Dysregulated Nephrin in Diabetic Nephropathy of Type 2 Diabetes: A Cross Sectional Study

Podocyte specific proteins are dysregulated in diabetic nephropathy, though the extent of their expression loss is not identical and may be subject to different regulatory factors. Quantifying the degree of loss may help identify the most useful protein to use as an early biomarker of diabetic nephropathy.Protein expression of synaptopodin, podocin and nephrin were quantified in 15 Type 2 diabetic renal biopsies and 12 control patients. We found statistically significant downregulation of synaptopodin (P<0.0001), podocin (P = 0.0002), and nephrin (P<0.0001) in kidney biopsies of diabetic nephropathy as compared with controls. Urinary nephrin levels (nephrinuria) were then measured in 66 patients with Type 2 diabetes and 10 healthy controls by an enzyme-linked immunosorbent assay (Exocell, Philadelphia, PA). When divided into groups according to normo-, micro-, and macroalbuminuria, nephrinuria was found to be present in 100% of diabetic patients with micro- and macroalbuminuria, as well as 54% of patients with normoalbuminuria. Nephrinuria also correlated significantly with albuminuria (rho = 0.89, p<0.001), systolic blood pressure (rho = 0.32, p = 0.007), and correlated negatively with serum albumin (rho = -0.48, p<0.0001) and eGFR (rho = -0.33, p = 0.005).These data suggest that key podocyte-specific protein expressions are significantly and differentially downregulated in diabetic nephropathy. The finding that nephrinuria is observed in a majority of these normoalbuminuric patients demonstrates that it may precede microalbuminuria. If further research confirms nephrinuria to be a biomarker of pre-clinical diabetic nephropathy, it would shed light on podocyte metabolism in disease, and raise the possibility of new and earlier therapeutic targets

Long-Term Functional Recovery, Quality of Life, and Pregnancy After Solid Organ Transplantation.

This article reviews the salient features of functional recovery, health-related quality of life (HR-QOL), and reproductive health, with special emphasis on pregnancy outcomes in kidney and liver recipients. Transplantation results in improved functional status and HR-QOL. Addressing factors that limit the optimal rehabilitation of transplant recipients can improve transplant outcomes. After successful transplantation, there is a rapid return of fertility, warranting counseling regarding contraception. Practitioners should be aware of the teratogenic potential of mycophenolic acid products. Posttransplant pregnancies are high risk, with increased incidences of hypertension, preeclampsia, and prematurity. Most pregnancies in kidney and liver recipients have successful maternal and newborn outcomes

Pancreas Transplantation: Lessons Learned From a Decade of Experience at Wake Forest Baptist Medical Center

This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature

Clinical parameters of control and type 2 diabetic patients.

<p>Data are means +/− SD or median (interquartile range).</p>*<p>UACR: urine albumin-to-creatinine ratio.</p>†<p>UNCR: urine nephrin-to-creatinine ratio.</p>‡<p>P for trend across the 4 categories.</p>§<p>P <0.05 vs. Control.</p

Synaptopodin, podocin, and nephrin are significantly downregulated in diabetic nephropathy (DN) as compared to controls (Con).

<p>Representative staining of synaptopodin in Con (A), DN (B), podocin in Con (E) and DN (F), and nephrin in Con (I) and DN (J). Negative controls without administration of primary antibody are represented for synaptopodin (C), podocin (G), and nephrin (K). Quantification of synaptopodin (D), podocin (H), and nephrin (L) positive area per glomerular tuft in Con (12 patients) and DN (15 patients). Horizontal lines represent the median value. *Number of DN biopsies for nephrin was 11 due to lack of remaining tissue.</p

Correlations between urine nephrin-to-creatinine ratio (UNCR) and clinical markers of renal disease.

<p>A) Log transformed UNCR correlates significantly with macroalbuminuria (<i>rho</i> = 0.82, p<0.0001) and microalbuminuria (<i>rho</i> = 0.66, p = 0,02), and not significantly with normoalbuminuria (<i>rho</i> = 0.34, p = 0.09) when divided into groups according to level of albuminuria.</p

Correlations of urine nephrin-creatinine ratio (UNCR) with clinical parameters.

<p>Correlations were determined by calculations of Spearman <i>rho.</i></p>*<p>UACR: urine albumin-to-creatinine ratio.</p>†<p>ACEI: angiotensin converting enzyme inhibitor.</p>‡<p>ARB: angiotensin receptor blocker.</p

Clinical characteristics of control and Type 2 diabetic nephropathy patients.

<p>Data are presented as median (interquartile range) for continuous variables and % for categorical variables.</p>*<p>Urine protein-creatinine ratio not available for control patients as their urinalyses did not show proteinuria.</p>†<p>ACEI: angiotensin converting enzyme inhibitors.</p>‡<p>ARB: angiotensin receptor blockers.</p