Relationship between High-density Lipoprotein Cholesterol and Insulin Resistance in Non-diabetic Chronic Kidney Disease Patients.

Insulin resistance is linked to cardiovascular disease (CVD), even in non-diabetic patients. Therefore, insulin resistance contributes to the development of CVDs, which are the most important cause of morbidity and mortality in chronic kidney disease (CKD) and patients receiving dialysis replacement therapy. Furthermore, CKD greatly affects the enzyme activities responsible for the metabolism of high-density lipoprotein (HDL), causing an abnormal composition and function of HDL, which results in the loss of the anti-inflammatory effect of HDL and its protective effect against CVD. The study aimed to find the relationship between HDL-C, inflammation, and insulin resistance in nondiabetic CKD patients undergoing different modalities of treatment. This prospective cross-sectional comparative study included 80 subjects divided into the control group (20 healthy participants), Group 1 (15 predialysis CKD patients on conservative treatment), Group 2 (10 peritoneal dialysis patients), and Group 3 (35 hemodialysis patients). A full history, medical examination, and a laboratory investigation were carried out on all subjects from June 2018 to June 2019. The patient groups had significantly lower HDL and higher serum insulin than the control group. HDL was negatively correlated with the Homeostatic Model Assessment of Insulin Resistance. There was a strong negative association between HDL and insulin resistance in CKD patients. Therefore, lifestyle modifications and dyslipidemia treatment in CKD might help to prevent cardiovascular events even in nondiabetic nonobese CKD patients.

Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus / Zinco-alfa2-glicoproteina (ZAG) como biomarcador precoce de nefropatia diabética em pacientes com diabetes mellitus tipo 2

Abstract Introduction: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. Objective: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. Methods: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. Results: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. Conclusion: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Resumo Introdução: Embora a microalbuminúria continue sendo o padrão ouro para a detecção precoce da nefropatia diabética (ND), ela não é um preditor suficientemente preciso do risco de ND. Assim, novos biomarcadores para prever mais precocemente o risco de ND e possivelmente evitar a ocorrência de doença renal terminal estão sendo investigados. Objetivo: Investigar a zinco-alfa2-glicoproteína (ZAG) como marcador precoce de ND em pacientes com debates mellitus tipo 2 (DM2). Métodos: Os 88 indivíduos incluídos foram divididos em quatro grupos: grupo controle (Grupo I), composto por voluntários saudáveis normais; e três grupos de pacientes com DM2 assim divididos: grupo normoalbuminúria (Grupo II), subdivididos em TFG normal e TFG > 120 mL/min/1,73 m2), grupo microalbuminúria (Grupo III) e grupo macroalbuminúria (Grupo IV). Todos foram submetidos a urinálise e exames para determinar glicemia, HbA1c, função hepática, creatinina sérica, ácido úrico, perfil lipídico, cálculo da TFG, relação albumina/creatinina (RAC) e dosagem urinária e sérica de ZAG. Resultados: Os níveis séricos e urinários de ZAG foram mais elevados nos pacientes com DM2 em comparação aos controles. Foi identificada diferença estatisticamente significativa entre os grupos estudados em relação aos níveis séricos e urinários de ZAG. Os níveis urinários de ZAG foram positivamente correlacionados com a RAC. Ambos os níveis de ZAG foram negativamente correlacionados com TFG. Os níveis urinários de ZAG no subgrupo com TFG ˃ 120 mL/min/1,73m2 foram maiores do que no subgrupo com TFG normal. Conclusão: Constatamos que a ZAG sérica e urinária pode ser um útil biomarcador precoce para detecção de ND em pacientes com DM2, sendo detectável mais precocemente que microalbuminúria.

Zinc alpha 2 glycoprotein as an early biomarker of diabetic nephropathy in patients with type 2 diabetes mellitus.

INTRODUCTION: Although microalbuminuria remains the gold standard for early detection of diabetic nephropathy (DN), it is not a sufficiently accurate predictor of DN risk. Thus, new biomarkers that would help to predict DN risk earlier and possibly prevent the occurrence of end-stage kidney disease are being investigated. OBJECTIVE: To investigate the role of zinc-alpha-2-glycoprotein (ZAG) as an early marker of DN in type 2 diabetic (T2DM) patients. METHODS: 88 persons were included and classified into 4 groups: Control group (group I), composed of normal healthy volunteers, and three patient groups with type 2 diabetes mellitus divided into: normo-albuminuria group (group II), subdivided into normal eGFR subgroup and increased eGFR subgroup > 120 mL/min/1.73m2), microalbuminuria group (group III), and macroalbuminuria group (group IV). All subjects were submitted to urine analysis, blood glucose levels, HbA1c, liver function tests, serum creatinine, uric acid, lipid profile and calculation of eGFR, urinary albumin creatinine ratio (UACR), and measurement of urinary and serum ZAG. RESULTS: The levels of serum and urine ZAG were higher in patients with T2DM compared to control subjects and a statistically significant difference among studied groups regarding serum and urinary ZAG was found. Urine ZAG levels were positively correlated with UACR. Both ZAG levels were negatively correlated with eGFR. Urine ZAG levels in the eGFR ˃ 120 mL/min/1.73m2 subgroup were higher than that in the normal eGFR subgroup. CONCLUSION: These findings suggest that urine and serum ZAG might be useful as early biomarkers for detection of DN in T2DM patients, detectable earlier than microalbuminuria.

Treatment of Chronic Hepatitis C Infection Among Egyptian Kidney Transplant Recipients: A Pilot Study.

OBJECTIVES: Chronic hepatitis C infection incidence and prevalence are high in Egypt and represent a major health burden. Hepatitis C virus infection can affect graft outcomes in kidney transplant recipients. Treatment of hepatitis C virus infection among this special group was difficult during the interferon era; however, with advances in direct-acting antivirals, treatment outcomes have become more promising. MATERIALS AND METHODS: This is a pilot, observational, single-center, one arm study that included 50 kidney transplant recipients seen at the Mansoura (Egypt) Urology and Nephrology Center. Patients were consented to receive a sofosbuvir-based regimen as all had creatinine clearance of greater than 30 mL/min/1.73 m2. RESULTS: All patients achieved rapid virologic responses 4 weeks after starting treatment. Forty-nine of 50 patients achieved 12-week and 24-week sustained viral responses. Six patients had increased serum creatinine levels. Four graft biopsies were performed. Anemia was the most common adverse effect among the patients who were maintained on ribavirin. CONCLUSIONS: Treatment of chronic hepatitis C infection has become easier and safe with the advance of new direct-acting antivirals.

Postrenal transplant malignancy: Incidence, risk factors, and prognosis.

The newer and potent immunosuppressive agents have successfully reduced the risk of rejection after kidney transplantation, but the development of cardiovascular diseases, infections, and malignancy is major factors limiting their success. Posttransplantation malignancy is the second most common cause of death in renal transplant recipients after cardiovascular disease; it is expected that mortality due to malignancy may become the most common cause of death within the next two decades. This study is designed to evaluate the incidence, risk factors, and types of malignancies occurring after renal transplantation and their impact on patient and graft survival. A total of 2288 patients underwent living donor renal allotransplantation in the Urology and Nephrology Center, Mansoura University, during the period between 1975 and 2011. Among these patients, 100 patients developed posttransplantation malignancy. Patients were categorized into five major groups according to their type of malignancy; Kaposi's sarcoma (KS), non-Kaposi's skin tumors (non-KS), posttransplant lymphoproliferative disorders (PTLD), solid tumors, and genitourinary and reproductive system (GU and RS). Overall, the incidence of cancer in renal transplant recipients was 4%. There were 83 male (83%) and 17 female patients (17%). The most frequent cancer was KS seen in 33 patients (33%). The lowest median time to development of cancer was observed in KS (35 months). The highest median time to development of cancer was observed in PTLD (133 months). The best graft survival was observed in PTLD and the worst in non-KS tumors. The best patient survival was observed in KS and the worst in GU and RS tumors. Azathioprine-based regimen was associated with a higher rate of cancer. The number of patients who died was 65 (65%). Our results indicate that the occurrence of malignancy has an important impact on short- and long-term graft and patient survival.

Clinicopathological correlations of renal pathology: A single center experience.

To evaluate the clinicopathological correlation of renal pathology and outline the frequencies of different renal diseases, beside assessment of lupus nephritis (LN), we studied 150 patients [72 (48%) males and mean age of 33.82 ± 15.4 years] who were subjected to native renal biopsy; 112 (72.8%) biopsied patients were diagnosed to have glomerulonephritis (GN). The most frequent clinical renal syndrome was nephrotic syndrome found in 55 (36.6%) patients, followed by nephritic syndrome in 38 (25.3%) patients, chronic kidney disease in 28 (18.6%) patients, acute kidney injury (AKI) in 17 (11.3 %) patients, and subnephrotic proteinuria (SNP) in 12 (8%) patients. Focal segmental glomerulosclerosis (FSGS) was the most common patterns in primary GN (16.6%), LN was the most common pathology in secondary GN (33.3%). LN represented 18.1% of nephrotic syndrome, 68.3% of nephritic syndrome, 35.2% of AKI, and 58% of SNP. FSGS was the most common pattern in obese patients (58%), membranoproliferative GN (MPGN) was the most common pattern in hepatitis-C virus +ve patients (66.6%) and mem- branous GN was the most common pattern in hepatitis-B virus +ve patients (66.6%). In conclusion, GN was the most common pathology in this study, FSGS and MPGN were the most common patterns in primary GN.

Frequency of the Original Kidney Disease and Its Effect on the Outcome of Kidney Transplant in the Urology-Nephrology Center Mansoura University.

OBJECTIVES: Renal allograft function and graft survival depends on many factors, including the source of the graft, immunologic matching between donor and recipient, incidence of acute rejection, and recurrence of the original kidney disease. This work aimed to evaluate the effects of the original kidney disease on patient and graft survival. MATERIALS AND METHODS: This was a retrospective, single-center study that included 2189 kidney transplant recipients who were transplanted at The Urology and Nephrology Centre, Mansoura University, between 1976 and 2010. Of 2189 recipients, 1350 patients with unknown original kidney disease were excluded, with the remaining 839 patients divided into 4 groups according to their original kidney disease. RESULTS: We found pretransplant dialysis and blood transfusion to be statistically significant among the 4 groups. Regarding induction immunosuppressive therapy, a statistical significance was found between the 4 groups regarding the presence and type of induction therapy, with no statistical significance regarding the type of maintenance immunosuppression. There was no statistical significance between the 4 groups regarding the incidence of acute and chronic rejection. We also found recurrence of original kidney disease to be statistically significant in the 4 groups, particularly in the group that included patients with glomerular disease, where the highest rate of recurrence was reported in patients with focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis, and patient and graft survival was also statistically significant. CONCLUSIONS: The original kidney disease has an effect on renal allograft function and graft and patient survival.

Effect of pretransplant hepatitis C virus on the development of new-onset diabetes mellitus after transplant in Egyptian living-donor renal allotransplant recipients at Mansoura Urology and Nephrology Center.

OBJECTIVES: New-onset diabetes mellitus after transplant is a common complication in renal allograft recipients. Recently, a high prevalence of diabetes mellitus has been reported in patients with chronic hepatitis C virus. The association between hepatitis C and diabetes mellitus is well demonstrated in the general population, but some controversy still exists. This work aimed to study the effect of pretransplant hepatitis C virus on the development of new-onset diabetes mellitus after transplant in Egyptian living-donor renal allotransplant recipients. MATERIALS AND METHODS: This retrospective single center study included 913 kidney transplant recipients who were transplanted at Mansoura Urology and Nephrology Center between 2000 and 2010. The patients were divided into 4 groups according to their hepatitis C virus serology and diabetic status. RESULTS: Pretransplant dialysis duration and number of blood transfusion units were statistically significant among both viremic and nonviremic groups. With respect to induction therapy, a highly statistical significance was observed between the 4 groups regarding presence and type of adjuvant therapy (P < .001). With respect to maintenance immunosuppression, high statistically significant results were observed regarding steroid and rapamycin between the 4 groups (P < .001) with lower significance regarding mycophenolate mofetil (P = .04) but no significance regarding azathioprine, cyclosporine, or tacrolimus therapy. Incidence of new-onset diabetes mellitus after transplant was statistically higher in the viremic than nonviremic group (P < .001). CONCLUSIONS: There was a positive correlation between incidence of new-onset diabetes mellitus after transplant and positive pretransplant hepatitis C virus status.

Endothelial nitric oxide synthase gene polymorphisms and the risk of diabetic nephropathy in type 2 diabetes mellitus.

Endothelial dysfunction plays an important role in the pathogenesis of diabetic vascular disease, including diabetic nephropathy (DN). Endothelial nitric oxide synthase (eNOS) gene polymorphisms that affect eNOS activity are associated with endothelial dysfunction. The aim of this study was to evaluate the association of three polymorphisms of the eNOS gene (894G>T, -786T>C, and 27-bp-VNTR) with the risk of DN among type 2 diabetic patients. A total of 400 type 2 diabetic patients were enrolled in this study. The DN group comprised 200 patients; the group of diabetics without nephropathy comprised another 200 patients. Genetic analysis for eNOS gene polymorphisms was done in all subjects. Measurement of nitric oxide levels was estimated. The C allele for -786T>C and the T allele for 894G>T were significantly more frequent in diabetics with nephropathy than in diabetics without nephropathy (p<0.001; odds ratio [OR] and 95% confidence interval [CI] for the C allele=1.64 [1.24-2.17] and p<0.001; OR and 95% CI=1.7 [1.27-2.26] for the T allele). The haplotypes CTa (with all the mutant alleles) and CTb were significantly more common in patients with DN (p=0.01 and 0.003, respectively). These results suggested that the eNOS polymorphisms might represent genetic determinants for developing DN in type 2 diabetic Egyptians.