Non-diabetic nephropathy in diabetic patients: incidence, HbA1c variability and other predictive factors, and implications.

PURPOSE: Diabetes mellitus (DM) is the leading cause of chronic kidney disease (CKD) in the population. In patients with diabetes mellitus, the incidence of non-diabetic nephropathy (NDNP) has been estimated to range from 3% to 69.5%. Personal judgment is frequently employed while deciding whether or not to do a kidney biopsy (KB) on diabetic patients. NDNP alters the prognosis and course of treatment for people with DM. In our study, we examined the incidence of NDNP concurrent with the progression of diabetes mellitus, as well as the laboratory and clinical indicators that could be utilized to forecast it. METHODS: A retrospective analysis of 76 diabetic patients who underwent KB was conducted. Based on the pathological diagnoses of these patients, they were categorized as DNP (diabetic nephropathy) or NDNP. The definition of HbA1c variability was determined by calculating the mean HbA1c and the average value of the HbA1c measurements, as well as the standard deviation (SD) for each participant. RESULTS: NDNP was detected in 50% of 76 patients. Among patients with NDNP, 36.8% had focal segmental glomerulosclerosis (FSGS), 23.6% had membranous glomerulonephritis, and 7.8% had IgA nephritis. The NDNP group exhibited significantly higher rates of female gender, absence of diabetic retinopathy, shorter time to diagnosis of diabetes mellitus, chronic kidney disease, and proteinuria, less intensive medication for diabetes mellitus, presence of hematuria and leukociduria, immunological serological marker positivity, and non-HbA1C variability. Risk factors for predicting non-diabetic nephropathy, as determined by multivariate analysis, included female gender, the absence of diabetic retinopathy, non-HbA1c variability and a positive immunological serological test. CONCLUSION: In this study, a significant number of diabetic patients with chronic kidney disease were diagnosed with NDNP. Identifying these patients allows for treatment of the specific underlying disease. Factors such as the absence of DR, non-HbA1c variability, female gender, and immunological serological test positivity can predict NDNP and guide the clinician's decision on kidney biopsy. Further prospective studies are warranted to validate the efficacy of potential predictive factors like HbA1c variability.

The liver-kidney axis: Is serum leptin a potential link in non-alcoholic fatty liver disease-associated chronic kidney disease?

BACKGROUND AND STUDY AIMS: Non-alcoholic fatty liver disease (NAFLD) is an independent risk factor for chronic kidney disease (CKD). Previous studies argued that leptin levels increase significantly with the progression of CKD. But the association between leptin and CKD has not been investigated in patients with NAFLD. Therefore, we conducted this study to establish whether increased leptin level is associated with CKD in NAFLD patients. PATIENTS AND METHODS: In our prospective study with a follow up period of six months thirty-five teetotaller biopsy-proven NAFLD patients were divided as groups with mild, versus advanced, fibrosis. Liver fibrosis was also assessed with Fibroscan. Serum leptin levels were measured by radioimmunoassay. For insulin resistance we used the homeostasis model assessment method (HOMA-IR). For the kidney function, we used the abbreviated formula Modification of Diet in Renal Disease (MDRD) formula, which estimates GFR. For statistical analysis, Student's-t test, Mann-Whitney test, linear regression-binary logistic regression analyses and the ROC curve analysis were used. RESULTS: Advanced fibrosis and increased HOMA-IR were risk factors for decreased eGFR. Leptin correlated inversely with advanced fibrosis (p: 0.03) and low leptin was a risk factor for CKD (p: 0.02). In ROC curve analysis, advanced fibrosis and low leptin were risk factors for decreased eGFR (p: 0.007 and 0.004, respectively). Low leptin level was dependently associated with decreased eGFR. CONCLUSION: Advanced fibrosis in NAFLD patients is a risk factor for CKD. Leptin correlated inversely with advanced fibrosis. Unlike the previous studies, which were not performed in NAFLD patients, we found decreased leptin in NAFLD patients with decreased eGFR. Low leptin level was found to be a dependent predictor for differentiating NAFLD patients with high risk for CKD.

Comparison of Cytotoxic Flow Cytometric Cross Match With Complement Dependent Lymphocytotoxicity and Flow Cytometric Cross Match in Renal Transplant Patients.

Cytotoxic flow cytometric crossmatch (cFCXM), identified by detecting complement-mediated cytotoxic cell death in addition to the capability of showing the alloantibodies binding onto lymphocytes at the same time, can reduce the necessary time and workload in evaluating alloantibodies. More data from clinical samples are needed for cFCXM to be accepted by tissue typing laboratories. In this study, we compared cFCXM with complement-dependent lymphocytotoxicity and standard flow cytometric crossmatch in 41 renal pretransplant patients. A comparison of the obtained data was performed using Spearman's correlation test. We found that cFCXM showed no statistically significant differences with complement-dependent lymphocytotoxicity and flow cytometric crossmatch. We believe that cFCXM can be used in clinical laboratories in the near future following intra-laboratory validation.

Gastrointestinal bleeding in patients with renal failure under hemodialysis treatment: a single-center experience.

PURPOSE: Gastrointestinal bleeding remains the leading cause of morbidity and mortality for patients who need hemodialysis treatment. Our aim was to evaluate patients who needed hemodialysis and presented with bleeding during their hospital stay (uremic bleeding patients). Factors that increased the risk of bleeding and death were evaluated. Additionally, uremic bleeding patients were compared to non-uremic bleeding patients regarding gastrointestinal findings. PATIENTS AND METHODS: Fifty-one uremic bleeding patients were compared to two control groups which included uremic (hemodialysis dependent and non-bleeding) and non-uremic (no renal insufficiency and bleeding) patients. RESULTS: NSAIDs and anti-ulcer drug usage were more common in uremic bleeding and in uremic non-bleeding groups, respectively. Dialysis vintage was longer in uremic bleeding group. Comparison of uremic bleeding and non-bleeding uremic patients regarding the usage of ACEI or ARB drugs yielded non-significant results. Acute kidney injury, lower plasma albumin level and high CRP level were significantly increased the risk of mortality in uremic bleeding patients. Hospital stay more than 1 week was the only strong factor for mortality when multivariate analysis was performed. Gastroduodenal and duodenal ulcers were significantly detected in uremic bleeding and non-uremic bleeding patients; respectively. CONCLUSIONS: Hemodialysis patients presenting with gastrointestinal bleeding should be evaluated regarding use of prescriptions and efforts should be done in order to shorten their hospital stay and decrease their mortality. Effect of ACEI or ARB drugs should also be evaluated in future studies.

Apoptosis and Disease Severity is Associated with Insulin Resistance in Non-alcoholic Fatty Liver Disease.

BACKGROUNDS AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with insulin resistance (IR). We evaluated whether IR contributes to hepatocyte apoptosis, inflammation, and fibrosis in NAFLD. METHODS: Forty-four teetotaller patients with biopsy-proven diagnosis of NAFLD were enrolled. Twenty-eight NAFLD patients with IR were compared with 16 subjects without IR. For apoptotic activity caspase 3 and 8, transcription nuclear factor kB (NF-kB), and anti-apoptotic Bcl-2 protein were determined through immunohistochemical methods. RESULTS: HOMA-IR index was significantly correlated with the stage and caspase 3- and 8 levels (p= 0.001, 0.02, and 0.01, respectively). HOMA-IR index was independently associated with the severity of fibrosis ( = 5.9, p = 0.001), caspase-3 ( = 0.16, p = 0.001), and caspase-8 (b =0.032, p = 0.018) levels. TNF-sRp55 level was positively correlated with HOMA-IR index (p = 0.024). Patients with IR had significantly higher necroinflammatory grade, stage, caspase-3, and caspase-8 levels than those without IR (p = 0.022, 0.007, 0.031, and p = 0.011, respectively). HOMA-IR index had statistically significant values for distinguishing of severe necroinflammatory grade, stage and for differentiating NASH from simple fatty liver (AUC = 0.78, 0.76, and 0.82, respectively). CONCLUSION: This study demonstrates that IR in NAFLD is associated with enhanced hepatocyte apoptosis and histopathologic disease severity. These data indicate that NAFLD patients with IR may have increased risk for disease progression.

Evaluation of Pre-Transplant Panel Reactive Antibody Levels and Sensitization: A Single-Center Study.

BACKGROUND Sensitization is one of the most important barriers against transplantation. Our aim was to evaluate the sensitization status of our patients awaiting cadaveric transplantation and to identify factors causing sensitization. MATERIAL AND METHODS A total of 140 patients on the cadaveric waiting list during January 2014 were included in this retrospective cross-sectional study. The parametric t-test and the non-parametric chi-square test were used to detect differences between PRA-positive and -negative patients. Multivariate analysis was used to identify factors associated with PRA positivity. One-way analysis of variance was used to compare PRA-negative and -positive results. RESULTS Anti-HCV positivity (p=0.040), history of transfusion (p=0.041), and mean number of blood product transfused (p=0.047) were significantly related to class 1 PRA positivity. History of transfusion (p=0.038) and mean number of blood product transfused (p=0.044) were related to class 2 PRA positivity. The multivariate analysis indicated that transfusion and more than 5 units of blood product transfused were related to either class 1 or class 2 PRA positivity. No associations were found between PRA positivity and pregnancy, transplantation, age, sex, infection, abortion, cardiovascular disease, diabetes mellitus, hepatitis B, or time spent on dialysis and being on the transplantation waiting list. CONCLUSIONS Anti-HCV positivity and transfusion are risk factors for sensitization. Particular emphasis should be given to sensitization and its prevention to reduce waiting time for transplantation.

Brown Tumors: A Case Report and Review of the Literature.

Brown tumors are focal bone lesions, encountered in patients with uncontrolled hyperparathyroidism. They can be located in any part of the skeleton. Clinically significant lesions in the craniofacial bones are rare. Craniofacial involvement may cause facial disfiguration and compromise social ease of the patient and normal functions, such as chewing, talking, and breathing. In this case report, we present a patient with a brown tumor of the craniofacial bones provoked by secondary hyperparathyroidism and review the last 10 years of craniofacial brown tumors associated with secondary hyperparathyroidism in the English literature.

Proteinuria associated with mTOR inhibitors after kidney transplant.

OBJECTIVES: The mammalian target of rapamycin inhibitors sirolimus and everolimus are immunosuppressive drugs for kidney transplant patients, but adverse events may include proteinuria. The purpose of this study was to compare the effects of sirolimus and everolimus on creatinine clearance and proteinuria after kidney transplant. MATERIALS AND METHODS: This study was a prospective evaluation period of 50 patients (age, 16-65 y) who had kidney transplant. There were 25 patients who used sirolimus and 25 patients who used everolimus. Evaluation at the beginning mTOR and end of the evaluation period included complete blood count, blood pressure, serum creatinine level, creatinine clearance, and proteinuria level in a 24-hour urine collection. RESULTS: Mean creatinine clearance at the beginning and end of the evaluation period was significantly less in the everolimus than sirolimus group. There was no significant change in creatinine clearance from the beginning to end of the evaluation period in either the sirolimus or everolimus group. Mean proteinuria at the beginning and end of the evaluation period was similar between the sirolimus and everolimus groups. Both groups had a significant increase in mean proteinuria from beginning to end of the evaluation period, but the increase in proteinuria was similar for the sirolimus and everolimus groups (difference not significant). CONCLUSIONS: In kidney transplant recipients, sirolimus and everolimus are associated with a similar level of increased mean proteinuria.

Ramsay Hunt syndrome with atypical progress in a renal transplant recipient: a case report.

Ramsay Hunt syndrome is a rare complication of herpes zoster disease in which reactivation of latent varicella zoster virus infection occurs in the geniculate ganglion causing otalgia, unilateral vesicular eruption in a restricted dermatomal distribution, and peripheral facial paralysis. Dermal infections caused by human pathogenic herpes viruses are common in organ transplant recipients. For a transplant surgeon, it is imperative to remember that viral prophylaxis is essential in the follow-up of the transplant patients. Here, we presented a case of renal transplant and Ramsay Hunt syndrome with multiple cranial nerve involvement, with an atypical course. Management and differential diagnosis of this particular case are discussed with a review of the literature.

Assessment of matrix Gla protein, Klotho gene polymorphisms, and oxidative stress in chronic kidney disease.

Increased vascular calcification and oxidative stress are considered as extra renal risk factors at the pathogenesis cardiovascular events in chronic kidney disease (CKD). We investigated matrix Gla protein (MGP) (T-138C, Glu60X, Thr83Ala) and Klotho (Cys370Ser) gene polymorphisms, serum MGP levels, and oxidative stress status of 84 CKD patients and 37 healthy controls. The MGP gene Glu60X and Thr83Ala polymorphisms were significantly associated with CKD. The correlation between T-138C genotype of MGP gene, Cys370Ser genotype of Klotho gene, and CKD was not significant (p > 0.05). At the haplotype analysis, the combination of the X allele of Glu60X and the Thr allele of Thr83Ala showed a significantly increased risk of CKD (p < 0.05). X allele, Thr allele, and C allele of T-138C were associated with diabetes mellitus and CKD phenotypes occurring concurrently (p < 0.01). Serum zinc levels were significantly low in end-stage renal disease (ESRD) patients (p = 0.0001). The total comet score frequency of ESRD patients was higher than that of control group (p < 0.05). The urinary 8-hydroxy-2'-deoxyguanosine levels were significantly high in CKD patients (p < 0.05). According to this study, analyzing the distribution of MGP gene and oxidative stress status would be very informative in order to detect their role at CKD.

Validation of biochemical markers for the prediction of liver fibrosis and necroinflammatory activity in hemodialysis patients with chronic hepatitis C.

BACKGROUND: Liver biopsy is an imperfect gold standard for assessing the disease severity in hemodialysis patients with chronic hepatitis C. Our purpose was to compare the accuracy of the FibroTest (FT) and ActiTest (AT) with liver biopsy and the AST-to-platelet ratio index (APRI) in determining hepatic fibrosis and necroinflammatory activity in hemodialysis patients with hepatitis C virus (HCV). METHODS: The FT-AT index combining 6 biochemical markers was assessed in 33 hemodialysis patients with HCV. Liver fibrosis and necroinflammatory activity was staged and graded according to the METAVIR scoring system. RESULTS: The accuracy of FT-AT versus biopsy was 0.46 for significant fibrosis and 0.36 for severe necroinflammatory activity. The FT index had a positive predictive value of 20% for scores greater than 0.6 and a negative predictive value of 45% for scores less than 0.2. Eleven of the 33 patients had scores ≤0.2, 6 had significant fibrosis on biopsy. Four out of 5 patients with FT scores >0.6 had mild fibrosis. APRI correlated well with the biopsy. CONCLUSION: The FT-AT test does not seem to be a reliable noninvasive marker for the prediction of necroinflammatory activity and fibrosis in hemodialysis patients with HCV and cannot be used as an alternative to either liver biopsy or APRI.

Is alanine aminotransferase level a surrogate biomarker of hepatic apoptosis in nonalcoholic fatty liver disease?

AIM: To evaluate the serum alanine aminotransferase (ALT) variabilities in nonalcoholic fatty liver disease (NAFLD) and correlate it with hepatocyte apoptosis and oxidative stress parameters. METHODS: 24 patients with NAFLD and normal ALT were compared with 26 subjects with NAFLD and elevated ALT. Liver oxidative stress was estimated on the basis of malondialdehyde, superoxide dismutase and glutathione. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor-kappaB, antiapoptotic Bcl-2 protein and serum TNF receptor levels were measured. RESULTS: The mean caspase 3 and 8 activity scores, oxidative stress parameters, necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Patients with nonalcoholic steatohepatitis had significantly higher caspase 3 and 8 activity (percentage of cells with positive staining per high power field), and serum malondialdehyde (mmol/l) levels than those with simple steatosis. ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis. A receiver operating characteristic curve did not demonstrate sensitivity and specificity for discriminative power of ALT. CONCLUSION: Apoptosis and oxidative stress are the main processes contributing to disease progression in NAFLD. ALT values do not correlate with the parameters of apoptosis and oxidative stress. The disease severity can only be determined by liver biopsy.

Icodextrine and insulin resistance in continuous ambulatory peritoneal dialysis patients.

Insulin resistance is commonly observed in uremic patients. Glucose-based peritoneal dialysis solutions have long-term metabolic complications like hyperinsulinemia, hyperlipidemia, and obesity. The purpose of this study was to examine the insulin resistance in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) with standard glucose and icodextrin containing solutions. The entire non diabetic CAPD patients of our center were studied: forty-four patients in all who were on CAPD treatment for 36.2 +/- 23.7 months. Twenty-seven of them (11 male and 16 female) with a mean age of 46 +/- 16 years were treated with standard glucose solutions (glucose group). The other 17 patients (10 male and 7 female) with a mean age of 49 +/- 16 years were treated with standard glucose solutions during the day and icodextrin dwell during the night, for a median of 12 +/- 6.3 months (icodextrin group). Morning fasting serum insulin levels were 20.59 +/- 17.86 in the glucose group and 10.15 +/- 6.87 in the icodextrin group (p = 0.0001). Homeostasis Model Assessment Method scores of the glucose group were significantly higher (4.8+/-4.1 vs 2.3+/- 1.7; p = 0.025) than the icodextrin group. A significant positive correlation of HOMA score with insulin, fasting plasma glucose, and triglyceride levels were found in HOMA (IR+) patients. Twenty patients of the icodextrin group (74%) and 15 patients of the glucose group (88%) were hypertensive, but there was no statistically significant difference between the two groups (p = 0.13). The groups showed no significant differences for body mass index and serum levels of glucose, total cholesterol, LDL cholesterol, VLDL cholesterol, HDL cholesterol, triglyceride, intact parathyroid hormone (iPTH), and fibrinogen. In conclusion, the use of icodextrin in the long nighttime dwell can reduce serum insulin levels and increase insulin sensitivity in CAPD patients.