SummaryBackground and objectives Little is known about the influence of dietary phosphate intake on fibroblast growth factor-23 (FGF23) and its subsequent effects on vitamin D levels. This study addresses changes in intact FGF23 (iFGF23) and C-terminal FGF23 (cFGF23), phosphaturia, and levels of vitamin D on high and low phosphate and calcium intake.Design, setting, participants, & measurements Ten healthy subjects adhered to a diet low or high in phosphate and calcium content for 36 hours each with a 1-week interval during which subjects adhered to their usual diet. Serum phosphate, calcium, vitamin D metabolites, parathyroid hormone (PTH), and FGF23 levels (cFGF23 and iFGF23) were measured several times a day. Phosphate, calcium, and creatinine excretion was measured in 24-hour urine on all study days.Results Serum phosphate levels and urinary phosphate increased during high dietary phosphate intake (from 1.11 to 1.32 mmol/L, P Ͻ 0.0001 and 21.6 to 28.8 mmol/d, P ϭ 0.0005, respectively). FGF23 serum levels increased during high dietary phosphate/calcium intake (cFGF23 from 60 to 72 RU/ml, P Ͻ 0.001; iFGF23 from 33 to 37 ng/L, P ϭ 0.003), whereas PTH declined. 1,25-Dihydroxyvitamin D (1,25D) showed an inverse relation with FGF23.Conclusions Variation in dietary phosphate and calcium intake induces changes in FGF23 (on top of a circadian rhythm) and 1,25D blood levels as well as in urinary phosphate excretion. These changes are detectable the day after the change in the phosphate content of meals. Higher FGF23 levels are associated with phosphaturia and a decline in 1,25D levels.

The presence of donor‐specific anti‐HLA antibodies (DSAs) is associated with increased risk of graft failure after kidney transplant. We hypothesized that DSAs against HLA class I, class II, or both classes indicate a different risk for graft loss between deceased and living donor transplant. In this study, we investigated the impact of pretransplant DSAs, by using single antigen bead assays, on long‐term graft survival in 3237 deceased and 1487 living donor kidney transplants with a negative complement‐dependent crossmatch. In living donor transplants, we found a limited effect on graft survival of DSAs against class I or II antigens after transplant. Class I and II DSAs combined resulted in decreased 10‐year graft survival (84% to 75%). In contrast, after deceased donor transplant, patients with class I or class II DSAs had a 10‐year graft survival of 59% and 60%, respectively, both significantly lower than the survival for patients without DSAs (76%). The combination of class I and II DSAs resulted in a 10‐year survival of 54% in deceased donor transplants. In conclusion, class I and II DSAs are a clear risk factor for graft loss in deceased donor transplants, while in living donor transplants, class I and II DSAs seem to be associated with an increased risk for graft failure, but this could not be assessed due to their low prevalence.

Background The use of patient-reported outcome measures (PROMs) is becoming increasingly important in healthcare. However, incorporation of PROMs into routine nephrological care is challenging. This study describes the first experience with PROMs in Dutch routine dialysis care. Methods A pilot study was conducted in dialysis patients in 16 centres. Patients were invited to complete PROMs at baseline and 3 and 6 months. PROMs consisted of the 12-item short-form and Dialysis Symptom Index to assess health-related quality of life (HRQoL) and symptom burden. Response rates, HRQoL and symptom burden scores were analysed. Qualitative research methods were used to gain insight into patients’ views on using PROMs in clinical practice. Results In total, 512 patients (36%) completed 908 PROMs (24%) across three time points. Response rates varied from 6 to 70% among centres. Mean scores for physical and mental HRQoL were 35.6 [standard deviation (SD) 10.2] and 47.7 (SD 10.6), respectively. Patients experienced on average 10.8 (SD 6.1) symptoms with a symptom burden score of 30.7 (SD 22.0). Only 1–3% of the variation in PROM scores can be explained by differences between centres. Patients perceived discussing their HRQoL and symptom scores as insightful and valuable. Individual feedback on results was considered crucial. Conclusions The first results show low average response rates with high variability among centres. Dialysis patients experienced a high symptom burden and poor HRQoL. Using PROMs at the individual patient level is suitable and may improve patient–professional communication and shared decision making. Further research is needed to investigate how the collection and the use of PROMs can be successfully integrated into routine care to improve healthcare quality and outcomes.

Background: Patients with chronic kidney disease have an increased risk of cardiovascular disease. Oxidative stress has been proposed to play a role in the development of cardiovascular disease among these patients. Methods:We conducted a randomized, double-blind trial in 93 patients (Cockcroft-Gault equation: creatinine clearance, 38±15 [mean±SD] mL/min per 1.73 m 2 [0.63±0.25 mL/s per m 2 ]) to investigate the effect of a treatment strategy designed primarily to achieve stepwise oxidative stress reduction on common carotid intima-media thickness (CC-IMT), brachial artery flow-mediated dilatation (BA-FMD), albuminuria, and renal function. The treatment group received a regimen of pravastatin to which vitamin E supplementation was added after 6 months and homocysteine-lowering therapy after another 6 months. Blood pressure in both groups was managed according to a standard protocol. The placebo group received matching placebos. Measurement of CC-IMT and BA-FMD was performed at randomization after 6, 12, and 18 months. Patients were followed up for 2 years. Generalized estimating equations were used for analysis.Results: Compared with placebo, active treatment was associated with a decrease in CC-IMT (after 18 months: from 0.68 to 0.63 mm in the treatment group and from 0.65 to 0.71 mm in the placebo group; PϽ.001), an increase in BA-FMD (after 18 months: from 4.66% to 7.56% in the treatment group and from 6.21% to 4.73% in the placebo group; PϽ.001), and an attenuated increase in urinary albumin excretion over time (P=.04 for betweengroup difference after 24 months), but no effect was observed on renal function. Conclusion:In patients with mild to moderate chronic kidney disease, 18 months of a treatment strategy along with well-controlled blood pressure reduced CC-IMT and urinary albumin excretion and increased BA-FMD.

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor–recipient couples that were transplanted between 1995 and 2005. For these donors–recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04–1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10–1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival.