Observational studies investigating the role of vitamin D in renal function have yielded inconsistent results.

We tested whether 25-hydroxyvitamin D (25[OH]D) serum levels are associated with renal function, and inversely, whether altered renal function causes changes in 25(OH)D, using Mendelian randomization (MR).

In this two-sample MR study, we used single nucleotide polymorphisms (SNP) associated with 25(OH)D in 443 734 Europeans and evaluated their effects on estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), chronic kidney disease (CKD) risk and progression in genome-wide association studies totaling over 1 million Europeans. To control for pleiotropy, we also used SNPs solely in DHCR7, CYP2R1, and GC, all genes with known roles in vitamin D metabolism. We performed a reverse MR, using SNPs for the above indices of renal function to study causal effects on 25(OH)D levels.

We did not find robust evidence supporting effects of 25(OH)D on eGFR, BUN, and CKD or its progression. Our inverse variance weighted MR demonstrated a 0.56 decrease in standardized log-transformed 25(OH)D (95% CI -0.73, -0.41; P = 2.89 × 10-12) per unit increase in log-transformed eGFR. Increased BUN was associated with increased 25(OH)D (β = 0.25, 95% CI 0.15, 0.36; P = 4.12 × 10-6 per unit increase in log-transformed BUN). Finally, genetically predicted CKD conferred a 0.05 increase in standardized log-transformed 25(OH)D level (95% CI 0.04, 0.06; P = 1.06 × 10-13). Other MR methods confirmed the findings of the main analyses.

Genetically predicted CKD, increased BUN, and decreased eGFR are associated with increased 25(OH)D levels, but we found no causal effect of 25(OH)D on renal function in Europeans.

Oliguria after cardiac surgery remains of uncertain clinical significance. Therefore, we investigated the relationship of acute kidney injury severity across urine output and creatinine domains with the risk for major adverse kidney events at 180 days. We aimed to determine the impact of acute kidney injury after cardiac surgery.

In a retrospective multicenter study, we investigated the relationship of acute kidney injury severity across urine output and creatinine categories with the risk for major adverse kidney events at 180 days-the composite of death, dialysis, and persistent renal dysfunction-using a large database of patients undergoing cardiac surgery at 1 of 5 hospitals within the regional medical system. We analyzed electronic records from 6637 patients treated between 2008 and 2014, of whom 5389 (81.2%) developed any acute kidney injury within 72 hours of surgery. We stratified patients by levels of urine output or serum creatinine according to Kidney Disease Improving Global Outcomes criteria for acute kidney injury.

Major adverse kidney events at 180 days increased from 4.5% for no acute kidney injury to 61.3% for stage 3 acute kidney injury (P < .001). Death or dialysis by day 180 was 2.4% for those with no acute kidney injury and 46.7% for those with acute kidney injury stage 3 (P < .001). Isolated oliguria was common (42.6%), and isolated azotemia was rare (6.1%). Even stage 1 acute kidney injury by oliguria alone was associated with an increased risk of major adverse kidney events at 180 days (odds ratio, 1.76; 1.20-2.57; P = .004), mainly driven by persistent renal dysfunction (odds ratio, 2.01; 1.26-3.18; P = .003).

Acute kidney injury is common in patients undergoing cardiac surgery, and even milder forms of acute kidney injury, including isolated stage 1 oliguria, are associated with adverse long-term consequences.

Vitamin D deficiency is still a common problem particularly in the elderly and in individuals with various degrees of renal impairment. The present study aimed to evaluate the association between plasma concentrations of 25(OH)D and death in a large cohort of prevalent patients on hemodialysis (HD) from south-east Romania, a typical Balkan region. This is an observational prospective study that included a total of 570 patients on maintenance HD. Study patients were classified into three groups by baseline 25(OH)D levels: (1) sufficient 25(OH)D--i.e., >30 ng/mL; (2) insufficient 25(OH)D--i.e., between 10 and 29 ng/mL; and (3) deficient 25(OH)D--i.e., <10 ng/mL. During the follow-up period of 14 months, 68 patients (11.9%) died, the Kaplan-Meier analysis showing significant differences in all-cause mortality for chronic kidney disease patients in different 25(OH)D groups (P = 0.002). Unadjusted Cox regression analysis also showed significant differences in survival. The multivariate Cox regression model showed no significant differences in survival according to vitamin D levels. Hazard ratio for death in the "<10 ng/mL" group was 1.619 (P = 0.190) and in the "10-30 ng/mL" group was 0.837 (P = 0.609). In our dialysis population with a high comorbidity burden, low 25(OH)D concentration was not associated with mortality in the adjusted Cox model, suggesting that vitamin D deficiency could represent only a non-specific marker for a poor health status, with less impact on mortality.

Chronic kidney disease strongly impacts on mineral and bone metabolism. Despite numerous medications, the biological targets recommended by international guidelines are often unmet. Among the treatment armamentarium, native or nutritional vitamin D (25OHD3) has been rediscovered in the early 2000s, and its general and specific actions further studied. Effects on bone, immunity, infection prevention, muscle function and phosphocalcic metabolism have been reviewed. Assessment of nutritional vitamin D status showed very low serum 25OHD3 levels and increase in nutritional vitamin D prescription led to improvement in these levels. However, about 45% of adult CKD patients still have insufficient serum 25OHD3 levels. Epidemiological studies should be enforced to describe further the mineral and bone disease management in CKD.

Patients with chronic kidney disease (CKD) represent 13% of the American population. CKD has been shown to significantly alter drug disposition of nonrenally eliminated drugs. Indeed, modifications in the expression and function of intestinal and hepatic drug metabolism enzymes and uptake and efflux transporters have been reported. Uremic toxins, inflammatory cytokines, and parathyroid hormone have been implicated as causes. These changes can have an important clinical impact on drug disposition and lead to unintended toxicity if they are administered without dose adjustment in patients with impaired kidney function. This review summarizes recent preclinical and clinical studies and presents the current understanding of the effect of CKD on drug absorption, distribution, metabolism, and excretion.

Calcidiol insufficiency is highly prevalent in chronic kidney disease (CKD), but the reasons for this are incompletely understood. CKD associates with a decrease in liver cytochrome P450 (CYP450) enzymes, and specific CYP450 isoforms mediate vitamin D(3) C-25-hydroxylation, which forms calcidiol. Abnormal levels of parathyroid hormone (PTH), which also modulates liver CYP450, could also contribute to the decrease in liver CYP450 associated with CKD. Here, we evaluated the effects of PTH and uremia on liver CYP450 isoforms involved in calcidiol synthesis in rats. Uremic rats had 52% lower concentrations of serum calcidiol than control rats (P < 0.002). Compared with controls, uremic rats produced 71% less calcidiol and 48% less calcitriol after the administration of vitamin D(3) or 1alpha-hydroxyvitamin D(3), respectively, suggesting impaired C-25-hydroxylation of vitamin D(3). Furthermore, uremia associated with a reduction of liver CYP2C11, 2J3, 3A2, and 27A1. Parathyroidectomy prevented the uremia-associated decreases in calcidiol and liver CYP450 isoforms. In conclusion, these data suggest that uremia decreases calcidiol synthesis secondary to a PTH-mediated reduction in liver CYP450 isoforms.