Clinical Kidney Journal最新文献

[This corrects the article DOI: 10.1093/ckj/sfae199.][This corrects the article DOI: 10.1093/ckj/sfae236.].

Background: After the risk of drug-induced liver injury was detected during tolvaptan clinical development for the treatment of autosomal dominant polycystic kidney disease (ADPKD), a post-marketing pharmacovigilance study was required for European Union regulatory approval.

Methods: This is an interim analysis from a prospective, observational study enrolling patients prescribed tolvaptan for ADPKD in routine clinical practice. Data were obtained through physician records collected during regular care. Per the prescribing label, liver transaminases were to be monitored monthly for the first 18 months of treatment and once every 3 months thereafter. Patients and physicians were required to report adverse events suggestive of serious and potentially fatal liver injury. Data collection was from October 2016 to April 2022.

Results: Of 2074 patients (median follow-up 528 days), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 times the upper limit of normal (ULN) were reported in 75 (3.6%) patients. At data cut-off, the enzyme elevations were confirmed for 65 patients. Among the 65 confirmed patients, in addition to transaminase elevations, there were 69 adverse events suggestive of liver injury. Tolvaptan was interrupted or withdrawn in 59/65 (90.8%) participants with confirmed ALT or AST ≥3 times the ULN, with most transaminase elevations and adverse events resolved or resolving at data cut-off. No liver enzyme elevations met laboratory criteria for Hy's law cases.

Conclusions: Transaminase elevations occurred post-marketing in a similar proportion of patients as reported in clinical trials (4.4-5.6%). Regular monitoring per label facilitates prompt detection of liver adverse events and intervention to mitigate the risk of severe injury.

Background: Patients with cardiovascular disease (CVD), diabetes mellitus (DM) and chronic kidney disease (CKD) often experience fragmented care, which negatively impacts outcomes and health-related quality of life (HRQoL). This study assessed whether multidisciplinary, person-centred care at an integrated clinic improves clinical outcomes and HRQoL.

Methods: This prospective, open, blinded-endpoint trial (CareHND; NCT03362983) included 131 patients with CVD, DM and CKD stages 3-4, most of whom were enrolled during or shortly after acute hospitalization. The intervention group received person-centred care from cardiologists, nephrologists, endocrinologists and specialist nurses at an integrated clinic; the control group received traditional care from separate specialists. Primary disease progression outcome was the composite of major adverse renal and cardiovascular events (MARCE) including death, heart failure (HF) readmission, myocardial infarction, percutaneous coronary intervention/coronary artery bypass graft, acute or end-stage kidney failure, or transient ischaemic attack/stroke at 2 years. Co-primary person-centred outcomes was self-reported HRQoL by RAND-36.

Results: In a pre-specified interim analysis, patients randomized to integrated care had lower estimated glomerular filtration rate and higher NT-proBNP (N-terminal pro brain natriuretic peptide) than traditional care. Follow-up ranged from 2.0 to 5.7 years. Kaplan-Meier analysis showed no difference in MARCE between groups. Cox-regression adjusting for baseline differences, indicated a trend towards reduced HF hospitalizations for integrated care (hazard ratio 0.53; confidence interval 0.28-1.01; P = .054). Integrated care improved role physical and social function scores, and self-rated health (P = .021, P = .019 and P = .011, respectively).

Conclusions: Integrated care improved several dimensions of HRQoL but did not improve MARCE compared with traditional care in this small trial. We observed a trend towards reduced HF hospitalizations. Overall, integrated care presents a promising alternative.

Background: Although the kidney failure risk equation (KFRE), a well-known predictive model for predicting dialysis dependency, is useful, it remains unclear whether the addition of biomarker changes to the KFRE model in patients with an estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m² will improve its predictive value.

Methods: We retrospectively identified adults with eGFR <30 ml/min/1.73 m² without dialysis dependency, and available health checkup data for two successive years using a large Japanese claims database (DeSC, Tokyo, Japan). We dichotomized the entire population into a training set (50%) and a validation set (the other half). To assess the incremental value in the predictive ability for dialysis dependency by the addition of changes in eGFR and proteinuria, we calculated the difference in the C-statistics and net reclassification index (NRI).

Results: We identified 4499 individuals and observed 422 individuals (incidence of 45.2 per 1000 person-years) who developed dialysis dependency during the observation period (9343 person-years). Adding biomarker changes to the KFRE model improved C-statistics from 0.862 to 0.921, with an improvement of 0.060 (95% confidence intervals (CI) of 0.043-0.076, P < .001). The corresponding NRI was 0.773 (95% CI: 0.637-0.908), with an NRI for events of 0.544 (95% CI of 0.415-0.672) and NRI for non-events of 0.229 (95% CI of 0.186-0.272).

Conclusions: The KFRE model was improved by incorporating yearly changes in its components. The added information may help clinicians identify high-risk individuals and improve their care.

Background: Sarcopenia is a common and serious problem in patients receiving peritoneal dialysis (PD). Lean tissue mass (LTM) by bioimpedance spectrometry is a reasonably accurate method for measuring muscle mass. Fat-free edema-free body mass (FEBM) as determined by the creatinine kinetics method is a traditional method but evidence to support its use is limited.

Methods: We studied 198 new PD patients. Their serial LTM and FEBM were reviewed and compared by the Bland and Altman method. Multi-variable regression model was used to determine factors associated with the disparity between the two methods.

Results: There was a significant but moderate correlation between LTM and FEBM (r = 0.309, P < .0001). LTM was consistently higher than FEBM, with an average difference 13.98 kg (95% confidence interval -5.90 to 33.86 kg), and the difference strongly correlated with LTM (r = 0.781, P < .0001). By multivariable linear regression analysis, LTM and residual renal function were independent predictors of the LTM-FEBM difference. Where the measurements were repeated in 12 months, there was no significant correlation between ∆LTM and ∆FEBM (r = -0.031, P = .799).

Conclusion: There is a significant difference between LTM and FFBM. This discrepancy correlated with LTM and residual renal function, highlighting the limitations of FFBM in assessing skeletal muscle mass.

[This corrects the article DOI: 10.1093/ckj/sfad281.].

Background: The effectiveness of tixagevimab-cilgavimab as pre-exposure prophylaxis (PrEP) against breakthrough coronavirus disease 2019 (COVID-19) in dialysis patients remains uncertain due to limited data.

Methods: In this multicenter prospective study, we enrolled vaccinated dialysis patients and divided them into two groups: a tixagevimab-cilgavimab group (received a 150 mg/150 mg intramuscular dose of tixagevimab-cilgavimab) and a control group (age-matched patients not receiving tixagevimab-cilgavimab). The primary outcome was the breakthrough COVID-19 rate at 6 months, whereas secondary outcomes included COVID-19-related hospitalization, intensive care unit admission, endotracheal intubation and mortality. The safety of tixagevimab-cilgavimab was assessed.

Results: Two hundred participants were enrolled, with equal numbers in each group (n = 100 each). Baseline characteristics were comparable between groups, except for a higher number of COVID-19 vaccine doses in the tixagevimab-cilgavimab group [median (IQR) 4 (3-5) vs. 3 (3-4); P = .01]. At 6 months, the breakthrough COVID-19 rates were comparable between the tixagevimab-cilgavimab (17%) and control (15%) groups (P = .66). However, the median (IQR) time to diagnosis of breakthrough infections tended to be longer in the tixagevimab-cilgavimab group [4.49 (2.81-4.98) vs 1.96 (1.65-2.91) months; P = .08]. Tixagevimab-cilgavimab significantly reduced COVID-19-related hospitalization rates (5.9% vs 40.0%; P = .02) among participants with breakthrough infections. All tixagevimab-cilgavimab-related adverse events were mild.

Conclusion: The use of tixagevimab-cilgavimab as PrEP in vaccinated dialysis patients during the Omicron surge did not prevent breakthrough infections but significantly reduced COVID-19-related hospitalizations. Further research should prioritize alternative strategies.

Background: Published studies have suggested a link between chronic kidney disease (CKD) and sleep disorders, although the exact nature of this association has not been uniformly described. Clarifying this relationship may facilitate evidence-based interventions that address the interplay between these disease entities. Such interventions could prevent obstructive sleep apnea (OSA) from worsening CKD and improve the quality of life for CKD patients by reducing the risk of developing OSA. Therefore, the objective of this meta-analysis is to assess the bidirectional association between sleep disorders and CKD.

Methods: Following a PROSPERO-registered protocol, three blinded reviewers conducted a systematic review of the Medline/PubMed, Embase, Cochrane Library and Cumulative Index of Nursing and Allied Health (CINAHL) databases for observational studies pertaining to the relationship between sleep disorders and CKD. A meta-analysis was conducted in risk ratios (RRs).

Results: From 63 studies (26 777 524 patients), OSA [RR 1.68; 95% confidence interval (CI) 1.45 to 1.93], albuminuria (RR 1.54; 95% CI 1.18 to 1.99), restless leg syndrome (RLS) (RR 1.88; 95% CI 1.48 to 2.38) and insomnia (RR 1.24; 95% CI 1.01 to 1.54) were significantly associated with CKD. There was a significant association between OSA (RR 1.77; 95% CI 1.56 to 2.01) with incident CKD. There was a significant association of OSA (RR 1.74; 95% CI 1.55 to 1.96), RLS (RR 1.73; 95% CI 1.32 to 2.25) and insomnia (RR 1.14; 95% CI 1.03 to 1.27) in patients with CKD compared with healthy controls. CKD was also significantly associated with incident OSA (RR 1.60; 95% CI 1.35 to 1.89).

Conclusion: The bidirectional associations of obstructive sleep apnea with CKD remained consistent across different stages of CKD, modes of diagnosis of sleep disorder and geographical region. A bidirectional association was observed between CKD and obstructive sleep apnea, RLS and insomnia. The treatment of sleep disorders may reduce the risk of CKD, and vice versa.

[This corrects the article DOI: 10.1093/ckj/sfae194.].