American Journal of Nephrology最新文献

Introduction: Rituximab has become the first-line therapy for patients with membranous nephropathy (MN). However, approximately 30-40% of patients with MN do not respond to rituximab. We presented our single-center experience of treating rituximab-refractory MN with obinutuzumab which is a humanized and glycoengineered type II anti-CD20 monoclonal antibody.

Methods: Seventeen patients with rituximab-refractory phospholipase A₂ receptor (PLA₂R)-associated MN who received obinutuzumab at the First Affiliated Hospital of Xi'an Jiaotong University were included in this case series study. Clinical and laboratory parameters were evaluated at presentation, before and after obinutuzumab administration.

Results: Of all patients with an average age of 49.7 ± 13.7 years, 11 (64.7%) patients were men. The median disease duration was 12 (12, 42) months. At presentation, the proteinuria and serum albumin levels were 7.51 ± 3.55 g/day and 22.1 ± 3.6 g/L, respectively. The mean estimated glomerular filtration rate level was 103.5 ± 12.9 mL/min/1.73 m2, and the patients had a baseline anti-PLA₂R level of 183.2 ± 92.9 RU/mL. At obinutuzumab administration, proteinuria and albumin levels were still consistent with nephrotic syndrome. After a median follow-up of 12.6 ± 5.0 months, complete remission was achieved in 9 (52.9%) and partial remission was achieved in 6 (41.2%) cases. Of the patients who achieved remission, the median remission time was 4.4 (4.0, 6.0) months. At 6 months, 12 (70.6%) patients achieved remission and 11 of 12 patients with available PLA₂R measurements reached immunological remission.

Conclusion: Obinutuzumab may represent an attractive alternative therapy in rituximab-refractory patients. Larger prospective studies are needed to validate these findings.

Introduction: Vaccination rates for influenza and COVID-19 remain low among people with chronic kidney disease (CKD). Nephrology care offers an opportunity to boost vaccination rates. Understanding provider perceptions can be key to developing effective intervention programs.

Methods: We conducted a nationwide survey among nephrology care providers. In a questionnaire, we assessed the providers' agreement with potential barriers to recommending influenza and COVID-19 vaccines and perceptions of selected vaccination programs on their acceptability, appropriateness, and feasibility.

Results: Between February and June 2023, 312 providers responded to the survey. Most providers agreed that there is sufficient evidence for influenza vaccines (270/311, 86.8%) and that vaccines reduce the risk of serious complications of influenza (277/310, 89.4%). However, 40/312 (12.8%) felt that recommending influenza vaccines is less important than other issues they must address. By profession, more physicians agreed with the evidence (112/123 or 91.1% vs. 39/49 or 79.5% for NPs and 83/101 or 82.2% for RNs, p = 0.007) than nurse practitioners (NPs) or nurses (RNs). The most perceived barrier was lack of self-efficacy: 95/311 (30.5%) felt that many patients will not get vaccinated even if they recommend it. Similar responses were seen for COVID-19 vaccines. Regarding vaccination programs, 209/235 (88.9%), 197/224 (87.9%), and 183/222 (82.4%) providers considered provider reminders acceptable, appropriate, and feasible. 209/239 (87.4%), 198/226 (87.6%), and 187/224 (83.5%) did so for standing orders. Onsite/walk-in vaccinations were viewed as acceptable by 192/242 (79.3%) but less feasible (137/222 or 61.7%). Fewer than 33% of providers perceived patient incentives as acceptable, appropriate, or feasible.

Conclusions: Most nephrology care providers believe that influenza and COVID-19 vaccinations offer evidence-based benefits, with slightly higher belief among physicians compared to NPs or RNs. However, important barriers to vaccination remain. Standing orders, provider reminders, and onsite/walk-in vaccination are favorably perceived by providers.

Introduction: Patients with end-stage kidney disease develop cognitive impairment due to comorbidities and dialysis dependence. Among community-dwelling older adults, cognitive (CT) and exercise training (ET) are promising interventions to preserve cognition; these interventions may be tailored for adults undergoing in-center hemodialysis.

Methods: Adult (≥18 years) English-speaking patients undergoing hemodialysis (within 3 months to 3 years of initiation) were enrolled in a 2 × 2 factorial randomized controlled trial: Interventions Made to Preserve Cognitive Function Trial (IMPCT). Participants (n = 121) were block-randomized (September, 2018-February, 2023) into 4 arms: control (SC) (n = 26), intradialytic web-based CT (n = 31), ET using foot peddler (n = 29), and combined CT+ET (n = 35). Participants underwent assessments at baseline and 3 months for executive function, global cognitive function, clinical outcomes, and patient-centered outcomes. We estimated 3-month executive function change (primary outcome) and secondary outcomes using linear regression.

Results: There were no differences in 3-month executive function change by arm. Participants exhibited improvement in 3-month global cognitive function in CT+ET arm (Montreal Cognitive Assessment score difference = 2.1, 95% CI: 0.4-3.9), and self-reported 3-month improvement in perceived health change (score difference = 0.8, 95% CI: 0.2-1.4) in ET arm.

Conclusion: Clinicians may encourage CT+ET for hemodialysis patients to improve short-term global cognitive function and perceived health. The long-term benefits of these interventions warrant further study.

Introduction: Serum concentrations of 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D) decline as chronic kidney disease (CKD) advances, becoming insufficient without effective vitamin D repletion and driving onset of secondary hyperparathyroidism (SHPT). Randomized controlled trials (RCTs) in non-dialysis CKD patients have established that extended-release calcifediol (ERC) effectively raises 25D and 1,25D and reduces elevated intact parathyroid hormone (iPTH) despite the progressive loss of renal cytochrome P450 25D-1α-hydroxylase (CYP27B1), suggesting its potential usefulness in treating SHPT in end-stage kidney disease (ESKD).

Methods: This pilot RCT explored the safety and efficacy of oral ERC to raise serum total 25D to ≥50 ng/mL, normalize circulating 1,25D, and reduce elevated iPTH in ESKD patients requiring regular hemodialysis (HD). Forty-four adults from 13 US clinics requiring HD three times per week were washed out from iPTH-lowering therapies and randomized 3:1 to 26 weeks of treatment with ERC (300 µg/HD) or placebo. Participants had a mean age of 56.4 ± 11.6 years, body mass index of 32.7 ± 8.1 kg/m2, 46% were female, 68% black, 30% white, and 24% Hispanic. At randomization, iPTH had to be 300 to <1,200 pg/mL, 25D <50 ng/mL, corrected serum calcium <9.8 mg/dL, and phosphorus <6.5 mg/dL. These parameters were monitored weekly or biweekly and 1,25D quarterly.

Results: Mean (±SE) serum total 25D rose with ERC treatment from 24.1 ± 1.7 ng/mL at baseline (BL) to steady-state levels of 157.7 ± 10.4 (p < 0.001) after 12 weeks, with all individual levels exceeding 50 ng/mL but varying inversely with body weight. Serum 25D levels declined with placebo treatment from 36.0 ± 5.3 to 30.6 ± 5.5 ng/mL. Mean 1,25D rose from 9.4 ± 1.2 to 50.7 ± 7.8 pg/mL (p < 0.001) with ERC and concentrations surpassed 19.9 pg/mL (lower limit of normal) in 93% of participants. Mean iPTH increased 19.8 ± 10.6% from BL with placebo (497.6 ± 69.2 to 593.1 ± 95.1 pg/mL) but decreased 1.7 ± 4.7% (p < 0.05) with ERC (530.4 ± 29.4 to 529.6 ± 43.7 pg/mL). A strong correlation was observed with ERC treatment between serum 1,25D and 25D (R2 = 0.8248; p < 0.001) indicating that, on average, 1,25D normalized as 25D reached ≥50 ng/mL. Increases in mean serum calcium or phosphorus, episodes of hypercalcemia, or treatment-emergent adverse events were not observed with ERC treatment.

Conclusion: ERC safely raised serum total 25D, normalized low serum 1,25D, and stabilized elevated plasma iPTH in this pilot placebo-controlled RCT involving ESKD patients requiring regular HD. The observed increases in 1,25D indicated that ERC restored adequate endogenous vitamin D hormone production via substrate-driven conversion to calcitriol in extrarenal tissues expressing CYP27B1, thereby preventing further SHPT progression.

Introduction: Kidney dysfunction (KD) is a major metabolic risk factor for cardiovascular disease (CVD) and has been playing an increasingly significant role in the global burden of disease. However, there is still a lack of comprehensive, long-term, and systematic research assessing the global burden of CVD attributable to KD.

Methods: Using data from the Global Burden of Disease (GBD) 2021 database, we extracted burden indicators related to KD-associated CVD, including the number of deaths, disability-adjusted life years (DALYs), years of life lost (YLLs), years lived with disability (YLDs), and their corresponding age-standardized rates, and evaluated annual trends using estimated annual percentage change. We performed decomposition analysis to identify three main drivers of burden changes-population, aging, and epidemiological change; and applied an autoregressive integrated moving average model to project future trends from 2022 to 2050.

Results: From 1990 to 2021, the global absolute numbers of deaths, DALYs, YLLs, and YLDs caused by KD-related CVD increased, while the corresponding age-standardized rates generally declined. Males exhibited a higher disease burden compared to females, and the elderly population, particularly those aged 75-84 years, represented the primary burden group. Middle-SDI countries experienced the highest burden, while inequality remained pronounced in low-SDI countries. Decomposition analysis revealed that, however, the increase in burden was primarily driven by population and aging, epidemiological change showed improvement. Forecasting results indicated that by 2050, the total number of cases will continue to rise, age-standardized rates will keep declining, but the YLD among females is expected to increase.

Conclusion: The burden of CVD attributable to KD is expected to continue rising in the future, characterized by increasing absolute numbers and declining age-standardized rates. This trend suggests that stratified prevention strategies may be needed across countries with varying SDI levels, with particular attention to older populations and integrated heart-kidney disease management to reduce the global burden of the disease.

Introduction: Time in target range of systolic blood pressure (SBP-TTR) is the percentage of time that the SBP remains within 110-130 mm Hg. The association between the SBP-TTR and clinical outcomes in patients with chronic kidney disease (CKD) remains unclear. We evaluated the risks of cardiovascular disease (CVD), all-cause mortality, and renal events across the SBP-TTR groups.

Methods: Overall, 193,289 patients with CKD who underwent at least two health checkups between 2012 and 2015 were selected from the Korean National Health Insurance Database. The patients were categorized into three categories based on their SBP-TTR levels: 76-100%, 26-75%, and 0-25%. The primary outcome was CVD risk and the secondary outcomes were all-cause mortality and progression to end-stage kidney disease (ESKD) according to SBP-TTR using Cox regression analysis.

Results: Compared with patients with SBP-TTR of 76-100%, the adjusted hazard ratios (HRs) for CVD were 1.07 (95% confidence interval [CI], 1.03-1.10) and 1.09 (95% CI: 1.06-1.13) for patients with SBP-TTR of 26-75%, and 0-25%, respectively. The adjusted HR for all-cause mortality was 1.04 (95% CI: 1.003-1.07) and 1.37 (95% CI: 1.28-1.46) for patients with SBP-TTR of 26-75% and 0-25%, respectively. The adjusted HRs for ESKD progression increased gradually: 1.14-fold (95% CI: 1.07-1.21) for the SBP-TTR 26-75% group and 1.37-fold (95% CI: 1.28-1.46) for the SBP-TTR 0-25% group. For patients not taking antihypertensive medications, a lower SBP-TTR was associated with a higher risk of CVD events and ESKD progression than in those taking antihypertensive medications.

Conclusion: Among patients with CKD, those with a lower SBP-TTR had a higher risk of cardiovascular events, mortality, and progression to ESKD.

Introduction: Patients with chronic kidney disease (CKD) are at risk of medication therapy problems (MTPs) due to high comorbidity and medication burden. Using data from the Kidney Coordinated HeAlth Management Partnership (Kidney CHAMP) trial, we used machine learning to build a predictive model to identify MTP high-risk patients with CKD in the primary care setting.

Methods: We used baseline data from patients enrolled in the intervention arm of the Kidney CHAMP trial, completed May 2019-July 2022, which tested a population health management strategy, including medication management, for improving CKD care. The dataset was divided into 80% training and 20% testing subsets. The area under the ROC curve (AUROC) was used to assess classification accuracy in distinguishing between patients with and without MTP. Eight candidate models were considered, and the top three performing models (random forest, support vector machines, and gradient boosting), based on cross-validated AUROC on training data, underwent further refinement. The model with the highest AUROC in the testing set, while considering the bias/variance trade-off, was selected as the best-performing model. SHapley Additive exPlanations was then leveraged using the best-performing model to evaluate the impact of each predictor to the final risk score.

Results: Among 730 patients who received medication review at baseline, 566 (77.5%) had at least 1 MTP. Key demographics were mean age 74 years, 55% female, 92% white, 64% with diabetes, and the mean number of medications 5.8 at baseline. The random forest model had the best performance on the testing set with AUROC 0.72, sensitivity 0.80, and specificity 0.64. The five most influential variables, ranked in descending order of importance for predicting individuals with MTP, were diabetes status (yes/no), hemoglobin A1C (HbA1C), urine albumin-to-creatinine ratio (UACR), systolic blood pressure, and age.

Conclusion: In outpatient primary care, a machine learning-based MTP risk calculator that uses routinely available clinical data can identify patients with moderate-high-risk CKD who are at high risk for developing MTPs.

Background: Chronic kidney disease (CKD) is highly prevalent and associated with an increasing burden on patients and the healthcare system. Its complex causes and diverse manifestations pose considerable challenges in slowing disease progression. Over the last few decades, pharmacotherapeutic strategies have primarily focused on reducing albuminuria, managing complications, and alleviating symptoms. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, known for their glycemic control and cardiovascular benefits in diabetic patients, have shown promise in renal protection, offering hope for slowing CKD progression in a broader patient population.

Summary: The DAPA-CKD and EMPA-KIDNEY trials have provided compelling evidence that dapagliflozin and empagliflozin reduced the risk of a series of renal events and slowed the chronic decline of estimated glomerular filtration rate in patients with CKD, irrespective of diabetic status. The results of these trials strongly support the notion that SGLT-2 inhibitors are effective in renal protection across CKD patients with diverse primary diseases and in varying CKD risk categories. EMPA-KIDNEY also demonstrated that empagliflozin can potentially slow CKD progression in patients without albuminuria, a finding corroborated by results from several other studies. The long-term cardiorenal benefits of empagliflozin were further demonstrated in the post-trial follow-up sub-study of EMPA-KIDNEY. The synergistic effect of SGLT-2 inhibitors with other drugs that have different mechanisms of action is being researched for broader applications.

Key messages: Emerging evidence underscores the potential of SGLT-2 inhibitors to benefit a wide range of CKD patients, regardless of causes and albuminuria status. Further research in this area will improve our understanding of the roles of this new class of drug in renal protection and potentially shift the paradigm of CKD management.

Introduction: Erythropoietin and roxadustat are commonly used to manage anemia in hemodialysis-dependent chronic kidney disease (CKD) patients, but the comparative safety and effectiveness are unknown.

Methods: This is a retrospective cohort study. Data were extracted from Tianjin Healthcare and Medical Big Data Platform. We screened all patients with CKD stage G5 and anemia (hemoglobin <100 g/L) who were treated with either erythropoietin or roxadustat between January 1, 2015, and December 31, 2021. The primary endpoints included expanded composite of major adverse cardiovascular events (MACE+), cardio-cerebrovascular events, and thromboembolic events in the peridialytic period, defined as the duration from the time of estimated glomerular filtration rate decrease to <15 mL/min × 1.73 m2 to 3 months after dialysis initiation. A propensity score-matched analysis (1:1 ratio; caliper width: 0.02) was conducted to minimize the impact of confounding factors.

Results: The initial screen identified a total of 40,324 patients; 1,092 were included in the propensity score-matched analysis (546 in each group). In comparison to the roxadustat group, the erythropoietin group had a lower rate of MACE+ events within 6 months (13.4% vs. 21.2%, p < 0.001) and 12 months of treatment initiation (17.0% vs. 24.0%, p = 0.004), as well as within 3 months of hemodialysis initiation (12.9% vs. 28.7%, p < 0.001). The rate of cardio-cerebrovascular events was also lower in the erythropoietin group within 6 months (38.5% vs. 50.7%, p < 0.001) and 12 months of treatment initiation (49.1% vs. 56.2%, p < 0.001). The rate of thromboembolic events did not differ between the two groups.

Conclusion: Peridialytic erythropoietin was associated with a more favorable cardiovascular safety profile versus roxadustat in hemodialysis-dependent CKD patients.

Background: Diabetic kidney disease (DKD) is a common chronic microvascular complication of diabetes, and the increasing number of patients with this condition imposes a great economic burden globally. The rapid development of biotechnology has revealed more in-depth pathogenic mechanisms related to the occurrence of DKD. Lots of studies have provided evidence that communication between various cell types, including podocytes, mesangial cells, glomerular endothelial cells, and renal tubular epithelial cells, plays an irreplaceable role in the development of DKD. Stem cells have the unique advantages of establishing adaptive communication with renal cells to alleviate the damage in DKD. In addition, some drugs can also affect cell communication in DKD.

Summary: This review presents a review of recent progress on renal cellular crosstalk in the pathogenesis of DKD, and the findings of the review may shed light on the development of a novel therapeutic approach from the perspective of cellular communication.

Key message: Cellular communication in DKD not only reveals the new pathogenic mechanisms but also provides potential therapeutic targets.