Circulating Plasma Biomarkers in Biopsy-Confirmed Kidney Disease.

BACKGROUND AND OBJECTIVES: Biomarkers for noninvasive assessment of histopathology and prognosis are needed in patients with kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a proteomics assay, we measured a multimarker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semiquantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of KRT) and death. RESULTS: After multivariable adjustment and correction for multiple testing, 46 different proteins were associated with histopathologic lesions. The top-performing markers positively associated with acute tubular injury and interstitial fibrosis/tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and Ig domain-containing protein 2 (VSIG2), respectively. Thirty proteins were significantly associated with kidney disease progression, and 35 were significantly associated with death. The top-performing markers for kidney disease progression were placental growth factor (hazard ratio per doubling, 5.4; 95% confidence interval, 3.4 to 8.7) and BMP and activin membrane-bound inhibitor (hazard ratio, 3.0; 95% confidence interval, 2.1 to 4.2); the top-performing markers for death were TNF-related apoptosis-inducing ligand receptor-2 (hazard ratio, 2.9; 95% confidence interval, 2.0 to 4.0) and CUB domain-containing protein-1 (hazard ratio, 2.4; 95% confidence interval, 1.8 to 3.3). CONCLUSION: We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_28_CJN09380721.mp3.

A randomized controlled trial of two dialysate sodium concentrations in hospitalized hemodialysis patients.

BACKGROUND: Several large dialysis organizations have lowered the dialysate sodium concentration (DNa) in an effort to ameliorate hypervolemia. The implications of lower DNa on intra-dialytic hypotension (IDH) during hospitalizations of hemodialysis (HD) patients is unclear. METHODS: In this double-blind, single center, randomized controlled trial (RCT), hospitalized maintenance HD patients were randomized to receive higher (142 mmol/L) or lower (138 mmol/L) DNa for up to six sessions. Blood pressure (BP) was measured in a standardized fashion pre-HD, post-HD and every 15 min during HD. The endpoints were: (i) the average decline in systolic BP (pre-HD minus lowest intra-HD, primary endpoint) and (ii) the proportion of total sessions complicated by IDH (drop of ≥20 mmHg from the pre-HD systolic BP, secondary endpoint). RESULTS: A total of 139 patients completed the trial, contributing 311 study visits. There were no significant differences in the average systolic blood pressure (SBP) decline between the higher and lower DNa groups (23 ± 16 versus 26 ± 16 mmHg; P = 0.57). The proportion of total sessions complicated by IDH was similar in the higher DNa group, compared with the lower DNa group [54% versus 59%; odds ratio 0.72; 95% confidence interval (95% CI) 0.36-1.44; P = 0.35]. In post hoc analyses adjusting for imbalances in baseline characteristics, higher DNa was associated with 8 mmHg (95% CI 2-13 mmHg) less decline in SBP, compared with lower DNa. Patient symptoms and adverse events were similar between the groups. CONCLUSIONS: In this RCT for hospitalized maintenance of HD patients, we found no difference in the absolute SBP decline between those who received higher versus lower DNa in intention-to-treat analyses. Post hoc adjusted analyses suggested a lower risk of IDH with higher DNa; thus, larger, multi-center studies to confirm these findings are warranted.

Factors Associated With Death in Critically Ill Patients With Coronavirus Disease 2019 in the US.

Importance: The US is currently an epicenter of the coronavirus disease 2019 (COVID-19) pandemic, yet few national data are available on patient characteristics, treatment, and outcomes of critical illness from COVID-19. Objectives: To assess factors associated with death and to examine interhospital variation in treatment and outcomes for patients with COVID-19. Design, Setting, and Participants: This multicenter cohort study assessed 2215 adults with laboratory-confirmed COVID-19 who were admitted to intensive care units (ICUs) at 65 hospitals across the US from March 4 to April 4, 2020. Exposures: Patient-level data, including demographics, comorbidities, and organ dysfunction, and hospital characteristics, including number of ICU beds. Main Outcomes and Measures: The primary outcome was 28-day in-hospital mortality. Multilevel logistic regression was used to evaluate factors associated with death and to examine interhospital variation in treatment and outcomes. Results: A total of 2215 patients (mean [SD] age, 60.5 [14.5] years; 1436 [64.8%] male; 1738 [78.5%] with at least 1 chronic comorbidity) were included in the study. At 28 days after ICU admission, 784 patients (35.4%) had died, 824 (37.2%) were discharged, and 607 (27.4%) remained hospitalized. At the end of study follow-up (median, 16 days; interquartile range, 8-28 days), 875 patients (39.5%) had died, 1203 (54.3%) were discharged, and 137 (6.2%) remained hospitalized. Factors independently associated with death included older age (≥80 vs <40 years of age: odds ratio [OR], 11.15; 95% CI, 6.19-20.06), male sex (OR, 1.50; 95% CI, 1.19-1.90), higher body mass index (≥40 vs <25: OR, 1.51; 95% CI, 1.01-2.25), coronary artery disease (OR, 1.47; 95% CI, 1.07-2.02), active cancer (OR, 2.15; 95% CI, 1.35-3.43), and the presence of hypoxemia (Pao2:Fio2<100 vs ≥300 mm Hg: OR, 2.94; 95% CI, 2.11-4.08), liver dysfunction (liver Sequential Organ Failure Assessment score of 2-4 vs 0: OR, 2.61; 95% CI, 1.30-5.25), and kidney dysfunction (renal Sequential Organ Failure Assessment score of 4 vs 0: OR, 2.43; 95% CI, 1.46-4.05) at ICU admission. Patients admitted to hospitals with fewer ICU beds had a higher risk of death (<50 vs ≥100 ICU beds: OR, 3.28; 95% CI, 2.16-4.99). Hospitals varied considerably in the risk-adjusted proportion of patients who died (range, 6.6%-80.8%) and in the percentage of patients who received hydroxychloroquine, tocilizumab, and other treatments and supportive therapies. Conclusions and Relevance: This study identified demographic, clinical, and hospital-level risk factors that may be associated with death in critically ill patients with COVID-19 and can facilitate the identification of medications and supportive therapies to improve outcomes.

Bleeding Complications After Percutaneous Native Kidney Biopsy: Results From the Boston Kidney Biopsy Cohort.

BACKGROUND: The major risk of kidney biopsy is severe bleeding. Numerous risk factors for bleeding after biopsy have been reported, but findings have been inconsistent. METHODS: We retrospectively reviewed medical records of adult patients enrolled in a native kidney biopsy cohort study to identify major bleeding events (red blood cell [RBC] transfusions, invasive procedures, kidney loss, or death). We used logistic and linear regression models to identify characteristics associated with postbiopsy RBC transfusions and decline in hemoglobin within a week after the procedure. RESULTS: Major bleeding events occurred in 28 of 644 (4.3%) patients (28 required an RBC transfusion, 4 underwent angiographic intervention, and 1 had open surgery to control bleeding). No patient lost a kidney or died because of the biopsy. Postbiopsy RBC transfusion risk was driven by the baseline hemoglobin level (odds ratio [OR] 13.6; 95% confidence interval [CI] 5.4-34.1 for hemoglobin <10 vs. ≥10 g/dl). After adjusting for hemoglobin, no other patient characteristics were independently associated with RBC transfusions. Female sex (ß = 0.18; 95% CI: 0.04-0.32), estimated glomerular filtration rate (eGFR) <30 ml/min per 1.73 m2 (ß = 0.32; 95% CI: 0.14-0.49), and baseline hemoglobin (ß = 0.09; 95% CI: 0.05-0.13, per g/dl increase) were independently associated with a larger drop in hemoglobin. Histopathologic lesions were not independently associated with major bleeding after biopsy. CONCLUSION: Biopsies were generally well tolerated. Baseline hemoglobin was the dominant risk factor for RBC transfusions, but female sex and eGFR <30 ml/min per 1.73 m2 were also associated with a larger decline in hemoglobin after the procedure.

Clinical Features and Outcomes of Immune Checkpoint Inhibitor-Associated AKI: A Multicenter Study.

BACKGROUND: Despite increasing recognition of the importance of immune checkpoint inhibitor-associated AKI, data on this complication of immunotherapy are sparse. METHODS: We conducted a multicenter study of 138 patients with immune checkpoint inhibitor-associated AKI, defined as a ≥2-fold increase in serum creatinine or new dialysis requirement directly attributed to an immune checkpoint inhibitor. We also collected data on 276 control patients who received these drugs but did not develop AKI. RESULTS: Lower baseline eGFR, proton pump inhibitor use, and combination immune checkpoint inhibitor therapy were each independently associated with an increased risk of immune checkpoint inhibitor-associated AKI. Median (interquartile range) time from immune checkpoint inhibitor initiation to AKI was 14 (6-37) weeks. Most patients had subnephrotic proteinuria, and approximately half had pyuria. Extrarenal immune-related adverse events occurred in 43% of patients; 69% were concurrently receiving a potential tubulointerstitial nephritis-causing medication. Tubulointerstitial nephritis was the dominant lesion in 93% of the 60 patients biopsied. Most patients (86%) were treated with steroids. Complete, partial, or no kidney recovery occurred in 40%, 45%, and 15% of patients, respectively. Concomitant extrarenal immune-related adverse events were associated with worse renal prognosis, whereas concomitant tubulointerstitial nephritis-causing medications and treatment with steroids were each associated with improved renal prognosis. Failure to achieve kidney recovery after immune checkpoint inhibitor-associated AKI was independently associated with higher mortality. Immune checkpoint inhibitor rechallenge occurred in 22% of patients, of whom 23% developed recurrent associated AKI. CONCLUSIONS: This multicenter study identifies insights into the risk factors, clinical features, histopathologic findings, and renal and overall outcomes in patients with immune checkpoint inhibitor-associated AKI.