different from proteins and this might influence the migration from one compartment to the other, in whichever direction. Actually we were able to detect fragments higher than 500 bp and this suggests that 'at least' 540 bp long DNA may traverse the membrane. This could happen during dialysis treatment where both the microorganism itself, as proposed by Hansard et al. 22 , or its DNA, freed from the bacterial cells, can pass through the membrane. and induce the production of cytokines such as IL-6. The study by Schindler et al. 17 deals with small DNA fragments in clinically used solutions and in dialysate, but they also performed PCR specific for larger fragments of bacterial DNA and were able to detect them. We were able to detect bacterial DNA in the whole blood of the patient prior to dialysis treatment, and for the same patient we were able to find the...

Complexity of Europe

Economics, Regulations and Framework for a Dialysis In the field of renal disease the comparison of the national economic strength (GDP) and the prevalence of end-stage renal disease (ESRD) patients suggests that economic factors may impose restrictions on treatments in European countries where the GDP per capita is below a limiting value (around USD 10,000) 14 . No correlation between economic strength and ESRD prevalence exists when the GDP per capita exceeds the USD 10,000 threshold (fig. 3). Among European countries, healthcare systems are funded either through taxation (the Beveridge model) or through premium-finance, mandatory social insurance (Bismarck model) 15 . The different structures of funding have certain implications regarding the organization of the provision of healthcare services. In countries in which the system is funded by taxation the presence of private healthcare providers is in general lower than in those countries where the funding system is based on social...

European Network

Fresenius started its activities as a dialysis provider at the end of 1996 following the merger of its dialysis business with the leading service provider in the US, the National Medical Care (Boston, Mass., USA). The creation of Fresenius Medical Care in Europe (FME) started from the original group of National Medical Care clinics in Portugal and Spain, and then FME decided to develop a European network in order to become a global player. Through strategic acquisitions, the construction of de novo clinics, privatizations and participation in public tenders, FME was able to build a network currently (end of August 2006) involving more than 320 clinics located in 15 countries and treating more than 24,000 patients, which corresponds to 9-10 of all HD patients in those countries (fig. 8). Other functions directly involved in the provision of dialysis services are (1) Innovation and Technology Dialysis Care which supports and coordinates the construction of new facilities and the...

Acknowledgements

3 NKF-DOQI Clinical Practice Guidelines for Peritoneal Dialysis Adequacy. New York, National Kidney Foundation, 1997. 4 NKF-DOQI Clinical Practice Guidelines for the Treatment of Anemia of Chronic Renal Failure. New York, National Kidney Foundation, 1997. 6 NKF-DOQI Clinical Practice Guidelines for Nutrition in Chronic Renal Failure. New York, National Kidney Foundation, 2000. 7 European best practice guidelines for the management of anaemia in patients with chronic renal failure. Working Party for European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure. Nephrol Dial Transplant 1999 14(suppl 5) S1-50. 8 Renal Association. Treatment of Adult Patients with Renal Failure Recommended Standards and Audit Measures, ed 2. Peters-field, Renal Association, 1997. 10 Marcelli D, Moscardo V, Steil H, Day M, Kirchgessner J, Mitteregger A, Orlandini G, Gatti E. Data management and quality assurance for dialysis network in Ronco C, La Greca G (eds)...

Managing Complexity

As pointed out, while different country settings impose different combinations of services and require adaptation to local practices, international clinical outcome guidelines determine the same level of quality care to be delivered. The challenge today is to give the right answer to satisfy the expectations of payers and to achieve the same level of good dialysis outcome that all patients deserve. This standardization, and the way it is built and communicated, is not meant to make the world flat, on the contrary it drives resources on the important issue managing specific and variable aspects of treating an individual dialysis patient. The NCXL framework system provides solutions to standard problems, so the organization can promptly react to deviations and, as applicable, can redefine the platform. The first step is to define and share 'core' values and technologies on a 'meta-national' basis. Consensus on the 'core' elements was the result of a long process involving FME as a...

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