Mutationsin NPHS1, which encodes nephrin, classically lead to nephroticsyndrome within the first 3 mo of life. Philippe et al. hypothesizedthat NPHS1 mutations may also contribute to some cases of steroid-resistantnephrotic syndrome in older children. They report compound heterozygousNPHS1 mutations in one familial and nine sporadic cases of nephroticsyndrome that presented 3 mo after birth. Functional assessmentsof the mutations seem to explain the later onset and mildercourse of disease in these patients. Further study of genotype–phenotypeassociations for these NPHS1 mutations may have prognostic andtherapeutic implications. See Philippe et al., pages 1871–1878.
Glomerularparietal epithelial cells (PEC), which form the outer wall ofBowman's capsule, proliferate to form crescents in crescenticglomerulonephritis and produce several cytokines and chemokines.Unfortunately, PEC cell lines have not been available, limitingour current knowledge of the biology of these important glomerularconstituents. Ohse et al. now report the creation of an immortalizedmouse PEC line that expresses PEC-specific proteins but notpodocyte-specific proteins, despite the mesenchymal origin ofboth cell types. These cells will be instrumental in furtherdefining the mechanisms underlying glomerular disease. See Ohseet al., pages 1879–1890.
High-Normal Albumin Excretion Predicts Hypertension
Recentstudies demonstrate that increasing urinary albumin excretion,even within the normal range, is associated with cardiovascularmorbidity among individuals at high cardiovascular risk, butsimilar associations among low-risk individuals are unknown.Forman et al. analyzed data from >2000 women who did nothave diabetes, hypertension, or microalbuminuria and participatedin the first or second Nurses’ Health Study. Women withan albumin/creatinine ratio (ACR) in the highest quartile, whichspanned approximately 4 to 24 mg/g creatinine, were significantlymore likely to develop hypertension than those with an ACR inthe lowest quartile. These results suggest that the normal rangeof albumin excretion may need reevaluation. See Forman et al.,pages 1983–1988.
TCF7L2 Variants Predict CKD
Specificvariants in the TCF7L2 gene confer increased risk for type 2diabetes in several populations, but whether variants in thisgene increase the risk for chronic kidney disease (CKD) is unknown.Köttgen et al. genotyped >18,000 participants of theAtherosclerosis Risk in Communities Study, Framingham HeartOffspring Cohort, and Heredity and Phenotype Intervention HeartStudy at common TCF7L2 variants. They found that the same diabetes-susceptibilityalleles are significantly associated with both CKD progressionand lower estimated GFR. Identification of potential mechanisticlinks among TCF7L2, diabetes, and CKD will require further investigation.See Köttgen et al., pages 1989–1999.
The concomitantoccurrence of membranous lesions and diffuse proliferative lupusnephritis (class V+IV) is often refractory to treatment withcyclophosphamide, suggesting a need for new therapeutic regimens.Bao et al. randomly assigned 40 Chinese patients with classV+IV lupus nephritis to either intravenous cyclophosphamideor "multitarget therapy" (tacrolimus, mycophenolate mofetil,and steroids) for 6 to 9 mo. Their intention-to-treat analysisshows that 50 and 65% of patients who received multitarget therapyachieved complete remission at 6 and 9 mo, respectively, comparedwith 5 and 15% of patients who received cyclophosphamide. Althoughlong-term outcomes are not yet available, multitarget therapyshows promise as induction therapy for class V+IV lupus nephritis.See Bao et al., pages 2001–2010.
RET Variant Reduces Kidney Size
Individualsborn with fewer nephrons may have an increased lifetime riskfor hypertension. Little is known, however, about the regulationof nephron number during development. Zhang et al. sought todetermine whether a common hypomorphic variant of the RET gene,which encodes a receptor involved in branching morphogenesis,is associated with subtle renal hypoplasia in normal newborns.They found that normal newborns carrying the variant allelehave 10% smaller kidney volumes, which correlate with glomerularnumber, and 9% higher cystatin C levels in cord blood. Whetherthis RET gene variant is associated with clinical outcomes,such as the development of hypertension, awaits further study.See Zhang et al., pages 2027–2034.
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3 mo after birth. Functional assessments of the mutations seem to explain the later onset and milder course of disease in these patients. Further study of genotype–phenotype associations for these NPHS1 mutations may have prognostic and therapeutic implications. See Philippe et al., pages 1871–1878. 
