Thin Glomerular Basement Membrane in a Kidney Transplant of an Alport's Syndrome Patient: A Case Report.

Alport syndrome (AS) and thin basement membrane lesions are caused by various mutations in type IV collagen genes. Although AS is considered a rare disease, thin basement membrane is a frequent pattern, especially in families with a history of persistent hematuria. We report a patient with a diagnosis of AS who developed end-stage kidney disease (ESKD) and received a kidney transplant from a living unrelated donor. The graft biopsy specimen surprisingly showed a pattern of thin basement membranes.

Blood pressure targets in hemodialysis patients.

Guidelines on blood pressure control in dialysis patients are opinion-based. Effectiveness and risk analyses were not performed prior to implementation. We discuss this in the context of a study auditing blood pressure control in this population.

Patient education: can it maximize the success of therapy?

The majority of patients with chronic renal insufficiency (CRI) have only limited knowledge of their condition. Various studies of the benefits of patient education programmes have shown that educated patients have a reduced incidence of emergency dialysis compared with control patients. Additionally, more educated patients are able to start dialysis as an outpatient rather than in hospital. An education programme also allowed a greater number of blue-collar workers to remain employed after starting dialysis. The US National Pre-End-Stage Renal Disease (pre-ESRD) Education Initiative, which is currently in progress, aims to educate a large number of pre-ESRD patients on kidney function, renal failure, dialysis, and transplant options. Preliminary results suggest that the initiative influences the choice of dialysis and that, regardless of race, age, and co-morbidities, the incidence of peritoneal dialysis could be increased in ESRD patients in the US. Education on other components of therapy may also influence patient outcomes. In the management of renal anaemia, improved education, and advances in the delivery systems available for administration of erythropoietin may be important factors in improving patient compliance and maximizing the success of treatment. Thus, education of patients early in the course of CRI offers many potential benefits for patients and healthcare professionals, including improved treatment outcomes, reduced anxiety, greater prospect for continued employment, improved timing for the start of dialysis, and a greater opportunity for intervention to delay disease progression.

Chronic kidney disease: why is current management uncoordinated and suboptimal?

Morbidity and mortality associated with chronic kidney disease (CKD) is higher than that of the normal population, and the incidence of end-stage renal disease (ESRD) continues to increase. Several factors contribute to the uncoordinated and suboptimal management of CKD, including the attitude and behaviour of nephrologists, referring physicians and patients, and economic constraints on healthcare systems. Late referral of at-risk patients to specialist care is an area of particular concern, as this denies nephrologists adequate opportunity to prevent progression of CKD and associated complications such as anaemia. Due to the ageing population and advances in technology, the costs of treating CKD and ESRD continue to escalate and represent another barrier to the delivery of optimal care. Optimizing the care provided to CKD patients requires a coordinated approach to the management of the condition. Closer collaboration and improved communication across specialities is important for the timely referral of patients and for efficient utilization of available resources. A multidisciplinary approach may facilitate patient identification and improve the management of CKD.

Sustained low-efficiency dialysis for critically ill patients requiring renal replacement therapy.

BACKGROUND: The replacement of renal function for critically ill patients is procedurally complex and expensive, and none of the available techniques have proven superiority in terms of benefit to patient mortality. In hemodynamically unstable or severely catabolic patients, however, the continuous therapies have practical and theoretical advantages when compared with conventional intermittent hemodialysis (IHD). METHODS: We present a single center experience accumulated over 18 months since July 1998 with a hybrid technique named sustained low-efficiency dialysis (SLED), in which standard IHD equipment was used with reduced dialysate and blood flow rates. Twelve-hour treatments were performed nocturnally, allowing unrestricted access to the patient for daytime procedures and tests. RESULTS: One hundred forty-five SLED treatments were performed in 37 critically ill patients in whom IHD had failed or been withheld. The overall mean SLED treatment duration was 10.4 hours because 51 SLED treatments were prematurely discontinued. Of these discontinuations, 11 were for intractable hypotension, and the majority of the remainder was for extracorporeal blood circuit clotting. Hemodynamic stability was maintained during most SLED treatments, allowing the achievement of prescribed ultrafiltration goals in most cases with an overall mean shortfall of only 240 mL per treatment. Direct dialysis quantification in nine patients showed a mean delivered double-pool Kt/V of 1.36 per (completed) treatment. Mean phosphate removal was 1.5 g per treatment. Mild hypophosphatemia and/or hypokalemia requiring supplementation were observed in 25 treatments. Observed hospital mortality was 62.2%, which was not significantly different from the expected mortality as determined from the APACHE II illness severity scoring system. CONCLUSIONS: SLED is a viable alternative to traditional continuous renal replacement therapies for critically ill patients in whom IHD has failed or been withheld, although prospective studies directly comparing two modalities are required to define the exact role for SLED in this setting.

Indications for vancomycin in dialysis patients.

Resistance to vancomycin has emerged among Staphylococcus aureus, coagulase-negative staphylococci (CNS), and enterococci, and this emergence has particular prevalence in dialysis units. It has therefore become imperative that physicians use vancomycin judiciously. General recommendations regarding the appropriate use of vancomycin have been developed. Although in theory implementation of these guidelines should not be difficult, the medical community may be unable or unwilling to make the necessary adjustments in practice. The onslaught of cost constraints and bureaucratic encumbrance has occurred simultaneously with the increase in vancomycin resistance among pathogens commonly isolated among the dialysis population. When a patient responds to empiric antibiotic therapy and susceptibility data indicate that an antibiotic other than vancomycin would be appropriate, the clinician far too often does not make the change to this alternative. Previously there was no biological imperative to change the antibiotic. That complacency has infected an entire generation of physicians, and especially nephrologists. Furthermore, there is an active movement against change, driven by concerns such as malpractice accusations and frank errors in the interpretation of medical facts.

Methods used to evaluate the quality of evidence underlying the National Kidney Foundation-Dialysis Outcomes Quality Initiative Clinical Practice Guidelines: description, findings, and implications.

This report describes the approach the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) used to assess the strength of published evidence pertinent to individual NKF-DOQI Clinical Practice Guidelines, as well as the relationship between that approach and methods used by the US Preventive Services Task Force, the Cochrane Collaboration, and the Agency for Health Care Policy and Research to rate the quality and/or strength of evidence. We also present the results of an analysis of the strength of evidence underlying the NKF-DOQI Guidelines showing that one cannot infer the quality of evidence reported in a study (rated either on a 0-to-1 scale or categorically as excellent, very good, good, fair, or poor) simply by knowing the type of study design used (randomized trial, nonrandomized trial, natural experiment, cohort study, cross-sectional study, case-control study, case report). Issues related to assessment of the strength of evidence underlying a practice guideline opposed to that reported in an individual study are highlighted.

Impaired biological activity of erythropoietin by cyanate carbamylation.

AIMS: During advanced renal failure, particularly in patients with end-stage renal disease (ESRD), proteins are carbamylated as a result of a reaction with cyanate. Some or all of the cyanate is derived from urea. If the carbamylation of proteins adversely alters their biologic activities, then urea must be viewed as an uremic toxin, rather than a surrogate. Therefore, we studied the effect of cyanate carbamylation on the erythropoietic activity of erythropoietin (EPO) in a rodent model. METHODS: EPO was carbamylated by incubation with cyanate at 37 degrees C. The extent of carbamylation was monitored using trinitrobenzenesulfonic acid. In Sprague-Dawley rats the erythrocyte count, hemoglobin concentration, and hematocrit were measured after the twice-weekly subcutaneous injection of either EPO or carbamylated EPO for 3 weeks. Two additional control groups received physiologic saline or 0.2 ml of 1 M cyanate. RESULTS: The level of carbamylated EPO was increased as the time of exposure to cyanate increased from 1 to 6 h, and as the cyanate concentration increased from 8 to 2,000 mM. EPO injections caused significantly large increases in all erythropoietic measures. Physiologic saline or 1 M cyanate-injected controls and the carbamylated EPO-injected animals demonstrated no change from baseline in erythropoietic parameters. CONCLUSION: These results support that EPO exposed to high levels of cyanate in vitro demonstrates diminished biologic activity in healthy Sprague-Dawley rats. This effect may be manifested by the carbamylation of EPO by the cyanate. Should this occur in ESRD patients, it may contribute to the suboptimal erythropoietic response to EPO therapy associated with high urea levels, especially related to inadequate dialysis. Targeting dialysis doses specifically to urea concentrations may be more important than previously considered.

Tumour lysis syndrome complicating high-dose treatment in patients with multiple myeloma.

Tumour lysis syndrome (TLS), because of its low proliferative activity, is thought to only rarely complicate the treatment of patients with multiple myeloma. However, as more aggressive therapeutic approaches are increasingly used in the management of this disease, it is conceivable that clinicians will encounter this complication more frequently. A retrospective analysis of > 800 patients with multiple myeloma treated at the University of Arkansas identified nine patients who developed a marked tumour lysis syndrome following intermediate- or high-dose chemotherapy. Evaluation of disease characteristics revealed association with high tumour mass, high proliferative activity, increased lactic dehydrogenase levels, plasmablastic morphology, and unfavourable cytogenetic abnormalities. Recognition of multiple myeloma patients at high risk for the development of tumour lysis syndrome and prompt intervention are required especially in the presence of abnormal baseline renal function frequently complicating the clinical course of these patients.

Morbidity and mortality in redefining adequacy of peritoneal dialysis: a step beyond the National Kidney Foundation Dialysis Outcomes Quality Initiative.

The National Kidney Foundation Dialysis Outcomes Quality Initiative (NKF-DOQI) Peritoneal Dialysis (PD) Adequacy Work Group intentionally limited the scope of its work to address adequacy in terms of small-solute removal. This decision was based on the need for rigorous evidence and that mortality is the most objective parameter in the literature. This review attempts to more broadly redefine the concept of the adequacy of PD, particularly as it relates to the most common general medical problems that PD patients experience; namely, cardiovascular disease and malnutrition. Whereas we are sensitive to the developmental process of the NKF-DOQI, we are critical that the definition of adequacy may be too narrow, leading clinicians to overlook other important morbidities. We have reiterated the evidence that suggests a weekly solute clearance (Kt/Vurea) of 1.7 or greater is associated with better patient survival. The arguments to target a greater Kt/Vurea of 2.0 are challenged, yet the concept is ultimately supported. Because cardiovascular disease is the cause of death in half of all patients with end-stage renal disease, dialysis adequacy must be defined, in part, by the potential of that therapy to diminish cardiovascular maladies. Blood pressure, volume, left ventricular hypertrophy, and dyslipidemias are discussed in this context. Lastly, assumptions that increasing total solute clearance leads to improved nutrition in PD patients are challenged. We have attempted to expand on what the NKF-DOQI did not include, and we urge the dialysis community to seek the answers to the many controversies that remain. We need to redefine the adequacy of PD in a holistic manner and find outcome parameters that are not as final as death.