Drug induced kidney injury is a frequent adverse event which contributes to morbidity and increased healthcare utilization. Our current knowledge of drug induced kidney disease is limited due to varying definitions of kidney injury, incomplete assessment of concurrent risk factors and lack of long term outcome reporting. Electronic surveillance presents a powerful tool to identify susceptible populations, improve recognition of events and provide decision support on preventative strategies or early intervention in the case of injury. Research in the area of biomarkers for detecting kidney injury and genetic predisposition for this adverse event will enhance detection of injury, identify those susceptible to injury and likely mitigate risk. In this review we will present a 6R framework to identify and mange drug induced kidney injury - risk, recognition, response, renal support, rehabilitation and research.

Objective

Regional citrate anticoagulation (RCA) is the preferred anticoagulation method for continuous kidney replacement therapy (CKRT) recommended by KDIGO. Limited availability of calcium-free solutions often imposes challenges to the implementation of RCA for CKRT (RCA-CKRT). The principal purpose of this study was to characterize the outcomes of RCA-CKRT using calcium-containing solutions.

Study design

Retrospective cohort study.

Setting & participants

We evaluated the safety and efficacy of RCA-CKRT with calcium-containing dialysate and replacement fluid used for 128 patients. A total of 571 filters and 1,227 days of CKRT were analyzed.

Exposures

Liver disease, sepsis in the absence of liver disease, and sepsis with liver disease.

Outcomes

Filter life and metabolic complications per 100 CKRT days.

Analytical approach

Linear mixed-effects model and generalized linear mixed-effects models.

Results

The majority of patients were male (91; 71.1%), 32 (25%) had liver disease, and 29 (22.7%) had sepsis without liver disease. Median filter life was 50.0 (interquartile range, 22.0-118.0) hours, with a maximum of 322 hours, and was significantly lower (33.5 [interquartile range, 17.5-60.5] h) in patients with liver disease. Calcium-containing replacement solutions were used in 41.6% of all CKRT hours and reduced intravenous calcium requirements by 31.7%. Hypocalcemia (ionized calcium<0.85mmol/L) and hypercalcemia (total calcium>10.6mg/dL) were observed in 6.0 and 6.7 per 100 CKRT days, respectively. Citrate accumulation was observed in 13.3% of all patients and was associated with metabolic acidosis in 3.9%, which was not significantly different in patients with liver disease (9.3%; P = 0.2).

Limitations

Lack of control groups that used calcium-free dialysate and replacement solutions with RCA-CKRT. Possible overestimation of filter life from incomplete data on cause of filter failure.

Conclusions

Our study suggests that RCA-CKRT with calcium-containing solutions is feasible and safe in critically ill patients, including those with sepsis and liver disease.

Background

Intradialytic hypotension (IDH) is a frequent complication of intermittent hemodialysis (IHD), occurring from 15 to 50% of ambulatory sessions, and is more frequent among hospitalized patients with hypoalbuminemia. IDH limits adequate fluid removal and increases the risk for vascular access thrombosis, early hemodialysis (HD) termination, and mortality. Albumin infusion before and during therapy has been used for treating IDH with the varying results. We evaluated the efficacy of albumin infusion in preventing IDH during IHD in hypoalbuminemic inpatients.

Methods

A randomized, crossover trial was performed in 65 AKI or ESKD patients with hypoalbuminemia (albumin < 3 g/dl) who required HD during hospitalization. Patients were randomized to receive 100 ml of either 0.9%sodium chloride or 25% albumin intravenously at the initiation of each dialysis. These two solutions were alternated for up to six sessions. Patients' vital signs and ultrafiltration removal rate were recorded every 15 to 30 min during dialysis. IDH was assessed by different definitions reported in the literature. All symptoms associated with a noted hypotensive event as well as interventions during the dialysis were recorded.

Results

Sixty-five patients were submitted to 249 sessions; the mean age was 58 ([Formula: see text] 12), and 46 (70%) were male with a mean weight of 76 ([Formula: see text] 18) kg. The presence of IDH was lower during albumin sessions based on all definitions. The hypotension risk was significantly decreased based on the Kidney Disease Outcomes Quality Initiative definition; (15% with NS vs. 7% with albumin, p = 0.002). The lowest intradialytic SBP was significantly worse in patients who received 0.9% sodium chloride than albumin (NS 83 vs. albumin 90 mmHg, p = 0.035). Overall ultrafiltration rate was significantly higher in the albumin therapies [NS - 8.25 ml/kg/h (- 11.18 5.80) vs. 8.27 ml/kg/h (- 12.22 to 5.53) with albumin, p = 0.011].

Conclusion

In hypoalbuminemic patients who need HD, albumin administration before the dialysis results in fewer episodes of hypotension and improves fluid removal. Albumin infusion may be of benefit to improve the safety of HD and achievement of fluid balance in these high-risk patients. ClinicalTrials.gov Identifier: NCT04522635.

The Brazilian Amazon is a vast area with limited health care resources. To assess the epidemiology of critically ill acute kidney injury (AKI) patients in this area, a prospective cohort study of 1029 adult patients of the three intensive care units (ICUs) of Rio Branco city, the capital of Acre state, were evaluated from February 2014 to February 2016. The incidence of AKI was 53.3%. Risk factors for AKI included higher age, nonsurgical patients, admission to the ICU from the ward, higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores at ICU admission, and positive fluid balance > 1500 ml/24 hours in the days before AKI development in the ICU, with aOR of 1.3 (95% CI 1.03-1.23), 1.47 (95% CI 1.07-2.03), 1.96 (95% CI 1.40-2.74), 1.05 (95% CI 1.03-1.08) for each unit increase, and 1.62 (95% CI 1.16-2.26), respectively. AKI was associated with higher ICU mortality (aOR 2.03, 95% CI 1.29-3.18). AKI mortality was independently associated with higher age, nonsurgical patients, sepsis at ICU admission, presence of shock or use of vasoactive drugs, mechanical ventilation and mean positive fluid balance in the ICU > 1500 ml/24 hours, both during ICU follow-up, with aOR 1.27 (95% CI 1.14-1.43) for each 10-year increase, 1.64 (95% CI 1.07-2.52), 2.35 (95% CI 1.14-4.83), 1.88 (95% CI 1.03-3.44), 6.73 (95% CI 4.08-11.09), 2.31 (95% CI 1.52-3.53), respectively. Adjusted hazard ratios for AKI mortality 30 and 31-180 days after ICU discharge were 3.13 (95% CI 1.84-5.31) and 1.69 (95% CI 0.99-2.90), respectively. AKI incidence was strikingly high among critically ill patients in the Brazilian Amazon. The AKI etiology, risk factors and outcomes were similar to those described in high-income countries, but mortality rates were higher.

The use of mobile devices by healthcare providers has transformed many aspects of clinical practice. Mobile devices and medical applications provide many benefits, perhaps most significantly increased access to point-of-care (POC) tools, which has been shown to support better clinical decision making and improved patient outcomes. In LMICs, where computer-based technology is limited, the use of mobile technology has the potential to immensely increase access to point of care tools. In this study, we conducted an interventional, pre-post study to determine whether the use of a medical application could help healthcare providers accurately recognize and diagnose AKI. After preparing 20 clinical vignettes based on AKI cases from our center Global Snapshot study report, we asked 50 last year medical students to identify the presence and stage of AKI first without and then with the use of the IRA SLANH App (IRA SLANH app, Island of the Moon^® V.1, 2014; Cochabamba-Bolivia), which was designed specifically for this study. Before the IRA SLANH app was introduced, the mean number of correctly identified cases of AKI was 14.7 ± 4.7 with a minimum of 3 and a maximum of 20. The stage of AKI was correctly identified in only 6.7 ± 4.4 of the cases. After the app was introduced, the number of correctly identified and staged cases of AKI was 20. Medical applications are useful point-of-care tools in the practice of evidence-based medicine. Their use has the potential to play a very important role in early identification and classification of AKI, particularly in LMICs potentially allowing for earlier intervention with preventive and treatment strategies to reverse kidney injury and improve recovery.

Acute kidney injury (AKI) can potentially lead to the accumulation of antimicrobial drugs with significant renal clearance. Drug dosing adjustments are commonly made using the Cockcroft-Gault estimate of creatinine clearance (CLcr). The Modified Jelliffe equation is significantly better at estimating kidney function than the Cockcroft-Gault equation in the setting of AKI. The objective of this study is to assess the degree of antimicrobial dosing discordance using different glomerular filtration rate (GFR) estimating equations. This is a retrospective evaluation of antimicrobial dosing using different estimating equations for kidney function in AKI and comparison to Cockcroft-Gault estimation as a reference. Considering the Cockcroft-Gault estimate as the criterion standard, antimicrobials were appropriately adjusted at most 80.7% of the time. On average, kidney function changed by 30 mL/min over the course of an AKI episode. The median clearance at the peak serum creatinine was 27.4 (9.3⁻66.3) mL/min for Cockcroft Gault, 19.8 (9.8⁻47.0) mL/min/1.73 m² for MDRD and 20.5 (4.9⁻49.6) mL/min for the Modified Jelliffe equations. The discordance rate for antimicrobial dosing ranged from a minimum of 8.6% to a maximum of 16.4%. In the event of discordance, the dose administered was supra-therapeutic 100% of the time using the Modified Jelliffe equation. Use of estimating equations other than the Cockcroft Gault equation may significantly alter dosing of antimicrobials in AKI.

Background

"Dynamic" baseline serum creatinine (sCr), based on a rolling 48-h window, and a static baseline sCr (previous outpatient sCr) were used to define acute kidney injury (AKI).

Methods

Retrospective cohort study of adult admissions to the University of Alabama (UAB) Health System hospitals for years 2016-2018. Included admissions had >1- and <180-day length of stay, >2 inpatient sCr measurements, and an averaged estimated glomerular filtration rate >15 mL/min/1.73 m2. The final cohort of 62,380 patients included 100,570 admissions, 3,509 inpatient deaths, and 1,916 admissions with inpatient dialysis. AKI was defined by Kidney Disease Improving Global Outcomes (KDIGO) criteria and a static or dynamic baseline sCr. Discrimination was evaluated with area under receiver operator curves (AUC), logistic regression, and net reclassification improvement (NRI).

Results

Preadmission outpatient "static" sCr values were available for 43,433 admissions. The lowest sCr value during a rolling 48-h window before each inpatient sCr defined a "dynamic" baseline sCr. Using point-wise comparisons, the dynamic baseline sCr performed better than static baseline sCr for inpatient mortality (AUC [0.819 vs. 0.741; p < 0.001] and NRI ≥0.306 [p < 0.001]) and inpatient dialysis (AUC [0.903 vs. 0.864; p < 0.001] and NRI ≥0.317 [p < 0.001]).

Conclusions

The dynamic baseline sCr is available without reference to preadmission sCr values and avoids confounding associated with missing outpatient sCr values. AKI defined with the dynamic baseline sCr significantly improved discrimination of risk for inpatient mortality and dialysis compared to static baseline sCr.

Sepsis commonly contributes to acute kidney injury (AKI); however, the frequency with which sepsis develops as a complication of AKI and the clinical consequences of this sepsis are unknown. This study examined the incidence of, and outcomes associated with, sepsis developing after AKI. We analyzed data from 618 critically ill patients enrolled in a multicenter observational study of AKI (PICARD). Patients were stratified according to their sepsis status and timing of incident sepsis relative to AKI diagnosis. We determined the associations among sepsis, clinical characteristics, provision of dialysis, in-hospital mortality, and length of stay (LOS), comparing outcomes among patients according to their sepsis status. Among the 611 patients with data on sepsis status, 174 (28%) had sepsis before AKI, 194 (32%) remained sepsis-free, and 243 (40%) developed sepsis a median of 5 days after AKI. Mortality rates for patients with sepsis developing after AKI were higher than in sepsis-free patients (44 vs. 21%; p < 0.0001) and similar to patients with sepsis preceding AKI (48 vs. 44%; p = 0.41). Compared with sepsis-free patients, those with sepsis developing after AKI were also more likely to be dialyzed (70 vs. 50%; p < 0.001) and had longer LOS (37 vs. 27 days; p < 0.001). Oliguria, higher fluid accumulation and severity of illness scores, non-surgical procedures after AKI, and provision of dialysis were predictors of sepsis after AKI. Sepsis frequently develops after AKI and portends a poor prognosis, with high mortality rates and relatively long LOS. Future studies should evaluate techniques to monitor for and manage this complication to improve overall prognosis.

Drug-induced kidney disease is a frequent cause of renal dysfunction; however, there are no standards to identify and characterize the spectrum of these disorders. We convened a panel of international, adult and pediatric, nephrologists and pharmacists to develop standardized phenotypes for drug-induced kidney disease as part of the phenotype standardization project initiated by the International Serious Adverse Events Consortium. We propose four phenotypes of drug-induced kidney disease based on clinical presentation: acute kidney injury, glomerular, tubular, and nephrolithiasis, along with the primary and secondary clinical criteria to support the phenotype definition, and a time course based on the KDIGO/AKIN definitions of acute kidney injury, acute kidney disease, and chronic kidney disease. Establishing causality in drug-induced kidney disease is challenging and requires knowledge of the biological plausibility for the specific drug, mechanism of injury, time course, and assessment of competing risk factors. These phenotypes provide a consistent framework for clinicians, investigators, industry, and regulatory agencies to evaluate drug nephrotoxicity across various settings. We believe that this is the first step to recognizing drug-induced kidney disease and developing strategies to prevent and manage this condition.

Background

Interstitial fibrosis (IF) on kidney biopsy is one of the most potent risk factors for kidney disease progression. The furosemide stress test (FST) is a validated tool that predicts the severity of acute kidney injury (especially at 2 h) in critically ill patients. Since furosemide is secreted through the kidney tubules, the response to FST represents the tubular secretory capacity. To our knowledge there is no data on the correlation between functional tubular capacity assessed by the FST with IF on kidney biopsies from patients with chronic kidney disease (CKD). The aim of this study was to determine the association between urine output (UO), Furosemide Excreted Mass (FEM) and IF on kidney biopsies after a FST.

Methods

This study included 84 patients who underwent kidney biopsy for clinical indications and a FST. The percentage of fibrosis was determined by morphometry technique and reviewed by a nephropathologist. All patients underwent a FST prior to the biopsy. Urine volume and urinary sodium were measured in addition to urine concentrations of furosemide at different times (2, 4 and 6 h). We used an established equation to determine the FEM. Values were expressed as mean, standard deviation or percentage and Pearson Correlation.

Results

The mean age of the participants was 38 years and 44% were male. The prevalence of diabetes mellitus, hypertension and diuretic use was significantly higher with more advanced degree of fibrosis. Nephrotic syndrome and acute kidney graft dysfunction were the most frequent indications for biopsy. eGFR was inversely related to the degree of fibrosis. Subjects with the highest degree of fibrosis (grade 3) showed a significant lower UO at first hour of the FST when compared to lower degrees of fibrosis (p = 0.015). Likewise, the total UO and the FEM was progressively lower with higher degrees of fibrosis. An inversely linear correlation between FEM and the degree of fibrosis (r = - 0.245, p = 0.02) was observed.

Conclusions

Our findings indicate that interstitial fibrosis correlates with total urine output and FEM. Further studies are needed to determine if UO and FST could be a non-invasive tool to evaluate interstitial fibrosis.

Trial registration

ClinicalTrials.gov NCT02417883.