Background: Patients with kidney disease may have concurrent hypertension and infection. Dihydropyridine calcium-channel blockers (CCB) are the most popular class of antihypertensive drugs used in clinical settings and can be metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4). Voriconazole is a commonly used antifungal treatment and a CYP3A4-inhibitor. Insufficient attention to drug interactions from the concomitant use of CCB and voriconazole may result in serious adverse reactions. Case presentation: Here, we report a patient with acute kidney injury on stable anti-neutrophil cytoplasm antibody associated vasculitis who developed hyperkalemia resulting in sinus arrest with junctional escape rhythm attributed to drug interactions of CCB with voriconazole. This is a very rarely reported case and may be an under-recognized complication. After continuous renal replacement therapy and changing the anti-hypertensive drugs, symptoms, and laboratory abnormalities of the patient fully recovered. Conclusions: This case warns us of severe consequences of drug interactions. Co-prescription of CYP3A4-inhibitors with calcium-channel blockers increases the risk of hypotension and acute kidney injury, which may further induce hyperkalemia and arrhythmia.

Renal anemia is one of the most common complications in dialysis patients. The shortened red blood cell (RBC) lifespan is an important mechanism of renal anemia. This study aims to investigate the RBC lifespan and its influencing factors in anemic dialysis patients. Prevalent patients on maintenance hemodialysis or peritoneal dialysis, treated with anti-anemia therapy including recombinant human erythropoietin (rHuEPO) or roxadustat for more than 4 months were enrolled. RBC lifespan was measured by the RBC lifespan analyzer RBCS-01A depended on Levitt's carbon monoxide (CO) breath test. Participants were primarily divided into low and high RBC lifespan groups by the average value. A total of 187 patients were included in this study. The average RBC lifespan was 65.2 ± 28.55 days. The logistic regression analysis indicated treating with roxadustat rather than rHuEPO [OR 2.94, 95% CI (1.46, 5.95), p < 0.01], male [OR 2.15, 95% CI (1.08, 4.29), p = 0.03], higher body mass index (BMI) [OR 1.17, 95% CI (1.07, 1.27), p < 0.01], and higher total iron-binding capacity (TIBC) [OR 1.04, 95% CI (1.01, 1.06), p = 0.01] were independent risk factors for the shorten of RBC lifespan. While higher adjusted calcium [OR 0.14, 95% CI (0.03, 0.70), p = 0.02] and older age [OR 0.96, 95% CI (0.94, 0.99), p = 0.01] were independent protective factors. This study demonstrated that independent risk factors contributing to this reduction in RBC lifespan include male, elevated BMI, increased TIBC, and decreased adjusted calcium levels. Additionally, the type of anti-anemia therapy administered appears to have an impact on RBC lifespan.

Background: The timing of when to initiate dialysis for progressive chronic kidney disease (CKD) patients has not been well established. There has been a strong trend for early dialysis initiation for these patients over the past decades. However, the perceived survival advantage of early dialysis has been questioned by a series of recent observational studies. The only randomized controlled trial (RCT) research on this issue found the all-cause mortality, comorbidities, and quality of life showed no difference between early and late dialysis starters. To better understand optimal timing for dialysis initiation, our research will evaluate the efficacy and safety of deferred dialysis initiation in a large Chinese population. Methods: The trial adopts a multicenter, cluster randomized, single-blind (outcomes assessor), and endpoint-driven design. Eligible participants are 18–80 years old, in stable CKD stages 4–5 (eGFR > 7 ml/min /1.73 m²), and with good heart function (NYHA grade I or II). Participants will be randomized into a routine or deferred dialysis group. The reference eGFR at initiating dialysis for asymptomatic patients is 7 ml/min /1.73 m² (routine dialysis group) and 5 ml/min/1.73 m² or less (deferred dialysis group) in each group. The primary endpoint will be the difference of all-cause mortality and acute nonfatal cerebro-cardiovascular events between the two groups. The secondary outcomes include hospitalization rate and other safety indices. The primary and secondary outcomes will be analyzed by appropriate statistical methods. Discussion: This study protocol represents a large, cluster randomized study evaluating deferred and routine dialysis intervention for an advanced CKD population. The reference eGFR to initiate dialysis for both treatment groups is targeted at less than 7 ml/min/1.73m². With this design, we aim to eliminate lead-time and survivor bias and avoid selection bias and confounding factors. We acknowledge that the study has limitations. Even so, given the low-targeted eGFR values of both arms, this study still has potential economic, health, and scientific implications. This research is unique in that such a low targeted eGFR value has never been studied in a clinical trial. Trial registration: The trial has been approved by ClinicalTrials.gov (Trial registration ID NCT02423655). The date of registration was April 22, 2015.

Bone remodeling relies on a balance between osteoclast-mediated resorption and osteoblast-mediated formation. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, promotes osteoblast differentiation but its effects on osteoclasts remain unclear. This study investigated roxadustat’s impact on osteoclast differentiation and function in vitro using primary murine bone marrow-derived mononuclear cells differentiated with M-CSF and RANKL. Cell viability, TRAP staining, bone resorption assays, RNA-seq, flow cytometry, immunofluorescence, Western blot for p27, and rescue experiments with the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor abemaciclib were performed. Roxadustat suppressed osteoclast differentiation and resorption without cytotoxicity in a concentration-dependent manner. RNA-seq revealed enrichment of cell cycle pathways; although differentiation was inhibited, roxadustat paradoxically promoted osteoclast precursor proliferation, evidenced by increased Ki67 and decreased p27 expression. The inhibitory effects on osteoclastogenesis and resorption were partially reversed by abemaciclib. Given that terminal differentiation typically requires cell cycle exit, these findings suggest that roxadustat may inhibit osteoclast differentiation at least in part by disrupting this process, promoting precursor proliferation, and downregulating p27. Together with its known anabolic effects on osteoblasts, roxadustat might have dual therapeutic potential for bone disorders with renal anemia, such as osteoporosis in chronic kidney disease.