2008 JASN IMPACT FACTOR 7.505	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

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

This Month’s Highlights

	Basic Science Articles

Top Basic Science Articles Clinical Science Articles

Expanding the Role of the Renin-Angiotensin System to Cellular Immunity.

The renin-angiotensin system (RAS) participates in hemodynamic homeostasis, contributes to the progression of chronic kidney and ischemic heart disease, and, in part through known chemoattractant properties, has been implicated as a regulator of inflammation. In the current issue of JASN, Jurewicz and colleagues provide evidence to support a functional role of the RAS in cellular immune responses. The investigators demonstrate that T cells and natural killer cells express mRNA for renin, angiotensin, and angiotensin-converting enzyme, and show that these cells express angiotensin receptors on their surfaces. Angiotensin II–augmented T cell proliferation induced by mitogen or anti-CD3 stimulation, and stimulation via angiotensin receptors on T cells, induced an associated calcium flux and chemotaxis. The demonstration that T lymphocytes are fully equipped with functioning elements of the RAS suggests that the T cell–derived RAS can participate in initiating and maintaining cell-mediated inflammatory injury. See Jurewicz et al., pages 1093–1102.

What Are T Cells Doing in a Model of Toxic Glomerulopathy?

Whereas the majority of T lymphocytes express T cell receptors (TCR), a small subset (up to 5%) express TCRs. T cells have been reported to have both proinflammatory and regulatory functions in the context of infectious disease models, but relatively little is known about this T cell subset with regard to renal disease. In this issue of JASN, Wu and colleagues provide new insights into the significance of T cells in a murine model of adriamycin nephropathy. After injection with adriamycin, the relative percentage of T cells was markedly upregulated within the diseased kidneys, in direct proportion to the serum creatinine and to the amount of glomerulosclerosis. The intrarenal T cells exhibited a limited TCR repertoire and predominantly produced TGF-. Additionally, depletion of T cells resulted in marked exacerbation of renal disease as manifested by increased creatinine and worsened glomerulosclerosis and tissue inflammation. The data implicate T cells as regulators of renal inflammation in murine adriamycin nephropathy. See Wu et al., pages 1180–1189.

A New HIF Isoform That Is Protective in Renal Ischemia.

Hypoxia-inducible factor (HIF) is known to be an important regulator of cellular adaptation to hypoxia and has been shown to serve as a protective factor against ischemic renal injury. In addition to the well-described isoform HIF-1, the kidney expresses a second isoform, HIF-2. HIF-1 is mainly induced in tubular and glomerular epithelial cells in response to hypoxia, whereas HIF-2 is localized in glomerular cells, peritubular endothelial cells, and fibroblasts. In the current issue of JASN, Kojima et al. utilized a HIF-2 knockdown mouse, which expressed only 50% of normal levels, to examine the role of HIF-2 in ischemic renal injury. The authors found that ischemia induced more damage in these animals, and that the injury could be prevented by selective re-expression of endothelial HIF-2. Therefore, these studies point to a novel role for HIF-2 in the endothelium to protect against hypoxic stress in the kidney. See Kojima et al., pages 1218–1226.

	Clinical Science Articles

Top Basic Science Articles Clinical Science Articles

 
Are ACE Polymorphisms Associated with Diabetic Nephropathy?

In 1990, Rigat et al. identified a polymorphism in the angiotensin-converting enzyme (ACE) gene that consisted of the presence (I) or absence (D) of a 287-bp sequence within intron 16. Since then, numerous studies have identified associations between ACE polymorphisms and the risk of cardiovascular disease or diabetic nephropathy. In this issue of JASN, Hadjadj et al. conducted one of the largest case-control and family studies to test the association between diabetic nephropathy and ACE polymorphisms. The investigators studied 1057 cases and 1127 controls recruited from France, Denmark, and Finland, as well as 532 family trios. Significant association between ACE polymorphisms, including the D allele, and diabetic nephropathy were identified in the case-control study but could not be confirmed in the family-based study, perhaps because the latter may have been underpowered. Moreover, the associations were only significant in the subjects from France; studies on the other populations were consistent but did not achieve statistical significance by themselves. Taken together with recent meta-analysis, the D allele seems to be associated with diabetic nephropathy. However, since this polymorphism is intronic, it is unlikely to be pathogenic. Rather, it may be in linkage disequilibrium with a pathogenic polymorphism, probably located in the 3' end of the gene. See Hadjadj et al., pages 1284–1291.

How Frequent Is Acute Kidney Injury?

In the past there was great confusion with respect to quantifying and categorizing acute kidney injury (AKI) as almost every investigator had introduced his own private scheme, rendering comparison of studies as well as evaluation of epidemiology and outcomes difficult. The recent universally accepted RIFLE nomenclature (risk, injury, failure, loss, end-stage) had been a laudable effort, but sufficient empirical data on incidence and outcome based on RIFLE remained in short supply. Ali et al. benefited from the relatively complete availability of clinical data in the Grampian region of Scotland to assess incidence and outcome of AKI. The investigators came to the conclusion that AKI was substantially more frequent than previously thought, and they confirmed that the RIFLE classification predicted clinical outcome well (e.g., in hospital mortality, renal replacement therapy, length of hospital stay, and recovery of renal function). See Ali et al., pages 1292–1298.

CKD Increases Risk of Subsequent Heart Failure Three-Fold.

The prevalence and incidence of heart failure are increasing, and a strong association between prevalent kidney disease and heart failure is well recognized. In this issue of JASN, Kottgen and her colleagues report that impaired kidney function is associated with increased risk of incident heart failure among participants in the Atherosclerosis Risk in Communities (ARIC) Study. During follow-up of individuals initially free of heart failure, the risk of incidence of subsequent death or first hospitalization for heart failure among individuals with an eGFR <60 ml/min per 1.73 m² was three times higher than individuals with an eGFR >90 ml/min per 1.73 m². As noted by the authors, it is unclear whether the observed association is a consequence of common risk factors or progressive kidney disease. Clinicians caring for patients with chronic kidney disease should be aware of the increased risk of cardiovascular disease in these patients and understand that aggressive blood pressure control directed at the renin-angiotensin system is an essential component of both renal and cardiovascular protection. See Kottgen et al., pages 1307–1315.

Combined Anti-GBM/ANCA Disease—The Same or Different from Anti-GBM Alone?

It has long been recognized that a subset of patients with anti–glomerular basement membrane (GBM) disease also have anti-neutrophil cytoplasmic antibodies (ANCA), a serologic combination that may be associated with more vasculitic symptoms and a better response to therapy. Whether these patients have the same pathogenic anti-GBM antibody as patients with anti-GBM antibody alone is not known. In this study, Yang and colleagues from Beijing carefully examine the quantity and specificity of anti-GBM antibodies in patients with (about 30%, mostly in older patients) and without ANCA. They find the specificity of the anti-GBM antibodies to be somewhat broader, but the quantity to be less in the ANCA-positive group, a finding that might account for the improved clinical course noted in some studies. These findings do not clarify whether one disease leads to the other in these patients or if they develop coincidentally, but they do help to better understand the nature of the nephritogenic autoimmune reactivity displayed by these patients. See Yang et al., pages 1338–1343.

Related Articles

Regulation of Renal Sodium Transporters during Severe Inflammation

Christoph Schmidt, Klaus Höcherl, Frank Schweda, Armin Kurtz, and Michael Bucher
J. Am. Soc. Nephrol. 2007 18: 1072-1083. [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