Ustekinumab associated thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder. Plasma exchange therapy has been shown to significantly reduce mortality in patients with TTP. Here, we report a case of TTP associated with ustekinumab therapy after a period of 2-3 years. Ustekinumab, a monoclonal antibody that inhibits interleukin 12 and interleukin 23, is one of the newer treatments for psoriasis. Although our patient experienced a prolonged course of TTP requiring 1 month of daily plasma exchange therapy, he recovered and remains in remission after 6 months.

Practice pattern variation in oral glucocorticoid therapy after the induction of response in proliferative lupus nephritis.

Glucocorticoids are standard therapy for induction of response in proliferative lupus nephritis. However, the optimal duration of glucocorticoid therapy is uncertain. We surveyed physicians who treat lupus nephritis regarding their use of glucocorticoids in proliferative lupus nephritis after induction of response and regarding factors associated with different practice patterns. We administered a questionnaire of standardized cases assessing glucocorticoid use after induction of response to specialists with expertise in proliferative lupus nephritis. We examined the association between continuation of glucocorticoids and patient and physician characteristics. Of 90 invited participants, 72 (80%) responded. A total of 24 (33%) respondents attempted to discontinue glucocorticoids in all scenarios, 21 (29%) continued glucocorticoids in all scenarios, and 27 (38%) attempted to discontinue in some scenarios but not others. Responses varied according to the physician group (p < 0.001) and by years in practice (p < 0.001). Of those who discontinued glucocorticoids in selected scenarios, 15/27 (55%) were influenced by the characteristics of the induction of response, 16/27 (59%) by past lupus history, and 9/27 (33%) by the tolerance and use of immunosuppression. We conclude that glucocorticoid therapy after induction of response in proliferative lupus nephritis is varied. This variability likely represents clinical equipoise. A randomized trial evaluating the effect of glucocorticoid use after induction of response is warranted.

Challenges for randomized controlled trials in nephrology: illustrations in vascular access science and care.

While randomized controlled trials (RCTs) are the gold standard for evidence in medicine, there is an overall paucity of RCTs in nephrology compared with other medical subspecialties. Consequently, the management of the dialysis population is often guided by nephrology clinical practice guidelines that are largely based on observational data or expert opinion. This review examines problems related to designing, conducting and completing RCTs in nephrology, highlighting major challenges, successes and frustrations, with specific examples as they pertain to the science of hemodialysis vascular access and their impact on clinical practice guidelines.

Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO).

Considerable variation in grading systems used to rate the strength of guideline recommendations and the quality of the supporting evidence in Nephrology highlights the need for a uniform, internationally accepted, rigorous system. In 2004, Kidney Disease: Improving Global Outcomes (KDIGO) commissioned a methods expert group to recommend an approach for grading in future nephrology guidelines. This position statement by KDIGO recommends adopting the Grades of Recommendation Assessment, Development, and Evaluation (GRADE) approach for the grading of evidence and guidelines on interventions. The GRADE approach appraises systematic reviews of the benefits and harms of an intervention to determine its net health benefit. The system considers the design, quality, and quantity of studies as well as the consistency and directness of findings when grading the quality of evidence. The strength of the recommendation builds on the quality of the evidence and additional considerations including costs. Adaptations of the GRADE approach are presented to address some issues pertinent to the field of nephrology, including (1) the need to extrapolate from studies performed predominantly in patients without kidney disease, and (2) the need to use qualitative summaries of effects when it is not feasible to quantitatively summarize them. Further refinement of the system will be required for grading of evidence on questions other than those related to intervention effects, such as diagnostic accuracy and prognosis.

Association between renal insufficiency and malnutrition in older adults: results from the NHANES III.

BACKGROUND: The extent to which relevant confounding variables influence the recognized association between renal insufficiency and malnutrition is not known. This study examined whether renal insufficiency was associated with malnutrition, independent of relevant demographic, social, and medical conditions in noninstitutionalized adults 60 years of age and older. METHODS: Participants (5248) in the United States Third National Health and Nutrition Examination Survey (NHANES III, 1988 to 1994), a cross-sectional study, were examined in a multivariate logistic regression model. Participants were stratified into three groups of glomerular filtration rate (GFR) by serum creatinine. Dietary and nutritional factors were estimated from 24-hour dietary recall, biochemistry measurements, anthropometry, and bioelectrical impedance. Participants were malnourished if they demonstrated at least three of the following five criteria: (1) serum albumin < or =37 g/L, (2) male weight < or =63.9 kg, female weight < or =51.8 kg, (3) serum cholesterol <4.1 mmol/L, (4) energy intake <15 kcal/kg/day, and (5) protein intake <0.5 g/kg/day. RESULTS: A GFR <30 mL/min/1.73 m(2) was present in 2.3% of men and 2.6% of women; these participants demonstrated low energy and protein intake and higher serum markers of inflammation. Thirty-one percent of individuals with malnutrition demonstrated a GFR <60 mL/min/1.73 m(2). In multivariate analysis, a GFR <30 mL/min/1.73 m(2) was independently associated with malnutrition [odds ratio 3.6 (2.0 to 6.6)] after adjustment for relevant demographic, social and medical conditions. CONCLUSIONS: It is probable that renal insufficiency is an important independent risk factor for malnutrition in older adults. Malnutrition should be considered, prevented, and treated as possible in persons with clinically important renal insufficiency. These results should be confirmed in a prospective longitudinal cohort study.

Building the evidence in peritoneal dialysis: use of randomized controlled trials, and observational and registry data.

Renal replacement therapy (RRT) has achieved widespread acceptance without being subjected to the rigors of randomized controlled clinical trials (RCCTs). The RCCT remains the "gold standard" of evidenced-based medicine, but ethical, logistic, and financial limitations mean that not all questions are amenable to a RCCT. Renal registries collect, aggregate, analyze, and interpret data on the occurrence and outcome of renal failure in a defined population. Observational data can be used only to show associations, not causality. Nevertheless, most clinical practice guidelines in nephrology are derived from observational data. The nephrology community needs to join forces to decide the questions that deserve the time, energy, and resources of an RCCT. Prospective observational data can be enhanced by collaboration, standardized definitions, development of a risk-adjustment tool, and consensus among the key players, including professional associations, government, industry, and hospitals. The challenge is to provide evidence-based practice guidelines for the delivery of care to the end-stage renal patient.

Plasma exchange in rapidly progressive renal failure due to multiple myeloma. A retrospective case series.

BACKGROUND/AIMS: To evaluate the effect of plasma exchange on renal function in patients with rapidly progressive renal failure secondary to multiple myeloma. METHODS: The study was done through a retrospective chart review using a standardized form at a tertiary care centre in southwestern Ontario. Patients were included in the study if they had a diagnosis of multiple myeloma and rapidly progressive renal failure. Multiple myeloma was defined by a bone marrow aspirate >15% plasma cells plus one of the following: serum monoclonal paraproteins, monoclonal light-chain excretion, or lytic lesions. Patients were excluded if they had evidence of chronic renal failure or failed to complete three plasma exchanges. Twenty-six patients were reviewed; of these 24 were followed up to 1 year. All patients received hydration, standard chemotherapy, and plasma exchange. The plasma exchange volume was 50 ml/kg of 50% normal saline and 50% human serum albumin. Primary outcome measures included (1) prevention of acute dialysis and (2) prevention of progression from acute to chronic dialysis; secondary end points included (1) a decrease in creatinine of 25% or more within 3 months of the last plasma exchange and (2) survival at 1 year. RESULTS: Sixteen of 24 patients, followed up to 1 year, did not require dialysis. Two patients required dialysis initially, but were able to come off dialysis after 3 months. Fourteen patients were alive at 1 year, 13 of whom were dialysis independent. Twelve of 13 dialysis-independent patients had a >25% reduction in creatinine at 3 months. Two patients were lost to follow-up after discharge and were not included in the analysis. CONCLUSIONS: This retrospective study suggests that plasma exchange may offer some benefit in preventing the initiation or continuation of dialysis in patients with rapidly progressive renal failure secondary to multiple myeloma. A randomized controlled prospective study is needed to determine whether plasma exchange should be recommended as a standard treatment for patients with rapidly progressive renal failure due to multiple myeloma.

Management of chronic renal insufficiency in lupus nephritis: role of proteinuria, hypertension and dyslipidemia in the progression of renal disease.

Non-immune mechanisms appear to be important in the majority of patients with lupus nephritis and progressive renal injury. Proteinuria, hypertension and dyslipidemia are associated non-immune risk factors often implicated in the deterioration of kidney function. There is ample animal experimental evidence that they are independent risk factors for progressive renal injury and their treatment results in amelioration of renal function. Proteinuria and hypertension, unlike dyslipidemia, have been shown to be independent risk factors for progressive renal injury in patients with lupus nephritis. Treatment of hypertension and proteinuria in the diabetic and non-diabetic progressive renal disease population results in stabilization of kidney function. Response to treatment should target both blood pressure of 120/80 and significant reductions in protein excretion. If protein excretion rate is unaltered by use of an angiotensin-converting enzyme inhibitor and salt restriction, one might resort to the use of an angiotensin II antagonist. Treatment of the dyslipidemia following good control of proteinuria, blood pressure and dietary change may not alter renal progression but should provide similar protection from accelerated vascular disease to the non-renal dyslipidemia population.