BASIC RESEARCH
Podocytes Require Prorenin Receptor
Podocytes express the prorenin receptor (PRR), but whether this receptor contributes to podocyte function is unknown. In this issue, Riediger et al. and Oshima et al. each generated podocyte-specific PRR-knockout mice, which develop nephrotic syndrome, and found that the PRR contributes to the proper function of protein-turnover machinery and controls lysosomal pH, which ultimately maintains cytoskeletal structure. These mice also exhibit effacement of podocyte foot processes with deranged localization of the slit diaphragm proteins nephrin and podocin. Taken together, these results demonstrate that the PRR is critical for normal podocyte structure and function. See Riediger et al., pages 2193–2202, and Oshima et al., pages 2203–2212.
AT1A Receptors Modulate AQP2 to Concentrate Urine
The renin-angiotensin system modulates the ability to concentrate urine, but the underlying mechanisms are not completely understood. Stegbauer et al. generated mice lacking AT1A receptors in the collecting duct and found that this does not affect basal levels of plasma and urine osmolality. The lack of AT1A receptors does, however, attenuate the increase in urine osmolality in response to water deprivation or vasopressin. Furthermore, this appears to be a result of AT1A receptors directly modulating aquaporin-2 levels and not a result of differences in sodium delivery. These data provide a mechanism by which the renin-angiotensin system contributes to urinary concentration. See Stegbauer et al., pages 2237–2246.
Mouse Models Allow Study of Fibrocystin Biology
The lack of specific antibodies has limited the exploration of the biology of fibrocystin, the product of the PKHD1 gene, which leads to autosomal recessive PKD when mutated. Bakeberg et al. successfully generated a null Pkhd1 strain of mice as well as a strain that expresses an epitope-tagged endogenous fibrocystin. They report that Pkhd1 does not seem to generate many splice forms in vivo as previously thought, and that exosome-like vesicles secrete the majority of fibrocystin in its mature, cleaved form. These mouse models should promote better understanding of both the intracellular processing and shedding of fibrocystin as well as the pathophysiology of PKD. See Bakeberg et al., pages 2266–2277.
CLINICAL EPIDEMIOLOGY
Inflammation May Explain Racial Differences in ESRD Survival
African Americans on dialysis survive longer than Caucasians, on average, but the reasons for this difference are not well understood. To determine whether inflammation may contribute, Crews et al. studied a prospective national cohort of >800 incident dialysis patients. They suggest that although African Americans have a 30% lower risk of death than Caucasians overall, this relative risk significantly varies by tertile of C-reactive protein or IL-6. Racial disparities in survival are most pronounced among patients exhibiting the most inflammation. Thus, differences in the prevalence and response to inflammation may contribute to the observed racial differences in survival on dialysis. See Crews et al., pages 2279–2286.
CLINICAL RESEARCH
Enteral Feeding Improves Growth of Infants with CKD
Inadequate nutrition contributes to short stature among very young children with advanced CKD. Analyzing data from the International Pediatric Peritoneal Dialysis Network, Rees et al. identified significant regional variation with respect to changes in body mass index (BMI) in this population. Compared with demand feeding, they report that feeding via nasogastric tube or gastrostomy associates with greater increases in BMI. Furthermore, gastrostomy feeding, the use of biocompatible dialysate, and the use of growth hormone associate with greater linear growth. These data highlight interventions to study in clinical trials with an aim to improve growth in young children with CKD. See Rees et al., pages 2303–2312.
Bedtime Dosing of BP Medications Reduces Cardiovascular Risk
The time of day that one takes antihypertensive therapy may impact clinical outcomes, possibly by modulating sleep-time BP. Hermida et al. randomly assigned 661 patients with CKD either to take all prescribed antihypertensives in the morning or at least one of them at bedtime and followed them for a median of 5.4 yr. Those who took at least one medication at bedtime had an approximately 70% lower risk of cardiovascular events than those who took all medications in the morning. These results suggest that it may be possible to significantly reduce the risk of cardiovascular disease in CKD simply by adjusting the time of day that patients take their antihypertensive medications. See Hermida et al., pages 2313–2321.
- Copyright © 2011 by the American Society of Nephrology