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Studies have shown that rituximab, a chimeric monoclonal antibody that targets the CD20 antigen of B cells, might be a valuable alternative to current therapies for idiopathic membranous nephropathy. In this Viewpoint article, Ruggenenti and colleagues discuss the use of rituximab in idiopathic membranous nephropathy and reason that titrating rituximab therapy to CD20⁺cell counts might be an effective way of limiting patient exposure to rituximab without reducing the efficacy of treatment, and would also substantially reduce treatment costs.

The slowly progressing nature of chronic kidney disease makes the design of clinical trials with hard end points extremely challenging. One way of establishing a drug's effectiveness is by demonstrating an effect on a surrogate end point. In this Perspectives article, the authors describe data supporting proteinuria as a valuable predictor of renal survival and argue that it should be used as a surrogate marker of renal disease progression in renal clinical trials.

Membranous nephropathy is an immune-mediated disease and is the leading cause of nephrotic syndrome in adults. Here, the authors discuss the role of B cell-depleting regimens in the treatment of this disease and the potential use of rescue therapy with agents that target plasma cells, which might prevent antigen–antibody interactions and immune complex-mediated complement activation.

The enthusiasm for pancreatic β-cell islet transplantation that followed the introduction of the 'Edmonton protocol' in 2000 has been tempered by evidence that the immunosuppressants used in the protocol might be nephrotoxic and that the resultant insulin independence is only short-term in most patients. Cravedi and colleagues analyze the risks and benefits of islet transplantation and argue that it should not be regarded as a general alternative to insulin replacement therapy for patients with type 1 diabetes mellitus.

Standard treatments to reduce cardiovascular risk, including mineralocorticoid receptor antagonists, have not lowered the high cardiovascular mortality and morbidity of patients on long-term haemodialysis. Future research should focus on targeting inflammatory pathways that are activated when blood interacts with dialysis membranes.

Angiotensin II and other components of the renin–angiotensin–aldosterone system (RAAS) have a central role in the pathogenesis and progression of diabetic renal disease. In this Review, Ruggenenti and colleagues describe the roles of angiotensin II and other effectors of the RAAS—such as aldosterone and renin—in the pathogenesis and progression of diabetic renal disease. In addition, they discuss the renoprotective and cardioprotective effects that inhibition of these effectors may have in individuals with diabetes.

Including proteinuria in the NKF KDOQI staging system for chronic kidney disease will increase the accuracy of risk stratification, but will not improve the precision of glomerular filtration rate (GFR) estimation by prediction formulas. Using markers of glomerular filtration other than serum creatinine will hopefully enable implementation of novel formulas that more precisely estimate true GFR, especially in individuals with near-normal renal function.

ONTARGET showed that dual renin–angiotensin system blockade prevents microalbuminuria but facilitates transient renal function impairment in nonproteinuric patients with atherosclerotic vascular disease or diabetes. These findings should not be used as an excuse not to optimize renin–angiotensin system inhibition and target urinary protein in patients with proteinuric nephropathies.

Candesartan doses in excess of the recommended antihypertensive maxima have been reported to lead to greater reductions of proteinuria than the advised doses. High-dose angiotensin-converting-enzyme inhibitors, however, are at least as effective as high-dose angiotensin blockers and less expensive. Angiotensin-converting-enzyme inhibition is thus the first-line strategy to halt kidney disease progression.

A new meta-analysis shows that dual blockade of the renin–angiotensin system is the most effective approach to prevent end-stage renal disease in patients with diabetes and kidney disease. Combination therapy should therefore be reconsidered as the most powerful tool for nephroprotection, provided that treatment is individually tailored by careful dose-titration.

A recent meta-analysis concluded that the risk-to-benefit ratio of dual (versus single-drug) renin–angiotensin system blockade argues against the use of dual therapy. This conclusion, however, seems inconsistent with the actual data and may convey to physicians a misleading message that could misdirect important decisions on treatment.

German health-care providers should be applauded for their heroic efforts in facing the 2011 Escherichia coli O104:H4 outbreak. However, a unique opportunity was missed to compare the efficacy of antibiotics, plasma therapy and eculizumab therapy in a randomized study, and the open questions concerning the optimal treatment of severe Shiga-toxin-associated haemolytic uraemic syndrome remained unanswered.

In this Perspectives article, Porrini and colleagues appraise the results of studies that have compared the performance of formulae developed to estimate glomerular filtration rate (GFR) against measured GFR reference methods. They contend that the persistence of errors in GFR estimation formulae indicates an inadequacy of serum creatinine and cystatin C levels as markers of actual renal function.

Here, the authors describe the determinants of ‘absolute’ and ‘relative’ glomerular hyperfiltration and discuss single-nephron haemodynamic changes as pathophysiological factors that might result in progressive kidney injury. They also explain how interventions that mitigate glomerular hyperfiltration might translate into long-term renoprotection.

A meta-analysis of individual-level patient data from 66 clinical studies supports the utility of glomerular filtration rate as a surrogate endpoint in clinical trials for chronic kidney disease, with potential to enable detection of events earlier in the disease course.

The incidence of obesity-related glomerulopathy (ORG) — a distinct entity featuring proteinuria, glomerulomegaly, progressive glomerulosclerosis and renal functional decline — is increasing in parallel with the obesity epidemic. Here, Vivette D'Agati and colleagues review the pathology, clinical features, treatment and pathogenesis of ORG.