American Journal of Kidney Diseases最新文献

Rationale & objective: People with advanced kidney disease undergo more non-cardiac operations compared to the general population, with a higher risk of perioperative cardiac events and death. However, little is known about the associations between severity of preoperative kidney dysfunction with postoperative length of hospitalization and discharge disposition; these were the focus of this study.

Study design: Population-based retrospective cohort.

Setting & participants: Adults from Alberta, Canada undergoing inpatient major noncardiac surgery between April 2005 and February 2019.

Exposure: Categorical preoperative outpatient estimated glomerular filtration rate (eGFR) or kidney failure status.

Outcomes: Length of stay (LOS), days alive at home after surgery within 30 and 90 days, and discharge disposition location.

Analytical approach: Associations were estimated with unadjusted and adjusted generalized estimating equation models.

Results: 927,560 inpatient surgeries in 666,770 people (55.9% female, median age 57.4 years) were identified. People receiving dialysis had the longest LOS (11 days [95% CI 6, 29), 2 times greater than that among people with normal kidney function (adjusted incidence rate ratio [IRR] 2.21 [95% CI 2.10, 2.32]). This group also had the fewest days alive at home within the first 30 days after surgery, with an IRR of 0.69 (95% CI 0.67, 0.70) compared to people with normal eGFR. The majority of people (82.8%) were discharged home without nursing support after surgery, though people receiving dialysis were discharged to a facility with 24-hour nursing care nearly 4 times more often. There were graded increases in risks of these outcomes with lower levels of kidney function.

Limitations: Many people did not have preoperative kidney function assessed, reflecting standard clinical practice in the general population.

Conclusions: After major surgery, people with kidney disease spend more time recovering in hospital and have less independence from post-discharge nursing supports than otherwise similar patients who have normal or near normal kidney function. These differences were more pronounced for those with the most severe stages of kidney disease.

Rationale & objective: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve cardiac and kidney outcomes in patients with diabetes; however their efficacy in individuals with reduced estimated glomerular filtration rate (eGFR) is uncertain. This study evaluated the effects of GLP-1RAs on kidney and cardiovascular (CV) outcomes in patients with chronic kidney disease (CKD).

Study design: Systematic review and meta-analysis of randomized controlled trials (RCTs) reported through May 25, 2024.

Setting & study populations: Adult participants in RCTs with baseline eGFR <60 mL/min/1.73 m².

Selection criteria for studies: RCTs including adults (≥18 years old) with varying degrees of kidney function, including individuals with CKD characterized by a baseline eGFR of less than 60 mL/min/1.73 m², that compared GLP-1RAs with control treatments with respect to a composite kidney outcome, all-cause mortality, or a composite CV disease outcome. From among 212 screened studies, 12 trials involving that included participants with baseline eGFR <60 mL/min/1.73 m² were included.

Data extraction: Two independent investigators extracted the data.

Analytical approach: Pooled odds ratios (ORs) for composite kidney outcome, all-cause mortality, and composite CV outcome were estimated using random-effects models. Evidence certainty was assessed using the GRADE system.

Results: 17,996 RCT participants with baseline eGFR <60 mL/min/1.73 m² were included in analyses. GLP-1RAs were significantly associated with a reduced risk of the composite kidney outcome (OR: 0.85 [95% CI 0.77-0.94]; p=0.001) with low heterogeneity (I²<0.01%). GLP-1RAs were also associated with a reduced the risk of a >30% eGFR decline (OR: 0.78, p=0.004), a >40% decline (OR: 0.76, p=0.01), and a >50% decline (OR: 0.72, p<0.001). Risk of all-cause mortality was also lower in the GLP-1RA group (OR: 0.77 [95% CI 0.60-0.98]; p=0.03), though there was high heterogeneity (I²=71.6%). Composite CV outcomes were also lower with the use of GLP-1R (OR: 0.86 [95% CI 0.74-0.99]; p=0.03; I²=40.3%). Sensitivity analyses restricted to human GLP-1 backbone agents showed enhanced benefits.

Limitations: Inconsistent kidney outcome definitions, focus on diabetic populations in most studies, and potential publication bias.

Conclusions: GLP-1RAs improved kidney and cardiovascular outcomes, and survival in patients with CKD enrolled in an array of clinical trials.

Renal tubular acidoses (RTAs) are a subset of non-anion gap metabolic acidoses that result from complex disturbances in renal acid excretion. Net acid excretion is primarily accomplished through the reclamation of sodium bicarbonate and the buffering of secreted protons with ammonia or dibasic phosphate, all of which require a series of highly complex and coordinated processes along the renal tubule. Flaws in any of these components lead to the development of metabolic acidosis and/or a failure to compensate fully for other systemic acidoses. Identification and diagnosis of RTA can be challenging, and the consequences of untreated RTA can be life-threatening. The use of serum and urinary indices can help elucidate the kidney's capacity to respond to acidemia, characterize these disturbances further, and guide treatment.

Rationale & objective: Arterial stiffness is associated with prevalent chronic kidney disease (CKD). Whether arterial stiffness is prospectively associated with incident CKD is inconclusive.

Study design: Longitudinal cohort study.

Setting & participants: Using data from the Atherosclerosis Risk in Communities (ARIC) Study, the primary analysis included 3,161 participants without prevalent CKD at visit 5; a secondary analysis studied 4,341 participants with any estimated glomerular filtration rate (eGFR) record across visits 5 to 7.

Exposure: Carotid-femoral pulse wave velocity (cfPWV), heart-femoral PWV (hfPWV), heart-ankle PWV (haPWV), brachial-ankle PWV (baPWV), heart-carotid PWV (hcPWV), and femoral-ankle PWV (faPWV).

Outcomes: Primary analysis - incident CKD, defined as an eGFR <60 ml/min/1.73m² accompanied by >25% decline eGFR or CKD hospitalization. Secondary analysis - eGFR slope.

Analytical approach: Primary analysis - Cox regression models to calculate hazard ratio (HR). Secondary analysis - multilevel mixed effects models to estimate the eGFR slope across visits.

Results: Median follow-up was 6.6 years. 460 participants developed incident CKD (incidence rate 22.0/1,000 person-years). The highest quartiles (Q4) of cfPWV, hfPWV, and haPWV were associated with an increased risk of incident CKD compared to the lowest quartile (Q1) (HRs, 1.53 [95% CI, 1.15 to 2.04] and 1.49 [95% CI, 1.12 to 1.99], and 1.56 [95% CI, 1.16 to 2.08], respectively). The results were consistent in subgroups. In the secondary analysis, the Q4s of cfPWV, hfPWV, haPWV, baPWV, and hcPWV were significantly associated with a faster eGFR decline compared to Q1 (e.g., for cfPWV, -0.44 mL/min/1.73 m²/year [95% CI, -0.56 to -0.33] in Q4 versus -0.37 [95% CI, -0.48 to -0.26] in Q1). All p-value <0.05. faPWV was not associated with incident CKD or eGFR slope.

Limitations: Residual confounding.

Conclusions: Greater arterial stiffness, especially higher cfPWV, hfPWV, and haPWV, was prospectively associated with a higher risk of incident CKD and faster decline in eGFR among community-dwelling older adults, supporting a pathophysiological contribution of arterial stiffness to the development of CKD.

Omitting outcomes of importance to patients with chronic kidney disease (CKD) and their caregivers from trials can impede decision-making based on patient-centered outcomes. As part of the global Standardized Outcomes in Nephrology - Chronic Kidney Disease (SONG-CKD) initiative, we aimed to establish a consensus-based set of core outcomes for trials in CKD (prior to the need for kidney replacement therapy). To finalize the proposed set of core outcomes that were identified through focus groups and an international Delphi survey, we convened two international stakeholder workshops in English and Spanish languages that involved 61 patients/caregivers and 75 health professionals from 18 countries. Participants were asked to discuss and endorse the potential core outcomes (mortality, kidney function, life participation, and cardiovascular disease), and to provide suggestions for implementing the core outcomes. The discussions were summarized into four themes: reflecting a comprehensive approach to health, facilitating patient empowerment in their own care, ensuring applicability to broad geographic areas and populations, and feasibility for implementation. Patients, caregivers, and health professionals agreed that mortality, kidney function, life participation and cardiovascular disease should be established as core outcomes for trials in CKD.

Rationale & objective: Molecular diagnosis of autosomal dominant tubulointerstitial kidney disease (ADTKD) due to variants in the MUC1 gene has long been challenging since variants lie in a large Variable Number of Tandem Repeat (VNTR) region, making identification impossible using standard short read techniques. Previously, we addressed this diagnostic limitation by developing a computational pipeline, named VNtyper, for easier reliable detection of MUC1 VNTR pathogenic variants from short read sequences. This led to unexpected diagnoses of ADTKD-MUC1 among patients with kidney disease referred for genetic testing, which we report here.

Study design: Cross-sectional observational study.

Settings & participants: 4,040 patients referred to Necker Enfants-Malades Hospital from 2017 to 2023 for genetic testing for (1) glomerular disease, (2) ciliopathy, (3) congenital anomalies of the kidneys and urinary tracts (CAKUT), (4) ADTKD, or (5) chronic kidney disease (CKD) of unknown origin, in whom MUC1 had not been previously tested by SNaPshot mini-sequencing.

Exposure: Clinical suspicion of ADTKD.

Outcomes: ADTKD-MUC1 diagnosed using VNtyper.

Analytical approach: Data were collected from patients in whom ADTKD-MUC1 was newly diagnosed and patients in whom ADTKD was clinically suspected were compared to those in whom ADTKD was not.

Results: We identified 40 patients with MUC1 variants by VNtyper, including 33 new index patients and 7 relatives. Of the 33 index cases, 20 had been suspected of having ADTKD based on clinical features, and in the other 13, ADTKD had not been considered. In patients in whom ADTKD had not been considered clinically, the detection rate was 0.05% (1/1895) among patients with glomerular disease, 1.2% (4/329) among patients with ciliopathy, 0.09% (1/1099) among patients with CAKUT and 2.5% (7/285) among patients with CKD of unknown origin. In six patients, there was no family history of kidney disease, and we confirmed de novo presentation in two patients by segregation studies.

Limitations: Observational study and selected referral population (may not represent the prevalence or phenotypes in the general kidney disease population).

Conclusions: With VNtyper, we were able to diagnose new cases of ADTKD-MUC1 in a large cohort of patients with various phenotypes. Some patients had atypical phenotypes due to a variant in another gene, and some had no family history of kidney disease, suggesting de novo disease which was confirmed in two patients.

Social connectedness, defined as a sense of belonging and inclusion among individuals and groups, is crucial for the well-being of end-stage kidney disease (ESKD) patients. This perspective employs a hypothetical case study to highlight the risks of social isolation and loneliness faced by ESKD patients. It offers guidance on how the ESKD community can effectively address these challenges. Although in-center hemodialysis provides an inherent environment for fostering social connections, the COVID-19 pandemic has intensified the risk of social disconnection. This paper delineates five key recommendations to mitigate this risk: 1) improve detection of loneliness and social isolation; 2) implement evidence-based social support interventions; 3) revitalize the in-center experience; 4) engage family caregivers; and 5) leverage technology for social connectedness. Neglecting opportunities to bolster social connections among ESKD patients would represent a significant interdisciplinary lapse. The proposed recommendations are feasible due to the integral role of interdisciplinary care within dialysis centers.