This Month's Highlights

doi:10.1681/ASN.2008060627

BASIC RESEARCH

Fenestral Diaphragms Come and Go

Endothelial cells of glomerular capillaries have fenestrae, which are transcellular pores that are highly permeable to water and small, hydrophilic solutes. Unlike most fenestrated endothelial cells, however, these fenestrae are thought to lack diaphragms, structures that impede passage of plasma proteins. Ichimura et al. report that glomerular endothelial cells of embryonic rats have diaphragmed fenestrae, but the diaphragms are predominantly lost during glomerulogenesis. With glomerular injury, however, the fenestral diaphragms return, perhaps reflecting remodeling of the damaged glomerular capillaries. The authors speculate that fenestral diaphragms may prevent protein passage during embryogenesis, compensating for an immature glomerular filtration barrier. See Ichimura et al., pages 1463–1471.

Biphasic Responses to Vitamin D

Observational studies have associated administration of active vitamin D analogs with improved survival among patients with ESRD, but these agents promote hyperphosphatemia and vascular calcification, both of which are associated with increased mortality. Mathew et al. sought to explain this apparent discrepancy in a mouse model of chronic kidney disease–induced aortic calcification. They report that vascular calcification is inhibited by dosages of vitamin D analogs that are just sufficient to lower parathyroid hormone, and this may be due to stimulation of osteoblast activity at the skeleton. Vascular calcification is stimulated, however, by higher dosages. If confirmed, then this biphasic response could have implications for vitamin D therapy in ESRD. See Mathew et al., pages 1509–1519.

Apoptosis of Thick Limb Yields AKI

Classic animal models of acute kidney injury (AKI) demonstrate an inflammatory response and widespread damage to the tubular epithelium. The extent of injury has confounded attempts to identify the relative contributions of each component to the overall syndrome. Srichai et al. report the creation of a transgenic mouse in which apoptosis can be selectively induced in epithelial cells of the thick ascending limb of Henle's loop. They found that this targeted acute injury is capable of leading to renal insufficiency, oliguria, and impaired concentrating ability. This unique approach provides a method to dissect the mechanisms underlying the complex AKI phenotype. See Srichai et al., pages 1538–1546.

CLINICAL EPIDEMIOLOGY

Pancreas Transplant Yields Long-term Benefits

The extent to which the pancreas allograft contributes to patient survival and long-term function of the kidney allograft in recipients of a simultaneous pancreas and kidney (SPK) transplant is controversial. Morath et al. analyzed data from >11,000 patients with type 1 diabetes and found that recipients of living-donor kidneys initially had superior rates of patient and graft survival, but recipients of SPK demonstrated a significant survival advantage beyond the 10th year after transplantation after adjusting for pretransplantation cardiovascular risk. This long-term benefit may result from the improved metabolic control conferred by a functioning pancreas. See Morath et al., pages 1557–1563.

Fatty Liver Predicts CKD Onset

Evidence is mounting that nonalcoholic fatty liver disease (NAFLD) is common among patients with type 2 diabetes, and it seems to be associated with other comorbidities (e.g., cardiovascular disease). Targher et al. hypothesized that NAFLD may predict new-onset chronic kidney disease (CKD), so they followed a cohort of nearly 2000 participants with type 2 diabetes but without CKD for 6.5 yr. Even after adjusting for multiple confounding factors, they found that NAFLD was associated with a 50% increased risk for development of CKD. These results suggest that individuals with type 2 diabetes and NAFLD may benefit from more intensive surveillance or therapy to decrease the risk for incident CKD. See Targher et al., pages 1564–1570.

CLINICAL RESEARCH

Calcitriol Beneficial in Stages 3 to 4 CKD

Oral activated vitamin D is used to reduce levels of parathyroid hormone in patients with pre-ESRD, but its effects on clinical outcomes are unknown. Shoben et al. studied data from nearly 1500 patients with stages 3 to 4 chronic kidney disease and hyperparathyroidism and found that use of calcitriol was associated with a 26% reduction in the risk for death and a 20% reduction in the risk for death or dialysis during a median follow-up of 2 yr. This study adds to the mounting observational evidence that associates vitamin D therapy with improved survival in patients with ESRD. See Shoben et al., pages 1613–1619.