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Background This study evaluates the effects of active (1α-hydroxylated) vitamin D (AVD) therapy on hypercalcaemia in patients with non-dialysis chronic kidney disease (ND-CKD) and secondary hyperparathyroidism (SHPT). Methods A systematic search of the PubMed, Embase and Cochrane Library databases (up to 14 May 2020) was performed to identify randomized, placebo-controlled trials of single-agent, oral AVD therapies in adults with ND-CKD and SHPT. Only studies with ≥30 participants per arm and ≥6 weeks in duration were eligible. The outcome of interest was the number of subjects with an episode of hypercalcaemia. A meta-analysis of eligible studies was conducted using Comprehensive Meta-Analysis software (version 3.0). Results Six studies (five evaluating paricalcitol, one evaluating alfacalcidol) involving 799 patients were identified. Treatment durations ranged from 16 weeks to 2 years. The weekly doses of paricalcitol administered were 7 (three studies) and 14 µg (two studies); the weekly dose of alfacalcidol was 1.75–7.0 µg. Across all studies, rates of hypercalcaemia were 1.1–43.3% with AVD versus 0–3.4% with placebo. Meta-analysis of the six studies showed that AVD was associated with a 6.6-fold greater probability of hypercalcaemia versus placebo (odds ratio: 6.63, 95% confidence interval: 2.37, 18.55; P < 0.001). Two separate sensitivity analyses (one excluded a study identified as having a high risk of bias; the second excluded two studies that accounted for a large proportion of observed hypercalcaemia events) indicated the primary meta-analysis findings were robust. Conclusions Compared with placebo, AVD significantly increased the risk of hypercalcaemia among ND-CKD patients with SHPT. [ABSTRACT FROM AUTHOR] more...

Background Secondary hyperparathyroidism (SHPT) is a common and major complication in chronic kidney disease (CKD), reflecting the increase of parathyroid hormone (PTH) in response to reduced vitamin D signalling and hypocalcaemia. This meta-analysis evaluated the impact of nutritional vitamin D (NVD) (cholecalciferol or ergocalciferol) on SHPT-related biomarkers. Methods A systematic literature search was performed in PubMed to identify relevant randomized control trials to be included in the meta-analysis. Fixed- and random-effects models were used to pool study-level results. Effects were studied within NVD study arms and relative to control groups (placebo/no treatment); the former in order to identify the effect of actively altering biomarkers levels. Results Reductions in PTH from supplementation with NVD were small when observed within the NVD study arms (pooled reduction: 10.5 pg/mL) and larger when compared with placebo/no treatment (pooled reduction: 49.7 pg/mL). NVD supplementation increased levels of 25-hydroxyvitamin D [25(OH)D] in both analyses (increase within NVD study arm: 20.6 ng/mL, increase versus placebo/no treatment: 26.9 ng/mL). While small and statistically non-significant changes in phosphate and fibroblast growth factor 23 were observed, NVD supplementation caused calcium levels to increase when compared with placebo/no treatment (increase: 0.23 mg/dL). Conclusions Our results suggest that supplementation with NVD can be used to increase 25(OH)D to a certain extent, while the potential of NVD to actively reduce PTH in non-dialysis-CKD patients with SHPT is limited. [ABSTRACT FROM AUTHOR] more...

Background Optimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation. Methods We studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4–6 (2009–18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9–12 months on HD. Results The 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9–12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150–300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9–12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation. Conclusions Increased PTH before HD start predicted a higher PTH level 9–12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients. [ABSTRACT FROM AUTHOR] more...

Deficient sensorimotor gating as indexed by prepulse inhibition (PPI) of the startle response has been reported repeatedly in patients suffering from schizophrenia. According to the widely accepted “protective hypothesis,” PPI reflects the protection of ongoing information processing against interference by other stimuli. Alternatively, it has been proposed that PPI might be regulated by startle reflex circuit excitability. In the present study, we evaluated these 2 conceptually divergent approaches underlying the regulation of PPI. To this end, we assessed sensorimotor gating as indexed by PPI, the reactivity to the prepulse-alone stimulus indexed as prepulse-elicited reactivity (PPER), and acoustic blink reflex excitability in terms of paired pulse suppression (PPS) within a single recording session in 13 unmedicated and 24 medicated (11 first break) schizophrenia patients in comparison to 43 healthy control subjects. The results showed that PPI was significantly reduced in unmedicated, but not in medicated schizophrenia patients. Furthermore, unmedicated patients could be distinguished from the medicated patients and control subjects in terms of PPER. In contrast to PPI, PPS did not differ between patients and control subjects. These findings are in line with the “protective hypothesis” of PPI and indicate that reduced sensorimotor gating in schizophrenia patients might be based on a reduced perception and/or processing of the prepulse stimulus. The extent to which PPER may or may not be causally associated with sensorimotor gating in schizophrenia has to be further investigated in human and animal studies. [ABSTRACT FROM PUBLISHER] more...