Julia Kanter

The effect of cholecalciferol for lowering albuminuria in chronic kidney disease: a prospective controlled study

BACKGROUND Growing evidence indicates that vitamin D receptor activation may have antiproteinuric effects. We aimed to evaluate whether vitamin D supplementation with daily cholecalciferol could reduce albuminuria in proteinuric chronic kidney disease (CKD) patients. METHODS This 6-month prospective, controlled, intervention study enrolled 101 non-dialysis CKD patients with albuminuria. Patients with low 25(OH) vitamin D [25(OH)D] and high parathyroid hormone (PTH) levels (n = 50; 49%) received oral cholecalciferol (666 IU/day), whereas those without hyperparathyroidism (n = 51; 51%), independent of their vitamin D status, did not receive any cholecalciferol, and were considered as the control group. RESULTS Cholecalciferol administration led to a rise in mean 25(OH)D levels by 53.0 ± 41.6% (P < 0.001). Urinary albumin-to-creatinine ratio (uACR) decreased from (geometric mean with 95% confidence interval) 284 (189-425) to 167 mg/g (105-266) at 6 months (P < 0.001) in the cholecalciferol group, and there was no change in the control group. Reduction in a uACR was observed in the absence of significant changes in other factors, which could affect proteinuria, like weight, blood pressure (BP) levels or antihypertensive treatment. Six-month changes in 25(OH)D levels were significantly and inversely associated with that in the uACR (Pearsons R = -0.519; P = 0.036), after adjustment by age, sex, body mass index, BP, glomerular filtration rate and antiproteinuric treatment. The mean PTH decreased by -13.8 ± 20.3% (P = 0.039) only in treated patients, with a mild rise in phosphate and calcium-phosphate product [7.0 ± 14.7% (P = 0.002) and 7.2 ± 15.2% (P = 0.003), respectively]. CONCLUSIONS In addition to improving hyperparathyroidism, vitamin D supplementation with daily cholecalciferol had a beneficial effect in decreasing albuminuria with potential effects on delaying the progression of CKD.

What is the optimal level of vitamin D in non-dialysis chronic kidney disease population?

AIM To evaluate thresholds for serum 25(OH)D concentrations in relation to death, kidney progression and hospitalization in non-dialysis chronic kidney disease (CKD) population. METHODS Four hundred and seventy non-dialysis 3-5 stage CKD patients participating in OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into 3 groups according to 25(OH)D levels at enrollment (less than 20 ng/mL, between 20 and 29 ng/mL, and at or above 30 ng/mL), considering 25(OH)D between 20 and 29 ng/mL as reference group. Association between 25(OH)D levels and death (primary outcome), and time to first hospitalization and renal progression (secondary outcomes) over a 3-year follow-up, were assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. To identify 25(OH)D levels at highest risk for outcomes, receiver operating characteristic (ROC) curves were performed. RESULTS Over 29 ± 12 mo of follow-up, 46 (10%) patients dead, 156 (33%) showed kidney progression, and 126 (27%) were hospitalized. After multivariate adjustment, 25(OH)D < 20 ng/mL was an independent predictor of all-cause mortality (HR = 2.33; 95%CI: 1.10-4.91; P = 0.027) and kidney progression (HR = 2.46; 95%CI: 1.63-3.71; P < 0.001), whereas the group with 25(OH)D at or above 30 ng/mL did not have a different hazard for outcomes from the reference group. Hospitalization outcomes were predicted by 25(OH) levels (HR = 0.98; 95%CI: 0.96-1.00; P = 0.027) in the unadjusted Cox proportional hazards model, but not after multivariate adjusting. ROC curves identified 25(OH)D levels at highest risk for death, kidney progression, and hospitalization, at 17.4 ng/mL [area under the curve (AUC) = 0.60; 95%CI: 0.52-0.69; P = 0.027], 18.6 ng/mL (AUC = 0.65; 95%CI: 0.60-0.71; P < 0.001), and 19.0 ng/mL (AUC = 0.56; 95%CI: 0.50-0.62; P = 0.048), respectively. CONCLUSION 25(OH)D < 20 ng/mL was an independent predictor of death and progression in patients with stage 3-5 CKD, with no additional benefits when patients reached the levels at or above 30 ng/mL suggested as optimal by CKD guidelines.

The effect of high-volume online haemodiafiltration on nutritional status and body composition: the ProtEin Stores prEservaTion (PESET) study

Background Compared with conventional haemodialysis (HD), online haemodiafiltration (OL-HDF) achieves a more efficient removal of uraemic toxins and reduces inflammation, which could favourably affect nutritional status. We evaluate the effect of OL-HDF on body composition and nutritional status in prevalent high-flux HD (HF-HD) patients. Methods In all, 33 adults with chronic kidney disease (CKD) Stage 5 undergoing maintenance HF-HD were assigned to post-dilution OL-HDF (n = 17) or to remain on HF-HD (n = 16, control group) for 12 months. The primary outcome was the change in lean tissue mass (LTM), intracellular water (ICW) and body cell mass (BCM) assessed by multifrequency bioimpedance spectroscopy (BIS) at baseline and 4, 8 and 12 months. The rate of change in these parameters was estimated with linear mixed-effects models. Results Compared with OL-HDF, patients assigned to HF-HD experienced a gradual reduction in LTM, ICW and BCM. These differences reached statistical significance at Month 12, with a relative difference of 7.31 kg [95% confidence interval (CI) 2.50-12.11; P = 0.003], 2.32 L (95% CI 0.63-4.01; P = 0.008) and 5.20 kg (95% CI 1.74-8.66; P = 0.004) for LTM, ICW and BCM, respectively. The normalized protein appearance increased in the OL-HDF group compared with the HF-HD group [0.26 g/kg/day (95% CI 0.05-0.47); P = 0.002], with a relative reduction in high-sensitive C-reactive protein [-13.31 mg/dL (95% CI -24.63 to -1.98); P = 0.02] at Month 12. Conclusions OL-HDF for 1 year compared with HF-HD preserved muscle mass, increased protein intake and reduced the inflammatory state related to uraemia and dialysis, supporting the hypothesis that high convection volume can benefit nutritional status and prevent protein-energy wasting in HD patients.

Effect of Steroid Withdrawal on the Appearance of De Novo Donor-Specific HLA Antibodies in Kidney Transplant Recipients: A Prospective, Randomized, Controlled, Parallel Group Study. Preliminary Results

Introduction Steroids represent one of the mainstays of immunosuppression after kidney transplant (KT). Steroid withdrawal reduces metabolic and cardiovascular complications, but whether it increases the risk of acute rejection and the generation of donor-specific anti-HLA antibodies (DSA) is currently undetermined. Materials and Methods In a controlled clinical trial (NCT02284464), a total of 176 KT patients with low immunological risk were recruited to randomly receive either conventional triple immunosuppression: steroids, TAC and MMF versus steroid withdrawal at the third post-KT month. We compared the incidence of de novo DSA, determined by Luminex Mixed and Luminex Single Antigen (One Lambda®), and its impact on graft histology in patients with steroid withdrawal at the 3 post-KT month (after a protocol biopsy) versus patients who continue to receive conventional triple immunosuppression. Results So far, 68 patients have been randomized (34 per group), with no significant differences in the clinical and demographic characteristics between the groups. The intermediate analysis in those patients who had completed one year of follow-up (n=28) showed no significant differences in the formation of DSA (0% vs. 0%), nor was there rejection in those patients in whom prednisone was withdrawn after randomization. Patients with triple therapy showed a trend toward better renal function compared to those without steroids at the first post-KT year (1.29±0.25 vs. 1.56±0.42 mg/dL, P=0.088). HbA1c levels were similar between both group at the first post-KT year (5.79±0.59 vs. 5.68±0.81%, P=0.734). Conclusion The preliminary results show that steroid withdrawal at the 3 month post-KT seems safe when assessing the appearance of rejection and formation of DSA compared to the patients who continued to receive conventional triple immunosuppression. Spanish Ministry of Economy and Competitiveness (MINECO) (grant ICI14/00016) from the Instituto de Salud Carlos III co-funded by the Fondo Europeo de Desarrollo Regional–FEDER, RETICS (REDINREN RD12/0021/0015, RD16/0009/0006, RD16/0009/0003, RD16/0009/0030, RD16/0009/0031).

Randomized controlled trial assessing the impact of tacrolimus versus cyclosporine on the incidence of post-transplant diabetes mellitus

Introduction Despite the high incidence of posttransplant diabetes mellitus (PTDM) among high-risk recipients, no studies have investigated its prevention by immunosuppression optimization. Methods We conducted an open-label, multicenter, randomized trial testing whether a tacrolimus-based immunosuppression and rapid steroid withdrawal (SW) within 1 week (Tac-SW) or cyclosporine A (CsA) with steroid minimization (SM) (CsA-SM), decreased the incidence of PTDM compared with tacrolimus with SM (Tac-SM). All arms received basiliximab and mycophenolate mofetil. High risk was defined by age >60 or >45 years plus metabolic criteria based on body mass index, triglycerides, and high-density lipoprotein–cholesterol levels. The primary endpoint was the incidence of PTDM after 12 months. Results The study comprised 128 de novo renal transplant recipients without pretransplant diabetes (Tac-SW: 44, Tac-SM: 42, CsA-SM: 42). The 1-year incidence of PTDM in each arm was 37.8% for Tac-SW, 25.7% for Tac-SM, and 9.7% for CsA-SM (relative risk [RR] Tac-SW vs. CsA-SM 3.9 [1.2–12.4; P = 0.01]; RR Tac-SM vs. CsA-SM 2.7 [0.8–8.9; P = 0.1]). Antidiabetic therapy was required less commonly in the CsA-SM arm (P = 0.06); however, acute rejection rate was higher in CsA-SM arm (Tac-SW 11.4%, Tac-SM 4.8%, and CsA-SM 21.4% of patients; cumulative incidence P = 0.04). Graft and patient survival, and graft function were similar among arms. Conclusion In high-risk patients, tacrolimus-based immunosuppression with SM provides the best balance between PTDM and acute rejection incidence.