This Month’s Highlights

doi:10.1681/ASN.2008111198

BASIC RESEARCH

HNF-1β Meets Its Target

Mutations in the transcription factor hepatocyte nuclear factor 1β (HNF-1β) lead to cystic renal disease, but the relevant gene targets of HNF-1β are unknown. Using a functional genomics approach, Gong et al. found that HNF-1β regulates kinesin family member 12 (Kif12), a proposed candidate modifier gene in a mouse model of polycystic kidney disease. They show that lack of HNF-1β inhibits transcription of Kif12 by altering the recruitment of coactivators, which modifies histone acetylation and chromatin remodeling. In vivo, Kif12 is reduced in cystic kidneys from HNF-1β mutant mice. These results support a role for Kif12 in polycystic kidney disease. See Gong et al., pages 41–47.

Imatinib Treats Cryoglobulinemia and MPGN

Reliable therapies are not available for cryoglobulinemia and its associated membranoproliferative GN (MPGN). In an animal model that closely mimics this human disease, enhanced expression of PDGF-B and its receptor, PDGFRβ, correlates with glomerular cell proliferation and matrix expansion. Here, Iyoda et al. report that imatinib, which inhibits PDGFR, attenuates not only the development of renal manifestations but also the systemic features of cryoglobulinemia in this animal model. Furthermore, imatinib reverses established lesions. These data suggest that imatinib may have therapeutic potential for cryoglobulinemia and MPGN in humans. See Iyoda et al. on pages 68–77.

Al dosterone Activates NF-κB in Collecting Duct

Mounting evidence supports roles for aldosterone in inflammation, fibrosis, cell proliferation, and apoptosis in addition to sodium reabsorption in the collecting duct. The transcription factor NF-κB has been implicated in each of these processes, but its relationship with aldosterone is incompletely understood. Here, Leroy et al. report that aldosterone acts through the mineralocorticoid receptor to upregulate the serum and glucocorticoid-inducible kinase (SGK1), thereby activating NF-κB signaling in the collecting duct. These data suggest that activation of NF-κB by aldosterone in the collecting duct may promote renal inflammation and fibrosis, as well as modulate salt and water homeostasis. See Leroy et al. on pages 131–144.

CLINICAL EPIDEMIOLOGY

A Fresh Look at the Dialysis Modality Debate

Despite years of debate, the mortality benefits of peritoneal dialysis (PD) or hemodialysis (HD) remain controversial. McDonald et al. analyzed data from more than 27,000 patients treated with PD or HD. Categorizing patients by modality used at day 90, they found that PD conferred a survival advantage for the first year, but this effect was driven by younger patients without comorbidities. However, after 1 yr of dialytic therapy, PD was associated with a 30% increased risk for mortality overall. These results suggest that the mortality risks associated with dialysis modality may be dependent on time and patient characteristics such as age and comorbidities. See McDonald et al. on pages 155–163.

CLINICAL RESEARCH

Improved Ultrasonographic Criteria for PKD

Current ultrasonographic criteria for the diagnosis of polycystic kidney disease (PKD) were established from individuals with mutations in PKD1. These criteria may lead to false-negative results for patients with mutations in PKD2, who typically have less severe disease. Pei et al. assessed 577 and 371 at-risk subjects from PKD1 and PKD2 families, respectively, with ultrasound and molecular genotyping. They report that current diagnostic criteria are insensitive for the detection of PKD among individuals with PKD2 mutations and propose new criteria to be used when diagnosing at-risk individuals of unknown genotype by ultrasonography. See Pei et al. on pages 205–212.

Elderly with AKI at Risk for ESRD

The risk for ESRD among elderly patients who suffer acute kidney injury (AKI) is unknown. Combining data from Medicare claims and ESRD registration, Ishani et al. demonstrate that, after adjustment for multiple confounders, elderly patients with AKI have a seven-fold higher risk of developing ESRD compared with those who do not develop AKI. Pre-existing chronic kidney disease (CKD) significantly increases this risk; elderly patients with CKD who develop AKI have a 40-fold risk for progression to ESRD compared with those who have neither diagnosis. These results support close monitoring of kidney function after AKI in elderly patients and provide further impetus to develop strategies to reduce AKI. See Ishani et al. on pages 223–228.