Nephrology Dialysis Transplantation最新文献

The autonomic nervous system plays a crucial role in regulating physiological processes and maintaining homeostasis through its two branches: the sympathetic nervous system and the parasympathetic nervous system. Dysregulation of the autonomic system, characterized by increased sympathetic activity and reduced parasympathetic tone, is a common feature in chronic kidney disease (CKD) and cardiovascular disease. This imbalance contributes to a pro-inflammatory state, exacerbating disease progression and increasing the risk for cardiovascular events. The sympathetic system promotes inflammation by releasing catecholamines, which activate adrenergic receptors on immune cells. The parasympathetic system exerts anti-inflammatory effects via the cholinergic anti-inflammatory pathway mediated by the vagus nerve. Targeting the autonomic system to restore the balance between the sympathetic and the parasympathetic components offers promising approaches to reduce inflammation and improve outcomes in CKD and cardiovascular disease. β-Blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers are pharmacological agents that modulate sympathetic activity and have shown anti-inflammatory effects. Lifestyle interventions, such as a healthy diet, physical exercise, mindfulness, and meditation, enhance parasympathetic activity and improve autonomic function. Vagus nerve stimulation has emerged as a promising therapy, demonstrating significant potential in reducing inflammation and improving clinical outcomes in various conditions, including CKD, myocardial infarction, and stroke. Despite mixed results in heart failure trials, vagal nerve stimulation has consistently improved quality-of-life measures. Understanding the mechanisms underlying autonomic system regulation of inflammation can inform the development of novel therapeutic strategies to restore autonomic balance and improve patient outcomes in CKD and cardiovascular disease.

Background and hypothesis: Teclistamab, a novel bispecific monoclonal antibody targeting CD3 and B cell maturation antigen (BCMA), and chimeric antigen receptor T cell (CAR-T) therapy are promising options for treating relapsed/refractory multiple myeloma (MM). However, the rates of acute kidney injury (AKI) associated with teclistamab remain inadequately characterized. This study aims to compare the incidence, severity, and outcomes of AKI between patients receiving teclistamab and CAR-T therapy.

Methods: This was a retrospective study involving 64 patients with relapsed/refractory MM treated with either teclistamab or CAR-T therapy. All patients had previously received at least four lines of chemotherapy before being treated with either teclistamab or CAR-T. The primary outcome was the incidence of AKI, and secondary outcomes included AKI severity, kidney recovery rates, and mortality. Kaplan-Meier estimates for AKI-free survival were calculated, and hazard ratios (HRs) for AKI risk were determined using Cox proportional hazards models.

Results: Sixty-four patients met inclusion criteria for this study (30 received CAR-T and 34 received teclistamab therapy). Among these patients, 14 AKI events occurred in total (22%), with 10 events (29%) in the teclistamab group and four events (13%) in the CAR-T group. AKI-free survival estimates at 180 days after treatment initiation were 68% [95% confidence interval (CI): 53%-87%] for teclistamab patients and 90% (95% CI: 79%-100%) for CAR-T patients. While patients receiving teclistamab were found to have an increased risk of an AKI event compared to those receiving CAR-T therapy, the results were not statistically significant [HR (95% CI): 3.38 (0.93-12.31), P = .065].

Conclusions: This study suggests that patients treated with teclistamab may experience a higher incidence of AKI compared to those receiving CAR-T therapy. However, further research is required to determine whether this increased risk is attributable to disease progression or teclistamab itself. These results highlight the need for close kidney function monitoring in patients receiving teclistamab.

Background and hypothesis: Knowledge regarding access to first kidney transplantation (KT) and subsequent KT in patients commencing kidney replacement therapy (KRT) in childhood is limited.

Methods: Using European Renal Association (ERA) Registry data, we investigated European patients who started KRT below 20 years of age between 1978 and 2019. Access and determinants to first, second, and third KT were assessed using multivariable Cox regression.

Results: Totals of 12 623, 4077, and 1186 patients were included while awaiting first, second, and third KT, at median ages of 13.8 (IQR: 7.5-17.4), 20.9 (IQR: 16.5-26.1), and 26.6 (IQR: 20.3-32.8) years, respectively. During the study period, overall access was 87.8%, 72.7%, and 60.5% for first, second, and third KT, respectively, and median time to each KT was 0.9 (IQR: 0.2-2.1), 1.9 (0.6-4.5), and 2.6 (IQR: 1.0-5.3) years. Younger age at KRT initiation (aHR 0-4 vs. 10-14 years: 0.54; 95%CI: 0.51-0.57) and female sex (HR: 0.94; 95%CI: 0.90-0.98) were associated with lower access to first KT. KT candidates between 15 and 19 years had lower access to first and second KT (aHR: 0.69; 95%CI: 0.66-0.73, and aHR: 0.70; 95%CI: 0.61-0.81) compared to 10-14 year-olds. Compared to CAKUT, glomerulonephritis patients had lower access to KT (aHR: 0.75; 95%CI: 0.71-0.80 for first, aHR: 0.89; 95%CI: 0.81-0.98 for second, and aHR: 0.80; 95%CI: 0.66-0.97 for third KT). Similarly, patients with primary renal diseases with high risk of recurrence, had lower chances of receiving a first and second KT (aHR: 0.80; 95%CI: 0.76-0.85 for first, aHR: 0.86; 95%CI: 0.78-0.95 for second KT). Access to re-transplantation was also higher with previous pre-emptive KT and previous graft survival exceeding 5 years.

Conclusion: Our study highlights KT access disparities particularly for females, the youngest recipients, high-risk age (15-19 years), and diseases with recurrence risk. Notably, pre-emptive transplants and enduring previous grafts offer advantages regarding re-transplantation.

Chronic kidney disease (CKD) is the fastest growing cause of death, expected to become the fifth global cause of death and the third in some countries with long life expectancy, such as Japan and Spain, by 2050. This reflects societal aging, as advancing kidney age is the main risk factor for CKD. The forecasted 140% increase in the death rate from CKD by 2050 is reduced to 33% when adjusted for age. The increasing mortality burden is paralleled by higher personal, healthcare, socio-economic and environmental burdens and the need for kidney replacement therapy to treat kidney failure. To some extent, the higher CKD burden represents the price of success in prolonging longevity by decreasing other causes of death. Now is the time to act to minimize the negative impact of CKD on aging societies through primary prevention and early diagnosis and treatment of CKD. Action aimed at maintaining kidney health and delaying biological kidney aging will contribute to healthy aging, as the kidneys have gerosuppressor functions and CKD has the highest negative impact on body aging among chronic non-communicable diseases. This action should be part of a move towards novel holistic approaches to healthy longevity represented by concepts such as cardiovascular-kidney-metabolic health, geromedicine, gerosuppressors and organ rejuvenation. We discuss a conceptual framework for the present and future of kidney aging and kidney health in the elderly, emphasizing opportunities for intervention that underlie the Japanese Society of Nephrology and European Renal Association call to action on Achieving Kidney Health in Aging/Aged Societies.

Background: Renal red blood cell casts (RBCC) are common in IgA nephropathy (IgAN), but their role in kidney disease progression of patients with IgAN remains unclear.

Methods: In total, 1425 patients in a Peking University First Hospital IgAN (PKU-IgAN) cohort and 279 patients in the TESTING trial were enrolled to test the association between RBCC and kidney outcome. RBCC was defined as positive (+) when at least one cast was identified within the renal tubules by light microscopy. Kidney endpoint was the composite of the first occurrence of a sustained 30% decrease in estimated glomerular filtration rate or end stage kidney disease or death due to kidney disease. Cox regression analysis was used.

Results: In PKU-IgAN, 529 patients (37%) had RBCC; in the TESTING trial, 78 patients (28%) had RBCC. Patients with RBCC had more crescentic lesions, and less segmental sclerosis compared with patients without RBCC. In PKU-IgAN, after a median follow-up of 54 months, 119 patients (22%) with RBCC and 260 patients (29%) without RBCC reached the composite kidney endpoint (P = .009). In multivariable analysis, RBCC was independently associated with composite kidney endpoint [hazard ratios (HR) 0.79; 95% confidence interval (CI) 0.63-0.99; P = .038]. RBCC and immunosuppressive therapy (IST) had an interaction (P = .001). RBCC was independently associated with composite kidney endpoint in patients who received IST (HR 0.56; 95%CI 0.40-0.77; P < .001). In the TESTING trial, after a median follow-up of 57 months, 26 patients (33%) with RBCC, and 96 patients (48%) without RBCC reached the composite kidney endpoint (P = .041). In univariate analysis, RBCC was associated with composite kidney endpoint (HR 0.64; 95%CI 0.42-0.99; P = .047).

Conclusion: Renal RBCC was frequent in IgAN and was associated with a higher incidence of acute active lesions and better renal prognosis, especially in those who received IST, warranting particular attention.

Background: Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, and sodium-glucose cotransporter 2 inhibitors (SGLT2is) both reduce chronic kidney disease (CKD) progression and improve kidney/cardiovascular (CV) outcomes. The CONFIDENCE (COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint) study (NCT05254002; EudraCT 2021-003037-11) hypothesis is that early combination of finerenone and empagliflozin, an SGLT2i, is superior to either drug alone in reducing urine albumin-to-creatinine ratio (UACR) over 6 months.

Methods: CONFIDENCE is an ongoing, fully enrolled, randomized, controlled, double-blind, multicentre phase 2 clinical trial in adults (≥18 years of age) with CKD and type 2 diabetes (T2D), estimated glomerular filtration rate (eGFR) of 30-90 mL/min/1.73 m2 and UACR of ≥100 to <5000 mg/g. Participants taking the clinically maximum tolerated dose of a renin-angiotensin system inhibitor for >1 month at screening were eligible. Participants were randomized 1:1:1 to once-daily finerenone plus empagliflozin, finerenone plus placebo, or empagliflozin plus placebo; doses were 10 mg once daily for empagliflozin and 10 or 20 mg once daily for finerenone, depending on eGFR at baseline. Randomization was stratified by eGFR (<60 or ≥60 mL/min/1.73 m2) and UACR (≤850 or >850 mg/g). The primary efficacy outcome is the relative change in UACR from baseline at Day 180.

Results: There were 818 participants randomized across 143 sites from 14 countries between July 2022 and August 2024. Mean (standard deviation) eGFR was 54.2 (17.1) mL/min/1.73 m2. Median (interquartile range) UACR was 583 (292, 1140) mg/g. Mean (standard deviation) HbA1c was 7.3 (1.2)%. Mean systolic/diastolic blood pressure was 135.2/77.3 mmHg. Glucagon-like peptide-1 receptor agonists and insulin were used by 182 (23%) and 313 (39%) participants, respectively. Atherosclerotic CV disease, diabetic retinopathy and a history of heart failure were present in 223 (28%), 126 (16%) and 30 (4%) participants, respectively.

Conclusions: The CONFIDENCE trial enrolled a diverse population with CKD and T2D, and will determine the impact of simultaneous initiation of combination finerenone and an SGLT2i versus individual therapy on potentially mitigating the progression of CKD in people with T2D.

Trial registration number: ClinicalTrials.gov NCT05254002; EudraCT 2021-003037-11.