Glomerular Filtration Rate

ImportanceCOVID-19 infection has been associated with acute kidney injury. However, its possible association with long-term kidney function is not well understood.ObjectiveTo investigate whether kidney function decline accelerated after COVID-19 compared with after other respiratory tract infections.Design, setting, and participantsThis cohort study used linked data from the Stockholm Creatinine Measurements (SCREAM) Project between February 1, 2018, and January 1, 2022, in Stockholm, Sweden. All hospitalized and nonhospitalized adults in the database with at least 1 estimated glomerular filtration rate (eGFR) measurement in the 2 years prior to a COVID-19 positive test result or pneumonia diagnosis were selected. Statistical analyses were conducted between June 2023 and October 2024.ExposureCOVID-19 and pneumonia (including influenza).Main outcomes and measuresMean annual change in eGFR after COVID-19 and after pneumonia was calculated with a linear regression model.ResultsThe COVID-19 cohort comprised 134 565 individuals (74 819 females [55.6%]; median [IQR] age, 51 [37-64] years). The pneumonia cohort consisted of 35 987 individuals (19 359 females [53.8%]; median [IQR] age, 71 [56-81] years). The median (IQR) baseline eGFR was 94 (79-107) mL/min/1.73m2 for the COVID-19 cohort and 79 (61-92) mL/min/1.73m2 for the pneumonia cohort. After adjustment for covariates, both infections demonstrated accelerated annual eGFR decline, with greater magnitude of decline after COVID-19 (3.4% [95% CI, 3.2%-3.5%] after COVID-19; 2.3% [95% CI, 2.1%-2.5%] after pneumonia). This decline was more severe among individuals hospitalized for COVID-19 (5.4%; 95% CI, 5.2%-5.6%) but remained similar among those hospitalized for pneumonia.Conclusions and relevanceThis cohort study found an association between COVID-19 and accelerated decline in kidney function, particularly after hospitalization, compared with pneumonia. People who were hospitalized for COVID-19 should receive closer monitoring of kidney function to ensure early diagnosis and optimized management of chronic kidney disease to effectively prevent complications and further decline.

BACKGROUNDMen with chronic kidney disease (CKD) experience faster kidney function decline than women. Studies in individuals undergoing sex hormone therapy suggest a role for sex hormones, as estimated glomerular filtration rate (eGFR) increases with feminizing therapy and decreases with masculinizing therapy. However, effects on measured GFR (mGFR), glomerular and tubular function, and involved molecular mechanisms remain unexplored.METHODSThis prospective, observational study included individuals initiating feminizing (estradiol and antiandrogens; n = 23) or masculinizing (testosterone; n = 21) therapy. Baseline and 3-month assessments included mGFR (iohexol clearance), kidney perfusion (para-aminohippuric acid clearance), tubular injury biomarkers, and plasma proteomics.RESULTSDuring feminizing therapy, mGFR and kidney perfusion increased (+3.6% and +9.1%, respectively; P < 0.05) without increased glomerular pressure. Tubular injury biomarkers, including urine neutrophil gelatinase-associated lipocalin, epidermal growth factor (EGF), monocyte chemoattractant protein-1, and chitinase 3-like protein 1 (YKL-40), decreased significantly (-53%, -42%, -45%, and -58%, respectively). During masculinizing therapy, mGFR and kidney perfusion remained unchanged, but urine YKL-40 and plasma tumor necrosis factor receptor 1 (TNFR-1) increased (+134% and +8%, respectively; P < 0.05). Proteomic analysis revealed differential expression of 49 proteins during feminizing and 356 proteins during masculinizing therapy. Many kidney-protective proteins were positively associated with estradiol and negatively associated with testosterone, including proteins involved in endothelial function (SFRP4, SOD3), inflammation reduction (TSG-6), and maintaining kidney tissue structure (agrin).CONCLUSIONSex hormones influence kidney physiology, with estradiol showing protective effects on glomerular and tubular function, while testosterone predominantly exerts opposing effects. These findings emphasize the role of sex hormones in sexual dimorphism observed in kidney function and physiology and suggest new approaches for sex-specific precision medicine.TRIAL REGISTRATIONDutch Trial Register (ID: NL9517); ClinicalTrials.gov (ID: NCT04482920).

Background and objectivesImpaired kidney function has been linked to altered concentrations of blood biomarkers of Alzheimer disease (AD), but the underlying mechanisms and its potential role in dementia development remain poorly understood. We explored the associations between estimated glomerular filtration rate (eGFR), blood-based biomarkers of AD, and dementia development.MethodsData were extracted from the Swedish National Study on Aging and Care in Kungsholmen, an ongoing longitudinal population-based study. Kidney function was assessed using eGFR based on serum creatinine. AD biomarkers (amyloid beta [Aβ42/40], phosphorylated tau [p-tau181 and p-tau217] and total tau [t-tau] proteins, neurofilament light chain [NfL], and glial fibrillary acidic protein [GFAP]) were measured from peripheral blood samples using the Simoa platform. Dementia was diagnosed according to DSM-IV criteria. Quantile regression models assessed the cross-sectional associations between eGFR and AD biomarkers; Cox regression models were used to examine the association of kidney function and biomarkers with incident dementia.ResultsAt baseline, 2,279 dementia-free participants with available blood samples were included (median age 72 (interquartile range, 61-81) years; 62% female). Lower eGFR was associated with higher median z-score levels of all examined AD blood biomarkers, except Aβ42/40, following a nonlinear relationship. At eGFR = 30 mL/min/1.73 m2, estimated differences were as follows: p-tau181: β, 0.22 [95% CI 0.09-0.35]; p-tau217: β, 0.20 [95% CI 0.10-0.31]; t-tau: β, 0.24 [95% CI 0.05-0.42]; NfL: β, 0.88 [95% CI 0.80-0.95]; GFAP: β, 0.10 [95% CI 0.03-0.16]. During a mean follow-up period of 8.3 (SD, 4.3) years, 362 participants developed dementia. In multivariable-adjusted models, impaired kidney function (eGFR 2) was not associated with an increased hazard of dementia compared with preserved kidney function (eGFR ≥ 60 mL/min/1.73 m2) (hazard ratio [HR], 0.93 [95% CI 0.72-1.21]). The relationship between increased (high vs low) NfL and dementia was stronger among individuals with impaired (vs preserved) kidney function (HR, 3.85 [95% CI 1.87-7.95] vs HR, 1.84 [95% CI 1.34-2.53], respectively).Discussion.Impaired kidney function was associated with elevated circulating level of most AD blood biomarkers. However, the presence of impaired kidney function did not independently increase the risk of dementia but rather seemed to accelerate the clinical expression of underlying neurodegenerative pathology.