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This Month's Highlights

	Basic Science Articles

Top Basic Science Articles Clinical Science Articles

Stem Cell Marker in Developing Kidney and Podocytes.

Nestin is an intermediate filament protein expressed in progenitor cells in the developing nervous system, hair follicles, and pancreas. In adults, nestin is primarily expressed in areas of tissue regeneration. Chen et al. studied the expression of nestin in the developing and adult mouse kidney. In the developing kidney, nestin was expressed in the metanephric mesenchyme but was excluded from the ureteric bud. Cell lineage analysis using nestin-Cre mice showed that the nestin-expressing mesenchymal cells differentiated into the glomerulus and proximal and distal tubules but did not contribute to renal collecting ducts. Glomerular capillary endothelial cells were also derived from nestin-expressing progenitor cells. In the adult kidney, nestin was restricted to podocytes. Inhibition of nestin expression in cultured podocytes reduced the formation of cell processes. Taken together, these results identify nestin as a novel marker of renal progenitor cells and mature podocytes. See Chen et al., pages 1283–1291.

Cardiac Malfunction in Renal Failure—More Than Atherosclerosis.

Even in early renal failure, cardiovascular mortality is excessive. Initially, this was thought to be fully explained by accelerated coronary atherosclerosis, but additional cardiac abnormalities (left ventricular hypertrophy, interstitial fibrosis, microvessel disease) have meanwhile been well documented. There had remained, however, a dearth of information concerning functional abnormalities. The study of Kingma et al. is therefore a most welcome partial correction of this deficit. This group studied coronary blood flow, assessing autoregulation, vascular reserve, and endocardial/epicardial flow distribution in acute renal failure (which may not exactly replicate chronic renal failure, but has the advantage of avoiding the potentially confounding changes of heart structure seen in chronic renal failure). The autoregulatory pressure–flow relationship was shifted, and the endothelium-dependent as well as -independent vascular reactivity was blunted. This information is potentially important because, in a renal patient with coronary stenosis, functional abnormalities of coronary perfusion, further jeopardizing potential compensatory adjustments of flow, is the last thing one wants to have. See Kingma et al., pages 1316–1324.

ILK and the Podocyte.

Integrin-linked kinase (ILK) has been implicated in podocyte cell matrix interaction. In this issue of JASN, El-Aouni et al. directly investigated the role of ILK in the podocyte by Cre-mediated podocyte-specific podocyte inactivation of ILK. Mice developed progressive glomerulosclerosis and thickened glomerular basement membranes, with altered 3 integrin distribution, though other key podocyte moelcues were not altered. These elegant studies indicate a direct role for ILK in glomerular basement membrane structure and podocyte function. See El-Aouni et al., pages 1334–1344.

Spironolactone and Diabetes.

In these interesting studies, Han et al. investigate the role of spironolactone in a rat type 2 diabetic model with corresponding in vitro studies in mesangial and proximal tubular cells. Spironolactone had no effect on blood pressure or blood glucose, but significantly decreased albuminuria and glomerular mesangial expansion. These changes were associated with decreased monocyte chemotactic peptide-1 (MCP-1) and macrophage migration inhibitory factor, with corresponding decrease in infiltrating macrophages. In vitro, spironolactone also decreased MCP-1, linked to decreased NFB. These data suggest novel actions of sprionolactone in diabetic injury. See Han et al., pages 1362–1372.

mTOR and Diabetes.

In this issue of JASN, Lloberas et al. investigate the effect of mammalian target of rapamycin (mTOR) blockade on diabetic injury in a rat streptozotocin diabetic model. Sirolimus decreased mesangial matrix expansion, although neither glucose levels nor macrophage infiltration were affected. Activation of mesangial cells was decreased, as was expression of TGF- and connective tissue growth factor, a downstream effector of TGF- effects. AKT phosphorylation was also decreased. There was corresponding improvement in functional derangements. These studies suggest that the mTOR pathway might modulate injury in diabetes. See Lloberas et al., pages 1395–1404.

	Clinical Science Articles

Top Basic Science Articles Clinical Science Articles

 
Can Dipsticks Alone Predict ESRD?

The article by Ishani and colleagues in this issue of JASN brings further attention to the importance of an incidental measurement of proteinuria as a predictor of subsequent kidney disease. The authors analyzed 25-year follow-up of Multiple Risk Factor Intervention Study (MRFIT) participants with linkage to the United States Renal Data System’s (USRDS) data and National Death Index to ascertain outcomes. They observed a strong association between baseline proteinuria and subsequent development of ESRD that was independent of baseline kidney function, blood pressure, and other cardiovascular and kidney risk factors measured in the study. These findings amplify those recently reported in JASN from the PREVEND cohort study that an elevated albumin excretion rate is independently associated with development of hypertension over follow-up periods a quarter as long as those reported in the Ishani study. Clearly, the role of proteinuria of all magnitudes as a predictor of risk for progressive kidney injury and its applicability as a therapeutic target will continue to demand our attention. See Ishani et al., pages 1444–1452.

Can We Diagnose Analgesic Nephropathy by CT?

Among the goals of the National Analgesic Nephropathy Study was to confirm or refute prior reports that computed tomography (CT) was a sensitive and specific imaging technique that could be used to secure the diagnosis of analgesic nephropathy in patients with chronic kidney disease in the absence of diabetes, glomerulonephritis, or other obvious cause. Three criteria were used to identify patients who might have analgesic nephropathy: (reduced) size, indentations, and calcifications. While these characteristic CT findings were statistically associated with greater cumulative exposure to analgesics, the sensitivity of CT findings was low, approximately 5 to 25%. The findings of this excellent "negative" report highlight the capacity of carefully conducted observational studies to counter conventional wisdom with an evidence base. More generally, this study should focus attention on the epidemiology of progressive "idiopathic" chronic kidney disease, as the etiology of disease for a large fraction of the global ESRD population remains unexplained. See Henrich et al., pages 1472–1480.

Related Articles

Mammalian Target of Rapamycin Pathway Blockade Slows Progression of Diabetic Kidney Disease in Rats

Núria Lloberas, Josep M. Cruzado, Marcella Franquesa, Immaculada Herrero-Fresneda, Joan Torras, Gabriela Alperovich, Inés Rama, August Vidal, and Josep M. Grinyó
J. Am. Soc. Nephrol. 2006 17: 1395-1404. [Abstract] [Full Text] [PDF]

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