American Journal of Nephrology最新文献

Introduction: Oxidative stress has been implicated in complications after kidney transplantation (KT), including delayed graft function (DGF) and rejection. However, its role in long-term posttransplant outcomes remains unclear.

Methods: We investigated oxidative damage and antioxidant defense dynamics, and their impact on the graft outcomes, in 41 KT recipients categorized by type of donation over 12 months. Oxidative status was determined using OxyScore and AntioxyScore indexes, which comprise several circulating biomarkers of oxidative damage and antioxidant defense. Donor types included donation after brain death (DBD [61.0%]), donation after circulatory death (DCD [26.8%]), and living donation (LD [12.1%]).

Results: There was an overall increase in oxidative damage early after transplantation, which was significantly higher in DCD as compared to DBD and LD recipients. The multivariate adjustment confirmed the independent association of OxyScore and type of deceased donation with DGF, donor kidney function, and induction therapy with antithymocyte globulin. There were no differences in terms of antioxidant defense. Lower oxidative damage at day 7 predicted better graft function at 1-year posttransplant only in DBD recipients.

Conclusion: DCD induced greater short-term oxidative damage after KT, whereas the early levels of oxidative damage were predictive of the graft function 1 year after KT among DBD recipients.

Background: Sickle cell disease is an inherited red blood cell disorder that affects approximately 100,000 people in the USA and 25 million people worldwide. Vaso-occlusion and chronic hemolysis lead to dysfunction of vital organ systems, with the kidneys being among the most commonly affected organs.

Summary: Early renal manifestations include medullary ischemia with the loss of urine-concentrating ability and hyperfiltration. This can be followed by progressive damage characterized by persistent albuminuria and a decline in the estimated glomerular filtration rate. The risk of sickle nephropathy is greater in those with the APOL1 G1 and G2 kidney risk variants and variants in HMOX1 and lower in those that coinherit α-thalassemia. Therapies to treat sickle cell disease-related kidney damage focus on sickle cell disease-modifying therapies (e.g., hydroxyurea) or those adopted from the nonsickle cell disease kidney literature (e.g., renin-angiotensin-aldosterone system inhibitors), although data on their clinical efficacy are limited to small studies with short follow-up periods. Kidney transplantation for end-stage kidney disease improves survival compared to hemodialysis but is underutilized in this patient population.

Key messages: Kidney disease is a major contributor to early mortality, and more research is needed to understand the pathophysiology and develop targeted therapies to improve kidney health in sickle cell disease.

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: 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: 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: 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: While Asian and Native Hawaiian and other Pacific Islander (NHOPI) patients have a high prevalence of kidney disease risk factors, there are sparse data examining their end-stage kidney disease (ESKD) outcomes. As Hawaii has high representation of Asian and NHOPI individuals, we compared their ESKD outcomes based on residence in the mainland USA versus Hawaii/Pacific Islands (PIs).

Materials and methods: Using United States Renal Data System data, we examined the impact of geographic residence in the mainland versus Hawaii/PIs on race-mortality associations among incident ESKD patients transitioning to dialysis over January 1, 2000-December 31, 2016 using Cox regression. We examined likelihood of post-dialysis kidney transplantation using Cox models and cumulative incidence curves.

Results: Compared with White patients in the mainland, Asian and NHOPI patients in the mainland had lower mortality: adjusted HRs (95% CIs) 0.67 (0.66-0.67) and 0.72 (0.70-0.73), respectively. When examining Asian and NHOPI patients in Hawaii/PIs, survival benefit was attenuated in Asian and diminished to the null in NHOPI patients (ref: mainland White patients). Cumulative incidence curves comparing Asian, NHOPI, and White patients showed Asian and NHOPI patients in the mainland had the highest likelihood of transplantation, whereas NHOPI and Asian patients in Hawaii/PIs had the lowest likelihood.

Conclusion: In the mainland, Asian and NHOPI patients had lower mortality versus White patients, whereas in Hawaii/PIs, this survival benefit was diminished in Asian and mitigated in NHOPI patients. NHOPI and Asian patients in Hawaii/PIs had less transplantation versus those in the mainland. Further research is needed to uncover factors contributing to differential ESKD outcomes among Asian and NHOPI patients across geographic residence.

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: Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD) mortality. We investigated vascular biomarkers, angiopoietin-1, and angiopoietin-2 (angpt-1, -2), in CVD development in KTRs.

Methods: This ancillary study from the FAVORIT evaluates the associations of baseline plasma angpt-1, -2 levels in CVD development (primary outcome) and graft failure (GF) and death (secondary outcomes) in 2000 deceased donor KTRs. We used Cox regression to analyze the association of biomarker quartiles with outcomes. We adjusted for demographic; CVD- and transplant-related variables; medications; urine albumin-to-creatinine ratio; and randomization status. We calculated areas under the curves (AUCs) to predict CVD or death, and GF or death by incorporating biomarkers alongside clinical variables.

Results: Participants' median age was 52 IQR [45, 59] years: with 37% women and 73% identifying as white. Median time from transplantation was 3.99 IQR [1.58, 7.93] years and to CVD development was 2.54 IQR [1.11-3.80] years. Quartiles of angpt-1 were not associated with outcomes. Whereas higher levels of angpt-2 (quartile 4) were associated with about 2 times the risk of CVD, GF, and death (aHR 1.85 [1.25-2.73], p < 0.01; 2.24 [1.36-3.70)], p < 0.01; 2.30 [1.48-3.58], p < 0.01, respectively) as compared to quartile 1. Adding angiopoietins to preexisting clinical variables improved prediction of CVD or death (AUC improved from 0.70 to 0.72, p = 0.005) and GF or death (AUC improved from 0.68 to 0.70, p = 0.005). Angpt-2 may partially explain the increased risk of future CVD in KTRs. Further research is needed to assess the utility of using angiopoietins in the clinical care of KTRs.

Conclusion: Angpt-2 may be a useful prognostic tool for future CVD in KTRs. Combining angiopoietins with clinical markers may tailor follow-up to mitigate CVD risk.

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.