The Vitamin D Metabolite Diagnostic Ratio Associates With Phenotypic Traits of Idiopathic Hypercalciuria.

Introduction: Underlying mechanisms for hypercalciuria remain unknown in most cases; thus, the designation "idiopathic." We hypothesized that the vitamin D-inactivating enzyme, CYP24A1 contributes to the pathogenesis of hypercalciuria in kidney stone formers. Methods: We conducted association analyses between CYP24A1 activity, estimated by the vitamin D metabolite diagnostic ratio (25(OH) vitamin D3/total 24,25 (OH)2 vitamin D ratio; VMDR), and the phenotype of participants in 2 observational cohorts of kidney stone formers, the Swiss Kidney Stone Cohort (SKSC) and the Bern Kidney Stone Registry (BKSR). Circulating 25(OH)- and 24,25 (OH)2 vitamin D were quantified using a validated liquid chromatography tandem mass spectrometry assay. Results: A total of 974 participants were included in the analysis. We found a positive association of VMDR (and hence negative association of CYP24A1 activity) with total (ß 0.009 mmol/l; 95% confidence interval [CI]: 0.002, 0.016; P = 0.02) and ionized plasma calcium (ß 0.005 mmol/l; 95% CI: 0.002, 0.008; P < 0.01), absolute and fractional excretion of urinary calcium (ß 0.054 mmol/24h; 95% CI: 0.010, 0.097; P = 0.02 and ß 0.046%; 95% CI: 0.018, 0.074; P < 0.01, respectively). Further, VMDR was associated with an increased likelihood of forming calcium oxalate dihydrate stones (Odds ratio [OR] 1.64; 95% CI: 1.22, 2.35; P < 0.01) and reduced bone mineral density (BMD) at the femoral neck (ß -0.005 g/cm2; 95% CI: -0.010, -0.001; P = 0.04). The described associations became stronger when the analysis was confined to idiopathic calcium stone formers. Conclusion: Our study reveals that CYP24A1 activity, estimated by VMDR, is associated with clinical traits previously linked to idiopathic hypercalciuria.

Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence.

BACKGROUND: Nephrolithiasis is one of the most common conditions affecting the kidney and is characterized by a high risk of recurrence. Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited. Furthermore, dose-response data are also limited. METHODS: In this double-blind trial, we randomly assigned patients with recurrent calcium-containing kidney stones to receive hydrochlorothiazide at a dose of 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily. The main objective was to investigate the dose-response effect for the primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Radiologic recurrence was defined as the appearance of new stones on imaging or the enlargement of preexisting stones that had been observed on the baseline image. Safety was also assessed. RESULTS: In all, 416 patients underwent randomization and were followed for a median of 2.9 years. A primary end-point event occurred in 60 of 102 patients (59%) in the placebo group, in 62 of 105 patients (59%) in the 12.5-mg hydrochlorothiazide group (rate ratio vs. placebo, 1.33; 95% confidence interval [CI], 0.92 to 1.93), in 61 of 108 patients (56%) in the 25-mg group (rate ratio, 1.24; 95% CI, 0.86 to 1.79), and in 49 of 101 patients (49%) in the 50-mg group (rate ratio, 0.92; 95% CI, 0.63 to 1.36). There was no relation between the hydrochlorothiazide dose and the occurrence of a primary end-point event (P = 0.66). Hypokalemia, gout, new-onset diabetes mellitus, skin allergy, and a plasma creatinine level exceeding 150% of the baseline level were more common among patients who received hydrochlorothiazide than among those who received placebo. CONCLUSIONS: Among patients with recurrent kidney stones, the incidence of recurrence did not appear to differ substantially among patients receiving hydrochlorothiazide once daily at a dose of 12.5 mg, 25 mg, or 50 mg or placebo once daily. (Funded by the Swiss National Science Foundation and Inselspital; NOSTONE ClinicalTrials.gov number, NCT03057431.).

Novice and Advanced Learners' Satisfaction and Perceptions of an e-Learning Renal Semiology Module During the COVID-19 Pandemic: Mixed Methods Study.

BACKGROUND: Nephrotic syndrome is a unique clinical disorder, which provides interesting teaching opportunities that connect physiological and pathological aspects to clinical practice. During the current COVID-19 outbreak, in-person teaching in our institution was not permitted, thus creating a unique challenge for clinical skills teaching. A case-based electronic learning (e-learning) activity was designed to replace the traditional in-person teaching of renal semiology. e-Learning activities have been shown to be effective for knowledge retention and increasing novice learners' performance. However, major knowledge gaps exist concerning the satisfaction of learners with e-learning activities as the sole form of teaching, specifically for undergraduate clinical skills education. OBJECTIVE: Our study aimed to prospectively assess undergraduate medical students' perceptions of and satisfaction with an e-learning activity teaching renal semiology. METHODS: All second-year medical students (novice learners) from the medical faculty of the University of Geneva, Switzerland, undertook the e-learning activity and were invited to participate in a nonmandatory, validated web-based survey, comprising questions answered using a 10-point Likert scale and one qualitative open-ended question. For comparison and to provide further insights, 17 fourth- to sixth-year students (advanced learners) were prospectively recruited to participate in both the e-learning activity and the evaluation. A mixed methods analysis was performed. RESULTS: A total of 88 (63%) out of 141 novice learners and all advanced learners responded to the evaluation survey. Advanced learners reported significantly higher satisfaction with the e-learning activity (mean 8.7, SD 1.0 vs mean 7.3, SD 1.8; P<.001), clarity of objectives (mean 9.6, SD 0.8 vs mean 7.7, SD 1.7; P<.001), and attainability of objectives (mean 9.8, SD 0.5 vs mean 7.3, SD 1.3; P<.001). Both groups showed high interest in the inclusion of the activity as part of a blended learning approach; however, there was low interest in the activity being the sole means of teaching. CONCLUSIONS: Case-based e-learning activities might be better suited for advanced learners and could increase learners' satisfaction within a blended teaching instructional design. More research on students' satisfaction with e-learning activities in the field of clinical skills education should be done. In addition, more effort should be put into finding alternative teaching tools for clinical skills education in light of the ongoing COVID-19 pandemic and future health crises.

Efficacy of standard and low dose hydrochlorothiazide in the recurrence prevention of calcium nephrolithiasis (NOSTONE trial): protocol for a randomized double-blind placebo-controlled trial.

BACKGROUND: Nephrolithiasis is a global healthcare problem with a current lifetime risk of 18.8% in men and 9.4% in women. Given the high cost of medical treatments and surgical interventions as well as the morbidity related to symptomatic stone disease, medical prophylaxis for stone recurrence is an attractive approach. Thiazide diuretics have been the cornerstone of pharmacologic metaphylaxis for more than 40 years. However, evidence for benefits and harms of thiazides in the prevention of calcium containing kidney stones in general remains unclear. In addition, the efficacy of the currently employed low dose thiazide regimens to prevent stone recurrence is not known. METHODS: The NOSTONE trial is an investigator-initiated 3-year prospective, multicenter, double-blind, placebo-controlled trial to assess the efficacy of standard and low dose hydrochlorothiazide treatment in the recurrence prevention of calcium containing kidney stones. We plan to include 416 adult (≥ 18 years) patients with recurrent (≥ 2 stone episodes in the last 10 years) calcium containing kidney stones (containing ≥50% of calcium oxalate, calcium phosphate or a mixture of both). Patients will be randomly allocated to 50 mg or 25 mg or 12.5 mg hydrochlorothiazide or placebo. The primary outcome will be incidence of stone recurrence (a composite of symptomatic or radiologic recurrence). Secondary outcomes will be individual components of the composite primary outcome, safety and tolerability of hydrochlorothiazide treatment, changes in urinary biochemistry elicited by hydrochlorothiazide treatment and impact of baseline disease severity, biochemical abnormalities and stone composition on treatment response. DISCUSSION: The NOSTONE study will provide long-sought information on the efficacy of hydrochlorothiazide in the recurrence prevention of calcium containing kidney stones. Strengths of the study include the randomized, double-blind and placebo-controlled design, the large amount of patients studied, the employment of high sensitivity and high specificity imaging and the exclusive public funding support. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03057431 . Registered on February 20 2017.

[Calcific uremic arteriolopathy (calciphylaxis) : update in 2018]. / Artériolopathie urémique calcifiante (calciphylaxie) : mise au point en 2018.

Calciphylaxis is a rare disease with a poor prognostic that mostly occurs in patients with renal failure. Diagnosis is difficult and skin biopsy is the gold standard diagnostic procedure, although it may aggravate skin lesions. Identification of the typical cutaneous signs is important to initiate adequate medical care. Several differential diagnoses must be excluded. Treatments should include appropriate pain management, local wound pain, daily dialysis, intravenous sodium thiosulfate treatment, hyperbaric oxygenotherapy, thigh control of calcium-phosphate metabolism and interruption of medications that could contribute to calciphylaxis. Palliative care should be considered in uncontrolled clinical course.

L'artériolopathie urémique calcifiante ou calciphylaxie est une maladie rare mais mortelle associée à l'insuffisance rénale chronique. Son diagnostic n'est pas aisé. La biopsie cutanée est le gold standard pour poser le diagnostic, mais ce geste n'est pas dénué de risque. La reconnaissance des lésions cutanées typiques est importante afin d'initier une prise en charge adéquate. Plusieurs diagnostics différentiels doivent être exclus. La prise en charge de ces patients comprend une intensification de la dialyse, un traitement de thiosulfate de sodium, une antalgie, un soin minutieux des plaies, des séances d'oxygénothérapie hyperbare, une éviction de certains médicaments incriminés et une correction du bilan phosphocalcique. Dans certains cas, la situation clinique ne permet pas une guérison, et des soins palliatifs seront alors proposés.

[Vitamin D and chronic kidney disease: increasing role for an old vitamin]. / Vitamine D et insuffisance rénale chronique: regain d'intérêt pour une vitamine oubliée.

Patients with chronic kidney disease exhibit a high mortality risk that is not fully explained by the classical cardiovascular risk factors. Vitamin D deficiency highly prevalent among CKD patients is independently associated with an increased mortality risk in this population. Advances in the understanding of vitamin D physiology dramatically changed the view on the role of this vitamin in kidney disease. Extra-renal actions on a variety of tissues have been identified. By its cardiovascular effects for instance, correction of vitamin D insufficiency might help to reduce the excess of mortality among patients with chronic kidney disease. This article summarizes the sum of knowledge on the roles of vitamin D in kidney disease. Recommendations on screening and substitution with vitamin D in this high-risk population are then proposed.

[Lithium and chronic kidney disease: a pathology which remains relevant]. / Lithium et atteintes rénales chroniques: un sujet toujours d'actualité.

Lithium continues to be the standard for acute and maintenance treatment of bipolar mood disorders despite the availability of alternative agents. Lithium has a narrow therapeutic index and can result in considerable toxicity. Acute renal intoxication is well-known but chronic kidney disease should be in each doctor's mind. The main manifestations are nephrogenic diabetes insipidus (NDI) and tubulointerstitial nephritis. For NDI, the potassium sparing diuretic amiloride or a thiazide diuretic can improve polyuria. Lithium-induced ESRD in chronic tubulointerstitial nephritis is not uncommon and more prevalent (> 1% among long-term lithium patients) than previously thought. The risk of renal failure may persist even after lithium discontinuation. Additional kidney manifestations of lithium exposure include renal tubular acidosis and hypercalcemia.

[Statins: what is their place in the treatment of chronic kidney insufficiency?]. / Statines: quelle place dans le traitement de l'insuffisance rénale chronique?

Dyslipidemia is highly prevalent in patients with chronic kidney disease (CKD), contributing to their high cardiovascular morbidity/ mortality risk and kidney damage. The lipid profile of patients with CKD commonly shows elevation of triglycerides, accumulation of atherogenic lipoproteins and decrease of HDL cholesterol. Statins are as safe and secure in CKD patients as in the general population. Used as secondary prevention in predialysis patients they seem to reduce cardiovascular mortality, but such beneficence has not been confirmed in dialysis patients. Data are still lacking in primary prevention. Ongoing studies may help to draw more precise recommendations. Meanwhile, we suggest starting lipid lowering drugs as secondary prevention in all patients at all stages of CKD.