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A rapid urine test for early detection of kidney injury.

ABSTRACT: Kidney injury molecule-1 (Kim-1) has been qualified by the Food and Drug Administration and European Medicines Agency as a highly sensitive and specific urinary biomarker to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Here we report the development and evaluation of a rapid direct immunochromatographic lateral flow 15-min assay for detection of urinary Kim-1 (rat) or KIM-1 (human). The urinary Kim-1 band intensity using the rat Kim-1 dipstick significantly correlated with levels of Kim-1 as measured by a microbead-based assay, histopathological damage, and immunohistochemical assessment of renal Kim-1 in a dose- and time-dependent manner. Kim-1 was detected following kidney injury induced in rats by cadmium, gentamicin, or bilateral renal ischemia/reperfusion. In humans, the urinary KIM-1 band intensity was significantly greater in urine from patients with acute kidney injury than in urine from healthy volunteers. The KIM-1 dipstick also enabled temporal evaluation of kidney injury and recovery in two patients who developed postoperative acute kidney injury following cytoreductive surgery for malignant mesothelioma with intraoperative local cisplatin administration. We hope that future, more extensive studies will confirm the utility of these results, which show that the Kim-1/KIM-1 dipsticks can provide a sensitive and accurate detection of Kim-1/KIM-1, thereby providing a rapid diagnostic assay for kidney damage and facilitating the rapid and early detection of kidney injury in preclinical and clinical studies.

SUBMITTER: Vaidya VS

PROVIDER: S-EPMC2737345 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

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A rapid urine test for early detection of kidney injury.

Vaidya Vishal S VS Ford Glen M GM Waikar Sushrut S SS Wang Yizhuo Y Clement Matthew B MB Ramirez Victoria V Glaab Warren E WE Troth Sean P SP Sistare Frank D FD Prozialeck Walter C WC Edwards Joshua R JR Bobadilla Norma A NA Mefferd Stephen C SC Bonventre Joseph V JV

Kidney international 20090422 1

Kidney injury molecule-1 (Kim-1) has been qualified by the Food and Drug Administration and European Medicines Agency as a highly sensitive and specific urinary biomarker to monitor drug-induced kidney injury in preclinical studies and on a case-by-case basis in clinical trials. Here we report the development and evaluation of a rapid direct immunochromatographic lateral flow 15-min assay for detection of urinary Kim-1 (rat) or KIM-1 (human). The urinary Kim-1 band intensity using the rat Kim-1 ...[more]

PMID: 19387469

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Project description:Acute kidney injury (AKI) is common in the intensive care unit, where it is associated with increased mortality. AKI is often defined using creatinine and urine output criteria. The creatinine-based definition is more reliable but less expedient, whereas the urine output based definition is rapid but less reliable. Our goal is to examine the urine output criterion and augment it with physiological features for better agreement with creatinine-based definitions of AKI. The objectives are threefold: (1) to characterize the baseline agreement of urine output and creatinine definitions of AKI; (2) to refine the urine output criteria to identify the thresholds that best agree with the creatinine-based definition; and (3) to build generalized estimating equation (GEE) and generalized linear mixed-effects (GLME) models with static and time-varying features to improve the accuracy of a near-real-time marker for AKI. We performed a retrospective observational study using data from two independent critical care databases, MIMIC-III and eICU, for critically ill patients who developed AKI in intensive care units. We found that the conventional urine output criterion (6 hr, 0.5 ml/kg/h) has specificity and sensitivity of 0.49 and 0.54 for MIMIC-III database; and specificity and sensitivity of 0.38 and 0.56 for eICU. Secondly, urine output thresholds of 12 hours and 0.6 ml/kg/h have specificity and sensitivity of 0.58 and 0.48 for MIMIC-III; and urine output thresholds of 10 hours and 0.6 ml/kg/h have specificity and sensitivity of 0.49 and 0.48 for eICU. Thirdly, the GEE model of four hours duration augmented with static and time-varying features can achieve a specificity and sensitivity of 0.66 and 0.61 for MIMIC-III; and specificity and sensitivity of 0.66 and 0.64 for eICU. The GLME model of four hours duration augmented with static and time-varying features can achieve a specificity and sensitivity of 0.71 and 0.55 for MIMIC-III; and specificity and sensitivity of 0.66 and 0.60 for eICU. The GEE model has greater performance than the GLME model, however, the GLME model is more reflective of the variables as fixed effects or random effects. The significant improvement in performance, relative to current definitions, when augmenting with patient features, suggest the need of incorporating these features when detecting disease onset and modeling at window-level rather than patient-level.

Project description:Background: The relationship between urine output (UO) and severe-stage progression in the early phase of acute kidney injury (AKI) remains unclear. This study aimed to investigate the relationship between early-phase UO6-12h [UO within 6 h after diagnosis of stage 1 AKI by Kidney Disease: Improving Global Outcomes (KDIGO) UO criteria] and severe-stage progression of AKI and to identify a reference value of early-phase UO6-12h for guiding initial therapy in critical care. Methods: Adult patients with UO < 0.5 ml/kg/h for the first 6 h after intensive care unit (ICU) admission (meeting stage 1 AKI by UO) and UO6-12h ≥ 0.5 ml/kg/h were identified from the Medical Information Mart for Intensive Care (MIMIC) III database. The primary outcome was progression to stage 2/3 AKI by UO. After other variables were adjusted through multivariate analysis, generalized additive model (GAM) was used to visualize the relationship between early-phase UO6-12h and progression to stage 2/3 AKI by UO. A two-piecewise linear regression model was employed to identify the inflection point of early-phase UO6-12h above which progression risk significantly leveled off. Sensitivity and subgroup analyses were performed to assess the robustness of our findings. Results: Of 2,984 individuals, 1,870 (62.7%) with KDIGO stage 1 UO criteria progressed to stage 2/3 AKI. In the multivariate analysis, early-phase UO6-12h showed a significant association with progression to stage 2/3 AKI by UO (odds ratio, 0.40; 95% confidence interval, 0.34-0.46; p < 0.001). There was a non-linear relationship between early-phase UO6-12h and progression of AKI. Early-phase UO6-12h of 1.1 ml/kg/h was identified as the inflection point, above which progression risk significantly leveled off (p = 0.780). Patients with early-phase UO6-12h ≥ 1.1 ml/kg/h had significantly shorter length of ICU stay (3.82 vs. 4.17 days, p < 0.001) and hospital stay (9.28 vs. 10.43 days, p < 0.001) and lower 30-day mortality (11.05 vs. 18.42%, p < 0.001). The robustness of our findings was confirmed by sensitivity and subgroup analyses. Conclusions: Among early-stage AKI patients in critical care, there was a non-linear relationship between early-phase UO6-12h and progression of AKI. Early-phase UO6-12h of 1.1 ml/kg/h was the inflection point above which progression risk significantly leveled off.

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A rapid urine test for early detection of kidney injury.

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A rapid urine test for early detection of kidney injury.

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