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This Month’s Highlights

	Basic Science Articles

Top Basic Science Articles Clinical Science Articles

ACE2—A Potential Beneficial Component of the Renin-Angiotensin System.

In elegant studies, Ye et al. examine the localization and significance of angiotensin-converting enzyme (ACE) and its homolog ACE2. ACE2 was postulated to counteract ACE by degrading both angiotensin I (AngI) and AngII into inactive ANg1-9 and vasodilatory Ang1-7, respectively. Indeed, in diabetic db/db mice, glomerular ACE and ACE2 were altered compared with normal, with increased ACE and decreased ACE2, the former localized to endothelial cells and the latter to podocytes. To investigate the functional significance of these changes, the authors inhibited ACE2 in db/db mice, which worsened proteinuria and increased fibronectin in glomeruli. These data point to an important regulatory function of ACE2, which could provide additional useful therapeutic targets in renal disease. See Ye et al., pages 3067–3075.

Anti-GBM Antibody—Do We Know the Whole Story Yet?

Although we now have a detailed understanding of the molecular structure of the nephritogenic GBM antigen, it is not clear that autoimmunity to this small peptide fragment is the only, or even the most important, pathogenic process occurring in Goodpasture syndrome, particularly in later phases where tissue injury could induce immunity to other self antigens, or epitope spreading. In this study, Chen and colleagues induce anti-GBM nephritis with 13 amino acid fragments of the rat Goodpasture antigen and show that nephritic animals do develop other, non–cross-reactive antibodies to antigenic determinants confined to the 3(III) and 4(IV) NC1 domains of collagen. The study does not address the issue of whether these new antibodies are pathogenic or involved in disease progression. However, the observation provides important new insight into the extension and perpetuation of the autoimmune process in glomerular disease and could have therapeutic implications in the future. See Chen et al., pages 3076–3081.

VEGF—A New Therapeutic Target in Diabetic Nephropathy?

Previous studies in experimental models of diabetes have indicated that distinct signaling pathways may underlie development of mesangial expansion and albuminuria. Blocking antibodies to TGF- prevented increases in mesangial matrix deposition but were ineffective against albuminuria, whereas blocking antibodies to VEGF decreased diabetic albuminuria. In this issue of JASN, Sung et al. utilized a VEGF receptor tyrosine kinase inhibitor, SU5416, to further examine the potential role of VEGF in glomerular abnormalities developing in db/db mice, a model of type II diabetes. The authors not only confirm that inhibition of VEGF signaling inhibits albuminuria, but also show that development of albuminuria parallels basement membrane thickening, but is dissociated from mesangial matrix expansion. These studies further implicate the VEGF signaling pathway as a feasible target for amelioration of diabetic proteinuria. See Sung et al., pages 3093–3104.

	Clinical Science Articles

Top Basic Science Articles Clinical Science Articles

 
Which Is Better for Acute Renal Failure—Continuous or Intermittent Therapy?

The optimal renal replacement therapy (RRT) for patients with acute kidney injury (AKI) remains uncertain. The report in this issue of JASN by Cho and colleagues uses data from the Program to Improve Care in Acute Renal Disease (PICARD) study to examine the relative benefit of intermittent versus continuous RRT (CRRT). They report that 60-day mortality was substantially higher among patients treated with CRRT, and that these differences persisted after controlling for other patient characteristics. They also point out that mortality risk factors and markers for severity of illness differed among individuals receiving the two modalities, and controlling for this selection bias with multivariate models did not attenuate the increased mortality risk associated with CRRT. This study fails to support a benefit for CRRT compared with intermittent therapy and suggests that selection of CRRT for patients with AKI and treatment should reflect the individual patient and treatment center circumstances. Second, as noted by the authors, clinical trials that are sufficiently powered and reflecting the factors associated with selection for continuous therapy are urgently needed. See Cho et al., pages 3132–3138.

Cytokine Polymorphisms and CVD Risk.

Hemodialysis is a proinflammatory state that is characterized by elevated levels of circulating cytokines and greatly increased risk of cardiovascular disease (CVD). However, it has been difficult to distinguish whether the elevated cytokine levels cause accelerated atherosclerosis or are secondary to concomitant inflammation. One way to address this question is to determine whether genetic variants that produce elevated or reduced levels of cytokines are associated with corresponding changes in the risk of CVD. In this issue of JASN, Liu and colleagues examined polymorphisms in the LTA gene, which encodes the proinflammatory cytokine TNF-, and found an association with CVD in dialysis patients. The strengths of this study include large sample size, prospective design, correlation with markers of inflammation, and correction for population stratification. Further laboratory studies will be required to elucidate the mechanism by which the observed polymorphisms alter TNF activity, and this type of translational research should be encouraged. See Liu et al., pages 3158–3166.

Hip Fracture and Kidney Disease—It’s Not Just the Elderly with ESRD Who Are at Risk.

Because chronic kidney disease (CKD) is a progressive condition, it is not unexpected that the high risk of hip fracture observed among individuals with ESRD also is experienced by those with less severe stages of CKD. Nickolas et al. confirm that a history of hip fracture was substantially increased among individuals with stage 3 and higher CKD and that this association was stronger among younger individuals. These observations continue the growing contribution of the National Health and Nutrition Examination Survey (NHANES) data to our growing understanding of the prevalence and associated morbidity of CKD in the US population. The message for clinicians caring for patients with CKD is to recognize the increased risk of hip fracture, particularly among younger patients, and manage this risk with guideline-based treatment of osteoporosis and renal osteodystrophy, fall prevention and home safety measures, and patient education. See Nickolas et al., pages 3223–3232.

Posttransplant Anemia as a Risk Factor.

Anemia is a common occurrence after kidney transplantation, but whether its presence affects patient outcome has not been carefully evaluated. In a retrospective cohort study in this month’s issue of JASN, Imoagene-Oyedeji et al. at the University of Pennsylvania report the relationship between anemia and posttransplant outcome in >600 recipients. The major findings of the study were that anemia detected 12 mo posttransplant independently associated with mortality and, more specifically, with cardiovascular mortality. Moreover, anemia detected at 3 mo was highly associated with anemia at 12 mo, suggesting that it might be possible to identify at-risk individuals early on. These findings, linking anemia to posttransplantation patient survival, have potentially important therapeutic implications. See Imoagene-Oyedeji et al., pages 3240–3247.

Related Articles

Relationship between Moderate to Severe Kidney Disease and Hip Fracture in the United States

Thomas L. Nickolas, Donald J. McMahon, and Elizabeth Shane
J. Am. Soc. Nephrol. 2006 17: 3223-3232. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Related Collections Related Articles