The latest medical research on Nephrology
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Request AccessThe Degree of Aortic Occlusion in the Setting of Trauma Alters the Extent of Acute Kidney Injury Associated with Mitochondrial Preservation.
American Journal ofResuscitative endovascular balloon occlusion of the aorta (REBOA) is used to control non-compressible hemorrhage not addressed with traditional tou...
Mitochondrial dysfunction in the pathophysiology of renal diseases.
American Journal ofMitochondria are essential organelles in the human body, serving as the metabolic factory of the whole organism. When mitochondria are dysfunctiona...
Combined Serologic and Genetic Risk Score and Prognostication of PLA2R-Associated Membranous Nephropathy.
Clinical Journal of the AmericanThe aim of this study was to test whether a combined risk score based on genetic risk and serology can improve the prediction of kidney failure in PLA2R-associated primary membranous nephropathy.
We performed a retrospective analysis of 519 biopsy-proven PLA2R-associated primary membranous nephropathy patients with baseline eGFR ≥ 25ml/min/1.73m2. The combined risk score was calculated by combining the genetic risk score with PLA2R ELISA antibody titers. The primary endpoint was kidney disease progression defined as a 50% reduction in eGFR or kidney failure. Cox proportional hazard regression analysis and C-statistics were applied to compare the performance of PLA2R antibody, genetic risk score, and combined risk score, as compared to clinical factors alone, in predicting primary outcomes.
Median age was 56 years (range 15-82 years); male-to-female ratio was 1:0.6, median eGFR at biopsy was 99 ml/min/1.73m2 (range: 26-167 ml/min/1.73m2) and median proteinuria was 5.3 g/24h (range: 1.5-25.8 g/24h). During a median follow-up of 67 (5-200) months, 66 (13%) had kidney disease progression. In Cox proportional hazard regression models, PLA2R antibody titers, genetic risk score and combined risk score were all individually associated with kidney disease progression with and without adjustments for age, sex, proteinuria, eGFR and tubulo-interstitial lesions. The best-performing clinical model to predict kidney disease progression included age, eGFR, proteinuria, serum albumin, diabetes, and tubule-interstitial lesions [C-statistic 0.76 (0.69-0.82), adjusted R2 0.51]. While the addition of PLA2R antibody titer improved the performance of this model [C-statistic: 0.78 (0.72-0.84), adjusted R2 0.61], replacing PLA2R antibody with the combined risk score improved the model further [C-statistic: 0.82 (0.77-0.87), adjusted R2 0.69, difference of C-statistics with clinical model = 0.06 (0.03-0.10), P<0.001; difference of C-statistics with clinical-serological model = 0.04 (0.01-0.06), P<0.001 ].
In patients with PLA2R-associated membranous nephropathy, the combined risk score incorporating inherited risk alleles and PLA2R antibody enhanced prediction of kidney disease progression compared to PLA2R serology and clinical factors alone.
Effect of Spironolactone on Kidney Function in Kidney Transplant Recipients: A Randomized Placebo-Controlled Clinical Trial.
Clinical Journal of the AmericanLong-term kidney allograft survival is hampered by progressive interstitial fibrosis and tubular atrophy. The SPIREN trial tested the hypothesis that the mineralocorticoid receptor antagonist spironolactone stabilizes kidney function and attenuates glomerular barrier injury in kidney transplant patients treated with calcineurin inhibitors.
Randomized, placebo-controlled, double blind clinical trial including 188 prevalent kidney transplant patients. Patients were randomized to spironolactone or placebo for three years. Glomerular filtration rate was measured along with proteinuria and kidney fibrosis. The primary endpoint was change in measured glomerular filtration rate. Secondary outcomes were 24h proteinuria, kidney allograft fibrosis and cardiovascular events. Measured glomerular filtration rates, 24h proteinuria and blood pressure were determined yearly. Kidney biopsies were collected at baseline and after two years (n=48). Fibrosis was evaluated by quantitative stereology and classified according to Banff.
The groups were comparable at baseline except for slightly older allografts in the spironolactone group. Spironolactone reduced measured glomerular filtration rates (up to -7.6 (95% CI -10.9;-4.3) ml/min compared to placebo) independently of time since transplantation and blood pressure with no impact on the kidney function curve over time and reduced 24h proteinuria after one year. There was no significant effect of spironolactone on the development of interstitial fibrosis.
Spironolactone added to standard therapy for three years in kidney transplant patients did not improve kidney function, long-term proteinuria or interstitial fibrosis.
Different interdialytic intervals and cardiorespiratory fitness in patients undergoing hemodialysis.
Clinical Journal of the AmericanLong interdialytic interval in thrice-weekly hemodialysis is associated with excess cardiovascular and all-cause mortality risk. Impaired cardiorespiratory fitness is a strong predictor of mortality in hemodialysis. This study investigated differences in cardiorespiratory fitness assessed with cardiopulmonary exercise testing (CPET) between the end of the 2-day and the 3-day interdialytic interval.
A total of 28 hemodialysis patients, randomized in two different sequences of evaluation underwent CPET and spirometry examination at the end of the 2-day and the 3-day intervals. The primary outcome was the difference in oxygen uptake at peak exercise [VO2peak(ml/kg/min)] assessed with CPET. Volume status was assessed with interdialytic-weight-gain, lung-ultrasound, bioimpedance spectroscopy (BIS), and inferior vena cava measurements. A total of 14 age- and sex-matched controls were also evaluated. Comparisons of changes in parameters of interest were performed with paired or independent t-tests, or relevant non-parametric tests, as appropriate. Bivariate correlation analyses and generalized-linear-mixed-models were employed to examine associations between changes in CPET parameters and volume indices.
Hemodialysis patients at the end of both 2-day and 3-day intervals presented lower values in all major CPET parameters than controls. VO2peak(ml/kg/min) was significantly higher at the end of the 2-day than the 3-day interval (15.2±4.2 vs 13.6±2.8;p<0.001); similar were the results for VO2peak(ml/min) (1188±257 vs 1074±224;p<0.001) and VO2peak(%predicted) (58.9±9.2 vs 52.3±8.6;p<0.001). Numerical but no statistically significant differences were detected in VO2-anaerobic-threshold(ml/kg/min) and VO2-anaerobic-threshold(ml/min) between the two time-points. Maximal work load (90.1±23.2 vs 79.3±25.1;p<0.001), exercise duration, heart rate at peak exercise and oxygen pulse also showed lower values at the end of the 3-day interval. Forced-expiratory-volume in 1 second levels were similar between the two evaluations. Generalized-linear-mixed-model analysis including interdialytic-weight-gain as random covariate attenuated the observed differences in VO2peak(ml/kg/min). Changes in BIS-derived overhydration indexes were moderately correlated with changes of VO2peak(ml/kg/min).
The 3-day interval was associated with further impairment of VO2 at peak exercise. This effect was predominantly driven by excess fluid accumulation during the extra interdialytic day.
Validation of the Mayo Imaging Classification System for Predicting Kidney Outcomes in ADPKD.
Clinical Journal of the AmericanThe Mayo Imaging Classification (MIC) was developed to predict the rate of disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD). This study aimed to validate its ability to predict kidney outcomes in a large multicenter ADPKD cohort.
Included were patients with ≥1 height-adjusted total kidney volume (HtTKV) measurement and ≥3 estimated glomerular filtration rate (eGFR) values during ≥1 year follow-up. Mayo HtTKV class stability, kidney growth rates and eGFR decline rates were calculated. The observed eGFR decline was compared to predictions from the Mayo Clinic future eGFR equation. The future eGFR prediction equation was also tested for non-linear eGFR decline. Kaplan-Meier survival analysis and Cox regression models were used to assess time to kidney failure using Mayo HtTKV class as a predictor variable.
We analyzed 618 patients with a mean age of 47 ± 11 years and mean eGFR of 64 ± 25 ml/min/1.73m2 at baseline. Most patients (82%) remained in their baseline Mayo HtTKV class. During a mean follow-up of 5.1 ± 2.2 years, the mean TKV growth rates and eGFR decline were 5.33 ± 3.90 %/year and -3.31 ± 2.53 ml/min/1.73m2/year, respectively. Kidney growth and eGFR decline showed considerable overlap between the classes. The observed annual eGFR decline was not significantly different from the predicted values for classes 1A, 1B, 1C, and 1D but significantly slower for class 1E. This was also observed in patients aged <40 and >60 years and those with PKD2 mutations. A polynomial model allowing non-linear eGFR decline provided more accurate slope predictions. Ninety-seven patients (16%) developed kidney failure during follow-up. The classification predicted the development of kidney failure, although the sensitivity and positive predictive values were limited.
The MIC demonstrated acceptable stability and generally predicted kidney failure and eGFR decline rate. However, there was marked interindividual variability in the rate of disease progression within each class.
Trends in Automated Peritoneal Dialysis Prescriptions in a Large Dialysis Organization in the United States.
Clinical Journal of the AmericanChanges in health care policies and recognition of patient benefit have contributed to increases in home-based dialysis, including peritoneal dialysis (PD). Frequent monitoring and early individualization of PD prescriptions are key prerequisites for the delivery of high-quality PD. The present analysis aimed to assess variations in PD prescriptions among incident automated PD (APD) patients who remain on PD for 120+ days.
This retrospective analysis examined data from patients within a large dialysis organization that initiated PD with APD between 2015 and 2019. PD prescription data was described by calendar year, timing of PD, and residual renal function categories. Changes in prescriptions from PD initiation (day 1) to day 120 were assessed descriptively.
The cohort included 11,659 patients. The mean age at PD initiation increased from 2015 (56 (15) years) through 2019 (58 (15) years), whereas most other variables demonstrated no clear temporal change. Most patients (86%) had nighttime PD prescribed, with an average of 4.9 (1.3) cycles per day, a mean total treatment volume of 9.3 (2.5) L, and a median daily total dwell time of 7 (6,9.5) hours. Relative to day 1 nighttime prescriptions, there were 1) small increases in the proportion of patients receiving 3 or fewer cycles per day and those receiving 6+ cycles per day, 2) a 100 ml mean increase in fill volume per exchange, and 3) a mean 0.5 L increase in total nighttime treatment volume at day 120. When changes in nighttime APD prescriptions were examined at the patient level, 49% of patients had day 120 prescriptions that were unchanged from their initial prescription.
In the largest analysis of incident APD prescriptions conducted in the United States to date, the vast majority of patients were prescribed nocturnal PD only with limited variability across the first 4 months of therapy.
Dialysate Sodium Lowering in Maintenance Hemodialysis A Randomized Clinical Trial.
Clinical Journal of the AmericanLowering dialysate sodium may improve volume and blood pressure control in maintenance hemodialysis patients.
We randomized 42 participants 2:1 to dialysate sodium 135 vs. 138 mEq/L for 6 months. This was followed by a 12 week extension in which sodium was increased to 140 mEq/L in low arm participants. The primary outcome was intradialytic hypotension (IDH). Secondary outcomes included dialysis disequilibrium symptoms, ER visits/hospitalizations, interdialytic weight gain, blood pressure (BP). Longitudinal changes across arms were analyzed using linear mixed regression.
Treatment to dialysate sodium 135 vs. 138 mEq/L was not associated with a difference in a change in the rate of IDH (mean change (95%CI) 2.8 (0.8,9.5) vs. 2.7 (1.1, 6.2) events per 100 treatments per month; ratio of slopes 0.96(0.26,3.61) or ER visits/hospitalizations (7.3 (2.3, 12.4) vs. 6.7 (2.9, 10.6) events per 100 patient months; difference 0.6(-6.9,5.8). Symptom score was unchanged in the 135 mEq/L arm (0.7 (-1.4,2.7) and decreased in the 138 mEq/l arm (5.0,8.5,2.0); difference 6.0 (2.1,9.8)). Interdialytic weight gain declined in the 135 mEq/L arm and was unchanged in the 138 mEq/L arm,(-0.3(-0.5,0.0) vs. 0.3 (0.0, 0.6) kg over 6 months; difference (-0.6 (-0.1,-1.0) kg). In the extension phase, raising dialysate sodium from 135 to 140 mEq/L was associated with an increase in interdialytic weight gain (0.2 (0.1, 0.3) kg), predialysis BP (7.0 (4.8, 9.2)/ 3.9 (2.6, 5.1) mm Hg) and a reduction in IDH [OR 0.66 (0.45, 0.97)].
Use of a dialysate sodium of 135 as compared with 138 mEq/L was associated with a small reduction in interdialytic weight gain without impact on IDH or predialysis BP, but with an increase in symptoms. Raising dialysate sodium from 135 to 140mEq/L was associated with a reduction in IDH, a small increase in interdialytic weight gain and a marked increase in predialysis BP.
Preventive Pharmacological Therapy and Risk of Recurrent Urinary Stone Disease.
Clinical Journal of the AmericanUrinary stone disease is a prevalent condition associated with a high recurrence risk. Preventive pharmacological therapy has been proposed to reduce recurrent stone episodes. However, limited evidence exists regarding its effectiveness, contributing to its underutilization by physicians. This study aimed to evaluate the association between preventive pharmacological therapy (thiazide diuretics, alkali therapy, and uric acid lowering medications) and clinically significant urinary stone disease recurrence.
Using data from the Veterans Health Administration, adults with an index episode of urinary stone disease from 2012 through 2019 and at least one urinary abnormality (hypercalciuria, hypocitraturia, or hyperuricosuria) on 24-hour urine collection were included. The primary outcome was a composite variable representing recurrent stone events that resulted in emergency department visits, hospitalizations, or surgery for urinary stone disease. Cox proportional hazards regression was performed to estimate the association between preventive pharmacological therapy use and recurrent urinary stone disease while adjusting for relevant baseline patient characteristics.
Among the cohort of patients with urinary abnormalities (n=5,637), treatment with PPT was associated with a significant 19% lower risk of recurrent urinary stone disease during the 12-36-month period following the initial urine collection (hazard ratio [HR] 0.81; 95% confidence interval [CI] 0.65-1.00, p = 0.0496. However, the effectiveness of preventive pharmacological therapy diminished over longer follow-up periods (12-48 months and 12-60 months following the urine collection) and did not reach statistical significance. When examining specific urinary abnormalities, only alkali therapy for hypocitraturia was associated with a significant 26% lower recurrence risk within the 12-36-month timeframe (HR 0.74, 95%CI 0.56-0.97, p=0.03).
When considering all urinary abnormalities together, this study demonstrates that use of preventive pharmacological therapy is associated with a lower risk of clinically significant recurrent episodes of urinary stone disease in the 12-36 month timeframe following urine collection, though only the association with use of alkali therapy for hypocitraturia was significant when individual abnormalities were examined.
Should Transplant Nephrology pursue recognition from the Accreditation Council for Graduate Medical Education (ACGME)?
Clinical Journal of the AmericanKidney transplant is not only the best treatment for patients with advanced kidney disease, but it also reduces health-care expenditure. The manage...
Pregnancy in Patients Receiving Home Dialysis.
Clinical Journal of the AmericanPregnancy is an important goal for many women with chronic kidney disease (CKD) or kidney failure, but important barriers exist, particularly as CK...
Sotagliflozin and Kidney Outcomes, Kidney Function, and Albuminuria in T2DM and CKD: A Secondary Analysis of the SCORED Trial.
Clinical Journal of the AmericanIn the initial analysis of SCORED, due to early trial termination and suspension of adjudication, reconciliation of eGFR laboratory data and case report forms had not been completed. This resulted in a small number of kidney composite events and a nominal effect of sotagliflozin versus placebo on this outcome. This exploratory analysis uses laboratory eGFR data, regardless of case report form completion, to assess the effects of sotagliflozin on the predefined kidney composite endpoint in SCORED and additional cardiorenal composite endpoints.
SCORED was a multicenter, randomized trial evaluating cardiorenal outcomes with sotagliflozin versus placebo in 10,584 patients with type 2 diabetes and chronic kidney disease (CKD). The present exploratory analyses used laboratory data to derive the eGFR components and case report form data for the non-laboratory defined components that together made up the kidney and cardiorenal composites. Acute kidney injury (AKI) was also assessed in this dataset.
Using laboratory data, 223 events were identified and sotagliflozin reduced the risk of the composite of first event of sustained ≥50% decline in eGFR, eGFR<15 mL/min/1.73m2, dialysis, or kidney transplant with 87 events (1.6%) in the sotagliflozin group and 136 events (2.6%) in the placebo group (HR [95% CI] = 0.62 [0.48, 0.82]), p<0.001). Sotagliflozin reduced the risk of a cardiorenal composite endpoint defined as the above composite plus cardiovascular or kidney death with 239 events (4.5%) in the sotagliflozin group and 306 events (5.7%) in the placebo group (HR [95% CI] = 0.77 [0.65, 0.91], p=0.0023). Results were consistent when using different eGFR decline thresholds and when only including kidney death in composites (all p<0.01). The incidence of AKI was similar between treatment groups.
In this exploratory analysis using the complete laboratory dataset, sotagliflozin reduced the risk of kidney and cardiorenal composite endpoints in patients with type 2 diabetes and CKD.