Effect modification of polypharmacy on incident frailty by chronic kidney disease in older adults.

BACKGROUND: Frailty and polypharmacy are common conditions in older adults, especially in those with chronic kidney disease (CKD). Therefore, we analyzed the association of polypharmacy and incident frailty and the effect modification by CKD in very old adults. METHODS: In non-frail individuals within the Berlin Initiative (cohort) Study, polypharmacy (≥ 5 medications) was assessed according to multiple definitions based on the number of regular and on demand prescription and over the counter drugs, as well as vitamins and supplements. CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73m2 and/or an albumin-creatinine ratio ≥ 30 mg/g. Incident frailty was assessed at follow-up using Fried criteria. Logistic regression was applied to assess (1) the association of different polypharmacy definitions with incident frailty and (2) effect modification by CKD. RESULTS: In this cohort study, out of 757 non-frail participants (mean age 82.9 years, 52% female, 74% CKD), 298 (39%) participants reported polypharmacy. Over the observation period of 2.1 years, 105 became frail. Individuals with polypharmacy had 1.96 adjusted odds (95% confidence interval (CI): 1.20-3.19) of becoming frail compared to participants without polypharmacy. The effect of polypharmacy on incident frailty was modified by CKD on the additive scale (relative excess risk due to interaction: 1.56; 95% CI 0.01-3.12). CONCLUSIONS: This study demonstrates an association of polypharmacy and incident frailty and suggests strong evidence for an effect modification of CKD on polypharmacy and incident frailty. Revision of prescriptions could be a target strategy to prevent frailty occurrence, especially in older adults with CKD.

Bicarbonate Supplement Restores Urinary Klotho Excretion in Chronic Kidney Disease: A Pilot Study.

OBJECTIVE: We tested the hypothesis that correcting acidosis may improve urinary Klotho excretion and serum α-Klotho. DESIGN: This is a prospective, interventional, nonrandomized, open-label trial study. In this study setting, metabolic acidosis is commonly observed during chronic kidney disease (CKD). We reported a positive relationship between serum bicarbonate (Sbicar) and serum α-Klotho in these patients. SUBJECTS: The study involved 20 patients with a known kidney disease referred for renal checkup. Inclusion criteria were age ≥ 18 years, CKD stage 3-5 non dialysis, Sbicar < 22 mmol/L, and not receiving bicarbonate supplementation. INTERVENTION: Patients were then prescribed 1 g of oral sodium bicarbonate 3 times per day for 4 weeks. MAIN OUTCOME MEASURE: Patients were evaluated at two and 4 weeks by blood and urine measurements. RESULTS: Mean serum Klotho was 615 ± 287 pg/mL, and mean serum Sbicar was 19.3 ± 1.7 mmol/L at baseline. Sbicar increased from baseline at two (23.9 ± 2.9 mmol/L, P < .001) and 4 weeks (23.4 ± 1.9 mmol/L, P < .001). There was no change in serum Klotho at two (630 ± 333 mmol/L) and 4 weeks (632 ± 285 mmol/L). By contrast, urine Klotho/creatinine ratio, which was very low at baseline (34.6 ± 31.6 pg/mmoL), increased by 320% at two weeks (P < .005) and by 280% at 4 weeks (P < .01). CONCLUSIONS: Correcting acidosis by oral administration of sodium bicarbonate rapidly increases the urine excretion of soluble α-Klotho in CKD patients. However, a 4-week bicarbonate treatment was not able to increase serum α-Klotho. A longer study may confirm this pilot observation and increase serum Klotho, which has been shown to exert a protective cardiovascular effect during CKD.

[Hypercalcemia and inactive mutation of CYP24A1. Case-study and literature review]. / Hypercalcémie par mutation inactivatrice du CYP24A1. Étude d'un cas et revue de la littérature.

We present the case of a family whose members have high levels of serum calcium (hypercalcaemia) by loss of function of the enzyme vitamin D 24-hydroxylase due to bi-allelic mutations in the CYP24A1 gene: c.443 T>C (p.Leu148Pro) and c.1187 G>A (p.Arg396Gln). 24-VITD hydroxylase is a key player in regulating the circulating calcitriol, its tissue concentration and its biological effects. Transmission is recessive. The estimated prevalence of stones in the affected subjects is estimated between 10 and 15%. The loss of peripheral catabolism of vitamin D metabolites in patients with an inactivating mutation of CYP24A1 is responsible for persistent high levels of 1,25-dihydroxyvitamin D especially after sun exposure and a charge of native vitamin D. Although there are currently no recommendations (French review) on this subject, this disease should be suspected in association with recurrent calcium stones with nephrocalcinosis, and a calcitriol-dependent hypercalcaemia with adapted low parathyroid hormone levels. Resistance to corticosteroid therapy distinguishes it from other calcitriol-dependent hypercalcemia. A ratio of 25-hydroxyvitamin D/24.25 hydroxyvitamin D>50, is in favor of hypercalcemia with vitamin D deficiency 24-hydroxylase. Genetic analysis of CYP24A1 should be performed at the second step. The current therapeutic management includes the restriction native vitamin D supplementation and the limitation of sun exposure. Biological monitoring will be based on serum calcium control and modulation of parathyroid hormone concentrations.