The aim of the present study was to evaluate the dose of postdialysis cholecalciferol needed to maintain the 25-hydroxyvitamin D [25(OH)D] levels in the optimal range of 75–150 nmol/L. Twenty-six patients who had low baseline 25(OH)D levels (mean 27.5 ± 14.9 nmol/L) were studied. The 25(OH)D levels were measured every 2 months for one year. During the first two months, all the patients received 2000 IU of cholecalciferol after each hemodialysis (=6000 IU/wk). Thereafter, the dose was individualized and adapted every 2 months by administering 1 to 6 cholecalciferol tablets (2000 IU each) per week (total weekly dose = 2000–12000 IU/wk). During cholecalciferol supplementation, the 25(OH)D concentrations rapidly increased from baseline to 140.1 ± 28.3 nmol/L at month 6 and 95.6 ± 20.9 nmol/L at month 12. At month twelve, 86% of the patients had 25(OH)D levels within the target range with a mean dose of 5917 ± 4106 IU/wk of cholecalciferol; however, the amount needed to maintain these levels varied widely from 0 (n = 2) to 12000 IU/wk (n = 5). In conclusion, postdialysis cholecalciferol prescription is quite effective in correcting vitamin D deficiency/insufficiency, but the amount of cholecalciferol needed to maintain the 25(OH)D levels within the optimal range over the long-term varies widely among patients and must be individualized.

Direct oral anticoagulants (DOACs) are among the most commonly prescribed medications, and DOAC-associated kidney dysfunction may be a problem that is underrecognized by clinicians. We report on the case of an 82-year-old patient who, two weeks after the prescription of rivaroxaban for atrial fibrillation, was hospitalized for a drug-induced hypersensitivity syndrome whose main clinical manifestations were low-grade fever with a petechial rash in the legs and acute renal failure (ARF). Within one week after rivaroxaban withdrawal, the patient’s clinical condition improved and the renal function normalized. In a review of the literature, we only found five case reports of rivaroxaban-related ARF: two patients had tubulo-interstitial nephritis (TIN), two had anticoagulant-related nephropathy (ARN), and the last one had IgA nephropathy. As some recent publications suggest that kidney injury due to anticoagulation drugs may be largely underdiagnosed, we also analyzed the data from the VigiAccess database, the World Health Organization pharmacovigilance program that collects drug-related adverse events from 134 national registries worldwide. Among all the rivaroxaban-associated adverse events reported in VigiAccess since 2006, 4,323 (3.5%) were renal side effects, of which 2,351 (54.3%) were due to unspecified ARF, 363 (8.4%) were due to renal hemorrhage (characteristically associated with ARN), and 24 (0.6%) were due to TIN. We also compared these results with those reported in VigiAccess for other DOACs and vitamin K antagonists. This analysis suggests that the frequency of renal adverse events associated with rivaroxaban and other DOACs may be appreciably higher than what one might currently consider based only on the small number of fully published cases.

BackgroundIn hemodialysis patients, post-dialysis treatment with intravenous antibiotics permits even severe infections to be managed on an outpatient basis. Cefepime is a fourth-generation cephalosporin with a broad spectrum of action in monotherapy. We report on the pharmacokinetics of cefepime in post-dialysis therapy.MethodsSince June 2012, twelve infections were treated with post-dialysis cefepime in 9 patients on high-flux hemodialysis. The initial post-dialysis dose of cefepime was approximately 15 mg/kg. The following doses were adapted according to the trough serum levels obtained before the subsequent dialysis in order to be above the EUCAST breakpoints for susceptible organisms and above the MIC90. Residual plasma concentrations were determined before (n = 30) and after (n = 17) dialysis by liquid chromatography–mass spectrometry.ResultsOverall, the mean ± SD dose of cefepime was 920 ± 270 mg (14.5 ± 5.1 mg/kg), but it was significantly lower before the 48 h interval (775 ± 210 mg or 12.7 ± 4.5 mg/kg) compared to the 72 h interval (1125 ± 225 mg or 17.2 ± 4.9 mg/kg) (p < 0.05). The mean trough pre-dialysis concentrations were 10.7 ± 3.9 mg/l and 11.3 ± 5.6 mg/l at 48 and 72 h, respectively. These levels always largely exceeded the EUCAST susceptibility breakpoints for all the targeted bacteria (>1 mg/l) with the exception of Pseudomonas aeruginosa (>8 mg/l). Cefepime concentrations were higher in anuric patients compared to those with preserved diuresis (15.6 ± 3.5 vs 9.25 ± 3.6 mg/l; p < 0.001) and decreased on average by 81 % during dialysis (from 10.5 ± 3.7 to 1.96 ± 1.2 mg/l; p < 0.001). The clinical outcome of all patients was good.ConclusionsOutpatient treatment with cefepime administered post-dialysis three-times-weekly was effective and well-tolerated in our patients. According to our data, in patients infected by highly susceptible pathogens a fixed dose of cefepime of 1 g before every 48-h interval and of 1.5 g before every 72-h interval should be recommended, without need of routine monitoring of the cefepime blood levels. In patients having an infection with less susceptibles pathogens as P. aeruginosa, and particularly in those among them exhibiting residual renal function, higher initial doses are necessary (1.5 g before a 48-h interval and 2.0 g before a 72-h interval) with adaption according to the subsequent pre-dialysis trough serum levels.

Contrast-induced acute kidney injury (CI-AKI) classically occurs following the intravascular administration of iodinated contrast medium (CM). However, some cases of iodine-induced nephrotoxicity have been reported in patients who did not receive intravascular CM, as a consequence of iodine absorption through mucosae, burned skin or interstitial tissues. Recently, we observed the first case of CI-AKI occurring after an enteroclysis without any direct intravascular injection of CM. Here, we report this case, and review other clinical situations in which renal toxicity has been reported following the non-intravascular use of iodinated compounds.

Background: Cardiology guidelines recommend measuring high-sensitivity cardiac troponin (hs-cTn) for the diagnostic work-up of acute coronary syndromes (ACS). Many hospitals measure hs-cTnT, but preliminary data have shown that hs-cTnT is higher than normal in many hemodialysis patients without evidence of ACS. The purpose of this study was therefore to determine the hs-cTnT levels every month for 1 year in asymptomatic hemodialysis patients, in order to assess their changes over time relative to creatine kinase. Methods: Fourty-four hemodialysis patients (mean age 67 AE 14 years) were included. The predialysis levels of fifth-generation hs-cTnT, CK, and CK-MB were measured every month for 1 year using a Cobas ® 6000 analyzer (Roche Diagnostics, Switzerland).Results: Almost 100% of hs-cTnT measurements were higher than normal (N < 14 ng/L); the mean AE SD annual level was 84 AE 59 ng/L, ranging from a minimum of 24 AE 2 to 241 AE 28 ng/L in individual patients. The mean levels of CK and CK-MB were normal. Thirteen myocardial infarctions were analyzed, which were all associated with an initial elevation in hs-cTnT >45% from the individual baseline value. By comparison, CK and CK-MB only increased in 38% and 31% of these myocardial infarctions, respectively. Discussion: hs-cTnT is persistently higher than normal in chronic hemodialysis patients. Standard algorithms for diagnosing ACS can obviously not be used and alternative diagnostic strategies need to be developed. According to our data, and given the huge variation in baseline hs-cTnT levels among patients, the use of higher cut-offs as proposed in the literature cannot be recommended. Instead, we consider that hs-cTnT should be checked at regular intervals (e.g., every 3-6 months) in order to establish individual baseline levels for hs-cTnT. This approach, in most instances, not only makes it