Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism

Background. Cinacalcet lowers plasma parathyroid hormone (PTH) levels in primary and secondary hyperparathyroidism. The efficacy and safety of cinacalcet have not been examined in renal transplant patients with persistent hyperparathyroidism. The aim of this study was to evaluate the effect of cinacalcet as a novel therapy for the management of such patients. Methods. Eleven renal allograft recipients with persistent hyperparathyroidism were treated with cinacalcet. The total study time was 10 weeks. Individual cinacalcet doses were adjusted to obtain a serum calcium in the predefined normal target range of 2.10-2.60 mmol/l. Results. Serum calcium decreased significantly from 2.73±0.05 mmol/l to 2.44±0.05 and 2.42± 0.04 mmol/l after 2 and 10 weeks of treatment, respectively. All patients reached the target range rapidly and remained normocalcaemic throughout the study. Serum PTH significantly decreased 16.1 and 21.8% at study weeks 2 and 10, respectively, compared with week 0. Serum phosphate increased. Renal function remained stable and no allograft rejection was observed. From weeks 2 to 10, daily cinacalcet doses administered were 30 mg (n = 8), 15 mg (n = 1) and 60 mg (n = 1), respectively. Conclusion. Cinacalcet was effective in correcting the hypercalcaemia associated with persistent hyperparathyroidism after renal transplantation. It appears to be safe. Thus, cinacalcet represents a promising alternative for parathyroidectomy in these patient

Sirolimus ameliorates the enhanced expression of metalloproteinases in a rat model of autosomal dominant polycystic kidney disease

Background. Remodelling of matrix and tubular basement membranes (TBM) is a characteristic of polycystic kidney disease. We hypothesized that matrix and TBM degradation by metalloproteinases (MMPs) could promote cyst formation. We therefore investigated the renal expression of MMPs in the Han:SPRD rat model of autosomal dominant polycystic kidney disease (ADPKD) and examined the effect of sirolimus treatment on MMPs. Methods. 5-week-old male heterozygous (Cy/+) and wild-type normal (+/+) rats were treated with sirolimus (2 mg/kg/day) through drinking water for 3 months. Results. The mRNA and protein levels of MMP-2 and MMP-14 were markedly increased in the kidneys of heterozygous Cy/+ animals compared to wild-type +/+ as shown by RT-PCR and Western blot analyses for MMP-2 and MMP-14, and by zymography for MMP-2. Strong MMP-2 expression was detected by immunoperoxidase staining in cystic epithelial cells that also displayed an altered, thickened TBM. Tissue inhibitor of metalloproteinases-2 (TIMP-2) expression was not changed in Cy/+ kidneys. Sirolimus treatment leads to decreased protein expression of MMP-2 and MMP-14 in Cy/+, whereas MMP-2 and MMP-14 mRNA levels and TIMP-2 protein levels were not affected by sirolimus. Conclusion. In summary, in kidneys of the Han:SPRD rat model of ADPKD, there is a marked upregulation of MMP-2 and MMP-14. Sirolimus treatment was associated with a marked improvement of MMP-2 and MMP-14 overexpression, and this correlated also with less matrix and TBM alterations and milder cystic diseas

First Testing of Literature-Based Models for Predicting Increase in Body Weight and Adipose Tissue Mass After Kidney Transplantation

Introduction: Weight gain is a risk factor for poor clinical outcomes following kidney transplantation. Research Question: This study's aim was a first testing of 2 models to identify patients early after kidney transplantation who are at risk for weight gain and increase in adipose tissue mass in the first year after kidney transplantation. Design: The literature-based models were evaluated on longitudinal data of 88, respectively 79 kidney transplant recipients via ordinary and Firth regression, using gains ≥ 5% in weight and adipose tissue mass respectively as primary and secondary endpoints. Results: The models included physical activity, smoking cessation at time of kidney transplantation, self-reported health status, depressive symptomatology, gender, age, education, baseline body mass index and baseline trunk fat as predictors. Area under the curve was 0.797 (95%-CI 0.702 to 0.893) for the weight model and 0.767 (95%-CI 0.656 to 0.878) for the adipose tissue mass model-showing good, respectively fair discriminative ability. For weight gain ≥ 5%, main risk factors were smoking cessation at time of transplantation (OR 16.425, 95%-CI 1.737-155.288) and better self-reported baseline health state (OR 1.068 for each 1-unit increase, 95%-CI 1.012-1.128). For the adipose tissue mass gain ≥ 5%, main risk factor was overweight/obesity (BMI ≥ 25) at baseline (odds ratio 7.659, 95%-CI 1.789-32.789). Conclusions: The models have potential to assess patients' risk for weight or adipose tissue mass gain during the year after transplantation, but further testing is needed before implementation in clinical practice. Keywords: addictive; behavior; cardiovascular disease; clinical outcomes; depression; exercise outcomes; nutrition; performance improvement; quality; quality of life; quantitative methods; regression; research

Podoplanin-positive cells are a hallmark of encapsulating peritoneal sclerosis

Background. Encapsulating peritoneal sclerosis (EPS) and simple peritoneal sclerosis are important complications of long-term peritoneal dialysis (PD). Podoplanin is expressed by mesothelial cells and lymphatic vessels, which are involved in inflammatory reactions in the peritoneal cavity. Methods. We studied 69 peritoneal biopsies from patients on PD (n = 16), patients with EPS (n = 18) and control biopsies taken at the time of hernia repair (n = 15) or appendectomy (n = 20). Immunohistochemistry was performed to localize podoplanin. Additionally, markers of endothelial cells, mesothelial cells, myofibroblasts (smooth muscle actin), proliferating cells, and double labelling for smooth muscle actin/podoplanin were used on selected biopsies. Results. Podoplanin was present on the endothelium of lymphatic vessels in the submesothelial fibrous tissue and on mesothelial cells. In patients on PD and in biopsies with appendicitis, the mesothelial cells demonstrated a cuboidal appearance and circumferential podoplanin staining, with gaps between the cells. The number of lymphatic vessels was variable, but prominent at sites of fibrosis. In patients with EPS, a diffuse infiltration of podoplanin-positive cells with a fibroblastic appearance was present in 15 out of 18 biopsies. This pattern was focally present in 3 out of 16 on PD and none in the 35 controls. The podoplanin-positive cells did not express the endothelial marker or the mesothelial marker (calretinin). Conclusions. EPS is characterized by a population of podoplanin and smooth muscle actin double-positive cells. Podoplanin might be a suitable morphological marker supporting the diagnosis and might be involved in the pathogenesis of EP

Comparison of a Behavioral Versus an Educational Weight Management Intervention After Renal Transplantation: A Randomized Controlled Trial

Background In the first year following renal transplantation, preventing weight gain to minimize overweight or obesity is particularly important. The aim of this study is to test the effect of an 8-month behavioral intervention BMI and physical activity. Methods This randomized controlled study included 123 adult kidney or kidney-pancreas recipients. Patients were randomized to usual (1 educational session, then weight self-monitoring) and intervention care (usual care plus 7-8 counseling sessions). Alongside weight, body composition, and physical activity, satisfaction and perceptions regarding care were measured at weeks 2-6 (baseline), then at months 8 and 12. Results Both groups reported comparably high satisfaction. The intervention group (IG) reported more chronic care-related activities. In patients with BMIs ≥ 18.5, mean weight gain (from baseline) was unexpectedly low in both groups: at month 8, +0.04 kg/m$^{2}$ in IG patients and +0.14 kg/m$^{2}$ in the control group (P = 0.590), and respectively, +0.03 kg/m$^{2}$ and +0.19 kg/m$^{2}$ at month 12 (P = 0.454). Both groups were physically active, walking averages of 10 807 (IG) and 11 093 (control group) steps per day at month 8 (P = 0.823), and respectively 9773 and 11 217 at month 12 (P = 0.195). Conclusions The behavioral intervention had high patient acceptance and supported patients in maintaining their weight, but had no superior effect on a single educational session. Further research is needed to assess patient weight gain risk profiles to stratify the intervention

Successful treatment of hypercalcemia with cinacalcet in renal transplant recipients with persistent hyperparathyroidism

Background. Cinacalcet lowers plasma parathyroid hormone (PTH) levels in primary and secondary hyperparathyroidism. The efficacy and safety of cinacalcet have not been examined in renal transplant patients with persistent hyperparathyroidism. The aim of this study was to evaluate the effect of cinacalcet as a novel therapy for the management of such patients. Methods. Eleven renal allograft recipients with persistent hyperparathyroidism were treated with cinacalcet. The total study time was 10 weeks. Individual cinacalcet doses were adjusted to obtain a serum calcium in the predefined normal target range of 2.10-2.60 mmol/l. Results. Serum calcium decreased significantly from 2.73±0.05 mmol/l to 2.44±0.05 and 2.42± 0.04 mmol/l after 2 and 10 weeks of treatment, respectively. All patients reached the target range rapidly and remained normocalcaemic throughout the study. Serum PTH significantly decreased 16.1 and 21.8% at study weeks 2 and 10, respectively, compared with week 0. Serum phosphate increased. Renal function remained stable and no allograft rejection was observed. From weeks 2 to 10, daily cinacalcet doses administered were 30 mg (n = 8), 15 mg (n = 1) and 60 mg (n = 1), respectively. Conclusion. Cinacalcet was effective in correcting the hypercalcaemia associated with persistent hyperparathyroidism after renal transplantation. It appears to be safe. Thus, cinacalcet represents a promising alternative for parathyroidectomy in these patient

Association of serum bicarbonate with graft survival and mortality in kidney transplant recipients

BACKGROUND Metabolic acidosis is an independent risk factor for kidney disease progression with a high prevalence after kidney transplantation (KTx). Remarkably, it is still unclear if there is an impact of metabolic acidosis on graft function and death after KTx. Thus, we wanted to investigate if serum bicarbonate is associated with long-term graft outcome and mortality after KTx. METHODS We performed a single-center retrospective study including adult de novo KTx patients between 1999 and 2015. Cox proportional hazard model was used to analyze a possible association between time-dependent serum bicarbonate measurements and graft failure or death. RESULTS Four hundred thirty KTRs were included in the analysis with a mean age of 50.9 ± 13.4 years. Mean observation time was 4.7 ± 2.8 years. Two hundred eighty-four (66%) patients were male and 318 (74%) had received a deceased donor kidney transplant. Mean bicarbonate and eGFR levels 1 year post-transplant amounted to 22.9 ± 3.1 mEq/L and 61 ± 26 ml/min/1.73 m$^{2}$, respectively. Prevalence of metabolic acidosis was 31% 1 year after transplantation. Fourteen (3%) patients died and 31 (7%) suffered from graft failure. Higher bicarbonate levels were associated with significantly lower hazards for graft failure (Hazard Ratio (HR) = 0.88; 95% Confidence Interval (CI): 0.79-0.98) and mortality (HR = 0.79; 95% CI 0.66-0.93) after adjusting for potential confounders such as age, donor type and time-varying eGFR. CONCLUSIONS Our analysis showed that higher serum bicarbonate levels are positively associated with long-term graft and patient survival in kidney transplant recipients. Thus, serum bicarbonate may serve as a predictor and independent risk factor for graft and patient outcome after KTx as has been previously shown for patients with CKD