Hybrid Glomeruli Provide Clues About Glomerulogenesis
Lamininsare integral components of glomerular basement membranes. Abrahamsonand colleagues explored the role of laminins in glomerulogenesisby studying hybrid glomeruli comprising podocytes from laminin5 knockout mice and endothelial cells from wild-type mice. Bylocalizing the different isoforms of laminin expressed by podocytesand endothelial cells in these hybrids, the authors demonstratethat both cell types contribute significantly to the formationof the glomerular basement membrane, that the laminins remainattached to their cell of origin, and that proper developmentof podocyte foot processes requires normal composition of theunderlying basement membranes. See Abrahamson et al., pages2285–2293.
Angiotensin II Blockade Stabilizes Atherosclerotic Plaques
Atherosclerosisravages patients with kidney disease. Blockade of the renin-angiotensinsystem reduces the associated morbidity and mortality, but themechanisms underlying these effects are incompletely understood.Using apolipoprotein E–deficient mice with establishedatherosclerosis, Suganuma and colleagues found that treatmentwith the renin-angiotensin system inhibitor losartan not onlyslows progression of atherosclerotic plaques but also alterstheir composition. Losartan increases the relative amount ofcollagen in plaques and reduces the destruction of elastin inthe arterial wall. Therefore, angiotensin II blockade may reducethe risk of plaque rupture in addition to reducing the atheroscleroticburden. See Suganuma et al., pages 2311–2319.
Anti-PR3 Antibodies Stimulate the Expression of Their Own Antigen
ANCA (anti-neutrophilcytoplasmic antibodies) directed against neutrophil proteinase3 (PR3) are found in a subset of vasculitides, but their contributionto the pathogenesis of disease is not well understood. Brachemiand colleagues demonstrate that anti-PR3 interacts with membrane-boundantigen (mPR3) only after mPR3-expressing neutrophils have beenactivated by inflammatory cytokines and have adhered to vascularendothelial cells. Moreover, this antibody–neutrophilinteraction stimulates additional translocation of PR3 to thecell surface, which may lead to a destructive positive feedbackloop in the small vessels where neutrophils are known to wreakhavoc in these autoimmune diseases. See Brachemi et al., pages2330–2339.
The hemoglobinconcentration of a patient treated with epoetin often fluctuatesaround a target value as the drug regimen is adjusted in responseto laboratory data. Using patient-level data from a previouslypublished trial, West and colleagues describe a method by whicha treatment algorithm can be evaluated for how well it achievesand maintains hemoglobin targets. They modeled individual trajectoriesof hemoglobin values over time with mathematical functions,and then analyzed these functions to assess how well protocol-drivenadjustments in dosage stabilized hemoglobin levels at target.This type of approach may prove useful for the development oftreatment protocols in clinical practice or future trials. SeeWest et al., pages 2371–2376.
Nondiabetics May Need to Worry about Fasting Glucose
Diabeticpatients on hemodialysis are often chronically inflamed, malnourished,and at increased risk for cardiovascular death. The associationof fasting glucose level with these characteristics has notreceived as much attention among nondiabetic patients on dialysis.Lin-Tan and colleagues prospectively assessed markers of bothnutritional status and inflammation in 693 hemodialysis patientsin Taiwan. Their analysis suggests that higher fasting glucoselevels are associated with reduced serum albumin, increasedhigh-sensitivity C-reactive protein, and increased 1-year mortality,even among nondiabetic patients. Whether interventions targetingglucose metabolism in these patients will affect outcome remainsto be determined. See Lin-Tan et al., pages 2385–2391.
Mutations in Complement Pathway Affect HUS Course
Dysregulationof the complement cascade has been implicated in the pathogenesisof atypical hemolytic uremic syndrome (HUS). Sellier-Leclercand colleagues studied 46 pediatric patients with atypical HUSand found associations between genetic susceptibility traitsand clinical course. Half of the children had mutations in FactorH, Factor I, or membrane cofactor protein. Age at onset of symptoms,number of relapses during the first 10 years, and renal survivaldiffered on the basis of which protein was mutated. In addition,triggering events were often identified in mutation carriers,suggesting that these mutations may modify risk rather thancause the syndrome. See Sellier-Leclerc et al., pages 2392–2400.
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BASIC RESEARCH
CLINICAL EPIDEMIOLOGY
5 knockout mice and endothelial cells from wild-type mice. By localizing the different isoforms of laminin expressed by podocytes and endothelial cells in these hybrids, the authors demonstrate that both cell types contribute significantly to the formation of the glomerular basement membrane, that the laminins remain attached to their cell of origin, and that proper development of podocyte foot processes requires normal composition of the underlying basement membranes. See Abrahamson et al., pages 2285–2293. 
ois Bouissou, Georges Deschenes, Sophie Gie, Michel Tsimaratos, Michel Fischbach, Denis Morin, Hubert Nivet, Corinne Alberti, Chantal Loirat for the French Society of Pediatric Nephrology
