The risk factors associated with post-transplantation BKPyV nephropathy and BKPyV DNAemia: a prospective study in kidney transplant recipients.

BACKGROUND: BK polyomavirus (BKPyV) infection after kidney transplantation can lead to serious complications such as BKPyV-associated nephropathy (BKPyVAN) and graft loss. The aim of this study was to investigate the incidence of BKPyVAN after implementing a BKPyV screening program, to map the distribution of BKPyV genotypes and subtypes in the Uppsala-Örebro region and to identify host and viral risk factors for clinically significant events. METHODS: This single-center prospective cohort study included kidney transplant patients aged ≥ 18 years at the Uppsala University Hospital in Sweden between 2016 and 2018. BKPyV DNA was analyzed in plasma and urine every 3 months until 18 months after transplantation. Also genotype and subtype were determined. A logistic regression model was used to analyze selected risk factors including recipient sex and age, AB0 incompatibility and rejection treatment prior to BKPyVAN or high-level BKPyV DNAemia. RESULTS: In total, 205 patients were included. Of these, 151 (73.7%) followed the screening protocol with 6 plasma samples, while184 (89.8%) were sampled at least 5 times. Ten (4.9%) patients developed biopsy confirmed BKPyVAN and 33 (16.1%) patients met criteria for high-level BKPyV DNAemia. Male sex (OR 2.85, p = 0.025) and age (OR 1.03 per year, p = 0.020) were identified as significant risk factors for developing BKPyVAN or high-level BKPyV DNAemia. BKPyVAN was associated with increased viral load at 3 months post transplantation (82,000 vs. < 400 copies/mL; p = 0.0029) and with transient, high-level DNAemia (n = 7 (27%); p < 0.0001). The most common genotypes were subtype Ib2 (n = 50 (65.8%)) and IVc2 (n = 20 (26.3%)). CONCLUSIONS: Male sex and increasing age are related to an increased risk of BKPyVAN or high-level BKPyV DNAemia. BKPyVAN is associated with transient, high-level DNAemia but no differences related to viral genotype were detected.

Biocompatibility and tolerability of a purely bicarbonate-buffered peritoneal dialysis solution.

BACKGROUND: Novel peritoneal dialysis solutions are characterized by a minimal content of glucose degradation products and a neutral pH. Many studies have shown the biocompatibility of neutral lactate-buffered solutions; however, until now, the effect of purely bicarbonate-buffered solutions has not been intensively studied in vivo. METHODS: This study was an open label, prospective, crossover multicenter trial to investigate the biocompatibility of a purely bicarbonate-buffered solution (bicPDF) by measuring biocompatibility parameters such as cancer antigen 125 (CA125) in peritoneal effluent. 55 patients were enrolled in the study. After a 2-week run-in phase, 53 patients could be randomized into 2 groups, starting with either standard lactate-buffered peritoneal dialysis fluid (SPDF) for 12 weeks (phase 1) and then switching to bicPDF for 12 weeks (phase 2), or vice versa. Overnight peritoneal effluents were collected at baseline and at the end of phases 1 and 2 and were tested for CA125, hyaluronic acid, vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), interferon gamma (IFNgamma), and transforming growth factor-beta(1) (TGF-beta1). Total ultrafiltration and residual renal function were also assessed. At the end of the study, pain during fluid exchange and dwell was evaluated using special questionnaires. RESULTS: 34 patients completed the study; 27 of them provided data for analysis of the biocompatibility parameters. CA125 levels in overnight effluent were significantly higher with bicPDF (61.9 +/- 33.2 U/L) than with SPDF (18.6 +/- 18.2 U/L, p < 0.001). Hyaluronic acid levels were significantly lower after the use of bicPDF (185.0 +/- 119.6 ng/mL) than after SPDF (257.4 +/- 174.0 ng/mL, p = 0.013). Both TNF-alpha and TGF-beta1 showed higher levels with the use of bicPDF than with SPDF. No differences were observed for IL-6, VEGF, or IFNgamma levels. We observed an improvement in the glomerular filtration rate with the use of bicPDF but no differences were observed for total fluid loss. Pain scores could be analyzed in 23 patients: there was no difference between the solutions. CONCLUSIONS: The use of a purely bicarbonate-buffered low-glucose degradation product solution significantly changes most of the peritoneal effluent markers measured, suggesting an improvement in peritoneal membrane integrity. Additionally, it seems to have a positive effect on residual renal function.