Publications (26) View all
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Article: The impact of C4d and microvascular inflammation before we knew them.
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ABSTRACT: It is important to identify prognostically important morphologic criteria in post-transplant management to tailor therapy and improve outcomes. Therefore, using biopsies carried out for cause <1-yr post-transplant, from an era when C4d staining and microvascular inflammation (MVI) were not clinically utilized, we studied the importance of C4d and MVI on graft survival. Snap-frozen first renal allograft biopsy specimens (done for cause) in the first post-transplant year from 1996 to 2001 were stained/examined for C4d, and pathology re-examined by a separate blinded pathologist. Graft outcomes in patients with and without MVI and/or C4d were compared. Of 128 patients, 39 (30.5%) biopsies were C4d+ and 89 (69.5%) were C4d-; 67 (52.3%) had no MVI (MVI-) while 61 (47.7%) had glomerulitis, peritubular capillaritis, or both (MVI+). There were no significant demographic differences between MVI+ and MVI- patients. A greater proportion of C4d+ biopsies was MVI+ (67%) than MVI- (33%; p = 0.004). C4d positivity had no impact on death-censored graft survival (DCGS). In contrast DCGS was worse in MVI+ than MVI- regardless of presence/absence of C4d (p = 0.005). In biopsies for cause carried out <1-yr post-transplant, MVI is associated with decreased DCGS, independent of the presence of C4d.Clinical Transplantation 03/2013; · 1.67 Impact Factor -
Article: Morphologic features of declining renal function in type 1 diabetes.
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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.Seminars in Nephrology 09/2012; 32(5):415-22. · 2.12 Impact Factor -
Article: Renal complications of Fabry disease in children.
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ABSTRACT: Fabry disease is an X-linked α-galactosidase A deficiency, resulting in accumulation of glycosphingolipids, especially globotriaosylceramide, in cells in different organs in the body. Renal failure is a serious complication of this disease. Fabry nephropathy lesions are present and progress in childhood while the disease commonly remains silent by routine clinical measures. Early and timely diagnosis of Fabry nephropathy is crucial since late initiation of enzyme replacement therapy may not halt progressive renal dysfunction. This may be challenging due to difficulties in diagnosis of Fabry disease in children and absence of a sensitive non-invasive biomarker of early Fabry nephropathy. Accurate measurement of glomerular filtration rate and regular assessment for proteinuria and microalbuminuria are useful, though not sensitive enough to detect early lesions in the kidney. Recent studies support the value of renal biopsy in providing histological information relevant to kidney function and prognosis, and renal biopsy could potentially be used to guide treatment decisions in young Fabry patients. This review aims to provide an update of the current understanding, challenges, and needs to better approach renal complications of Fabry disease in children.Pediatric Nephrology 08/2012; · 2.52 Impact Factor -
Article: Prevention of Acute Kidney Injury by Tauroursodeoxycholic Acid in Rat and Cell Culture Models.
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ABSTRACT: BACKGROUND: Acute kidney injury (AKI) has grave short- and long-term consequences. Often the onset of AKI is predictable, such as following surgery that compromises blood flow to the kidney. Even in such situations, present therapies cannot prevent AKI. As apoptosis is a major form of cell death following AKI, we determined the efficacy and mechanisms of action of tauroursodeoxycholic acid (TUDCA), a molecule with potent anti-apoptotic and pro-survival properties, in prevention of AKI in rat and cell culture models. TUDCA is particularly attractive from a translational standpoint, as it has a proven safety record in animals and humans. METHODOLOGY/PRINCIPAL FINDINGS: We chose an ischemia-reperfusion model in rats to simulate AKI in native kidneys, and a human kidney cell culture model to simulate AKI associated with cryopreservation in transplanted kidneys. TUDCA significantly ameliorated AKI in the test models due to inhibition of the mitochondrial pathway of apoptosis and upregulation of survival pathways. CONCLUSIONS: This study sets the stage for testing TUDCA in future clinical trials for prevention of AKI, an area that needs urgent attention due to lack of effective therapies.PLoS ONE 01/2012; 7(11):e48950. · 4.09 Impact Factor -
Article: Podocyte disorders: Core Curriculum 2011.
American Journal of Kidney Diseases 08/2011; 58(4):666-77. · 5.43 Impact Factor
