This Month's Highlights

doi:10.1681/ASN.2008080889

BRIEF COMMUNICATION

Expanding Spectrum of Nephrin-Based Disease

Mutations in NPHS1, which encodes nephrin, classically lead to nephrotic syndrome within the first 3 mo of life. Philippe et al. hypothesized that NPHS1 mutations may also contribute to some cases of steroid-resistant nephrotic syndrome in older children. They report compound heterozygous NPHS1 mutations in one familial and nine sporadic cases of nephrotic syndrome that presented ≥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.

BASIC RESEARCH

Dishing Up Parietal Epithelial Cells

Glomerular parietal epithelial cells (PEC), which form the outer wall of Bowman's capsule, proliferate to form crescents in crescentic glomerulonephritis and produce several cytokines and chemokines. Unfortunately, PEC cell lines have not been available, limiting our current knowledge of the biology of these important glomerular constituents. Ohse et al. now report the creation of an immortalized mouse PEC line that expresses PEC-specific proteins but not podocyte-specific proteins, despite the mesenchymal origin of both cell types. These cells will be instrumental in further defining the mechanisms underlying glomerular disease. See Ohse et al., pages 1879–1890.

CLINICAL EPIDEMIOLOGY

High-Normal Albumin Excretion Predicts Hypertension

Recent studies demonstrate that increasing urinary albumin excretion, even within the normal range, is associated with cardiovascular morbidity among individuals at high cardiovascular risk, but similar associations among low-risk individuals are unknown. Forman et al. analyzed data from >2000 women who did not have diabetes, hypertension, or microalbuminuria and participated in the first or second Nurses’ Health Study. Women with an albumin/creatinine ratio (ACR) in the highest quartile, which spanned approximately 4 to 24 mg/g creatinine, were significantly more likely to develop hypertension than those with an ACR in the lowest quartile. These results suggest that the normal range of albumin excretion may need reevaluation. See Forman et al., pages 1983–1988.

TCF7L2 Variants Predict CKD

Specific variants in the TCF7L2 gene confer increased risk for type 2 diabetes in several populations, but whether variants in this gene increase the risk for chronic kidney disease (CKD) is unknown. Köttgen et al. genotyped >18,000 participants of the Atherosclerosis Risk in Communities Study, Framingham Heart Offspring Cohort, and Heredity and Phenotype Intervention Heart Study at common TCF7L2 variants. They found that the same diabetes-susceptibility alleles are significantly associated with both CKD progression and lower estimated GFR. Identification of potential mechanistic links among TCF7L2, diabetes, and CKD will require further investigation. See Köttgen et al., pages 1989–1999.

CLINICAL RESEARCH

Multitarget Therapy Benefits Class V+IV Lupus

The concomitant occurrence of membranous lesions and diffuse proliferative lupus nephritis (class V+IV) is often refractory to treatment with cyclophosphamide, suggesting a need for new therapeutic regimens. Bao et al. randomly assigned 40 Chinese patients with class V+IV lupus nephritis to either intravenous cyclophosphamide or “multitarget therapy” (tacrolimus, mycophenolate mofetil, and steroids) for 6 to 9 mo. Their intention-to-treat analysis shows that 50 and 65% of patients who received multitarget therapy achieved complete remission at 6 and 9 mo, respectively, compared with 5 and 15% of patients who received cyclophosphamide. Although long-term outcomes are not yet available, multitarget therapy shows promise as induction therapy for class V+IV lupus nephritis. See Bao et al., pages 2001–2010.

RET Variant Reduces Kidney Size

Individuals born with fewer nephrons may have an increased lifetime risk for hypertension. Little is known, however, about the regulation of nephron number during development. Zhang et al. sought to determine 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 allele have 10% smaller kidney volumes, which correlate with glomerular number, and 9% higher cystatin C levels in cord blood. Whether this RET gene variant is associated with clinical outcomes, such as the development of hypertension, awaits further study. See Zhang et al., pages 2027–2034.