Ongoingdevelopment of connecting tubules and collecting ducts may accountfor the changes in acid/base balance that occur shortly afterbirth. Pendrin is an apical anion exchanger, involved in bicarbonatesecretion, that is found in the type B and nonA-nonB intercalatedcells of the distal nephron. Song and colleagues detail theirobservations that pendrin-positive cells arise from two separatefoci simultaneously: one in the connecting tubule, derived fromthe metanephrogenic blastema, and the other in the medullarycollecting duct, derived from the ureteric bud. Moreover, itappears that these cells do not proliferate, but rather arisefrom undifferentiated precursor cells in the connecting tubulesand collecting ducts. See Song et al., pages 2672–2682.
Potassium, Uric Acid, and Thiazides in Metabolic Syndrome
Althoughhydrochlorothiazide is a first-line antihypertensive agent,its use can exacerbate metabolic syndrome. Using rats with fructose-inducedmetabolic syndrome, Reungjui and colleagues show that correctingthe serum potassium and uric acid abnormalities that accompanytreatment with hydrochlorothiazide largely ameliorates its metaboliceffects. Potassium supplementation reduces systolic blood pressureand improves insulin sensitivity. Lowering thiazide-inducedhyperuricemia with allopurinol has similar effects, and reduceshypertriglyceridemia and hyperglycemia. Whether these interventionswill treat or prevent metabolic syndrome in humans taking thiazidesrequires further study. See Reungjui et al., pages 2724–2731.
Pathogenic Stem Cells In Idiopathic Nephrotic Syndrome
Idiopathicnephrotic syndrome is characterized by glomerular proteinuriawithout infiltrating cells or immune-complex deposits. Sellier-Leclercand colleagues created a humanized mouse model of this diseaseby injecting cells from afflicted patients into immunocompromisedmice. Mice injected with human CD34+ stem cells develop albuminuriaand effacement of the podocyte foot processes, whereas thoseinjected with CD34– peripheral mononuclear cells do not.The authors conclude that immature differentiating cells areresponsible for the pathogenesis of idiopathic nephrotic syndrome.See Sellier-Leclerc et al., pages 2732–2739.
Blacks Are More Likely to Survive Acute Renal Failure
Severalstudies have shown that black Americans survive longer on maintenancehemodialysis than whites. Waikar and colleagues extend thisobservation to cases of acute renal failure by analyzing datafrom nearly 440,000 hospitalizations that included this diagnosis.The adjusted odds of in-hospital mortality is 16–18% lowerfor blacks with acute renal failure than whites. Their findingswere consistent across age, sex, hospital types, geographicalregion, and hospital volume of patients with acute renal failurethat require dialysis. Whether this disparity is a result ofbiological variation remains an unanswered question. See Waikaret al., pages 2740–2748.
Age Influences Chronic Kidney Disease Outcomes
It isunknown how the clinical course varies for older and youngerpatients with chronic kidney disease. By analyzing a cohortof 209,622 veterans, O’Hare and colleagues found thatthe rates of death and progression to end-stage renal diseaseare inversely related to estimated glomerular filtration rate(eGFR), and that these rates are significantly modified by age.For example, older patients have higher rates of death and lowerrates of progression to end-stage renal disease than youngerpatients. Current guidelines for the treatment of chronic kidneydisease are based on ranges of eGFR, but these data suggestthat age should be considered as well. See O’Hare et al.,pages 2758–2765.
Nephronophthisis,a cystic renal disease that leads to end-stage renal diseasewithin the first two decades of life, is a genetically heterogeneousdisorder with six different causative genes identified (NPHP1–6).Hoefele and colleagues studied 94 individuals from afflictedfamilies to determine whether oligogenic inheritance—mutationsin more than one gene in one individual—can also leadto nephronophthisis. In six families, the authors detected twomutations in one of the NPHP genes combined with a third mutationin another NPHP gene. It is possible that this third mutationmodifies the onset or severity of the clinical phenotype. SeeHoefele et al., pages 2789–2795.
Related Articles
Race and Mortality after Acute Renal Failure
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J. Am. Soc. Nephrol. 2007 18: 2740-2748.
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Evidence of Oligogenic Inheritance in Nephronophthisis
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J. Am. Soc. Nephrol. 2007 18: 2724-2731.
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Age Affects Outcomes in Chronic Kidney Disease
Ann M. O'Hare, Andy I. Choi, Daniel Bertenthal, Peter Bacchetti, Amit X. Garg, James S. Kaufman, Louise C. Walter, Kala M. Mehta, Michael A. Steinman, Michael Allon, William M. McClellan, and C. Seth Landefeld
J. Am. Soc. Nephrol. 2007 18: 2758-2765.
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