A quantitative, noninvasive method of assessing autonomic control, based on the spectral analysis of beat-to-beat fluctuations in heart rate (HR), was applied to patients with chronic renal failure (RF). Since the power spectrum of HR fluctuations measures the dynamic nervous control of HR, it can be used to quantitate a normal control system as opposed to a disturbed or depressed system. Indeed, in RF patients, a strong reduction in the HR power spectrum was observed in all frequency ranges, both sympathetically and parasympathetically mediated. A similar depression in autonomic control was demonstrated in patients on hemodialysis or peritoneal dialysis. RF patients not yet undergoing dialysis show a lesser degree of depression. Spectral analysis of HR fluctuations in RF patients makes it possible to quantitate autonomic dysfunction and to reliably measure its development as a function of time, and requires only a 10-min standard electrocardiogram recording.

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The Cohen diabetic rat is an experimental model reminiscent of human type 2 diabetes. The aim of this study was to characterize the development of end-organ damage in this model. Cohen diabetic sensitive (CDs) and Cohen diabetic resistant (CDr) rats were fed regular diet or a diabetogenic diet. Glucose tolerance, renal function, and renal and retinal histology were studied at set intervals. CDs fed diabetogenic diet were the only strain that expressed the diabetic metabolic phenotype. In this strain, urinary protein excretion did not increase with the development of diabetes, but plasma urea and creatinine levels increased and creatinine clearance decreased. Light microscopy revealed in CDs enlarged glomeruli with increased mesangial matrix and thickening of the glomerular capillary wall; electron microscopy demonstrated thickened basement membrane and mesangial abundance. There was increased staining for type IV collagen in glomeruli and interstitium of CDs. The retinas of diabetic CDs demonstrated pathology consistent with nonproliferative diabetic retinopathy. The histological findings in the kidneys, the absence of proteinuria, the impairment in glomerular filtration, and the development of retinopathy in CDs are consistent with diabetes-associated nephropathy that is similar to a nonalbuminuric type of nephropathy associated with type 2 diabetes in humans. Diabetes 54:1487-1496, 2005 T he Cohen diabetic rat is an experimental rodent model reminiscent of human type 2 diabetes (1,2). The model consists of two strains: the Cohen diabetic sensitive (CDs) rat, which invariably develops diabetes when fed a diabetogenic diet, and the Cohen diabetic resistant (CDr) rat, which remains normoglycemic even when fed a similar diet (1). The original colony was established over 30 years ago (2). We recently rebred animals from the original colony and characterized the metabolic phenotype of the new colony (1). We subsequently set forth to investigate whether target organ damage related to diabetes develops in this model. Because nephropathy is among the most common and morbid complications of diabetes, our focus was on the kidney.Earlier studies on the renal phenotype of this model placed much emphasis on histopathology, but paid little or no attention to kidney function (3-13). Preliminary studies by our group indicated that in the CDs strain, an unusual type of nephropathy evolves with no significant proteinuria but with progressive impairment of kidney function. In the current study, we present the results of our investigation on the development of end-organ damage in animals from the new Cohen diabetic rat colony. We provide histopathological evidence of the diabetes-related renal and retinal lesions and characterize functional aspects of the diabetic renal injury in this model. We demonstrate that the CDs is an experimental model of type 2 diabetes that develops a nonproteinuric type of diabetic nephropathy. RESEARCH DESIGN AND METHODSThe animals that were used in this study were male CDs and CDr rats that had been r...