Microvascular changes following exposure to iodinated contrast media in vitro. A qualitative comparison to serum creatinine concentrations in post-cardiac catheterization patients.

INTRODUCTION: Contrast-associated acute kidney injury (CA-AKI) is characterized as a loss of renal function following radiological contrast media administration. While all contrast media induce variable changes in microvascular endothelial cells in vitro, only few studies report clinical significance of their findings. A comprehensive assessment of the effect of iodinated contrast media on the renal function in vitro and in vivo is essential. The aim of our study was to morphometrically quantify the effect of two different contrast media (Iobitridol and Iodixanol) on vascular endothelial capillaries in vitro and to analyze their effect on the renal function of patients who underwent cardiac catheterization including the intra-arterial administration of contrast media, by measuring serum creatinine concentration (SCr), a byproduct of muscle metabolism, primarily excreted by the kidneys. Our hypothesis suggests that conducting a qualitative comparison of both outcomes will enable identification of differences and similarities between in vitro and in vivo exposure. MATERIAL AND METHODS: In vitro, co-cultures of human dermal fibroblasts and human dermal microvascular endothelial cells forming capillary beds were exposed to a mixture of phosphate buffered saline and either Iobitridol, Iodixanol, or one of their supplements EDTA or Trometamol for 1.5 or 5 min. Negative control co-cultures were exposed exclusively to phosphate buffered saline. Co-cultures were either directly fixed or underwent a regeneration time of 1, 3 or 7 days. An artificial intelligence software was trained for detection of labeled endothelial capillaries (CD31) on light microscope images and measurements of morphometric parameters. In vivo, we retrospectively analyzed data from patients who underwent intra-arterial administration of contrast media and for whom SCr values were available pre- and post-contrast exposition (1, 3, and 7 days following procedure). Temporal development of SCr and incidence of CA-AKI were assessed. Both exposure types were qualitatively compared. RESULTS: In vitro, Iobitridol, Iodixanol and EDTA induced a strong decrease of two morphometric parameters after 3 days of regeneration. In vivo, a significant increase of SCr and incidence of CA-AKI was observed 3 days following procedure in the post-contrast media patients. No difference was observed between groups. DISCUSSION: Two of the morphometric parameters were inversely proportional to the SCr of the patients. If the endothelial damages observed in vitro occur in vivo, it may result in renal hypoxia, inducing a loss of kidney function clinically translated into an increase of SCr. Further development of our in vitro model could allow closer replication of the internal structure of a kidney and bridge the gap between in vitro studies and their clinical findings.

Acute kidney injury in acute promyelocytic leukemia: a possible adverse effect of high dose arsenic trioxide in obese patients.

Arsenic trioxide (ATO)-based regimens are standard in acute promyelocytic leukemia (APL). ATO-related nephrotoxicity has not been reported. We reviewed APL patients treated with ATO to identify cases of acute kidney injury (AKI). Clinically significant cases were characterized. Multivariate analysis was performed to identify predictors of idiopathic, clinically significant AKI. One hundred and eight patients were included. ATO dose was 0.15 mg/kg/day using actual body weight with no dose cap. Thirty-one (28.7%) AKI cases were identified, 10 (32.3%) clinically significant. Six were idiopathic; five required dialysis. The proportion with significant, idiopathic AKI was 15.8% in patients receiving >15mg ATO versus 0% in those receiving ≤15mg (p = 0.001). On multivariate analysis, only ATO dose was a significant predictor of clinically significant AKI (odds ratio of 1.91, 95%CI, 1.19-3.07, p = 0.007). High-dose ATO may be associated with significant nephrotoxicity. We recommend that ATO dose be capped at 15 mg to minimize toxicity for this curable disease.

The impact of tubular dysfunction and its relationship with acute kidney injury in children.

BACKGROUND: Tubular dysfunction can cause electrolyte disturbances with potentially serious consequences. We studied the epidemiology and outcomes of electrolyte disturbances and tubular dysfunction among critically ill children and evaluated their relationships with acute kidney injury (AKI). METHODS: We conducted a prospective cohort study recruiting children aged 1 month to ≤ 18 years old admitted to the pediatric intensive care unit (PICU) from 6/2020 to 6/2021. The serum levels of sodium, potassium, calcium, phosphate, and magnesium were reviewed and simultaneous urinary investigations for tubular function were performed among children with electrolyte disturbances. RESULTS: Altogether there were 253 episodes of admission. The median (interquartile) age was 4.9 (1.3-11.0) years and 58.1% were male. The median number of electrolyte disorders was 3 (2-4) types. Hypophosphatemia (74.2%), hypocalcemia (70.3%) and hypermagnesemia (52.9%) were the three commonest types of disturbances. Urinary electrolyte wasting was commonly observed among children with hypomagnesemia (70.6%), hypophosphatemia (67.4%) and hypokalemia (28.6%). Tubular dysfunction was detected in 82.6% of patients and urinary ß2-microglobulin level significantly correlated with the severity of tubular dysfunction (p < 0.001). The development of tubular dysfunction was independent of AKI status. Tubular dysfunction was associated with mortality (p < 0.001) and was an independent predictor of PICU length of stay (LOS) (p < 0.001). The incorporation of the tubular dysfunction severity into the AKI staging system improved the prediction of PICU LOS. CONCLUSIONS: Tubular dysfunction was associated with both morbidity and mortality in critically ill children and its assessment may help to capture a more comprehensive picture of acute kidney insult.

Development and validation of a model to predict acute kidney injury following high-dose methotrexate in patients with lymphoma.

STUDY OBJECTIVE: To develop and validate a model for predicting acute kidney injury (AKI) after high-dose methotrexate (HDMTX) exposure. DESIGN: Retrospective analysis. SETTING: Multisite integrated health system throughout Minnesota and Wisconsin. PATIENTS: Adult patients with lymphoma who received HDMTX as a 4-h infusion. MEASUREMENTS AND MAIN RESULTS: LASSO methodology was used to identify factors available at the outset of therapy that predicted incident AKI within 7 days following HDMTX. The model was then validated in an independent cohort. The incidence of AKI within 7 days following HDMTX was 21.6% (95% confidence interval (CI) 18.4%-24.8%) in the derivation cohort (435 unique patients who received a total of 1642 doses of HDMTX) and 15.6% (95% CI 5.3%-24.8%) in the validation cohort (55 unique patients who received a total of 247 doses of HDMTX). Factors significantly associated with AKI after HDMTX in the multivariable model included age ≥ 55 years, male sex, and lower HDMTX dose number. Other factors that were not found to be significantly associated with AKI on multivariable analysis, but were included in the final model, were body surface area, Charlson Comorbidity Index, and estimated glomerular filtration rate. The c-statistic of the model was 0.72 (95% CI 0.69-0.75) in the derivation cohort and 0.72 (95% CI 0.60-0.84) in the validation cohort. CONCLUSION: This model utilizing identified sociodemographic and clinical factors is predictive of AKI following HDMTX administration in adult patients with lymphoma.

Vitamin D Deficiency Is Associated With Increased Length of Stay After Acute Burn Injury: A Multicenter Analysis.

In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis and infectious complications. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS). This was a multicenter retrospective study of adult patients at 7 burn centers admitted over a 3.5-year period, who had a 25-hydroxyvitamin D concentration drawn within the first 7 days of injury. Of 1147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, P < .001), acute kidney injury (AKI) requiring renal replacement therapy (7.3 vs 1.7%, P = .009), more days requiring vasopressors (mean 1.24 vs 0.58 days, P = .008), and fewer ventilator-free days of the first 28 days (mean 22.9 vs 25.1, P < .001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, vitamin D deficiency was associated with longer LOS. In conclusion, patients with thermal injuries and vitamin D deficiency on admission have increased LOS and worsened clinical outcomes when compared with patients with nondeficient vitamin D concentrations.

Acute kidney injury in critically ill children with COVID-19 and MIS-C.

BACKGROUND: This study's objective was to investigate the incidence of acute kidney injury (AKI) in children with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C) and to report our clinical experience. METHODS: Acute COVID-19 and MIS-C-diagnosed patients observed in two pediatric intensive care units (PICUs) between 2019 and 2021 were examined for AKI and retrospectively compared to children with AKI. RESULTS: The study comprised 163 children, of whom 98 (60.1%) were diagnosed with acute COVID-19 and 65 (39.9%) with MIS-C. AKI was observed in 40 (40.8%) of the acute COVID-19 patients and 18 (27.7%) of the MIS-C patients. Low calcium level and hypotension were linked with AKI at initial presentation (OR: 0.56, 95% CI: 0.369-0.560, p = 0.006 and OR: 3.64, 95% CI: 1.885-7.152, p = 0.001, respectively). A history of nephrotoxic medication usage played an essential role in the development of AKI in patients who acquired AKI after hospitalization (p = 0.001, odds ratio: 9.32, confidence interval: 3.106-27.973). In clinical practice, individuals with respiratory distress and cough had a high chance of having AKI (OR: 4.47, 95% confidence interval: 2.25-8,892 and OR: 3.48, 95% confidence interval: 1.76-6.88). AKI patients had a greater demand for respiratory assistance and a longer period of stay in the PICU. CONCLUSIONS: AKI in the COVID-19 and MIS-C patient groups is related with increased mortality and extended hospitalization, according to the findings. These statistics imply that identifying and preventing risk factors is necessary. A higher resolution version of the Graphical abstract is available as Supplementary information.

Associations between Serum 25-hydroxyvitamin D, Sun Exposure Time, Dietary Vitamin D Intake, and New-Onset Acute Kidney Injury among 413,169 UK Adults.

BACKGROUND: The prospective associations of serum 25(OH)D, sun exposure time, and dietary vitamin D with risk of acute kidney injury (AKI) are unclear. OBJECTIVES: We aimed to evaluate the relations of serum 25(OH)D, sun exposure time, and dietary vitamin D intake with new-onset AKI and examine whether genetic susceptibility modified such associations. METHODS: A total of 413,169 participants (mean age was 56.4 y, 47.2% were male) from UK Biobank without prior AKI were included. Sun exposure time was expressed as time spent outdoors. Genetic risk scores were calculated by 263 single nucleotide polymorphisms, which showed significant associations with the estimated glomerular filtration rate. The primary outcome was new-onset AKI. Cox proportional hazards models were used to estimate the HRs and (95% CIs). RESULTS: During a median follow-up duration of 12 y, 16,938 (4.1%) participates developed new-onset AKI. Compared with those with serum 25(OH)D <25 nmol/L, significantly lower risks of new-onset AKI were found between participants with 25(OH)D 25 to <50 nmol/L (adjusted HR: 0.76; 95% CI: 0.73, 0.80), and ≥50 nmol/L (adjusted HR: 0.69; 95% CI: 0.65, 0.72). Moreover, in summer, participants who spent ≥4 h outdoors per day (tertile 3) had a significantly lower risk of new-onset AKI (adjusted HR: 0.90; 95% CI: 0.86, 0.95) than those who spent <2 h outdoors per day (tertile 1). Similar results were found for time spent outdoors in winter. In addition, those in quintile 5 of dietary vitamin D intake showed a lower risk of new-onset AKI (≥4.2 µg/d, adjusted HR: 0.90; 95% CI: 0.82, 0.98) than those in quintile 1 (<1.0 µg/d). Genetic risks of kidney diseases did not significantly modify all the 3 above associations (all P-interactions >0.05). CONCLUSIONS: Serum 25(OH)D concentrations, time spent outdoors, and dietary vitamin D intake were all inversely associated with new-onset AKI, independent of genetic risks for kidney diseases.

A Retrospective Chart Review to Determine Hypophosphatemia Incidence and Phosphorus Supplementation Requirements in Patients With Severe Thermal Cutaneous Injuries Receiving High-Volume Hemofiltration.

Patients with severe thermal injuries have increased metabolic demands necessitating frequent phosphate supplementation. Patients with acute renal failure may have less requirements, due to reduced elimination. However, patients being supported with renal replacement therapy have varying degree of requirements. Little published evidence depicts the incidence of hypophosphatemia and repletion requirements in patients with severe thermal injuries treated with high-volume hemofiltration (HVHF) and a high-flux membrane. The objective of this retrospective chart review was to determine the incidence of hypophosphatemia and characterize repletion requirements and response in this population. Enrolled patients had at least 20% TBSA thermal injuries and required continuous hemofiltration with prefilter replacement fluid doses ≥35 mL/kg IBW/hr. A randomly selected cohort without acute kidney injury (AKI) and matched based on age and extent of TBSA was used to compare phosphorus requirements over an initial 14-day period. Demographics, diet, and variables affecting phosphorus concentrations were collected. Sixteen patients were included in the retrospective HVHF group and 16 patients in a case-control cohort to better depict the impact of HVHF. The average age was 60.2 ± 15.1 years and median TBSA was 30% (23.4, 56.3) in the HVHF group, compared to 53.3 ± 16.4 years (P = .22) and TBSA 29% (26.4, 33.9; P = .73). All patients in the HVHF group were started on HVHF with a 1.6 m2 polyethersulfone membrane for AKI. As expected, the HVHF group exhibited statistically higher than normal baseline potassium and phosphorous laboratory values. The HVHF group experienced more days with hypophosphatemia (49.6 ± 12.4% vs 29.3 ± 16.3%, P = .012), despite 0.75 mmol/kg/day phosphorous supplementation (compared to 0.66 mmol/kg/day for the control group, P = .45). Patients with longer durations of HVHF therapy experienced increasing risk of hypophosphatemia, reaching 100% by the end of the study period. This study demonstrates severe thermally injured patients receiving HVHF for AKI are at increased risk for hypophosphatemia, and require high phosphate supplementation.

Acute kidney injury in the tropics.

The tropics are a region consisting of more than 125 countries, accounting for 40% of the world's population. The region's population is expected to increase up to 60% in the coming decades. Many tropical countries continue to experience public health problems such as high rates of infectious diseases, lack of sanitation, climate change impacts, poor regulation of herbal medicines and low access to healthcare. These conditions produce the unique problem of tropical acute kidney injury (AKI), which is associated with high morbidity and mortality. Tropical infections such as leptospirosis, dengue and malaria have varied mechanisms of AKI, including both direct kidney invasion and indirect effects, depending on the disease characteristics. Animal toxins from snakebites and arthropods along with plant toxins, such as djenkol beans, starfruit and herbal medicine, are characterized by a harmful renal effect from each toxic substance. Environmental factors such as heat stress, natural disasters and chemical compounds also lead to AKI and have a systemic effect from their own pathogenesis. The long-term kidney prognosis varies among these etiologies depending on the cause and severity of disease. However, all these conditions are potentially preventable and treatable. Prompt management and good preventive approaches are needed. This article will focus on the epidemiology, pathogenesis and management of AKI associated with tropical infections, toxins and environment impacts.

Effect of Ascorbic Acid on Cardiac Surgery-Associated Acute Kidney Injury Incidence.

OBJECTIVES: Acute kidney injury (AKI) is associated with higher perioperative mortality and morbidity. Oxidative stress has been proposed as a cause of postoperative AKI. Ascorbic acid (AA) supplementation was suggested as a novel and promising antioxidant. The aim of this study was to evaluate the capability of AA to reduce the incidence of postoperative AKI in cardiac surgery patients. METHODS: A prospective randomized trial was conducted in patients scheduled for on-pump cardiac surgery. Subjects in the AA group received 2 g of AA intravenously during the induction of anesthesia, 2 g before aortic cross-clamp removal and 1 g every 8 hours for five postoperative days (the JERICA protocol). Postoperatively, the patients were monitored for AKI and other complications. Malondialdehyde levels were monitored in a subpopulation of 100 patients to evaluate the effect of AA on oxidative stress level. RESULTS: The AA and control group consisted of 163 and 169 patients, respectively. The groups were well matched for baseline demographics and had similar intraoperative characteristics. The incidence of AKI in the AA and control group was 20.9 and 28.4%, respectively (p = 0.127). The estimated glomerular filtration rate did not differ between the study groups in the entire postoperative period. There was a trend toward higher malondialdehyde values with statistical significance on postoperative day 1 and lower in-hospital mortality in the AA group (0.6 vs. 4.1%, p = 0.067). CONCLUSION: Our results do not support the effectiveness of AA supplementation in reducing the incidence of postoperative AKI in on-pump cardiac surgery patients. CLINICAL REGISTRATION NUMBER: This study was registered with the ISRCTN Registry under the trial registration number ISRCTN98572043.

N-Acetylcysteine's Renoprotective Effect in Cardiac Surgery: A Systematic Review and Meta-Analysis.

OBJECTIVE: To examine N-acetylcysteine's (NAC's) renoprotective effect in adult cardiac surgeryMethods: PubMed, Ovid Medline, and Embase were searched for randomized controlled trials published between January 1990 and May 2021 that investigated the effect of NAC in preventing acute kidney injury (AKI) in patients undergoing cardiac surgery. The inclusion criterion was studies that assessed the effect of NAC in comparison to placebo by measuring the incidence of AKI. RESULTS: Overall meta-analytic estimates of all 10 included trials showed that NAC did not have a significant effect (odds ratio [OR]: 0.84, 95% confidence interval [CI]: 0.64-1.10) on AKI. Further subgroup analysis did not show a significant benefit of NAC in preventing AKI. CONCLUSION: This meta-analysis suggests that NAC does not have a significant effect in reducing the incidence of AKI. However, there is notable heterogeneity among the included studies that could possibly account for the non-significant effect observed. It is worth noting that only one trial administered NAC high dosages perioperatively, and it is the only included trial to show a significant benefit in reducing the incidence of AKI (OR: 0.30, 95% CI: 0.11-0.81). Further studies on this dosage and duration of administration should be conducted to best elucidate the effect of administering NAC.

Outpatient vancomycin therapy: Acute kidney injury in individualized AUC-based goal trough ranges versus traditional trough dosing.

BACKGROUND: Recent changes to vancomycin guidelines recommend area under the curve concentration (AUC) monitoring in most patients, owing to similar effectiveness and reduced rates of acute kidney injury (AKI). OBJECTIVE: The purpose of this study was to assess the incidence of AKI in patients receiving vancomycin dosed by AUC-based goal troughs and vancomycin dosed by traditional trough goals (15-20 mcg/mL) in the outpatient setting. METHODS: Patients were included if they received vancomycin outpatient for at least 1 week. The primary objective was comparing the incidence of AKI in patients receiving vancomycin as an outpatient with trough goals derived from patient-specific AUC calculations determined as an inpatient with that of patients receiving vancomycin by traditional goal troughs. Secondary objectives included assessing the rate of treatment failure, AUC estimated trough range, and number of regimen changes required. RESULTS: There were 65 patients in the traditional trough dosing group and 53 patients in the AUC trough dosing group. The incidence of AKI was lower in the AUC trough group (5.7% vs. 23.1%; P = 0.01). There were no differences in the incidence of treatment failure. The median AUC estimated trough range was 11.4-17.1 mcg/mL. There were statistically significant less average regimen changes required in the AUC dosing group (1.13 vs. 1.64; P = 0.006). CONCLUSION: There was a statistically significant lower incidence of AKI in patients receiving vancomycin dosed by individualized AUC-based trough ranges compared with that of patients receiving traditional trough dosing. Developing a process for individualized AUC-based trough ranges can facilitate a convenient monitoring method to use the benefits of vancomycin AUC dosing as an outpatient.

Ionic homeostasis, acid-base balance and the risk of citrate accumulation in patients after cardiovascular surgery treated with continuous veno-venous haemofiltration with post-dilution regional citrate anticoagulation - An observational case-control study.

BACKGROUND: Patients after cardiovascular surgery, requiring renal replacement therapy, can benefit from adequate non-heparin circuit anticoagulation. Simplified regional citrate anticoagulation (RCA) protocol proposes the use of citric acid dextrose formula A (ACD-A) during post-dilutional continuous veno-venous hemofiltration (CVVH) with standard bicarbonate buffered calcium containing replacement solution. Citrate accumulation diagnosed upon total to ionized calcium ratio (tCa/iCa) and low ionized calcium (iCa) are considered as the biggest risks related to regional citrate accumulation. METHODS: This prospective observational case-control study evaluated electrolyte and acid-base homeostasis in cardiovascular surgery patients treated with post-dilution CVVH with a simplified RCA protocol with ACD-A. In total, 50 consecutive cardiovascular surgery patients were evaluated. Base excess, pH, bicarbonate, lactate, Na+, Cl-, Mg++, and inorganic phosphate concentrations, the total to ionized calcium ratio (tCa/iCa), and high anion gap metabolic acidosis were assessed during haemofiltration treatment in survivors and non-survivors. RESULTS: Thirty-three (66%) patients died. The therapies were very well balanced in sodium and chloride homeostasis. The lactate concentration and anion gap decreased during CVVH sessions lasting longer than 72 hours, but no inter-group difference was observed. The tCa/iCa ratio exceeded 4.5% and was significantly higher in non-survivors (p=0.037). Initial lactate concentration did not correlate with tCa/iCa ratio during haemofiltration. Magnesium and phosphate concentrations decreased and additional supplementation with magnesium was necessary. The magnesium concentration was lower in the non-survivors. CONCLUSIONS: The incidence of citrate accumulation exceeded 4% and was significantly higher in non-survivors. Supplementation with magnesium and phosphate ions is needed in CVVH with RCA.

Comprehensive versus standard care in post-severe acute kidney injury survivors, a randomized controlled trial.

BACKGROUND: Currently, there is a lack of evidence to guide optimal care for acute kidney injury (AKI) survivors. Therefore, post-discharge care by a multidisciplinary care team (MDCT) may improve these outcomes. This study aimed to demonstrate the outcomes of implementing comprehensive care by a MDCT in severe AKI survivors. METHODS: This study was a randomized controlled trial conducted between August 2018 to January 2021. Patients who survived severe AKI stage 2-3 were enrolled and randomized to be followed up with either comprehensive or standard care for 12 months. The comprehensive post-AKI care involved an MDCT (nephrologists, nurses, nutritionists, and pharmacists). The primary outcome was the feasibility outcomes; comprising of the rates of loss to follow up, 3-d dietary record, drug reconciliation, and drug alert rates at 12 months. Secondary outcomes included major adverse kidney events, estimated glomerular filtration rate (eGFR), and the amount of albuminuria at 12 months. RESULTS: Ninety-eight AKI stage 3 survivors were enrolled and randomized into comprehensive care and standard care groups (49 patients in each group). Compared to the standard care group, the comprehensive care group had significantly better feasibility outcomes; 3-d dietary record, drug reconciliation, and drug alerts (p < 0.001). The mean eGFR at 12 months were comparable between the two groups (66.74 vs. 61.12 mL/min/1.73 m2, p = 0.54). The urine albumin: creatinine ratio (UACR) was significantly lower in the comprehensive care group (36.83 vs. 177.70 mg/g, p = 0.036), while the blood pressure control was also better in the comprehensive care group (87.9% vs. 57.5%, p = 0.006). There were no differences in the other renal outcomes between the two groups. CONCLUSIONS: Comprehensive care by an MDCT is feasible and could be implemented for severe AKI survivors. MDCT involvement also yields better reduction of the UACR and better blood pressure control. Trial registration Clinicaltrial.gov: NCT04012008 (First registered July 9, 2019).

Acute Kidney Injury After CT in Emergency Patients with Chronic Kidney Disease: A Propensity Score-matched Analysis.

INTRODUCTION: Acute kidney injury (AKI) after intravenous contrast administration for computed tomography (CT) occurs infrequently, but certain patients may be susceptible. This study evaluated AKI incidence among emergency department (ED) patients with pre-existing chronic kidney disease (CKD) undergoing CT exams. METHODS: This retrospective cohort study in an integrated healthcare system included ED patients previously diagnosed with CKD stages 3-5 (estimated glomerular filtration rate <60 milliliters per minute per 1.73 meters squared over at least three months), undergoing CT exams with or without intravenous contrast, from January 1, 2013-December 31, 2017. We excluded patients with CT prior to (30 days) or following (14 days) index CT and missing serum creatinine (sCr) measurements. We applied propensity score matching, and then multivariable regression adjustment for post-CT ED disposition and ED diagnosis, to calculate adjusted risk of AKI. Secondary patient-centered outcomes included 30-day mortality, end-stage renal disease (ESRD) diagnosis, and dialysis initiation. RESULTS: Among 103,573 eligible ED patients undergoing CT, propensity score matching yielded 5,589 pairs. Adjusted risk ratio (ARR) for AKI was higher overall for contrast-enhanced CT (1.60; 95% confidence interval [CI], 1.43-1.79). However, secondary outcomes were infrequent: 19/5,589 non-contrast vs 40/5,589 contrast patients with new dialysis initiation at 30 days (adjusted risk 0.3% vs 0.7%; adjusted risk reduction 0.4%; 95% CI, 0.1%-0.7%). CONCLUSION: In ED patients with chronic kidney disease undergoing CT, intravenous contrast was associated with higher overall adjusted risk of AKI, but patient-centered secondary outcomes were rare. The clinical significance of transient kidney injury after CT is unclear, although patients with advanced chronic kidney disease appear to have elevated risk.

Early, empiric high-dose leucovorin rescue in lymphoma patients treated with sequential doses of high-dose methotrexate.

BACKGROUND: In patients exposed to high-dose methotrexate (HDMTX; >1g/m2) with a history of elevated methotrexate (MTX) concentrations during previous doses, it is unclear whether prescribing high-dose leucovorin (HDLV) rescue limits future high levels or reduces the likelihood of acute kidney injury (AKI). METHODS: This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (>1.0 µmol/L) and incident AKI after each HDMTX dose. RESULTS: The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75-4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38-3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5-1.7, p < 0.001). CONCLUSION: Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

Trends in the incidence and prevalence of end-stage renal disease with hemodialysis in entire Korean population: A nationwide population-based study.

ABSTRACT: Data on the overall epidemiology and temporal trends of end-stage renal disease (ESRD) requiring hemodialysis in Korea are scarce. We aimed to estimate the prevalence and incidence of ESRD requiring hemodialysis in Korea between 2002 and 2017.Using the National Health Insurance Service database, we analyzed data from the entire Korean population between 2002 and 2017. Hemodialysis patients were identified using rare incurable disease codes (V001) or prescription of medical fee codes of hemodialysis (O7020 and O7021). We only included patients who had been maintained on hemodialysis for more than 90 days from the date of dialysis initiation, to exclude patients who required short-term dialysis for acute kidney injury, conversion to peritoneal dialysis, or kidney transplantation.During the 16-year follow-up, the number of hemodialysis patients in Korea has steadily increased from 11,215 in 2002 to 67,486 in 2017. The mean age of these patients has gradually increased from 55.57 ±â€Š13.31 years in 2002 to 62.13 ±â€Š13.23 years in 2017. In 2017, the crude prevalence rate of hemodialysis was 1303.4 per million population. Overall, the number of men tended to be somewhat higher than that of women, and the proportion of men increased slightly from 55.56% in 2002 to 58.45% in 2017. The proportion of diabetic patients increased rapidly from 23.84% to 47.84%, and the percentage of dyslipidemic patients rose from 18.9% to 86.7%. The number of incident hemodialysis patients increased significantly from 4406 in 2003 to 12,134 in 2014, and then decreased to 8090 in 2017. In the incident cases of hemodialysis, the observed increase in the proportion of male patients and in diabetes and dyslipidemia were similar to that of prevalent patients. The more recent era of hemodialysis initiation, the better 5-year survival rates were observed.The prevalence and incidence of hemodialysis in Korea gradually increased between 2002 and 2017. The proportion of men, and patients with diabetes and dyslipidemia requiring hemodialysis also increased continuously. The survival rate of hemodialysis patients was gradually improving. These findings may serve as a reference for future epidemiological studies on hemodialysis in Korea.

The monitoring of vancomycin: a systematic review and meta-analyses of area under the concentration-time curve-guided dosing and trough-guided dosing.

BACKGROUND: This systematic review and meta-analysis explored the relationship between vancomycin (VCM) monitoring strategies and VCM effectiveness and safety. METHODS: We conducted our analysis using the MEDLINE, Web of Sciences, and Cochrane Register of Controlled Trials electronic databases searched on August 9, 2020. We calculated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Adult patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteraemia with VCM trough concentrations ≥15 µg/mL had significantly lower treatment failure rates (OR 0.63, 95% CI 0.47-0.85). The incidence of acute kidney injury (AKI) increased with increased trough concentrations and was significantly higher for trough concentrations ≥20 µg/mL compared to those at 15-20 µg/mL (OR 2.39, 95% CI 1.78-3.20). Analysis of the target area under the curve/minimum inhibitory concentration ratios (AUC/MIC) showed significantly lower treatment failure rates for high AUC/MIC (cut-off 400 ± 15%) (OR 0.28, 95% CI 0.18-0.45). The safety analysis revealed that high AUC value (cut-off 600 ± 15%) significantly increased the risk of AKI (OR 2.10, 95% CI 1.13-3.89). Our meta-analysis of differences in monitoring strategies included four studies. The incidence of AKI tended to be lower in AUC-guided monitoring than in trough-guided monitoring (OR 0.54, 95% CI 0.28-1.01); however, it was not significant in the analysis of mortality. CONCLUSIONS: We identified VCM trough concentrations and AUC values that correlated with effectiveness and safety. Furthermore, compared to trough-guided monitoring, AUC-guided monitoring showed potential for decreasing nephrotoxicity.

Acute Kidney Injury Impacts on Hypokalemia Associated with Yokukansan Preparation: A Retrospective Observational Study.

The time course of acute kidney injury and hypokalemia remains unelucidated. We investigated whether altered renal function impacts hypokalemia and clinical predictors for acute kidney injury in patients who used Yokukansan preparation. We performed a secondary analysis of retrospective observational cohort data from adult patients who started Yokukansan preparation. The study was conducted from June 2015 to May 2019 at Tokyo Women's Medical University, Medical Center East. The effect of acute kidney injury (>1.5-fold increase from baseline serum creatinine level) or renal function recovery on hypokalemia (serum potassium level <3.0 mEq/L) was investigated. The clinical predictors for acute kidney injury were determined using a multivariate Cox proportional hazard analysis. Out of 258 patients, 12 patients had both outcomes, and all but one patient experienced in the order of acute kidney injury and hypokalemia. Excluding one patient, hypokalemia occurred in 11/34 (32%) patients after acute kidney injury and 27/223 (12%) patients without acute kidney injury (p = 0.005). Hypokalemia occurred in 9/25 (36%) of acute kidney injury with recovery, 2/9 (22%) of acute kidney injury without recovery, and 27/223 (12%) of no acute kidney injury (p = 0.014). Patients with acute kidney injury showed a late onset of hypokalemia compared with those without acute kidney injury (p = 0.001). In 258 patients, multivariate Cox proportional hazard analysis showed that high systolic blood pressure and mean arterial pressure increased the risk of acute kidney injury. Clinicians should remember that hypokalemia developed after acute kidney injury while Yokukansan preparation treatment.

Management of Heart Failure Patient with CKD.

CKD is common in patients with heart failure, associated with high mortality and morbidity, which is even higher in people undergoing long-term dialysis. Despite increasing use of evidence-based drug and device therapy in patients with heart failure in the general population, patients with CKD have not benefitted. This review discusses prevalence and evidence of kidney replacement, device, and drug therapies for heart failure in CKD. Evidence for treatment with ß-blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, and sodium-glucose cotransporter inhibitors in mild-to-moderate CKD has emerged from general population studies in patients with heart failure with reduced ejection fraction (HFrEF). ß-Blockers have been shown to improve outcomes in patients with HFrEF in all stages of CKD, including patients on dialysis. However, studies of HFrEF selected patients with creatinine <2.5 mg/dl for ACE inhibitors, <3.0 mg/dl for angiotensin-receptor blockers, and <2.5 mg/dl for mineralocorticoid receptor antagonists, excluding patients with severe CKD. Angiotensin receptor neprilysin inhibitor therapy was successfully used in randomized trials in patients with eGFR as low as 20 ml/min per 1.73 m2 Hence, the benefits of renin-angiotensin-aldosterone axis inhibitor therapy in patients with mild-to-moderate CKD have been demonstrated, yet such therapy is not used in all suitable patients because of fear of hyperkalemia and worsening kidney function. Sodium-glucose cotransporter inhibitor therapy improved mortality and hospitalization in patients with HFrEF and CKD stages 3 and 4 (eGFR>20 ml/min per 1.73 m2). High-dose and combination diuretic therapy, often necessary, may be complicated with worsening kidney function and electrolyte imbalances, but has been used successfully in patients with CKD stages 3 and 4. Intravenous iron improved symptoms in patients with heart failure and CKD stage 3; and high-dose iron reduced heart failure hospitalizations by 44% in patients on dialysis. Cardiac resynchronization therapy reduced death and hospitalizations in patients with heart failure and CKD stage 3. Peritoneal dialysis in patients with symptomatic fluid overload improved symptoms and prevented hospital admissions. Evidence suggests that combined cardiology-nephrology clinics may help improve management of patients with HFrEF and CKD. A multidisciplinary approach may be necessary for implementation of evidence-based therapy.