Kidney360最新文献

Background: The cardiovascular-kidney-metabolic (CKM) syndrome, estimated to affect up to 90% of U.S. adults, is increasingly recognized as a disease spectrum that requires an interdisciplinary approach. The purpose of this descriptive study was to characterize the patients and the clinical outcomes of a specialized cardio-nephrology inpatient service. These data were compared to data from comparable patients prior to the service's launch.

Methods: This was a retrospective observational study of a specialized Kidney-Heart service that was launched at the University of Washington in 2020 to serve as the nephrology service for patients hospitalized with primary cardiac disease. Chart review was pursued to obtain patient demographics, reason for consult and hospital outcomes in the first 2.5 years of the service. We also obtained data from a historical cohort of patients with a cardiology diagnosis seen by the general nephrology consult service as a comparator. Descriptive analyses were performed to characterize demographics, consult categories, and primary reasons for hospitalization in patients seen on the Kidney-Heart Service versus the historical cohort.

Results: The mean age for the patients seen on the Kidney-Heart Service was 63 (SD 15) vs. 60 (SD 15) years in the comparator cohort (p<0.001). For the Kidney-Heart Service, AKI was the most common reason for consult (57.7%), followed by CKD G5D (30.9%), diuretic management (8.9%) and electrolyte abnormalities (7.8%). Patients seen by the Kidney-Heart Service were most commonly hospitalized for decompensated heart failure and cardiogenic shock (46.9%). Use of mechanical circulatory support was common (22%), and 48.2% of those patients required dialysis. AKI dialysis (36.7 vs 42%, p=0.05) and mortality rates (16.5% vs. 25%, p<0.01) were lower in the Kidney-Heart service cohort vs. the comparator cohort, although mean lengths of stay were longer (14 vs 11 days, p<0.001.) Follow- up in nephrology clinic within the University of Washington system was low for AKI patients at 1.7%.

Conclusions: Our single-center experience demonstrates a model by which a specialized cardio-nephrology service can be implemented and provide care for complex patients. Further implementation clinical trials are needed to determine whether integrated care models can improve CKM outcomes.

Background: Cystinosis is associated with growth failure, myopathy and multiple risk factors for impaired bone development. The objectives of this study were to quantify muscle mass, muscle strength, and bone mineral density (BMD) in children and adults with cystinosis.

Methods: This cross-sectional study assessed DXA regional lean mass, spine and hip BMD, handgrip and leg strength in 38 participants with cystinosis (ages 5-37 years) and 289 healthy controls. All BMD, muscle mass and muscle strength measures were expressed as sex-specific Z-scores relative to age and adjusted for height Z-score or limb length. Linear regression models were used to assess muscle strength relative to muscle mass (muscle specific force) and determine the impact of adjusting BMD results for muscle status.

Results: Among adults, arm and leg lean mass (p < 0.001), handgrip strength (p < 0.001), proximal and distal leg strength (p < 0.001), muscle specific force (p < 0.01) and femoral neck and total hip BMD (p<0.001) were markedly low, compared with controls. On average, muscle strength was more than 2 SD below normal, due to both low muscle mass and poor muscle quality. Among the children and adolescents, upper extremity lean mass and grip strength were preserved. However, leg lean mass (p < 0.01), strength (p < 0.001), muscle specific force (p < 0.001) and femoral neck and total hip BMD (p < 0.01) were reduced, compared with controls, approaching deficits seen in adults. Adjustment for lean mass and muscle strength markedly attenuated the BMD deficits.

Conclusions: Cystinosis is associated with deficits in muscle mass and strength that far exceed those observed in CKD alone and is associated with low proximal femur BMD. Future studies are needed to determine if physical activity or other interventions to address sarcopenia in cystinosis will improve physical function and bone strength.

Background: Hyperuricemia is a common metabolic disorder and a risk factor for multiple diseases, including CKD. Hyperuricemic nephropathy (HN) affects many individuals with hyperuricemia, yet its molecular mechanisms are not fully understood, and effective treatments are lacking.

Methods: In vitro, human tubular epithelial cells (HK-2) were exposed to uric acid for 36 hours, followed by transfection with microRNA mimic or FIH-1 siRNA. In vivo, HN was induced in mice using potassium oxonate (PO) and adenine (Ad) for two weeks. miR-295 mimic or anti-miR-295 was administered via tail vein injection, and mice were sacrificed for analysis.

Results: We demonstrated a significant increase of miR-295 in renal tubular cells in HN mice. Hyperuricemia led to the activation of hypoxia inducible factor-1α (HIF-1α), and inhibition of HIF-1α by YC-1 (a HIF-1α inhibitor) prevented the increase of miR-295. ChIP assay further verified HIF-1α binding to the miR-295 gene promoter directly. Functionally, Inhibition of miR-295 led to increased cell death and tubulointerstitial fibrosis in HN mice, whereas supplementation of miR-295 mimic had kidney protective effects in this model. miR-295 suppressed the expression of factor inhibiting hypoxia-inducible factor-1 (FIH-1) in both in vitro and in vivo models of HN. Luciferase microRNA target reporter assay further verified FIH-1 as a direct target of miR-295.In addition, knockdown of FIH-1 inhibits tubular cell apoptosis and profibrotic cytokines production in HK2 cells during uric acid treatment.

Conclusions: This study reveals a HIF-1α/miR-295/FIH-1 positive feedback loop that regulates tubular damage and fibrosis in HN.

Background: Glomerular disease (GD) is a prominent cause of kidney disease in adolescents and young adults (AYA), yet there is limited information on how this population fares compared to children and older adults.

Methods: We analyzed data from CureGN, a prospective cohort of patients of all ages with biopsy-proven GD. Patients with Minimal Change Disease (MCD), Focal Segmental Glomerulosclerosis (FSGS) and IgA Nephropathy (IgAN) were included. Patients were stratified into pediatric (≤13), AYA (14-25), and adult (≥26) groups, and compared by demographic, clinical, and disease characteristics. Associations between age group and relapse rate, change in kidney function, and time to remission were assessed using multivariate negative binomial, linear mixed effects, and Cox proportional hazards models respectively, stratified by disease type.

Results: Our study included 1868 patients (562 pediatric, 397 AYA, and 909 adults). Median follow up time was 4.9 years. Adults with MCD had fewer relapses (IRR 0.61, CI 0.41-0.91, P=0.01) while there was no difference between pediatric participants with MCD (IRR 1.23, CI 0.85 - 1.79, P=0.28) compared to AYA. Adults with IgAN had fewer relapses than AYA (IRR 0.55, CI 0.33 - 0.94, P=0.03). AYA had faster decline in kidney function compared to pediatric participants with FSGS (1.7 ml/min/1.73m2 per year vs 0.3 ml/min/1.73m2 per year, P=0.008) and IgAN (1.5 ml/min/1.73m2 per year vs 0.1 ml/min/1.73m2 increase per year, P=0.002). Pediatric participants with MCD achieved first observed remission sooner compared to AYA (HR 2.18, CI 1.03 -4.63, P=0.04). Adults with IgAN were slower to achieve first observed remission compared to AYA (HR 0.58, CI 0.37 - 0.91, P=0.02).

Conclusions: AYA with GD exhibit distinct clinical patterns compared to the pediatric and adult age groups, underscoring the need to approach care and research along an age-related continuum rather than a binary framework.

Background: Little is known regarding whether renal function during pregnancy among healthy women is associated with pregnancy outcomes. Evidence based on the universal screening of maternal eGFR is lacking. We investigated the association of maternal eGFR during the second trimester with fetal birthweight.

Methods: This prospective birth cohort study includes 1,666 singleton pregnant women (median age 36 years, median BMI 20.0) who had universal screening of eGFR during the second trimester. Participants were categorized into the quartile of eGFR. The 1st quartile group was defined as low eGFR, the 4th quartile group as high eGFR, and the 2nd and 3rd quartile group as reference. The primary outcomes are low birthweight (LBW) and small for gestational age (SGA). Multivariable logistic regression models were used to investigate the association of maternal eGFR and pregnancy outcomes.

Results: As compared to the reference group, the adjusted odds ratios (95% Confidence Intervals [CI]) for LBW and SGA in the low eGFR group were 2.25 (1.48-3.40) and 2.51 (1.63-3.87), respectively, and in the high eGFR group were 0.69 (0.40-1.19) and 0.55 (0.30-1.02), respectively. The adjusted odds ratios of eGFR per SD decrease (95% CI) for LBW and SGA were 1.92 (1.50-2.45) (p=0.013) and 2.07 (1.60-2.68) (p<.001). The prediction models were improved by adding eGFR to the models including covariates; for LBW (C statistics difference, +0.018; 95% CI, -0.004-0.040, net reclassification index (NRI), 0.377; 95% CI, 0.208-0.545, and integrated discrimination improvement (IDI), 0.0135; 95% CI, 0.005-0.022) and for SGA (C statistics difference, +0.041; 95% CI, 0.003-0.080, NRI, 0.408; 95% CI, 0.226-0.591, and IDI, 0.017; 95% CI, 0.009-0.025).

Conclusions: The lower maternal midterm eGFR is associated with LBW and SGA, while the higher eGFR is not. Evaluating midterm eGFR may help identify healthy women at risk of adverse birth outcomes.

Background: Dialysis may deplete the body of valuable solutes. We previously found that the diet-derived antioxidant ergothioneine was markedly depleted in hemodialysis (HD) patients. Standard peritoneal dialysis (PD) prescriptions provide lower clearances of small molecules than standard HD prescriptions. We therefore tested whether ergothioneine would be depleted in PD patients but to a lesser degree than in HD patients.

Methods: Blood levels of ergothioneine were compared in 16 PD patients, 16 HD patients, and 15 controls with normal kidney function. Levels were measured using liquid chromatography mass spectrometry in plasma and also in erythrocytes in which ergothioneine is normally highly concentrated. Ergothioneine clearances by PD and HD were also compared.

Results: Erythrocyte ergothioneine levels were much lower in both PD and HD patients than controls. The erythrocyte ergothioneine levels, however, were less depleted in PD patients than in HD patients. The erythrocyte levels in PD patients averaged 34% those of controls while levels in HD patients averaged only 10% those of controls. Plasma ergothioneine levels in dialysis patients were also lower than controls. The time-averaged clearance of ergothioneine was lower with PD than with HD, so that a standard PD regimen would remove less ergothioneine daily than a standard HD regimen at a given plasma level.

Conclusions: The antioxidant ergothioneine is depleted in PD patients but to a lesser extent than in HD patients. Benefits of ergothioneine repletion in dialysis patients remains to be assessed.