Acute Kidney Injury in Hospitalized Patients with COVID-19.

IMPORTANCE: Preliminary reports indicate that acute kidney injury (AKI) is common in coronavirus disease (COVID)-19 patients and is associated with worse outcomes. AKI in hospitalized COVID-19 patients in the United States is not well-described. OBJECTIVE: To provide information about frequency, outcomes and recovery associated with AKI and dialysis in hospitalized COVID-19 patients. DESIGN: Observational, retrospective study. SETTING: Admitted to hospital between February 27 and April 15, 2020. PARTICIPANTS: Patients aged ≥18 years with laboratory confirmed COVID-19 Exposures: AKI (peak serum creatinine increase of 0.3 mg/dL or 50% above baseline). Main Outcomes and Measures: Frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aOR) with mortality. We also trained and tested a machine learning model for predicting dialysis requirement with independent validation. RESULTS: A total of 3,235 hospitalized patients were diagnosed with COVID-19. AKI occurred in 1406 (46%) patients overall and 280 (20%) with AKI required renal replacement therapy. The incidence of AKI (admission plus new cases) in patients admitted to the intensive care unit was 68% (553 of 815). In the entire cohort, the proportion with stages 1, 2, and 3 AKI were 35%, 20%, 45%, respectively. In those needing intensive care, the respective proportions were 20%, 17%, 63%, and 34% received acute renal replacement therapy. Independent predictors of severe AKI were chronic kidney disease, systolic blood pressure, and potassium at baseline. In-hospital mortality in patients with AKI was 41% overall and 52% in intensive care. The aOR for mortality associated with AKI was 9.6 (95% CI 7.4-12.3) overall and 20.9 (95% CI 11.7-37.3) in patients receiving intensive care. 56% of patients with AKI who were discharged alive recovered kidney function back to baseline. The area under the curve (AUC) for the machine learned predictive model using baseline features for dialysis requirement was 0.79 in a validation test. CONCLUSIONS AND RELEVANCE: AKI is common in patients hospitalized with COVID-19, associated with worse mortality, and the majority of patients that survive do not recover kidney function. A machine-learned model using admission features had good performance for dialysis prediction and could be used for resource allocation.

The Role of Uric Acid in Acute Kidney Injury.

Studies have demonstrated the presence of a strong association between serum uric acid (SUA) and acute kidney injury (AKI) consistently across several disease models. Exposure to SUA at different time periods and concentrations has reliably resulted in AKI whether assessed by conventional or novel biomarkers or by kinetic estimated glomerular filtration rate (KeGFR) engineered for non-steady dynamic states. In experimental models, moderate hyperuricemia was associated with an absence of intrarenal crystals, manifestation of tubular injury, macrophage infiltration, and increased expression of inflammatory mediators that were attenuated with uric acid lowering therapy with rasburicase, a recombinant urate oxidase. In a pilot clinical trial, treatment with rasburicase was associated with a decreased incidence of AKI and evidence for less renal structural injury. Lowering SUA also improved KeGFR and estimated glomerular filtration rate in 2 separate studies. SUA has also been linked to diabetic nephropathy, hypertension, cardiovascular disease, chronic kidney disease, metabolic syndrome, and their mechanisms of action share many common traits. In this article, we explore the evidence for the causal role of SUA in AKI using Bradford Hill criteria as a guideline with data integration from related fields.

Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial.

BACKGROUND: Memory T-cells are mediators of transplant injury, and no therapy is known to prevent the development of cross-reactive memory alloimmunity. Activated vitamin D is immunomodulatory, and vitamin D deficiency, common in hemodialysis patients awaiting transplantation, is associated with a heightened alloimmune response. Thus, we tested the hypothesis that vitamin D3 supplementation would prevent alloreactive T-cell memory formation in vitamin D-deficient hemodialysis patients. METHODS AND FINDINGS: We performed a 12-month single-center pilot randomized, controlled trial of 50,000 IU/week of cholecalciferol (D3) versus no supplementation in 96 hemodialysis patients with serum 25(OH)D<25 ng/mL, measuring effects on serum 25(OH)D and phenotypic and functional properties of T-cells. Participants were randomized 2:1 to active treatment versus control. D3 supplementation increased serum 25(OH)D at 6 weeks (13.5 [11.2] ng/mL to 42.5 [18.5] ng/mL, p<0.001) and for the duration of the study. No episodes of sustained hypercalcemia occurred in either group. Results of IFNγ ELISPOT-based panel of reactive T-cell assays (PRT), quantifying alloreactive memory, demonstrated greater increases in the controls over 1 year compared to the treatment group (delta PRT in treatment 104.8+/-330.8 vs 252.9+/-431.3 in control), but these changes in PRT between groups did not reach statistical significance (p = 0.25). CONCLUSIONS: D3 supplements are safe, effective at treating vitamin D deficiency, and may prevent time-dependent increases in T-cell alloimmunity in hemodialysis patients, but their effects on alloimmunity need to be confirmed in larger studies. These findings support the routine supplementation of vitamin D-deficient transplant candidates on hemodialysis and highlight the need for large-scale prospective studies of vitamin D supplementation in transplant candidates and recipients. TRIAL REGISTRATION: Clinicaltrials.gov NCT01175798.

Utilization of parathyroidectomy for secondary hyperparathyroidism in end-stage renal disease.

BACKGROUND: The utilization of parathyroidectomy (PTX) to manage secondary hyperparathyroidism (SHPT) refractory to medical management (MTX) in end-stage renal disease (ESRD) in the era of calcimimetics is not well known. METHODS: Adult ESRD patients receiving dialysis between August 2007 and December 2011 at our institution with an intact parathyroid hormone (iPTH) level ≥88 pmol/L for 6 months associated with hypercalcemia and/or hyperphosphatemia for at least 50% of that period were included. Baseline characteristics and iPTH, calcium, phosphorus, calcium-phosphorus product and alkaline phosphatase (ALP) at baseline, 6 and 12 months were compared between the two groups (PTX versus MTX) using the χ (2) and paired t-tests. RESULTS: Of the total population of 687 patients, 80 (11.6%) satisfied KDOQI criteria for PTX, most of whom did not receive PTX (81.2%). At baseline, PTX patients had been on dialysis longer (P = 0.001), with higher iPTH (P < 0.001), calcium (P = 0.008) and ALP (P = 0.001) and were less likely to be African-American (P = 0.007). Complete follow-up data at 6 months were available on 75 patients (PTX = 15; MTX = 60). PTX had significantly greater reduction in iPTH (93 versus 23%) and ALP (68 versus 0%) compared with MTX. Changes from baseline in calcium, phosphate or calcium-phosphorus product levels and proportion of patients achieving KDOQI target values were not significant for either intervention. Findings were consistent at 12 months. CONCLUSIONS: A significant proportion of ESRD patients who met indications for PTX did not receive it. Additional studies are needed to understand the barriers that prevent patients from receiving PTX, thereby resulting in underutilization.

Where should electronic records for patients be stored?

INTRODUCTION: The importance of a nationwide health information infrastructure (NHII) is widely recognized. Patient data may be stored where it happens to be created (the distributed or institution-centric model) or in one place for a given patient (the centralized or patient-centric model). Minimal data is available regarding the performance implications of these alternative architectural choices. OBJECTIVE: To help identify the architecture best suited for efficient and complete nationwide health information exchange based on the large-scale operational characteristics of these architectures. DESIGN: We used simulation to study the impact of health care record (data) fragmentation and probability of encounter on transaction volume and data retrieval failure rate as markers of performance for each of the above architectures. RESULTS: Data fragmentation and the probability of encounter directly correlate with transaction volume and are significantly higher for the distributed model when the number of data nodes >4 (p<0.0001). The number of data retrieval failures increases in proportion to fragmentation and is significantly higher for the distributed model when the number of data nodes ≥2 (p<0.0059). CONCLUSION: In simulation studies, the distributed model scaled poorly in terms of data availability and integrity with a higher failure rate when compared to the centralized model of data storage. Choice of architecture may have implications on the efficiency, usability, and effectiveness of the NHII at the point of care.

Post-operative serum uric acid and acute kidney injury.

BACKGROUND: We hypothesized that post-operative serum uric acid (SUA) may be associated with acute kidney injury (AKI). METHODS: In this prospective, observational study, the relationships between SUA, urine neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin-18 (uIL-18), serum monocyte chemoattractant protein-1 (sMCP-1) and tumor necrosis factor-alpha (sTNF-alpha), and incidence of AKI were determined. SUA were divided into tertiles and their association with AKI investigated. RESULTS: A total of 100 cardiac surgery patients were included for analyses. The 1st, 2nd, and 3rd SUA tertiles were associated with 15.1%, 11.7%, and 54.5% incidence of AKI, respectively. The 3rd SUA tertile, compared to the referent 1st tertile, was associated with an eightfold (OR 8.38, CI95% 2.13-33.05, p=0.002) increased risk for AKI. Patients with AKI on post-operative day 1 (n=11) were then excluded for the purpose of determining the predictive value of SUA to diagnose AKI on postoperative day 2 and during hospital stay. In comparison to the referent 1st tertile, the 3rd tertile SUA was associated with an eightfold increased risk for AKI on post-operative day 2 (adjusted OR 7.94, CI95% 1.50-42.08, P=.015) and a five-fold increased risk for AKI during hospital stay (OR 4.83, CI95% 1.21-19.20, P=.025), respectively. SUA (Area Under Curve, AUC 0.77 (CI95% 0.66-0.88, P<.001), serum creatinine (0.73, CI95% 0.62-0.84, P<.001) and sTNF-alpha (0.76, CI95% 0.65-0.87, P<.001) had the best diagnostic performance measured by the Receiver Operating Characteristics curves. CONCLUSIONS: We conclude that post-operative SUA is associated with an increased risk for AKI and compares well to conventional markers of AKI.

Elevated uric acid increases the risk for acute kidney injury.

BACKGROUND: Uric acid has been proposed to play a role in acute kidney injury. We therefore investigated the potential influence of preoperative serum uric acid (SUA) on acute kidney injury in patients undergoing cardiovascular (CV) surgery. The primary aims were to investigate the incidence of acute kidney injury, peak serum creatinine (SCr) concentrations, hospital length of stay, and days on mechanical ventilation. METHODS: Retrospective study included patients who underwent CV surgery and had preoperative SUA available. Acute kidney injury was defined as an absolute increase in SCr ≥0.3 mg/dL from baseline within 48 hours after surgery. Univariate and multivariate logistic regression analysis was performed to determine the odds ratio for acute kidney injury. RESULTS: There were 190 patients included for analysis. SUA were divided into deciles. The incidences of acute kidney injury were higher with higher deciles of SUA. When the incidences of acute kidney injury were plotted against all available values of SUA at increments of 0.5 mg/dL, a J-shaped curve emerged demonstrating higher incidences of acute kidney injury associated with both hypo- and hyperuricemia. In the univariate analysis, SUA ≥5.5 mg/dL was associated with a 4-fold (odds ratio [OR] 4.4; 95% confidence interval [CI], 2.4-8.2), SUA ≥6 mg/dL with a 6-fold (OR 5.9; 95% CI, 3.2-11.3), SUA ≥6.5 mg/dL with an 8-fold (OR 7.9; 95% CI, 3.9-15.8), and SUA ≥7 mg/dL with a 40-fold (OR 39.1; 95% CI, 11.6-131.8) increased risk for acute kidney injury. In the multivariate analysis, SUA ≥7 mg/dL also was associated with a 35-fold (OR 35.4; 95% CI, 9.7-128.7) increased risk for acute kidney injury. The 48-hour postoperative and hospital-stay mean peak SCr levels also were higher in the SUA ≥5.5 mg/dL group compared with the SUA <5 mg/dL group. SUA ≥7 mg/dL was associated with increased length of hospital stay (SUA <7 mg/dL, 18.5 ± 1.8 days vs SUA ≥7 mg/dL, 32.0 ± 6.8 days, P = 0.058) and a longer duration of mechanical ventilation support (SUA <7 mg/dL, 2.4 ± 0.4 days vs SUA ≥7 mg/dL, 20.4 ± 4.5 days, P = 0.001). CONCLUSION: Preoperative SUA was associated with increased incidence and risk for acute kidney injury, higher postoperative SCr values, and longer hospital length of stay and duration of mechanical ventilation support in patients undergoing cardiac surgery. A J-shaped relationship appears to exist between SUA and acute kidney injury.

Critically ill obstetric patients in an American and an Indian public hospital: comparison of case-mix, organ dysfunction, intensive care requirements, and outcomes.

OBJECTIVE: To compare case-mix, health care practices, and outcome in obstetric ICU admissions in inner-city teaching hospitals in economically developed and developing countries. DESIGN: Retrospective study. SETTING: Ben Taub General Hospital (BTGH), Houston, Texas, and King Edward Memorial Hospital (KEMH), Mumbai, India. PATIENTS: Women admitted during pregnancy or 6 weeks postpartum between 1992 and 2001. MEASUREMENTS AND RESULTS: Patients from BTGH (n=174) and KEMH (n=754) had comparable age, number of organs affected, incidence of medical disorders (30%), liver dysfunction, and thrombocytopenia. Fewer KEMH patients received prenatal care (27 vs 86%) and came to hospital within 24 h of onset of symptoms (60 vs 90%). They had higher APACHE II scores (median 16 vs 10), greater incidence of neurological (63 vs 36%), renal (50 vs 37%), and cardiovascular dysfunction (39 vs 29%). Severe malaria, viral hepatitis, cerebral venous thrombosis, and poisoning were common medical disorders. The BTGH group had higher incidence of respiratory dysfunction (59 vs 46%) and disseminated intravascular coagulation (40 vs 23%), placental anomalies, HELLP syndrome, chorioamnionitis, peripartum cardiomyopathy, puerperal sepsis, urinary infection, bacteremia, substance abuse, and asthma. More BTGH patients required mechanical ventilation and blood component therapy, whereas more KEMH patients needed dialysis. Of BTGH patients, 78.2% were delivered by cesarean section (vs 15.4%). Maternal (2.3 vs 25%) and fetal (13 vs 51%) mortality were lower in BTGH patients. CONCLUSIONS: There were marked differences in medical diseases, organ failure, and intensive care needs. Higher mortality in the Indian ICU may be due to difference in case mix, inadequate prenatal care, delay in reaching hospital, and greater severity of illness.

Prognostic factors in obstetric patients admitted to an Indian intensive care unit.

OBJECTIVES: Obstetric patients form a significant proportion of intensive care unit admissions in countries like India, where maternal mortality is high (440 per 100,000 deliveries). We studied the diseases requiring intensive care and prognostic factors in obstetric patients. DESIGN: Retrospective chart review. Acute Physiology and Chronic Health Evaluation (APACHE) II data were prospectively collected. SETTING: Multidisciplinary intensive care unit of a public hospital in Mumbai, India. PATIENTS: Women admitted during pregnancy or 6 wks post-partum during a 5-yr study period (1997-2001). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Four hundred fifty-three obstetric patients (age 25.5 +/- 4.6 yrs [mean +/- SD], mean gestational age 31 wks) were admitted (548 intensive care unit admissions per 100,000 deliveries), 138 with single organ failure and 152 with multiple organ failure. Ninety-eight women died (mortality rate 21.6%). Mortality was comparable in antepartum (n = 216) and postpartum (n = 247) admissions but increased with increasing number of organs affected. There were 236 fetal deaths (52%), of which 104 occurred before hospital admission. Median APACHE II score was 16 (interquartile range, 10-24), and standardized mortality ratio (observed deaths/predicted deaths) was 0.78. Compared with pregnant patients admitted with obstetric disorders (n = 313), those with medical diseases (n = 140) had significantly lower APACHE II scores (median 14 vs. 17) but higher observed mortality rate (28.6% vs. 18.5%; odds ratio, 1.76; 95% confidence interval, 1.08-2.87) and standardized mortality ratio (1.09 vs. 0.66). On multivariate analysis, increased mortality rate was associated with acute cardiovascular (odds ratio, 5.8), nervous system (odds ratio, 4.73) and respiratory (odds ratio, 12.9) failure, disseminated intravascular coagulation (odds ratio, 2.4), viral hepatitis (odds ratio, 5.8), intracranial hemorrhage (odds ratio, 5.4), absence of prenatal care (odds ratio, 1.94), and >24 hrs interval between onset of acute symptoms and intensive care unit admission (odds ratio, 2.3). CONCLUSIONS: Multiple organ failure is common in obstetric patients; mortality rate increases with increasing organ failure. APACHE II scores overpredict mortality rate. Standardized mortality ratio is lower in obstetric disorders than in medical disorders. Lack of prenatal care and delay in intensive care unit referral adversely affect outcome and are easily preventable.