This Month's Highlights

doi:10.1681/ASN.2011030308

BRIEF COMMUNICATION

Nek1 and TAZ Partner to Regulate Polycystin 2

A diverse collection of genetic defects can lead to polycystic kidney disease (PKD) in mice. Yim et al. studied two proteins, both of which lead to PKD when mutated, to elucidate whether they share a common biochemical pathway. They found that the kinase Nek1 phosphorylates the protein TAZ, thereby promoting the degradation of the ciliary protein polycystin 2. Loss of Nek1 promotes abnormal accumulation of polycystin 2 and, furthermore, TAZ targets Nek1 for degradation. These data suggest that Nek1 and TAZ constitute a negative feedback loop, and their interaction maintains levels of polycystin 2 appropriate for ciliogenesis. See Yim et al., pages 832–837.

BASIC RESEARCH

Impaired Laminin Secretion Causes Nephrotic Syndrome

Missense mutations in LAMB2, which encodes the glomerular basement membrane (GBM) constituent laminin β2, can cause congenital nephrotic syndrome. Exploring the underlying mechanism, Chen et al. generated transgenic mice carrying the R246Q missense mutation in laminin β2. In these animals, the degree of proteinuria inversely correlates with expression of the mutant gene, suggesting that high levels of mutant protein can maintain structural integrity of the filtration barrier. Furthermore, they show that this mutation impairs the secretion of laminin from podocytes into the GBM. Taken together, these results shed light on the biology of laminin and the glomerular filtration barrier. See Chen et al., pages 849–858.

GSK3 Modulates Mineral Metabolism

Various factors, including hormones, regulate the reabsorption of phosphate by the kidney. Insulin and IGF1 both inactivate glycogen synthase kinase 3 (GSK3) and increase renal phosphorus reabsorption, suggesting that GSK3 may modulate the activity of phosphate transporters. Föller et al. genetically engineered mice with GSK3 resistant to inactivation by protein kinase B and serum-glucocorticoid kinase (PKB/SGK). Mutant mice exhibited multiple metabolic abnormalities, including greater urinary phosphate excretion despite lower plasma phosphate concentration, decreased parathyroid hormone levels, and low bone mineral density. These results demonstrate an important role for GSK3 in the regulation of mineral metabolism. See Föller et al., pages 873–880.

Clinical Epidemiology

eGFR Depends on More Than GFR

The association between modest reductions in the estimated GFR (eGFR) and cardiovascular (CV) morbidity is inconsistent. Mathisen et al. measured GFR by iohexol clearance in a sample from the general population without known CV disease, diabetes, or kidney disease to determine whether there are non–GFR-related associations between eGFR and CV risk factors. The associations vary depending on the estimating equation used, but traditional CV risk factors influence eGFR even after adjustment for measured GFR, suggesting that estimates of the effect of eGFR on CV risk may be biased in people with near-normal renal function. See Mathisen et al., pages 927–937.

Statins May Improve Postoperative Outcomes

Whether statins are renoprotective remains unknown. In this issue, Molnar et al. report their analysis of a retrospective cohort that included >210,000 older patients who underwent major elective surgery during a 13-year period. They found that after adjustment for patient and surgical characteristics, the use of statins associates with 16% lower odds of acute kidney injury, 17% lower odds of acute dialysis, and 21% lower odds of mortality in the postoperative period. These data suggest that statins may reduce morbidity and mortality after major elective surgery. See Molnar et al., pages 939–946.

Clinical Research

FGF23 Predicts Poor Transplant Outcomes

Increased levels of circulating fibroblast growth factor 23 (FGF23) predict mortality, cardiovascular disease, and progression of chronic kidney disease, but whether FGF23 levels associate with transplant survival is unknown. Wolf et al. analyzed data from a prospective cohort of nearly 1000 kidney transplant recipients and found that higher FGF23 levels increase the risk for both all-cause mortality and allograft loss. The association of outcomes with other measures of mineral metabolism, such as parathyroid hormone and serum phosphate levels, is less consistent. These results suggest that FGF23 may be directly detrimental to patients with chronic kidney disease, including transplant recipients. See Wolf et al., pages 956–966.