Effects of Dietary Intake on WNK Activity and Distal Transport.
Geneticstudies of familial hyperkalemic hypertension (autosomal dominant,hyperkalemic hypertension with normal GFR) have linked the WNKpathways to regulation of BP and electrolyte balance. WNK4 inhibitsthe thiazide-sensitive NaCl co-transporter and renal outer medullaryK+ (ROMK)-mediated K+ secretion. The long isoform of WNK1 inhibitsthe WNK4 effect, and the short isoform of WNK1 inhibits theinhibitory effect of WNK1-L. The major finding reported by O’Reillyet al. relates to the regulation of WNK1-S expression by changesin dietary K+ and Na+ intake, as well as separate effects ofaldosterone on this regulatory system. The complexity of thesepathways is just beginning to be unraveled, but potentiallycan explain the finely coordinated balance of distal Na+ reabsorptionbetween electroneutral modes and electrogenic modes, which couldwell provide a level of regulation of K+ secretion in responseto variations in dietary intake that has long been suspectedbut not clearly defined in previous studies. See O’Reillyet al., pages 2402–2413.
Stem Cells in Bowman’s Capsule.
Whetherstem cells exist in the adult kidney remains a highly controversialand intensely studied question. Sagrinati and colleagues fromthe University of Firenze in Italy provide evidence for theexistence of adult stem cells in an unexpected location, namelyBowman’s capsule. They found that a subset of cells inthe urinary pole of Bowman’s capsule expresses two stemcell markers, CD24 and CD133. These CD24 and CD133 double-positivecells were isolated from the kidney and had two key propertiesof stem cells, the capacity for self-renewal and the capacityfor multilineage differentiation. Importantly, these propertiescould be demonstrated in clones derived from a single cell.When injected into mice with acute kidney injury, the cellscontributed to tubular regeneration and improved blood ureanitrogen. These exciting and provocative findings provide someof the strongest evidence for the existence of stem cells inthe adult human kidney. Because they can be isolated by flowcytometry, the clinical application of the cells should be facilitated.See Sagrinati et al., pages 2443–2456.
Peritubular Capillary Preservation as a Therapeutic Goal in CKD.
It haslong been known that loss of peritubular capillaries correlateswith renal functional loss in chronic kidney disease (CKD),but whether it is a cause or a consequence of fibrosis is stilldebated. Kim and colleagues investigated the effects of treatmentwith cartilage oligomeric matrix protein–angiopoietin-1(COMP-Ang1), a potent angiopoietin-1 variant, given via an adenoviralvector to mice with unilateral ureteral obstruction. Ang1 isan activating ligand for endothelial cell Tie2 receptors. Severalcleaver techniques were used to follow its effects on the interstitialmicrocirculation, including the use of mice with green fluorescentprotein–labeled endothelial cells and laser Doppler ultrasonography.Not only was COMP-Ang1 effective at preserving renal corticalblood flow (shown in the figure to the left) and interstitialcapillary density, but these effects were associated with asignificant reduction in TGF- and kidney collagen levels andtubular injury. An additional benefit may an anti-inflammatoryeffect due to reduced endothelial cell adhesiveness as the numberof interstitial macrophages was significantly reduced in theCOMP-Ang1 group. See Kim et al., pages 2474–2483.
The MedicarePart D prescription drug benefit is intended to reduce medicationcosts among Medicare beneficiaries. A peculiarity of Part Dis the variable coverage of medication costs imposed by the"doughnut hole" provision, which increases co-payments afteran initial $250 deductible from 25% for the first $2250 of drugcosts to 100% co-pay for the next $2850. This coverage gap isof concern to ESRD patients who have considerable drug costs.Patel et al. report in this issue of JASN that individuals withESRD may be subject to unexpected increases in medication costsunder Part D. Clinicians need to carefully monitor the impactof the new benefit to identify and deal with the effects ofincreased drug costs if they occur. Any adverse impacts needto be systematically documented and reported as the new benefitis rolled out, and if there is an unintended negative impactfor ESRD patients, CMS and Congress must be appraised of thisproblem so that suitable remedies can be devised. See Patelet al., pages 2546–2553.
BP and the Elderly.
Is renoprotectivetherapy that includes aggressive BP reduction to a goal of <130/85mmHg indicated for individuals in the 9th and 10th decade oflife who have otherwise asymptomatic stage 3 to 4 chronic kidneydisease? The report by van Bemmel et al. in this issue of JASN,from the Leiden 85-Plus Study, suggests caution as the authorsreport an inverse association between BP the rate of declineof creatinine clearance. They also observed that a decliningBP during follow-up was associated with increased rate of lossof kidney function. The population of elderly is growing enormouslyas a consequence of increased life expectancy and the demographicbulge of the postwar baby boom. The main import of these resultsis to remind us once again that therapeutic extrapolation toelderly populations of survivors should be done with extremecaution in the absence of evidence. See van Bemmel et al., pages2561–2566.
Another Advantage of Nocturnal Peritoneal Dialysis: It Reduces Sleep Apnea.
Nocturnalhemodialysis has previously been shown to improve sleep apneacompared with patients receiving conventional hemodialysis.In this issue of JASN, Tang et al. demonstrate that nocturnalperitoneal dialysis (NPD) is also effective in alleviating sleepapnea compared with continuous ambulatory peritoneal dialysis(CAPD). In this study, overnight polysomnography was comparedin 46 stable NPD and CAPD patients matched for demographicsand other clinical attributes. There was a highly significantdifference in the prevalence of sleep apnea based on dialysismodality, defined as an apnea-hypopnea index. The investigatorswent on to validate these findings in a fixed sequence interventionstudy in which 24 incident peritoneal dialysis patients werestudied during NPD and CAPD. Of note, there were greater reductionsin total body water during NPD, which may have contributed tothe reduction in sleep apnea symptoms. This provocative studysuggests that all peritoneal dialysis may not be created equal.Increasingly, dialysis prescriptions may need to be tailoredto the individual patient’s needs. See Tang et al., pages2607–2616.
Absence of Detectable Impact of Untreated Subclinical Rejection Found on Protocol Renal Transplant Biopsies.
Protocolrenal allograft biopsies are increasingly used to detect subclinicalgraft injury and the findings could affect prognosis and subsequenttreatment strategies. The extent of cortical tubulointerstitialfibrosis detected at 6 or 12 mo posttransplant correlates withgraft survival and function, but the impact of subclinical acuterejection in these biopsies remains controversial. In an observationalanalysis of serial protocol biopsies from 126 renal allograftrecipients on calcineurin inhibitor–based immunosuppression,Scholten and colleagues noted a 31% prevalence of subclinicalacute rejection at 6 mo. None of the pathologic findings weretreated. In this cohort, there was no correlation between thepresence of subclinical rejection at 6 mo and progressive fibrosis,proteinuria or loss of renal function over 2 yr. The data provideevidence that the majority of subclinical rejection episodesare not deleterious within this time frame, and raise questionsabout the need for treatment. See Scholten et al., pages 2622–2632.
Related Articles
Prospective Study of the Effect of Blood Pressure on Renal Function in Old Age: The Leiden 85-Plus Study
Thomas van Bemmel, Karen Woittiez, Gerard J. Blauw, Femke van der Sman-de Beer, Friedo W. Dekker, Rudi G.J. Westendorp, and Jacobijn Gussekloo
J. Am. Soc. Nephrol. 2006 17: 2561-2566.
[Abstract][Full Text][PDF]
Alleviation of Sleep Apnea in Patients with Chronic Renal Failure by Nocturnal Cycler–Assisted Peritoneal Dialysis Compared with Conventional Continuous Ambulatory Peritoneal Dialysis
Sydney C.W. Tang, Bing Lam, Pui Pui Ku, Wah Shing Leung, Chung Ming Chu, Yiu Wing Ho, Mary S.M. Ip, and Kar Neng Lai
J. Am. Soc. Nephrol. 2006 17: 2607-2616.
[Abstract][Full Text][PDF]
Dietary Electrolyte–Driven Responses in the Renal WNK Kinase Pathway In Vivo
Michelle O’Reilly, Elaine Marshall, Thomas MacGillivray, Manish Mittal, Wei Xue, Chris J. Kenyon, and Roger W. Brown
J. Am. Soc. Nephrol. 2006 17: 2402-2413.
[Abstract][Full Text][PDF]
Falling into the Doughnut Hole: Drug Spending among Beneficiaries with End-Stage Renal Disease under Medicare Part D Plans
Isolation and Characterization of Multipotent Progenitor Cells from the Bowman’s Capsule of Adult Human Kidneys
Costanza Sagrinati, Giuseppe Stefano Netti, Benedetta Mazzinghi, Elena Lazzeri, Francesco Liotta, Francesca Frosali, Elisa Ronconi, Claudia Meini, Mauro Gacci, Roberta Squecco, Marco Carini, Loreto Gesualdo, Fabio Francini, Enrico Maggi, Francesco Annunziato, Laura Lasagni, Mario Serio, Sergio Romagnani, and Paola Romagnani
J. Am. Soc. Nephrol. 2006 17: 2443-2456.
[Abstract][Full Text][PDF]
COMP–Angiopoietin-1 Ameliorates Renal Fibrosis in a Unilateral Ureteral Obstruction Model
Won Kim, Sang-Ok Moon, Sang Yong Lee, Kyu Yun Jang, Chung-Hyun Cho, Gou Young Koh, Kyu-Sil Choi, Kwon-Ha Yoon, Mi Jeong Sung, Duk Hoon Kim, Sik Lee, Kyung Pyo Kang, and Sung Kwang Park
J. Am. Soc. Nephrol. 2006 17: 2474-2483.
[Abstract][Full Text][PDF]
Untreated Rejection in 6-Month Protocol Biopsies Is Not Associated with Fibrosis in Serial Biopsies or with Loss of Graft Function
Eduard M. Scholten, Ajda T. Rowshani, Serge Cremers, Frederike J. Bemelman, Michael Eikmans, Erik van Kan, Marko J. Mallat, Sandrine Florquin, Janto Surachno, Ineke J. ten Berge, Ingeborg M. Bajema, and Johan W. de Fijter
J. Am. Soc. Nephrol. 2006 17: 2622-2632.
[Abstract][Full Text][PDF]
Top
Basic Science Articles
Clinical Science Articles
and kidney collagen levels and tubular injury. An additional benefit may an anti-inflammatory effect due to reduced endothelial cell adhesiveness as the number of interstitial macrophages was significantly reduced in the COMP-Ang1 group. See Kim et al., pages 2474–2483. 
