The Efficacy and Safety of High-Dose Cholecalciferol Therapy in Hemodialysis Patients.

Vitamin D deficiency and insufficiency are highly prevalent in CKD, affecting over 80% of hemodialysis (HD) patients and requiring therapeutic intervention. Nephrological societies suggest the administration of cholecalciferol according to the guidelines for the general population. The aim of the observational study was to evaluate the efficacy and safety of the therapy with a high dose of cholecalciferol in HD patients with 25(OH)D deficiency and insufficiency to reach the target serum 25(OH)D level > 30 ng/mL. A total of 22 patients (16 M), with an average age of 72.5 ± 13.03 years and 25(OH)D concentration of 13.05 (9.00-17.90) ng/mL, were administered cholecalciferol at a therapeutic dose of 70,000 IU/week (20,000 IU + 20,000 IU + 30,000 IU, immediately after each dialysis session). All patients achieved the target value > 30 ng/mL, with a mean time of 2.86 ± 1.87 weeks. In the first week, the target level of 25(OH)D (100%) was reached by 2 patients (9.09%), in the second week by 15 patients (68.18%), in the fourth week by 18 patients (81.18%), and in the ninth week by all 22 patients (100%). A significant increase in 1,25(OH)2D levels was observed during the study. However, only 2 patients (9.09%) achieved a concentration of 1,25(OH)2D above 25 ng/mL-the lower limit of the reference range. The intact PTH concentrations remained unchanged during the observation period. No episodes of hypercalcemia were detected, and one new episode of hyperphosphatemia was observed. In conclusion, our study showed that the administration of a high-therapeutic dose of cholecalciferol allowed for a quick, effective, and safe leveling of 25(OH)D concentration in HD patients.

Intradialytic Tolerance and Recovery Time in Different High-Efficiency Hemodialysis Modalities.

There are several forms of maintenance high-efficiency hemodialysis (HD), including hemodiafiltrations (HDF) in different technical modes and expanded HD, using dialyzers with medium cut-off membranes. The aim of the study was to assess the intradialytic tolerance and length of dialysis recovery time (DRT) in these modalities. This is an exploratory, crossover study in maintenance HD patients with low comorbidity and no clinical indications for the use of high-efficiency HD, who were exposed to five intermittent dialyses in random order: high-flux hemodialysis (S-HD), expanded HD (HDx), pre-dilution HDF (PRE-HDF), mix-dilution HDF (MIX-HDF) and post-dilution HDF (POST-HDF). Twenty-four dialysis sessions of each method were included in the analysis. Dialysis parameters, including blood flow rate, dialysis fluid flow rate and temperature, and pharmacological treatment were constant. Average total convection volume for post-HDF, pre-HDF and mix-HDF were 25.6 (3.8), 61.5 (7.2) and 47.1 (11.4) L, respectively. During all therapies, patients were monitored for the similarity of their hydration statuses using bioimpedance spectroscopy, and for similar variability over time in systemic blood pressure and cardiac output, while peripheral resistance was monitored using impedance cardiography. The lowest frequency of all intradialytic adverse events were observed during HDx. Delayed DRT was the shortest during PRE-HDF. Patients were also more likely to report immediate recovery while receiving PRE-HDF. These differences did not reach statistical significance; however, the study results suggest that intradialytic tolerance and DRT may depend on the dialysis method used. This supports the need of taking into account patient preferences and quality of life while individualizing high-efficiency therapy in HD patients.

Antiphospholipid Syndrome in Renal Allograft Recipients-A Long-Term Multicenter Analysis.

Antiphospholipid syndrome (APS) is a devastating autoimmune disease and in renal transplant recipients may result in allograft thrombosis or in extra-renal manifestation, mostly venous thromboembolism. There are many non- and immune risk factors affecting renal allograft in recipients with APS. However, renal allograft outcome in recipients with APS without APS nephropathy remains unknown. Aim: The aim of the study was to assess renal allograft function and survival in recipients with APS. Methods: Retrospective, multicenter study included 19 adult renal recipients with definite APS (primary or lupus-related) from three Polish transplant centers. Renal allograft function was assessed using serum creatinine concentration (SCr1) at 3rd month post-transplant and at the end of the observation (SCr2) and glomerular filtration rate (GFR) was estimated based on modification of diet in renal disease (MDRD) formula. General linear model was used to assess 12 month GFR change over time. Kaplan-Meier curves and restricted mean survival time were used for allograft survival. Matched control group consisted of 21 stable renal recipients without history of thrombosis and without anticoagulation/antiplatelet treatment. Results: The study group differs in induction therapy (p = 0.019), high-urgency procedure (p = 0.04), proteinuria (p = 0.0058), primary disease (lupus) (p < 0.0001), re-transplantation in primary APS (p = 0.0046) and shorter time since engraftment to SCr2 (p = 0.016). Primary APS was more often diagnosed post-transplant (p = 0.0005). Allograft biopsy revealed thrombotic microangiopathy (TMA) with acute rejection (AR) or isolated AR vs AR or chronic rejection in controls but did not reach significance (p = 0.054). Renal allograft function was inferior in the study group but did not reach significance: mean SCr2 (mg/dL) was 2.18 ± 1.41 and 1.5 ± 0.68 in controls, respectively, p = 0.27; mean GFR2 (ml/min/1.73m2) was 39.9 ± 20.83 and 51.23 ± 19.03, respectively, p = 0.102. Renal allograft duration was inferior in patients with APS and was (in years) 11.22 ± 1.44 vs. 14.36 ± 0.42, respectively, p = 0.037, in patients with primary APS (p = 0.021), in patients with APS diagnosed post-transplant (p = 0.012) but not in lupus-related APS (p = ns). Fifteen year renal allograft survival was inferior in APS vs. controls (73,86% vs. 90.48%, respectively, p = 0.049). Conclusions: Recipients with APS are at higher risk for allograft loss due to immune and non-immune causes. Renal allograft survival was inferior in recipients with APS and renal function remains impaired but stable.

Screening for Polyomavirus Viruria Like Early Detection of Human Polyomavirus Infection and Replication: The Results of a Single-Center Observation.

BACKGROUND: Polyomavirus (PV) infection and PV-associated nephropathy (PVAN) are some of the most important problems in kidney transplantation. PURPOSE: Our objective was to determine the incidence of PV viruria and PV replication in single-center Polish kidney transplant recipients (KTR). METHODS: Urine samples from 155 cadaveric KTR were analyzed for PV viruria using quantitative real-time polymerase chain reaction and the patients were followed prospectively. The PV replication was recognized when the urine level was >107 PV DNA copies/mL of urine. RESULTS: Based on the PV DNA analysis, the patients were divided into 3 groups: Group 1 (n = 87; 56.1%) without viruria, Group 2 (n = 44; 28.4%) with viruria but without PV replication, and Group 3 (n =24; 15.5%) with PV replication. The presence of PV viruria was correlated with the type of immunosuppressive regimen, strongly associated with tacrolimus intake. There was no correlation between viruria and mycophenolate daily dose in the study population. In Group 3 there were 6 patients (3.9%) with high viruria (>1010 copies/mL), and 5 patients from this group had confirmed PVAN in allograft biopsy. CONCLUSIONS: The prevalence of BK virus infection in KTR is similar to that reported in studies from other countries. We confirmed that PV viruria can be both a good screening for PV infection and a good predictor of PVAN. Tacrolimus was the most important predictor of PV viruria and PV replication in KTR.

Total pancreatectomy with islet autotransplantation in diabetic and pre-diabetic patients with intractable chronic pancreatitis.

Total pancreatectomy with islet autotransplantation (TPIAT) is an effective treatment option for non-diabetic patients with intractable chronic pancreatitis. The outcome and potential benefits for pre-diabetic and diabetic patients are less well established. Thirty-four patients underwent TPIAT were retrospectively divided into 3 groups according to pre-operative glycemic control: diabetes mellitus (DM) (n=5, 15%), pre-DM (n=11, 32%) and non-DM (n=18, 54%). Pre-operative fasting c-peptide was detectable and similar in all 3 groups. Islet yield in the DM group was comparable to pre-DM and non-DM groups (median islet equivalents [IEQ] was 191,800, 111,800, and 232,000IEQ, respectively). Patients received islet mass of over the target level of 2000IEQ/kg in pre-DM and DM at lower but clinically meaningful rates compared to the non-DM group: 45% (5/11) and 60% (3/5) for a combined 50% (8/16) rate, respectively, compared to 83% (15/18) for the non-DM group. At 1 year, fasting c-peptide and HbA1c did not differ between DM and pre-DM groups but c-peptide was significantly higher in non-DM. Islet transplantation failed (negative c-peptide) only in 1 patient. Pre-operatively, all patients experienced pancreatic pain with daily opioid dependence in 60% to 70%. Pancreatic-type pain gradually subsided completely in all groups with no differences in other painful somatic symptoms. Diabetic patients with measurable pre-operative c-peptide can achieve similar benefit from TPIAT, with comparable outcomes to pre-diabetic and non-diabetic patients including pain relief and the metabolic benefit of transplanted islets. Not surprisingly, endocrine outcomes for diabetic and pre-diabetics patients are substantially worse than in those with normal pre-operative glucose control.

Alterations in peripheral blood B cells in systemic lupus erythematosus patients with renal insufficiency.

OBJECTIVE: Systemic lupus erythematosus (SLE) is one of the autoimmune diseases, believed to be closely related to hyperactivity of B cells, overproduction of autoantibodies and immune complex formation and deposition in affected tissue. The autoreactive inflammation leads to multiorgan damage with kidney dysfunction in the forefront. Studies on lupus nephritis (LN), affecting the majority of SLE patients, are mainly focused on cells causing local inflammation. The aim of our work was to detect alterations in more accessible peripheral blood B cells in the course of SLE focusing on the influence of renal insufficiency (RI) on those parameters. METHODS: We performed a comprehensive flow cytometry analysis of B cell subpopulations, analyzed gene expression patterns with qPCR, and examined serum cytokine levels with multiplex cytokine/chemokine assay. RESULTS: We discovered distribution of specific B cell subsets, especially CD38+ cells, plasmablasts, associated with the presence and severity of the disease. Changes in expression of MBD2, DNMT1 and APRIL genes were not only associated with activity of SLE but also were significantly changed in patients with RI. CONCLUSIONS: All these results shed new light on the role of circulating B cells, their subpopulations, function, and activity in the SLE with kidney manifestation.

Transcriptomic and Epigenetic Alterations in Dendritic Cells Correspond With Chronic Kidney Disease in Lupus Nephritis.

Systemic lupus erythematosus (SLE) is a serious autoimmune disease with variety of organ manifestations. The most dreadful one, affecting the majority of SLE patients, is kidney manifestation-lupus nephritis (LN). Dendritic cells (DC) are believed to be one of the culprits of immune dysregulation in LN. Flow cytometry analysis was applied to identify the frequency and activity of peripheral blood DCs subpopulations: myeloid and plasmacytoid, in LN patients. Magnetically isolated mDCs and pDCs were subjected to molecular analysis of genes expression, evaluation of global DNA methylation and histone H3 methylation. We observed distinctive features of DCs associated with the stages of nephritis in LN patients. Lower numbers of pDCs were observed in patients with severe LN, while increased co-stimulatory potential of mDCs was connected with the early, mild stage of this disease. IRF1 transcript upregulation was specific for mDCs from total LN patients, while exceptional amount of IRF1 mRNA was detected in mDCs from severe LN patients. DCs DNA hypermethylation seemed characteristic for severe LN, whereas a decrease in H3K4me3 and H3K27me3 marks was significant for the early stages of LN. These findings present dendritic cell alterations that may reflect renal involvement in SLE, laying foundations for new strategy of diagnosis and monitoring of LN patients, omitting invasive kidney biopsies.