Volume 5 Issue 7, July 2009

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.

An observational study suggests that administration of phosphorus binders dramatically improves survival rates in patients on incident hemodialysis—even in those without hyperphosphatemia. Randomized clinical trials should drive changes in the relevant clinical practice.

Regardless of baseline blood pressure, treatment with a combination of an angiotensin-converting enzyme inhibitor and a diuretic decreases incidence of renal events in patients with type 2 diabetes. The combination therapy approach could be the key to achieving renoprotection.

In participants of the CONVERT trial, which enrolled recipients of kidney transplants, conversion of immunosuppressive therapy from calcineurin inhibitors to sirolimus did not improve renal function. More importantly, the intervention was detrimental among patients with impaired kidney function and/or proteinuria. Sirolimus conversion resulted, however, in lower rates of malignancy.

The prevalence of chronic kidney disease (CKD) is increasing worldwide. The best therapies currently available aim to control blood pressure and maximize renin–angiotensin–aldosterone system blockade but are only partially effective in humans. A number of emerging therapies have shown benefit in animal models of CKD, and some have been tested to a limited extent in humans. This Review examines these emerging pharmacological strategies in the context of diabetic nephropathy, diabetic and nondiabetic CKD and autosomal dominant polycystic kidney disease.

Glomerular filtration rate usually decreases with advancing age as a result of structural and functional changes in the aging kidney, but women are substantially protected against the age-dependent decline in renal function. This sexual dimorphism is the product of differences in chromosomes, perinatal programming and gonadal hormones (sex steroids) that create sexual phenotype. In this Review, Chris Baylis focuses on the role of the sex steroids, with a particular emphasis on the effects of sex and age on the nitric oxide system.

The evaluation of diabetic nephropathy from both research and clinical viewpoints depends on the assessment of two continuous variables, albumin excretion rate (AER) and glomerular filtration rate (GFR). Although increases in AER generally precede a decline in GFR, some patients follow a non-albuminuric pathway to renal impairment. In this Review, George Jerums and colleagues explain why serial assessments of both AER and GFR should be performed at an early stage in patients being evaluated for diabetic nephropathy.

Sleep disturbances are much more prevalent in the dialysis population than in the general population, and have a major effect on the vitality and general health of these patients. In this Review, Koch and colleagues discuss circadian sleep–wake rhythm disturbances in individuals with end-stage renal disease. The possible external and internal influences on sleep–wake rhythmicity in such patients—such as the effect of dialysis, medications, melatonin and biochemical parameters—are presented, and possible approaches for strengthening the synchronization of the circadian sleep–wake rhythm are explored.

The lesions associated with the rare granulomatosus disease malacoplakia, which can result in serious complications, are often mistaken for renal abscesses or malignant growths. Sanchez and colleagues describe the presentation of a woman whose malacoplakia involved both ureters and the bladder and required the placement of bilateral percutaneous nephrostomy tubes.

Weibel–Palade bodies, organelles of storage and secretion in endothelial cells, harbor a range of bioactive substances, including von Willebrand factor, angiopoietin 2, and interleukin 8. The authors of this Perspectives article examine the biogenesis and exocytosis of Weibel–Palade bodies and propose that these organelles could have key roles in the development of endothelial dysfunction and as a first-line response to acute stressors such as ischemia.