Association Between Resistance to Cinacalcet and Parathyroid Gland Hyperplasia in Kidney Transplant Recipients with Persistent Hypercalcemia.

BACKGROUND: Persistent hypercalcemia and hyperparathyroidism after successful kidney transplantation can be detrimental in some recipients and should be ameliorated. OBJECTIVE: To point out the concerns regarding resistance to cinacalcet in kidney transplant recipients with persistent hypercalcemia. METHODS: 14 renal transplant recipients who received cinacalcet treatment because of persistent hypercalcemia were included in the study. Serum creatinine, estimated glomerular filtration rate (eGFR), calcium, phosphorus, and intact parathyroid hormone (PTH) levels at the baseline and throughout the treatment, and ultrasonography and parathyroid scintigraphy findings were recorded. RESULTS: Cinacalcet treatment was initiated after a mean±SD of 20.7±19.7 months of transplantation and maintained for 16.9±7.9 months. Serum calcium levels were significantly decreased with the cinacalcet treatment. There were no significant changes in serum creatinine, eGFR, phosphorus, and PTH levels. In all participants, serum calcium levels were increased from 9.8±0.6 to 11.1±0.6 mg/dL (p<0.001) within 1 month of cessation of cinacalcet. 7 recipients with adenoma-like hyperplastic glands underwent parathyroidectomy (PTx) due to failure with cinacalcet. CONCLUSION: Cinacalcet may be an appropriate treatment for a group of recipients with hypercalcemia without adenoma-like hyperplastic glands or who had a contraindication for surgery. Recipients with enlarged parathyroid gland may resist to cinacalcet-induced decrease in serum PTH, although the concomitant hypercalcemia may be corrected.

Transplantation Opportunities of Hepatitis C Virus-Seropositive Patients on the Kidney Waiting List.

OBJECTIVE: Besides severe organ shortage, hepatitis C virus (HCV) infection is an important obstacle for kidney transplantation because of long waiting times on deceased kidney donor waiting lists. We aimed to evaluate calling number of candidates according to HCV serology. METHOD: A total of 404 adults on the deceased donor waiting list invited for cadaveric transplantation was evaluated. Demographic data, waiting time, calling number for transplantation, and viral serology were obtained during the 6-year period. RESULTS: Mean waiting duration and calling number of all patients were 42.7 ± 34 months and 1.56 ± 4.37 times, respectively. Twenty-six candidates had chronic HCV infection and 12 of 26 were HCV RNA-positive. Mean waiting duration and calling number in anti-HCV-positive candidates were significantly higher compared with anti-HCV-negative candidates (85.3 ± 38.8 vs 39.8 ± 31.6 months, and 10.8 ± 10.3 vs 0.92 ± 2.6 times, respectively; P < .001). Mean waiting duration and total calling number in HCV-RNA-positive candidates were significantly higher than in HCV-RNA-negative ones (107.5 ± 7.5 vs 66.2 ± 44.8 months; P = .018; 15 ± 9.7 vs 7.3 ± 9.8 times, respectively; P = .026). CONCLUSIONS: Chronic HCV infection is an important issue leading to longer waiting time on the list. Our observation showed that waiting durations of anti-HCV-positive candidates were longer than that of negative patients, although they had more frequent opportunity for transplantation.

Encapsulating Peritoneal Sclerosis in Peritoneal Dialysis Patients After Kidney Transplantation.

OBJECTIVE: Encapsulating peritoneal sclerosis (EPS) is a serious complication for patients with chronic kidney disease (CKD) who were treated with long-term peritoneal dialysis (PD). The risk of EPS was increased after kidney transplantation. In our study we evaluated risk factors for EPS patients after kidney transplantation who were treated before with PD. MATERIALS AND METHODS: In our study, between January 2008 and August 2015, 47 PD patients (12 had EPS) who underwent kidney transplantation were analyzed. Age, gender, time of PD treatment, human leukocyte antigen (HLA) matching, cold ischemia time, kidney function (serum urea, creatinine, etc), comorbidities, immunosuppressive therapy, clinical features, and outcomes of PD patients were retrospectively evaluated in both groups. RESULTS: Mean age was 42 (range, 25-60) years in EPS patients, versus 43 (range, 22-77) years without EPS (P = .798). Distribution of gender was similar in both groups (P = .154). The C-reactive protein levels (P < .001), number of patients with peritonitis (P = .001), length of time on PD (P < .001), and serum ferritin levels (P = .020) were higher in EPS patients. The immunosuppressive therapy was changed; tamoxifen and steroids were used after diagnosis in EPS patients. HLA matching was higher in the non-EPS group (P = .006). EPS was more often seen in patients who were treated with continuous ambulatory peritoneal dialysis (CAPD; 75%; P = .036). EPS was more often detected in cadaveric transplant recipients (83.3%; P = .024). High peritoneal transmittance rate was more identified in EPS (+) patients (P = .001). EPS was more often seen in patients who were treated with icodextrin-based regimens in PD before transplantation (91.7%; P = .037). The length of time on PD and high ferritin levels increased EPS 1.08 and 1.01, respectively (P = .036 and .049, respectively), in multivariate analysis. CONCLUSION: The length of time on PD, type of PD, PD regimens with icodextrin, episodes of peritonitis, and peritoneal transmittance in patients with CKD affect the development of EPS after transplantation.

Risk Factors Affecting Graft and Patient Survivals After Transplantation From Deceased Donors in a Developing Country: A Single-Center Experience.

AIM: The aim of this study was to evaluate risk factors affecting graft and patient survival after transplantation from deceased donors. METHODS: We retrospectively analyzed the outcomes of 186 transplantations from deceased donors performed at our center between 2006 and 2014. The recipients were divided into two groups: Group I (141 recipients without graft loss) and Group II (45 recipients with graft loss). Kaplan-Meier, log-rank test, and Cox proportional hazard regressions were used. RESULTS: The characteristics of both groups were similar except renal resistive index at the last follow-ups. When graft survival and mortality at the first, third, and fifth years were analyzed, tacrolimus (Tac)-based regimens were superior to cyclosporine (CsA)-based regimens (P < .001). Risk factors associated with graft survival at the first year included cardiac cause of death (versus cerebrovascular accident [CVA]; hazard ratio [HR], 6.36; 95% confidence interval [CI], 1.84-22.05; P = .004), older transplant age (HR, 1.05; 95% CI, 1.02-1.08; P < .001), and high serum creatinine level at 6 months post-transplantation (HR, 1.74; 95% CI, 1.48-2.03; P < .001), whereas younger donor age decreased risk (HR, 0.97; 95% CI, 0.95-1.00; P = .019). Also, the Tac-based regimen had a 3.63-fold (95% CI, 1.47-8.97; P = .005) lower risk factor than the CsA-based regimen, and 2.93-fold (95% CI, 1.13-7.63; P = .027) than other regimens without calcineurin inhibitors. When graft survival at 3 years was analyzed, diabetes mellitus was lower than idiopathic causes and pyelonephritis (P = .035). In Cox regression analysis at year 3, older transplantation age (HR, 1.20; 95% CI, 1.04-1.39; P = .014) and serum creatinine level at month 6 post-transplantation (HR, 1.65; 95% CI, 1.42-1.90; P < .001) were significant risk factors for graft survival. Hemodialysis (HD) plus peritoneal dialysis (PD) treatment was 2.22-fold (95% CI, 1.08-4.58; P = .03) risk factor than only HD before transplantation. When graft survival and mortality at year 5 were analyzed, diabetes mellitus was lower compared with all other diseases. In Cox regression analysis at year 5, younger donor age (HR, 0.73; 95% CI, 0.62-0.86; P < .001) was protective for graft survival, whereas older transplantation age (HR, 1.40; 95% CI, 1.20-1.64; P < .001) and serum creatinine level at month 6 of post-transplantation (HR, 1.39; 95% CI, 1.19-1.61; P < .001) were significant risk factors. PD increased 3.32 (95% CI, 1.28-8.61; P = .014) times the risk than HD. In Cox regression analysis at year 1, cardiac cause of death (versus CVA; HR, 5.28; 95% CI, 1.37-20.31; P = .016), CsA-based regimen (versus Tac; HR, 4.95; 95% CI, 1.78-13.78; P = .002), HD plus PD treatment (versus alone HD; HR, 3.26; 95% CI, 1.28-8.30; P = .013), older transplantation age (HR, 1.08; 95% CI, 1.04-1.11; P < .001), serum creatinine level at month 6 post-transplantation (HR, 1.34; 95% CI, 1.11-1.62; P = .003), and low HLA mismatches (HR, 1.67; 95% CI 1.01-2.70; P = .044) were risk factors for mortality. At year 3, CsA-based regimen (versus Tac; HR, 3.54; 95% CI, 1.32-9.47; P = .012), PD (versus HD; HR, 5.04; 95% CI, 1.41-18.05; P = .013), HD plus PD treatment (versus alone HD; HR, 3.51; 95% CI, 1.37-9.04; P = .009), and older transplantation age (HR, 1.27; 95% CI 1.05-1.53; P = .015) were risk factors for mortality. At year 5, older age at transplantation (HR, 1.47; 95% CI, 1.23-1.77; P < .001), PD (versus HD; HR, 9.21; 95% CI, 3.09-27.45; P < .001), and CsA-based regimen (versus Tac; HR, 2.75; 95% CI, 1.04-7.23; P = .041) were risk factors for mortality, whereas younger donor age decreased risk (HR, 0.71; 95% CI, 0.56-0.86; P < .001). CONCLUSION: Death of donor with cardiac cause, CsA-based immunosuppressive regimen, donor age, serum creatinine level at month 6 post-transplantation, and renal replacement therapy before transplantation affected mortality and graft survival in deceased donors.

The effects of formoterol on the serum, peritoneal VEGF, MDA, and VEGF levels in the ovaries and endometrium of rats with OHSS.

PURPOSE: To investigate the effects of formoterol (a beta2-adrenoreceptor agonist) on serum and peritoneal fluid VEGF, malondialdehyde (MDA) levels, and on VEGF-stained cell counts in the ovaries and endometrium of rats with ovarian hyperstimulation syndrome (OHSS) within the framework of immunohistochemical analysis. MATERIALS AND METHODS: A total of 28 immature female Wistar rats were randomly divided into four groups. Three groups were given ten IU pregnant mare serum gonadotropin/day on days 22-25 of life. They were administered 30 IU hCG on day 26 of life to mimic OHSS. On days 26 and 27 of life, 24 mcg/kg/day formoterol in group 3 and 48 mcg/kg formoterol in group 4 were administered intraperitoneally per animal. RESULTS: Although, there were no statistically significant differences between the groups in terms of serum and peritoneal fluid VEGF or MDA levels (serum VEGF: p = 0.28 1, peritoneal VEGF: p = 0.674, serum MDA: p = 0.543, peritoneal MDA: p = 0.506), there was a significant difference between the control and the OHSS placebo groups (p = 0.013) regarding the VEGF in the ovarian cortex. There was a significant difference between the control and the other groups in terms of ovarian stroma (p = 0.001), and there was also a statistically significant difference between the OHSS placebo and the other groups regarding VEGF in the endometrium (OHSS placebo vs. control group p = 0.002, OHSS placebo vs. the formoterol 24 mcg/kg group, p = 0.008, and OHSS-placebo vs. the formoterol 48 mcg/kg group, p = 0.001). CONCLUSIONS: Formoterol represents a potential novel strategy for the management of OHSS. Further studies, including those examining the dosage of formoterol, are warranted.

A Study of Serum Soluble CD 163 Levels in Women with Polycystic Ovary Syndrome.

The aim of this study was to determine serum soluble CD163 levels in patients with polycystic ovary syndrome and its relation to clinical and metabolic parameters. Eighty-four women aged 18-45 years, 43 with polycystic ovary syndrome and 41 controls were recruited in this case-control study. Serum sCD163 levels of the groups were compared. Other metabolic, hormonal, and clinical parameters including, body mass index, HOMA-IR, highly sensitive C- reactive protein, glucose, glycated hemoglobin, lipids, luteinizing hormone, and total testosterone and waist/hip circumference were also investigated. Patients were further subgrouped according to body mass index and sCD163 levels were investigated in obese and normal weight subjects. We performed a multiple regression analysis to investigate the independent predictors affecting soluble CD163 levels. Significantly higher soluble CD163 levels were found in patients with polycystic ovary syndrome (2.11±0.65 ng/ml vs. 1.69±0.85 ng/ml, p=0.012). We detected positive correlations of sCD163 with total testosterone, total cholesterol, and luteinizing hormone (r=0.330, p=0.002, r=0.356, p<0.001 and r=0.239, p=0.030, respectively). In the multiple linear regression analysis, total testosterone was the variable associated with the elevation of serum soluble CD163 levels. Soluble CD163, which is identified as a marker of inflammation and type II diabetes, is elevated in polycystic ovary syndrome. Elevated sCD163 levels were found to be associated with total testosterone. Further studies to elucidate the exact mechanism underlying the elevation of serum soluble CD163 in polycystic ovary syndrome are needed.

The impact of follicular fluid adiponectin and ghrelin levels based on BMI on IVF outcomes in PCOS.

PURPOSE: This study aimed at evaluating the effects of polycystic ovary syndrome (PCOS) and body mass index (BMI) on follicular fluid (FF) adiponectin and ghrelin levels, and on in vitro fertilization outcomes in patients who underwent controlled ovarian hyperstimulation. METHODS: This prospective cross-sectional study was performed with a total of 120 primary infertile women [group 1; non-PCOS = 60 (BMI <25 = 30, BMI ≥25 = 30) and group 2; PCOS = 60 (BMI <25 = 30, BMI ≥25 = 30)]. On the day of oocyte pickup, FF samples were collected. RESULTS: The FF adiponectin levels were lower in the lean PCOS group than the lean non-PCOS group (p = 0.001), and these levels were lower in the overweight non-PCOS group compared to lean non-PCOS group (0.001). However, there was no difference in the FF ghrelin levels between the groups. Additionally, we could not find a relationship between clinical pregnancy and adiponectin and ghrelin levels. CONCLUSION: The FF adiponectin and ghrelin levels have no effects on clinical pregnancy in PCOS. Therefore, further studies are needed to elucidate this issue.

Fluvastatin Decreases Oxidative Stress in Kidney Transplant Patients.

OBJECTIVE: Oxidative stress has been suggested to have a pivotal role in the development of cardiovascular disease in kidney transplant patients (KTPs). The effects of fluvastatin on oxidative status in KTPs have not been well evaluated. The aim of the present study was to evaluate the effects of fluvastatin on oxidative status by investigating erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPx), serum paraoxonase (PON1), and serum arylesterase (ARE), along with lipid peroxidation products, serum malonldialdehyde, and apolipoprotein B malondialdehyde (ApoB MDA). METHODS: Eighteen KTPs were included in the present study. Blood samples were obtained after 1 night's fast. Erythrocyte SOD, erythrocyte GPx, serum PON1, serum ARE, serum MDA, and ApoB MDA were measured using methods described previously. Paired-sample t test was used for comparing the changes from week 0 to week 4 of parameters that might be associated with fluvastatin treatment. RESULTS: The present study has shown that erythrocyte SOD and GPx, and serum PON1 and ARE activities increased at the fourth week of the statin treatment. Furthermore an increase in the antioxidant enzymes following fluvastatin may be a clue for the antioxidant effects of this drug. Four weeks of fluvastatin long-acting tablets 80 mg/day led to a decrease in plasma Apo-MDA and MDA levels. CONCLUSION: The findings of the present study demonstrate that fluvastatin 80 mg long-acting tablets may be used safely for 4 weeks and decrease atherogenic lipoproteins in KTPs. Furthermore, after 4 weeks of fluvastatin treatment, the levels of antioxidant parameters increased and oxidative parameters decreased. Further placebo-controlled treatment studies would be helpful to evaluate the effects of fluvastatin on oxidant and antioxidant parameters including PON1 in patients with KT.

Serum adiponectin in gestational diabetes and its relation to pregnancy outcome.

We investigated adiponectin levels in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) at 24-28 gestational weeks. Fasting serum adiponectin, glucose and glycated haemoglobin (HbA1c) were determined in 88 pregnant women, 44 with GDM and 44 with NGT. Pre-pregnancy and current body mass indices (BMI), weight gain and pregnancy outcomes were investigated. Serum adiponectin was significantly reduced in GDM compared with the NGT group (p = 0.000). Adiponectin was negatively correlated with age (r = -0.419, p = 0.000); glucose (r = -0.263, p = 0.013); HbA1c (r = -0.274, p = 0.01); BMI (pre-pregnancy and current) (r = -0.317, p = 0.003 and r = -0.303, p = 0.004) and positively correlated with gestational age at delivery (r = 0.278, p = 0.009). The GDM group delivered significantly earlier than the NGT group (p = 0.001). Adverse pregnancy outcomes and abdominal delivery were higher in the GDM group (p = 0.000, p = 0.033, respectively), and adiponectin was significantly reduced in patients with adverse outcomes (p = 0.003) and abdominal delivery (p = 0.032). Adiponectin is reduced in patients with GDM. Association of adiponectin with adverse pregnancy outcomes remains to be elucidated.

Alterations in location of the mucogingival junction 5 years after coronally repositioned flap surgery.

BACKGROUND: The aim of this clinical study was to evaluate whether the mucogingival junction (MGJ) reverts back towards its original location following coronally repositioned flap (CRF) procedure over a 5-year follow-up period. METHODS: Thirteen systemically healthy patients with 26 Miller Class I buccal gingival recessions were treated using the CRF technique. At baseline, and 1, 6, 12, and 60 months after surgery, location of gingival margin (LGM), probing depth (PD), clinical attachment level (CAL), width of keratinized gingiua (WKG), and location of mucogingival junction (LMGJ) were recorded. The alterations in the clinical measurements at the different evaluation times were analyzed using the Friedman and the repeated measure analysis of variance (ANOVA) tests, where applicable. Degree of association between continuous variables was calculated by the Pearson's correlation coefficient. RESULTS: The mean percentage of root coverage obtained at the end of 1 month was 68.26% +/- 30.37% (P<0.05) and at 60 months, it was reduced to 44.86% +/- 33.91% (P<0.01). LGM (r=0.592, P<0.001), CAL (r=0.590, P<0.01), WKG (r=0.442, P<0.05), and LMGJ (r=0.653, P<0.001) were found to be significantly correlated with the 60-month postoperative values of LMGJ. At the end of the 60-month follow-up period, the mean apical displacement of LGM was 0.67 +/- 0.72 mm and the same mean apical displacement value for LMGJ was 0.98 +/- 1.19 mm. CONCLUSIONS: Within the limits of this study, the 60-month follow-up findings indicated that the CRF procedure failed to maintain the gingival tissue in a coronal position and that the observed movement of the MGJ back to its original position was partially dependent on the apical movement of gingival margin.