Volume 8 Issue 5, May 2012

Measurement of glomerular and peritubular capillaritis in kidney transplant biopsy samples identifies allograft dysfunction associated with alloantibodies. Sis et al. show that this technique has a higher sensitivity but lower specificity than the current diagnostic criteria using peritubular capillary C4d deposition, and that capillaritis is an independent predictor of progression to graft failure.

Aliskiren combined with other inhibitors of the renin–angiotensin system increases the risk of hyperkalemia. This risk does not translate into an increased incidence of acute kidney injury, suggest the results of a meta-analysis. However, further research is needed to fully evaluate the safety of combination therapy with aliskiren.

The association between obesity and mortality has been observed to be paradoxical in persons on dialysis. Hoogeveen et al. examined whether the association between obesity and mortality on dialysis differed by age in participants in the NECOSAD2 study.

Comparisons of sodium chloride and sodium bicarbonate for the prevention of contrast-induced acute kidney injury have produced inconclusive results. A new study by Klima et al. shows that sodium chloride provides greater renal protection than does sodium bicarbonate following exposure to contrast medium. However, this finding should be interpreted with caution.

A consistent association between hyponatremia and increased mortality has been shown in hospitalized patients. A new study investigating dysnatremia in non-dialysis-dependent patients with chronic kidney disease found that both hyponatremia and hypernatremia are associated with increased mortality, independently of other diseases known to cause hyponatremia.

Numerous epidemiologic studies have shown a strong association between being born with a low birth weight or being born small for gestational age and the development of renal and cardiovascular disease in adult life. Here, Abitbol and Rodriguez describe how this phenomenon might relate to developmental programming of adult disease during vulnerable periods of growthin uteroand during the early postnatal period. They also discuss potential early interventions that might alter the progression of such disease.

IgA nephropathy is a common cause of glomerulonephritis. The presence of aberrantly galactosylated IgA1 and production of glycan-specific antibodies initiates mesangial deposition of immune complexes and subsequent tubulointerstitial injury. In this Review, Kar Neng Lai summarizes the latest findings in the pathogenesis of IgA nephropathy, including genetic factors and mesangial-derived mediators that lead to podocyte and tubulointerstitial injury via mesangio–podocytic–tubular crosstalk.

Early initiation of dialysis has been recommended by guidelines over the past two decades, but recent studies and a randomized, controlled trial indicate that patients who start dialysis early might in fact have worse outcomes. The authors of this Review discuss studies of early and late dialysis initiation and highlight factors that influence the association between dialysis initiation and outcomes in transplant-naive patients with chronic kidney disease and in patients with a failed allograft.

Glomerular hyperfiltration occurs as a physiological response during pregnancy and after consumption of high-protein meals, but an elevation in glomerular filtration rate is also associated with various disease states. In this Review, the authors discuss the definitions of glomerular hyperfiltration as well as the underlying mechanisms and hemodynamic changes that can adversely affect kidney function. They also describe potential approaches to treat glomerular hyperfiltration.

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.

In this Perspectives article, Aliza Thompson from the FDA's Division of Cardiovascular and Renal Products argues that existing data do not support the adoption of proteinuria as a general-purpose surrogate end point for establishing a drug's effectiveness in treating chronic kidney disease. She suggests, however, that it may be reasonable to use changes in proteinuria as a basis for the accelerated approval of a drug if certain conditions are met.