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This Month’s Highlights

	Basic Science Articles

Top Basic Science Articles Clinical Science Articles

More on Carnitine and Uremic Cardiomyopathy—Is It Uremia or Carnitine Deficiency?

Cardiac complications are the leading cause of mortality in patients with chronic kidney disease (CKD). Clinically, secondary carnitine deficiency is frequently observed, as assessed by blood levels, in patients with CKD, and it has been suggested that impaired carnitine homeostasis may affect myocardial fatty acid oxidation and contribute to the development of left ventricular hypertrophy and congestive heart failure. In this issue of JASN, Reddy and colleagues use a two-stage rat 5/6 nephrectomy model to carefully examine cardiac energetics in uremia. Cardiac function and substrate oxidation were assessed using nuclear magnetic resonance spectroscopy. Whereas kidney impairment was associated with a decrease in serum free carnitine, myocardial tissue carnitine concentrations were unaffected. Uremic rats developed left ventricular hypertrophy without evidence of alterations in myocardial substrate utilization. This study suggests that changes in uremia other than myocardial carnitine deficiency contribute to the development of altered cardiac geometry. See Reddy et al., pages 84–92.

Proteinuria Locus on Rat Chromosome 6.

The rat has proven to be a useful model for dissecting the genetics of proteinuria and progressive chronic kidney disease. In a previous study published in JASN in 2003, Schulz and colleagues reported a locus on rat chromosome 6 that was linked to proteinuria in the Munich Wistar Frömter (MWF) rat. In this issue of JASN, the authors produced a so-called consomic strain of MWF rats in which chromosome 6 was replaced with a chromosome from the nonsusceptible spontaneously hypertensive rat strain. Replacing chromosome 6 prevented the development of nephrotic syndrome and renal interstitial fibrosis. This beneficial effect was not due to improvements in blood pressure. Although the responsible gene(s) has not yet been identified, these experiments provide definitive evidence for the existence of a locus on rat chromosome 6 that influences proteinuria and renal fibrosis. This locus and the synteneic region on human chromosome 14 should be investigated further. See Schulz et al., pages 113–121.

Bone Marrow–Derived Renal Interstitial Cells in the Injured Kidney.

The benefit of bone marrow–derived cells for the treatment of acute kidney injury has been controversial. Stem cells from bone marrow can contribute to tubular regeneration after injury and may improve renal function, but they can also differentiate into renal interstitial cells and may contribute to fibrosis. Broekema and colleagues studied rats transplanted with bone marrow cells expressing human alkaline phosphatase. After ischemia-reperfusion injury, bone marrow–derived cells expressing the human enzyme were identified in the renal interstitium. Their numbers peaked seven days after injury and decreased afterwards. The transplanted cells expressed -smooth muscle actin and produced procollagen I, which indicates that they were functional myofibroblasts. These results confirm that bone marrow–derived cells can differentiate into renal interstitial cells after acute kidney injury. The transplanted cells can produce extracellular matrix proteins, which may worsen renal fibrosis. See Broekema et al., pages 165–175.

	Clinical Science Articles

Top Basic Science Articles Clinical Science Articles

 
Increasing Waist Circumference Increases Risk of Microalbuminuria in Type I Diabetes.

The article by de Boer et al. in this issue of JASN examines the role of weight gain and central obesity in the occurrence of nephropathy in type 1 diabetes mellitus. The authors have used patients participating in the Epidemiology of Diabetes Interventions and Complications (EDIC) Study, the observational extension of the Diabetes Control and Complications Trial (DCCT), to examine the onset and time course of early type 1 diabetic nephropathy. They report a 34% increased risk of incident microalbuminuria for each 10-cm increase in waist circumference, and this risk persisted after controlling other risk factors for microalbuminuria. These findings are of interest given the risk of weight gain associated with tight control of hyperglycemia in type 1 diabetes. These findings suggest that additional attention to the early screening and aggressive management of risk factors associated with the development and progression of microalbuminuria, including increases in weight, might be warranted in patients with type 1 diabetes who develop increased central obesity during therapy. See de Boer et al., pages 235–243.

Solvent Exposure and GN—An Underappreciated Risk Factor for Progression?
Factors associated with the variability in risk and progression of primary kidney disease may well identify targets for primary and secondary prevention of kidney disease. The article by Jacob and associates in this issue of JASN examines the association between solvent exposure and the progression of glomerulonephritis to ESRD. They observed that solvent exposure before and after diagnosis of glomerulonephritis was associated with risk of progression from the time of first kidney biopsy, particularly among patients with membranous and IgA nephropathy. These observations support other studies of associations between kidney injury and solvents and serve to remind us that an occupational and recreational history should be obtained from patients with glomerulonephritis and that they should be counseled about relevant exposures. See Jacob et al., pages 274–281.

A BNP Derivative Is a Potent Predictor of Cardiovascular Risk in Patients on Peritoneal Dialysis.

There is currently interest in defining novel biomarkers that are associated with cardiovascular risk in dialysis patients. Brain-type natriuretic hormone (BNP) is a peptide hormone released primarily by ventricular myocytes in response to cardiac stretch and increased filling pressures. BNP is synthesized as an inactive hormone that is subsequently cleaved into the biologically active fragment and the N-terminal pro-BNP (NT-pro-BNP). Compared with BNP, circulating NT-pro-BNP has the advantage of a longer half-life and less biologic variability. In this issue of JASN, Wang and colleagues investigate the hypothesis that plasma NT-pro-BNP levels can predict subsequent episodes of congestive heart failure, mortality, and cardiovascular death in a cohort of peritoneal dialysis patients. In univariate and mutivariate regression models, NT-pro-BNP levels proved to be potent predictors of important cardiovascular outcomes. Although the precise clinical role of NT-pro-BNP levels remains to be fully elucidated, this molecule now joins the list of potentially useful biomarkers of cardiovascular risk in dialysis patients. See Wang et al., pages 321–330.

Hypoxia-Inducible Factor 1 and Kidney Allograft Injury.

Hypoxia-inducible factors (HIF) are regulated by oxygen-dependent enzymes, and tissue expression levels could theoretically be used as an indirect measure of local hypoxia. To investigate potential roles of hypoxia and HIF-1 as mediators of posttransplant kidney allograft injury, Rosenberger et al. used a high-amplification immunohistochemistry technique to detect HIF-1 in human biopsy material. Prolonged cold ischemia times of >15 hours were associated with abundant expression. In contrast, primary nonfunction was associated with low HIF-1 expression, possibly reflecting loss of oxygen consumption for tubular transport. Beyond three months posttransplant, stable renal function without subclinical rejection on a protocol biopsy was associated with an absence of HIF-1 expression, whereas high levels of the protein were detected in tissue with histologic evidence of rejection. Overall, the data support the hypothesis that hypoxia contributes to graft injury and raise the possibility that HIF-1 expression could be useful as an adjunct approach for the diagnosis of rejection. (See also the editorial by Nangaku, pages 13–15). See Rosenberger et al., pages 343–351.

Related Articles

Bone Marrow–Derived Myofibroblasts Contribute to the Renal Interstitial Myofibroblast Population and Produce Procollagen I after Ischemia/Reperfusion in Rats

Martine Broekema, Martin C. Harmsen, Marja J.A. van Luyn, Jasper A. Koerts, Arjen H. Petersen, Theo G. van Kooten, Harry van Goor, Gerjan Navis, and Eliane R. Popa
J. Am. Soc. Nephrol. 2007 18: 165-175. [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