American Journal of Nephrology最新文献

Introduction: The Center for Medicare and Medicaid Services introduced an End-Stage Renal Disease Prospective Payment System (PPS) in 2011 to increase the utilization of home dialysis modalities, including peritoneal dialysis (PD). Several studies have shown a significant increase in PD utilization after PPS implementation. However, its impact on patients with kidney allograft failure remains unknown.

Methods: We conducted an interrupted time series analysis using data from the US Renal Data System (USRDS) that include all adult kidney transplant recipients with allograft failure who started dialysis between 2005 and 2019. We compared the PD utilization in the pre-PPS period (2005-2010) to the fully implemented post-PPS period (2014-2019) for early (within 90 days) and late (91-365 days) PD experience.

Results: A total of 27,507 adult recipients with allograft failure started dialysis during the study period. There was no difference in early PD utilization between the pre-PPS and the post-PPS period in either immediate change (0.3% increase; 95% CI: -1.95%, 2.54%; p = 0.79) or rate of change over time (0.28% increase per year; 95% CI: -0.16%, 0.72%; p = 0.18). Subgroup analyses revealed a trend toward higher PD utilization post-PPS in for-profit and large-volume dialysis units. There was a significant increase in PD utilization in the post-PPS period in units with low PD experience in the pre-PPS period. Similar findings were seen for the late PD experience.

Conclusion: PPS did not significantly increase the overall utilization of PD in patients initiating dialysis after allograft failure.

Introduction: This study aimed to investigate the relationship between circulating soluble Klotho concentration and all-cause mortality in individuals with chronic kidney disease (CKD).

Methods: We conducted a prospective cohort study involving 2,456 participants with CKD from the National Health and Nutrition Examination Survey (NHANES) cycles spanning from 2007 to 2016. Complex sampling-weighted multivariate Cox proportional hazards models were used to estimate the association between serum Klotho level and all-cause mortality, presenting hazard ratios (HRs) and 95% confidence intervals (CIs). Additionally, a restricted cubic spline analysis was performed to explore potential nonlinear associations.

Results: During a median of 82 months of follow-up, 550 (22.40%) all-cause deaths were recorded. The median serum Klotho concentration was 760 pg/mL (interquartile ranges, 624, 958). After adjusting for potential covariates, the risk of all-cause mortality decreased by 4% for every 100 pg/mL increase in Klotho (HR = 0.96, 95% CI, 0.92, 0.99). The HR for the fourth quartile of Klotho compared to the first quartile was 0.73 (95% CI, 0.56, 0.96). The restricted cubic spline model revealed a distinctive "L"-shaped association between serum Klotho and all-cause mortality among patients with CKD, with a Klotho concentration of 760 pg/mL at the inflection point. When Klotho concentration was less than 760 pg/mL, a significant negative correlation between Klotho and all-cause mortality was observed (HR per 100 pg/mL increase in Klotho = 0.86, 95% CI, 0.78, 0.95).

Conclusion: This study documented a distinctive "L"-shaped association between serum Klotho levels and all-cause mortality among individuals with CKD. Further research is needed to validate these findings.

Introduction: Fibroblast growth factor 23 (FGF23) has direct effects on the vasculature and myocardium, and high levels of FGF23 are a risk factor for cardiovascular disease (CVD); however, the impact of FGF23 on CVD in primary proteinuric glomerulopathies has not been addressed.

Methods: The associations of baseline plasma intact FGF23 levels with resting blood pressure (BP) and lipids over time among adults and children with proteinuric glomerulopathies enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were analyzed using generalized estimating equation regression analyses. Models were adjusted for age, sex, glomerular diagnosis, follow-up time, estimated glomerular filtration rate, urine protein/creatinine ratio, obesity, and serum phosphorous levels.

Results: Two hundred and four adults with median FGF23 77.5 (IQR 51.3-119.3) pg/mL and 93 children with median FGF23 62.3 (IQR 44.6-83.6) pg/mL were followed for a median of 42 (IQR 20.5-54) months. In adjusted models, each 1 µg/mL increase in FGF23 was associated with a 0.3 increase in systolic BP index at follow-up (p < 0.001). Greater baseline FGF23 was associated with greater odds of hypertensive BP (OR = 1.0003; 95% CI 1.001-1.006, p = 0.03) over time. Compared to tertile 1, tertile 2 (OR = 2.1; 95% CI 1.12-3.99, p = 0.02), and tertile 3 (OR = 3; 95% CI 1.08-8.08, p = 0.04), FGF23 levels were associated with greater odds of hypertensive BP over time. Tertile 2 was associated with greater triglycerides compared to tertile 1 (OR = 48.1; 95% CI 4.4-91.9, p = 0.03).

Conclusion: Overall, higher baseline FGF23 was significantly associated with hypertensive BP over time in individuals with proteinuric glomerulopathies. Further study of FGF23 as a therapeutic target for reducing CVD in proteinuric glomerular disease is warranted.

Introduction: Rural areas face significant disparities in dialysis care compared to urban areas due to limited access to dialysis facilities, longer travel distances, and a shortage of healthcare professionals. The objective of this study was to conduct a national examination of rural-urban differences in quality of dialysis care offered across counties in the USA.

Methods: Data were gathered from Medicare-certified dialysis facilities in 2020 from the Centers for Medicare and Medicaid Services website. To identify high-need counties, county-level estimated crude prevalence of diabetes in adults was obtained from the 2022 CDC PLACES data portal. Our analysis reviewed 3,141 counties in the USA. The primary outcome measured was whether the county had a dialysis facility. Among those counties that had a dialysis facility, additional outcomes were the average star rating, whether peritoneal dialysis was offered, and whether home dialysis was offered.

Results: The type of services offered by dialysis facilities varied significantly, with peritoneal dialysis being the most commonly offered service (50.8%), followed by home hemodialysis (28.5%) and late-shift services (16.0%). These service availabilities are more prevalent in urban facilities than in rural facilities. The Centers for Medicare and Medicaid Services Five Star Quality ratings were quite different between urban and rural facilities, with 40.4% of rural facilities having a ranking of five, compared to 27.1% in urban.

Conclusion: The majority of rural counties lack a single dialysis facility. Counties with high rates of chronic kidney disease, diabetes, and blood pressure, deemed high need, were less likely to have a highly rated dialysis facility. The findings can be used to further inform targeted efforts to increase diabetes educational programming and design appropriate interventions to those residing in rural communities and high-need counties who may need it the most.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disease characterized by the accumulation of fluid-filled cysts in the kidneys, leading to renal volume enlargement and progressive kidney function impairment. Disease severity, though, may vary due to allelic and genetic heterogeneity. This study aimed to determine genotype-phenotype correlations between PKD1 truncating and non-truncating mutations and kidney function decline in ADPKD patients.

Methods: We established a single-center retrospective cohort study in Kuwait where we followed every patient with a confirmed PKD1-ADPKD diagnosis clinically and genetically. Renal function tests were performed annually. We fitted generalized additive mixed effects models with random intercepts for each individual to analyze repeated measures of kidney function across mutation type. We then calculated survival time to kidney failure in a cox proportional hazards model. Models were adjusted for sex, age at visit, and birth year.

Results: The study included 22 truncating and 20 non-truncating (42 total) patients followed for an average of 6.6 years (range: 1-12 years). Those with PKD1 truncating mutations had a more rapid rate of eGFR decline (-4.7 mL/min/1.73 m2 per year; 95% CI: -5.0, -4.4) compared to patients with PKD1 non-truncating mutations (-3.5 mL/min/1.73 m2 per year; 95% CI: -4.0, -3.1) (p for interaction <0.001). Kaplan-Meier survival analysis of time to kidney failure showed that patients with PKD1 truncating mutations had a shorter renal survival time (median 51 years) compared to those with non-truncating mutations (median 56 years) (P for log-rank = 0.008).

Conclusion: In longitudinal and survival analyses, patients with PKD1 truncating mutations showed a faster decline in kidney function compared to patients PKD1 non-truncating mutations. Early identification of patients with PKD1 truncating mutations can, at best, inform early clinical interventions or, at least, help suggest aggressive monitoring.

Introduction: Chronic kidney disease (CKD) negatively affects musculoskeletal health, leading to reduced mobility, and quality of life. In healthy populations, carnitine supplementation and aerobic exercise have been reported to improve musculoskeletal health. However, there are inconclusive results regarding their effectiveness and safety in CKD. We hypothesized that carnitine supplementation and individualized treadmill exercise would improve musculoskeletal health in CKD.

Methods: We used a spontaneously progressive CKD rat model (Cy/+ rat) (n = 11-12/gr): (1) Cy/+ (CKD-Ctrl), (2) CKD-carnitine (CKD-Carn), and (3) CKD-treadmill (CKD-TM). Carnitine (250 mg/kg) was injected daily for 10 weeks. Rats in the treadmill group ran 4 days/week on a 5° incline for 10 weeks progressing from 30 min/day for week one to 40 min/day for week two to 50 min/day for the remaining 8 weeks. At 32 weeks of age, we assessed overall cardiopulmonary fitness, muscle function, bone histology and architecture, and kidney function. Data were analyzed by one-way ANOVA with Tukey's multiple comparisons tests.

Results: Moderate to severe CKD was confirmed by biochemistries for blood urea nitrogen (mean 43 ± 5 mg/dL CKD-Ctrl), phosphorus (mean 8 ± 1 mg/dL CKD-Ctrl), parathyroid hormone (PTH; mean 625 ± 185 pg/mL CKD-Ctrl), and serum creatinine (mean 1.1 ± 0.2 mg/mL CKD-Ctrl). Carnitine worsened phosphorous (mean 11 ± 3 mg/dL CKD-Carn; p < 0.0001), PTH (mean 1,738 ± 1,233 pg/mL CKD-Carn; p < 0.0001), creatinine (mean 1 ± 0.3 mg/dL CKD-Carn; p < 0.0001), cortical bone thickness (mean 0.5 ± 0.1 mm CKD-Ctrl, 0.4 ± 0.1 mm CKD-Carn; p < 0.05). Treadmill running significantly improves maximal aerobic capacity when compared to CKD-Ctrl (mean 14 ± 2 min CKD-TM, 10 ± 2 min CKD-Ctrl; p < 0.01).

Conclusion: Carnitine supplementation worsened CKD progression, mineral metabolism biochemistries, and cortical porosity and did not have an impact on physical function. Individualized treadmill running improved maximal aerobic capacity but did not have an impact on CKD progression or bone properties. Future studies should seek to better understand carnitine doses in conditions of compromised renal function to prevent toxicity which may result from elevated carnitine levels and to optimize exercise prescriptions for musculoskeletal health.

Introduction: Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. However, they pose the risk of immune-related adverse events, including ICI-mediated acute kidney injury (ICI-AKI). Recent studies have implicated proton pump inhibitors (PPIs) as potential contributors to ICI-AKI development. This meta-analysis examines the association between PPI use and ICI-AKI, exploring a potential modifiable risk factor in ICI therapy while also reviewing the possible outcomes of ICI-AKI.

Methods: We conducted a comprehensive systematic review and meta-analysis of observational studies, assessing the risk of ICI-AKI in cancer patients concurrently using PPIs and potential outcomes. Odds ratios (ORs) were pooled using random-effects models. Subgroup analyses and sensitivity analyses were performed to evaluate heterogeneity and potential biases.

Results: A total of 14 studies involving 12,694 patients were included. In total, we analyzed 639 patients with all-cause AKI and 779 patients with ICI-AKI. The pooled OR for the overall incidence of AKI from all-causes was 1.57 (95% confidence interval [CI] 1.02-2.40) among patients on PPIs. Specifically, the risk of ICI-AKI associated with PPI use was significantly higher, with a pooled OR of 1.84 (95% CI 1.16-2.90). This indicates approximately 84% higher likelihood of developing ICI-AKI with concurrent use of PPIs. Additionally, among patients with ICI-AKI, 67% had complete or partial recovery of renal function, 32% progressed to chronic kidney disease (CKD), and about 36% died during a follow-up period of at least 3 months.

Conclusion: This meta-analysis highlights the importance of cautious PPI prescription in cancer patients undergoing ICI therapy. Clinicians are advised to evaluate the risks and benefits of PPI use and consider alternative therapies when feasible.

Introduction: Hypertensive nephrosclerosis (HN) ranks as one of the most frequent causes of chronic kidney disease (CKD), but its very existence has repeatedly been called into question, especially in young adults. Its diagnostic framework is established chiefly on non-specific clinical criteria, and its defining histopathological set of features is in fact shared by numerous other conditions. Genetic testing based on exome sequencing (ES) has emerged as a comprehensive tool to detect Mendelian diseases in timely fashion in nephrology, with a significant number of re-established diagnoses. The aim of this study was to investigate the diagnostic yield of ES in patients with a clinical diagnosis of hypertensive nephropathy.

Method: Since September 2018, ES has been readily available as part of the routine diagnostic work-up in our institution. The indication of ES includes hypertensive nephropathy of early onset (i.e., <45 years old). We retrospectively collected the ES data performed in the context of hypertensive nephropathy in our institution between September 2018 and February 2021.

Results: A total of 128 patients were sequenced in the context of hypertensive nephropathy with early onset. The chief indications of ES were an early onset of CKD (47%), family history of kidney disease (8%), or both (18%). We detected diagnostic variants in 19 of the 128 patients (15%), encompassing a total of 13 different monogenic disorders. The diagnostic yield of ES was lower in patients of African ancestry (diagnostic yield of 7 vs. 30% in non-African ancestry patients, p < 0.001).

Conclusions: The high diagnostic yield of ES (15%) in a population of patients thought to have HN casts further doubts on the validity of the existing diagnosis criteria, including histological criteria, supposed to characterize the condition. This was especially true in patients with no African ancestry, where ES positivity reached 30%.

Introduction: Serum activin A has been reported to contribute to vascular calcification and kidney fibrosis in chronic kidney disease. We aimed to investigate whether higher serum activin levels were associated with poor allograft outcomes in patients with kidney transplantation (KT).

Methods: A total of 860 KT patients from KNOW-KT (Korean Cohort Study for Outcome in Patients with Kidney Transplantation) were analyzed. We measured serum activin levels pre-KT and 1 year after KT. The primary outcome was the composite of a ≥50% decline in estimated glomerular filtration rate and graft failure. Multivariable cause-specific hazard model was used to analyze association of 1-year activin levels with the primary outcome. The secondary outcome was coronary artery calcification score (CACS) at 5 years after KT.

Results: During the median follow-up of 6.7 years, the primary outcome occurred in 109 (12.7%) patients. The serum activin levels at 1 year were significantly lower than those at pre-KT (488.2 ± 247.3 vs. 704.0 ± 349.6). When patients were grouped based on the median activin level at 1 year, the high-activin group had a 1.91-fold higher risk (95% CI, 1.25-2.91) for the primary outcome compared to the low-activin group. A one-standard deviation increase in activin levels as a continuous variable was associated with a 1.36-fold higher risk (95% CI, 1.16-1.60) for the primary outcome. Moreover, high activin levels were significantly associated with 1.56-fold higher CACS (95% CI, 1.12-2.18).

Conclusion: Post-transplant activin levels were independently associated with allograft functions as well as coronary artery calcification in KT patients.

Introduction: Collaborative management of kidney disease relies on coordinated and effective partnerships between multiple providers. Siloed traditional health systems often result in delays, barriers to treatment access, and inefficient monitoring.

Methods: We conducted a 1-year observational mixed-methods study. We included all consecutive referrals except for patients without telephone access. We assessed 4 domains of outcomes: (1) patient and caregiver experience, (2) provider experience (e.g., physicians and pharmacists), (3) clinical outcomes specific to medication-related outcomes (e.g., adherence, adverse drug events [ADEs]), and (4) value and efficiency (i.e., medication access, defined as time to treatment and resolution of medication reimbursement issues).

Results: Sixty-five patients were referred to the integrated virtual pharmacy (iVRx) model. Most (72%) patients were male. Patients had a median (min, max) age of 60 (27, 85) years and were taking 8 (4, 13) medications. Compared with traditional care delivery models, medication access improved for 56% of participants. Direct home delivery of medication resulted in 91% of patients receiving prescriptions within 2 days of a nephrologist visit. During more than 2,000 pharmacist-patient encounters, 208 ADEs were identified that required clinician intervention to prevent patient harm. When these ADEs were classified by severity, 53% were mild, 45% were moderate (e.g., delaying dose titration in patients initiated on glucagon-like peptide 1 (GLP-1) agonists due to intolerable gastrointestinal side effects), and the remaining 2% of ADEs were severe, meaning clinical intervention was required to prevent a serious outcome (e.g., uncontrolled blood pressure, prevention of acute kidney injury). Nephrologists reported high satisfaction with iVRx, citing efficiency, timely response, and collaboration with pharmacists as key facilitators. Of the 65 patient participants, 98% reported being extremely satisfied.

Conclusions: The iVRx is an acceptable and feasible clinical strategy. Our pilot program was associated with improved kidney care by increasing medication access for patients and avoiding potential harms associated with ADEs.