ISN Must-Read Trials List
Once a month, the ISN-ACT (Advancing Clinical Trials) initiative team collects and publishes a list of important nephrology trials from the latest medical literature.
Hypertension: Urate lowering has no impact on blood pressure
McMullan, et al. Clin J Am Soc Nephrol. 2017;12(5):807-816
Elevated urate is consistently associated with hypertension and chronic kidney disease but it remains unclear if lowering urate improves clinical outcomes. This blinded randomized trial of uric acid lowering (using allopurinol or probenecid) included 149 normotensive, overweight patients with normal renal function. They were assessed for change in markers of kidney-specific renin-angiotensin system (RAS) activity. No significant reduction in RAS or blood pressure was observed despite marked lowering of serum urate. The pathophysiology of the link between urate and cardiovascular and renal disease remains elusive. The results of ongoing studies of urate lowering therapy are eagerly awaited.
Hypertension: Intensive dietary sodium interventions may reduce proteinuria
Meuleman, et al. Am J Kidney Dis. 2017;69(5):576-586
A reduction in sodium intake is an important but often elusive goal for patients with CKD. This multicentre study randomized 151 patients with CKD to a 3-month structured support intervention designed to foster a self-managed reduction in dietary sodium intake. When compared to the control group at 3-months the intervention group showed a 30mmol/day reduction in sodium excretion and significant reduction in diastolic blood pressure and proteinuria. At 6 months, the differences in sodium excretion and BP were not maintained, although the reduction in proteinuria persisted. This study demonstrates the impact of dietary interventions on important renal and cardiovascular risk factors but also highlights the challenges in promoting durable changes in lifestyle.
Transplant: Improvement in eGFR with belatacept over CnI maintained at 3 years
Grinyo, et al. Am J Kidney Dis. 2017;69(5):587-594
Conversion from calcineurin inhibitor to co-stimulation blocker belatacept has been shown to result in improvement in renal function out to 2-years. Here Grinyo, et al. present the 3-year outcomes of their trial randomizing kidney transplant recipients to belatacept or continued use of calcineurin inhibitor at 6-36 months post-transplant. They found that the approximately 7ml/min/1.73m2 gain in eGFR seen at 2 years was maintained at 3-years. Notably, there was no difference in serious infections or malignancy (including no cases of post-transplant lymphoproliferative disorder). This study helps to solidify the role of belatacept as a useful agent in selected kidney transplant recipients.
CKD-MBD & Dialysis: Double dialyzers do not improve phosphate removal
Thompson, et al. Nephrol Dial Transplant. 2017;32(5):855-861
Control of hyperphosphataemia in patients with ESKD remains challenging and current dietary and pharmaceutical approaches are burdensome. Thompson, et al. designed a randomized crossover trial to test the novel strategy of using two high flux dialyzers in parallel to increase phosphate removal. Thirty-two patients spent ten weeks using either one or two dialyzers and, after a two week washout period, received a further ten weeks with the alternate therapy. At the end of the ten week period, predialysis serum phosphate and intradialytic phosphate removal did not differ between therapies. This study emphasises the intrinsic limitations of dialytic therapy on many uraemic toxins and the importance of studying other approaches such as increased time on dialysis or reduced toxin generation.
CKD-MBD & Dialysis: Tolerability limits use of nicotinamide as a phosphate lowering agent
Lenglet, et al. Nephrol Dial Transplant. 2017;32(5):870-879
Pill burden is a major limitation to the use of phosphate binders to control hyperphosphataemia in ESKD. Nicotinamide lowers serum phosphate via inhibition of phosphate transport across the intestinal and proximal tubular epithelium reducing phosphate absorption and increasing excretion. This open label trial randomized 100 participants to nicotinamide or sevelamer and followed them for 24 weeks. While nicotinamide did lower phosphate, non-inferiority compared with sevelamer could not be shown. Furthermore, the rate of withdrawal from therapy due to adverse events was higher in the nicotinamide group (24% vs 4%) mainly owing to gastrointestinal side effects and thrombocytopenia. While disappointing, this trial should encourage further work to identify agents that can be used either instead of, or in combination with, phosphate binders to improve phosphate control and quality of life for patients with ESKD.
General Medicine: Magnesium no better than placebo for leg cramps
Maor, et al. JAMA Intern Med. 2017;177(5):617-623
Nocturnal leg cramps are a frequent complaint among elderly patients with CKD but evidence-based therapies are few. This study of 94 older individuals with a history of frequent leg cramps randomized participants to magnesium oxide or matching placebo. Individuals with a creatinine over 2.0mg/dL were excluded. Over the four-week treatment period both groups experienced a reduction in leg cramps with no intervention effect apparent. This study challenges the commonly accepted use of magnesium for leg cramps and emphasises the importance of a placebo arm in studies with patient reported outcomes.