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Morphologic features of declining renal function in type 1 diabetes.

ABSTRACT: Progressive renal dysfunction is a major complication of type 1 diabetes. Studying relationships between evolution of diabetic nephropathy lesions and renal functional alterations (structural-functional relationships) helps to better understand the natural history of diabetic nephropathy. The focus of this review is our current understanding of the interplay between morphologic changes of diabetic nephropathy and glomerular filtration rate (GFR) loss. These morphologic changes often may not progress in parallel to each other or to the decline in GFR or increase in albumin excretion rate (AER). Quantitative measures of renal (mainly glomerular) structural changes can predict a substantially larger fraction of AER variability compared with that of GFR, especially using linear correlation analyses. However, nonlinear models better fit the structural-functional relationships across a wide range of GFRs and AERs. Currently, there are insufficient longitudinal data to show which structural changes predict the slope of GFR decline in type 1 diabetic patients. Based on cross-sectional studies, however, such a predictor would be about 10% more robust in patients whose GFR was 45 mL/min/1.73 m(2) or greater if comprised of a composite of glomerular, tubular, and interstitial parameters versus glomerular changes alone. For a slowly progressive disease, such as diabetic nephropathy, in which, especially in the earlier stages, it takes a long time for GFR to decline substantially, such predictors are much needed and, if sufficiently precise, could potentially serve as a surrogate of renal functional decline in clinical trials.

SUBMITTER: Najafian B

PROVIDER: S-EPMC3622555 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Morphologic features of declining renal function in type 1 diabetes.

Najafian Behzad B Mauer Michael M

Seminars in nephrology 20120901 5

Progressive renal dysfunction is a major complication of type 1 diabetes. Studying relationships between evolution of diabetic nephropathy lesions and renal functional alterations (structural-functional relationships) helps to better understand the natural history of diabetic nephropathy. The focus of this review is our current understanding of the interplay between morphologic changes of diabetic nephropathy and glomerular filtration rate (GFR) loss. These morphologic changes often may not prog ...[more]

PMID: 23062981

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Project description:To evaluate disease progression in a cohort of patients with a clinical and genetic diagnosis of Stargardt disease.Longitudinal cohort study.A total of 56 selected patients with a clinical and molecular diagnosis of Stargardt disease, an early age of onset, and a median follow-up length of 2 years.Patients underwent routine examination, including full-field electroretinography, microperimetry, and optical coherence tomography.Best-corrected visual acuity (BCVA), mean retinal sensitivity, fixation stability, preferred retinal locus, inner segment/outer segment (IS/OS) junction loss, and atrophic lesion area.A total of 56 patients with a mean age at disease onset of 15.3 years (range, 3-28 years), a mean disease duration of 12.1 years, and a mean age at baseline of 27.4 years were analyzed. The median BCVA was 20/200 in both eyes. Optical coherence tomography parameters (IS/OS alteration and retinal pigment epithelium lesion area) were obtained in only 49 patients because the signal quality was poor in the remaining 7 patients. Optical coherence tomography revealed a mean retinal pigment epithelium lesion area of 2.6 mm(2), preserved foveal IS/OS in 4.1% of patients, loss of foveal IS/OS in 59.2% of patients, and extensive loss of macular IS/OS in 36.7% of patients. Microperimetric findings showed a reduced macular sensitivity (mean, 10 decibels [dB]) and an unstable fixation in half of the patient cohort. The longitudinal analysis showed a significant progressive reduction of BCVA and macular sensitivity (at an estimated rate of 0.04 decimals and 1.19 dB/year, respectively) associated with a significant enlargement of retinal pigment epithelium lesion area (0.282 mm(2)/year). No significant changes in ophthalmoscopic findings and electroretinographic responses were detected.This study highlights the importance of microperimetry and optical coherence tomography in monitoring patients with Stargardt disease. Quantifying the decline of visual functionality and detecting morphologic macular changes prove useful in evaluating disease progression over a short-term follow-up and should be taken into account for the design of future clinical trials of gene therapy to treat retinal dystrophy.

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Morphologic features of declining renal function in type 1 diabetes.

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Morphologic features of declining renal function in type 1 diabetes.

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