Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis.

BACKGROUND: We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN. METHODS: In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-α) with estimated glomerular filtration rate measured 6 months after diagnosis (6 m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6 m-eGFR. RESULTS: In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6 m after AIN were 41 (27-69) and 28 (13-47) mL/min/1.73 m2, respectively. Patients with higher severity of interstitial fibrosis had lower 6 m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6 m-eGFR. IL-9 levels were associated with lower 6 m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, -6.0 (-9.4 to -2.6) mL/min/1.73 m2]. Corticosteroid use was associated with higher 6 m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m2] only in those with urine IL-9 above the median (>0.66 ng/g) but not in others. CONCLUSIONS: Urine IL-9 was associated with lower 6 m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6 m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN.

Unusual case of acute oesophageal necrosis.

Acute oesophageal necrosis is a rare clinical entity that commonly affects the distal oesophagus, giving it a characteristic black appearance. It is associated with a high mortality and predominantly impacts critically ill patients. In this case report, we present a male patient in his 50s with multiple comorbidities admitted for management of ketoacidosis. The patient was overall well appearing and remained haemodynamically stable throughout the entirety of his hospital course. Despite this, necrosis was found in the proximal, middle and distal portions of the patient's oesophagus. The presence of such extensive oesophageal injury was very atypical considering the lower severity of the patient's condition.

Comparison of Urine and Plasma Biomarker Concentrations Measured by Aptamer-Based versus Immunoassay Methods in Cardiac Surgery Patients.

BACKGROUND: Protein detection assays are invaluable tools in the field of biomarker discovery. However, only immunoassays are widely used and can measure 10-20 analytes per biosample. The novel SOMAmer-based assay uses nucleotide aptamer technology to measure over 1300 analytes per biosample. We compared the SOMAmer-based platform to traditional approaches to quantify analytes in a clinical setting with paired samples before and after cardiac surgery. METHODS: In a substudy of the Translational Research Investigating Biomarker Endpoints in Acute Kidney Injury cohort, 54 individuals with acute kidney injury after cardiac surgery were identified. Preoperative and postoperative plasma and urine samples that had been previously evaluated for biomarker concentrations via immunoassays were analyzed via SOMAmer-based assay. RESULTS: Spearman correlations were estimated when >50% of biomarker values were within detectable ranges by immunoassay (plasma biomarkers: preoperative, 26/33; postoperative, 31/33; urine biomarkers: preoperative, 13/16; postoperative, 16/16). Overall, 27% of reportable plasma preoperative biomarkers displayed correlations ≥0.75 between immunoassay and SOMAmer measurements; 23% displayed correlations of 0.50-0.75, and 50% displayed correlations <0.50. In urine these values were 15%, 39%, and 46%, respectively. Forty-two percent of reportable plasma postoperative biomarkers displayed correlations ≥0.75, 16% displayed correlations 0.50-0.75, and 42% displayed correlations <0.50. In urine, these values were 19%, 25%, and 56%, respectively. CONCLUSIONS: In cardiac surgery patients, the SOMAmer-based assay detects proteins with moderate to strong correlation to current immunoassay methods. The correlations in urine are weaker than those in plasma. SOMAmer-based assay technology should be further evaluated in multiple settings as a high-throughput screening tool for biomarker discovery.

The Role of Volume Regulation and Thermoregulation in AKI during Marathon Running.

BACKGROUND AND OBJECTIVES: Marathon runners develop transient AKI with urine sediments and injury biomarkers suggesting nephron damage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To investigate the etiology, we examined volume and thermoregulatory responses as possible mechanisms in runners' AKI using a prospective cohort of runners in the 2017 Hartford Marathon. Vitals, blood, and urine samples were collected in 23 runners 1 day premarathon and immediately and 1 day postmarathon. We measured copeptin at each time point. Continuous core body temperature, sweat sodium, and volume were assessed during the race. The primary outcome of interest was AKI, defined by AKIN criteria. RESULTS: Runners ranged from 22 to 63 years old; 43% were men. Runners lost a median (range) of 2.34 (0.50-7.21) g of sodium and 2.47 (0.36-6.81) L of volume via sweat. After accounting for intake, they had a net negative sodium and volume balance at the end of the race. The majority of runners had increases in core body temperature to 38.4 (35.8-41)°C during the race from their baseline. Fifty-five percent of runners developed AKI, yet 74% had positive urine microscopy for acute tubular injury. Runners with more running experience and increased participation in prior marathons developed a rise in creatinine as compared with those with lesser experience. Sweat sodium losses were higher in runners with AKI versus non-AKI (median, 3.41 [interquartile range (IQR), 1.7-4.8] versus median, 1.4 [IQR, 0.97-2.8] g; P=0.06, respectively). Sweat volume losses were higher in runners with AKI versus non-AKI (median, 3.89 [IQR, 1.49-5.09] versus median, 1.66 [IQR, 0.72-2.84] L; P=0.03, respectively). Copeptin was significantly higher in runners with AKI versus those without (median, 79.9 [IQR, 25.2-104.4] versus median, 11.3 [IQR, 6.6-43.7]; P=0.02, respectively). Estimated temperature was not significantly different. CONCLUSIONS: All runners experienced a substantial rise in copeptin and body temperature along with salt and water loss due to sweating. Sodium and volume loss via sweat as well as plasma copeptin concentrations were associated with AKI in runners. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_08_13_CJASNPodcast_19_09_.mp3.

Kidney Biopsy-Related Complications in Hospitalized Patients with Acute Kidney Disease.

BACKGROUND AND OBJECTIVES: Patients are informed of the risk of kidney biopsy-related complications using data from nonhospitalized patients, which may underestimate the risk for hospitalized patients. We evaluated the rate and risk factors of kidney biopsy-related complications in hospitalized patients with acute kidney disease (AKD) to better estimate the risk in this population. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used data from the Yale biopsy cohort to evaluate rates of kidney biopsy-related complications including adjudicated procedure-related bleeding requiring blood transfusions or angiographic interventions, medium- or large-sized hematomas, reimaging after biopsy including abdominal ultrasonography or computed tomography, and death in hospitalized patients with AKD (including AKI). We evaluated univariable and multivariable association of risk factors with transfusions. We compared rates of complications between hospitalized and nonhospitalized patients. RESULTS: Between 2015 and 2017, 159 hospitalized patients underwent a kidney biopsy for AKD evaluation, of which 80 (51%) had stage 1 AKI, 42 (27%) had stage 2 (or higher) AKI, and 27 (17%) had AKD (without AKI). Of these, 12 (8%; 95% confidence interval [95% CI], 5% to 15%) required a transfusion, three (2%; 95% CI, 1% to 5%) required an intervention, 11 (7%; 95% CI, 4% to 12%) had hematoma, and 31 (20%; 95% CI, 14% to 26%) required reimaging after biopsy. Of the four (3%; 95% CI, 1% to 6%) deaths during hospitalization, none were related to the biopsy. Female sex, lower platelet count, and higher BUN were associated with postbiopsy transfusions on univariable and multivariable analyses. Trainee as proceduralist and larger needle gauge were associated with transfusions in univariable, but not multivariable, analysis. Nonhospitalized patients had lower rates of transfusion than hospitalized patients, although the latter also had lower prebiopsy hemoglobin and greater surveillance after biopsy. CONCLUSIONS: Hospitalized patients experience higher risk of postbiopsy complications than previously reported and several factors, such as lower platelet count, female sex, and higher BUN, are associated with this risk.

A Survey of Patient Attitudes Toward Participation in Biopsy-Based Kidney Research.

INTRODUCTION: As part of the precision medicine initiative, the National Institutes of Health/National Institute of Diabetes and Digestive Kidney Diseases has proposed collecting human kidney tissue to discover novel therapeutic targets from patients with kidney diseases. Patient attitudes on participating in kidney biopsy-based research are largely unknown. METHODS: We evaluated attitudes toward donating kidney tissue to research among participants who had experienced a clinically indicated kidney biopsy, through a survey conducted 9 months (interquartile range, 5-13 months) after their biopsy. RESULTS: Of the 177 participants contacted, 117 (66%) participated in the survey. A total of 85 participants (73%) reported that they would allow additional needle passes during a clinically indicated biopsy to donate kidney tissue for research. As reasons for participating in such a study, the participants reported the desire to help others and to contribute to science, and the lack of additional burden while participating in such a study. In a multivariable logistic model, older and African American participants had lower odds of allowing an additional pass for research (odds ratio: age ≥65 years [vs. ≤40], 0.15 [95% confidence interval, 0.03-0.73]; African Americans (vs. all others), 0.15 [95% confidence interval, 0.05-0.44]). However, participants' self-reported biopsy complications such as pain, anxiety, and hematuria did not affect their willingness to allow additional passes. A total of 23 participants (20%) stated that they would agree to undergo a biopsy for research even if it was not clinically indicated. CONCLUSION: Among patients who had experienced a kidney biopsy, a majority were amenable to additional needle passes to donate kidney tissue for research during a future, clinically indicated biopsy, whereas a minority would undergo a biopsy for research purpose only.