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Role of the Furosemide Stress Test in Renal Injury Prognosis.

ABSTRACT: Risk stratification and accurate patient prognosis are pending issues in the management of patients with kidney disease. The furosemide stress test (FST) has been proposed as a low-cost, fast, safe, and easy-to-perform test to assess tubular integrity, especially when compared to novel plasma and urinary biomarkers. However, the findings regarding its clinical use published so far provide insufficient evidence to recommend the generalized application of the test in daily clinical routine. Dosage, timing, and clinical outcomes of the FST proposed thus far have been significantly different, which further accentuates the need for standardization in the application of the test in order to facilitate the comparison of results between series. This review will summarize published research regarding the usefulness of the FST in different settings, providing the reader some insights about the possible implications of FST in clinical decision-making in patients with kidney disease and the challenges that research will have to address in the near future before widely applying the FST.

SUBMITTER: Coca A

PROVIDER: S-EPMC7247682 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Role of the Furosemide Stress Test in Renal Injury Prognosis.

Coca Armando A Aller Carmen C Reinaldo Sánchez Jimmy J Valencia Ana Lucía AL Bustamante-Munguira Elena E Bustamante-Munguira Juan J

International journal of molecular sciences 20200427 9

Risk stratification and accurate patient prognosis are pending issues in the management of patients with kidney disease. The furosemide stress test (FST) has been proposed as a low-cost, fast, safe, and easy-to-perform test to assess tubular integrity, especially when compared to novel plasma and urinary biomarkers. However, the findings regarding its clinical use published so far provide insufficient evidence to recommend the generalized application of the test in daily clinical routine. Dosage ...[more]

PMID: 32349337

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Project description:BackgroundThe use of the furosemide stress test (FST) as an acute kidney injury (AKI) severity marker has been described in several trials. However, the diagnostic performance of the FST in predicting AKI progression has not yet been fully discussed.MethodsIn accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we searched the PubMed, Embase, and Cochrane databases up to March 2020. The diagnostic performance of the FST (in terms of sensitivity, specificity, number of events, true positive, false positive) was extracted and evaluated.ResultsWe identified eleven trials that enrolled a total of 1366 patients, including 517 patients and 1017 patients for whom the outcomes in terms of AKI stage progression and renal replacement therapy (RRT), respectively, were reported. The pooled sensitivity and specificity results of the FST for AKI progression prediction were 0.81 (95% CI 0.74-0.87) and 0.88 (95% CI 0.82-0.92), respectively. The pooled positive likelihood ratio (LR) was 5.45 (95% CI 3.96-7.50), the pooled negative LR was 0.26 (95% CI 0.19-0.36), and the pooled diagnostic odds ratio (DOR) was 29.69 (95% CI 17.00-51.85). The summary receiver operating characteristics (SROC) with pooled diagnostic accuracy was 0.88. The diagnostic performance of the FST in predicting AKI progression was not affected by different AKI criteria or underlying chronic kidney disease. The pooled sensitivity and specificity results of the FST for RRT prediction were 0.84 (95% CI 0.72-0.91) and 0.77 (95% CI 0.64-0.87), respectively. The pooled positive LR and pooled negative LR were 3.16 (95% CI 2.06-4.86) and 0.25 (95% CI 0.14-0.44), respectively. The pooled diagnostic odds ratio (DOR) was 13.59 (95% CI 5.74-32.17), and SROC with pooled diagnostic accuracy was 0.86. The diagnostic performance of FST for RRT prediction is better in stage 1-2 AKI compared to stage 3 AKI (relative DOR 5.75, 95% CI 2.51-13.33).ConclusionThe FST is a simple tool for the identification of AKI populations at high risk of AKI progression and the need for RRT, and the diagnostic performance of FST in RRT prediction is better in early AKI population.

Project description:ObjectivesThe furosemide stress test measures the volume of urine produced after a furosemide challenge. Furosemide stress test has previously demonstrated sensitive and specific prediction of progression to Kidney Disease: Improving Global Outcomes guideline defined acute kidney injury stage III in the ICU. Furosemide is actively excreted into the nephron lumen where it inhibits the sodium-potassium-chloride cotransporter, causing diuresis. We hypothesize that furosemide excretion is a more direct measure of tubule health than diuresis.DesignWe developed a furosemide excretion stress test to evaluate this hypothesis in a murine model of septic-acute kidney injury.SettingBasic science laboratory.SubjectsMale and female 8-week old CD-1 mice.InterventionsSepsis was induced by cecal ligation and puncture in male and female mice. Furosemide stress test/furosemide excretion stress test started 42 hours post-cecal ligation and puncture with a 1 mg/kg furosemide bolus and urine was collected for 12 hours. The mice were then euthanized or monitored until 7 days post-cecal ligation and puncture. In another cohort, mice were treated with vasopressin, which decreases urine volume. Furosemide concentration was determined by high performance liquid chromatography.Measurements and main resultsUrine production during the 12-hour collection varied from 0.08 to 2.62 mL. Both urine production (furosemide stress test) and furosemide excretion (furosemide excretion stress test) predicted mortality (area under the receiver operating characteristic curve = 0.925 and 0.916) and time of death (R 2 = 0.26 and 0.74). Male and female mice demonstrated consistent results. Following vasopressin treatment, furosemide stress test specificity fell to 33% (p = 0.016) but furosemide excretion stress test specificity was maintained.ConclusionsThe furosemide stress test and furosemide excretion stress test performed similarly in predicting mortality; however, furosemide excretion stress test was superior in predicting time to death and maintained performance when challenged with vasopressin treatment in a mouse sepsis model.

Project description:BackgroundIn sepsis, initial resuscitation with fluids is followed by efforts to achieve a negative fluid balance. However, patients with sepsis-associated acute kidney injury (SA-AKI) often need diuretic or renal replacement therapy (RRT). The dilemma is to predict whether early RRT might be advantageous or diuretics will suffice. Both the Furosemide Stress Test (FST) and measurements of the urinary biomarkers TIMP-2*IGFBP-7, if applied solely, do not provide sufficient guidance. We tested the hypothesis that a combination of two tests, i.e., an upstream FST combined with downstream measurements of urinary TIMP-2*IGFBP-7 concentrations improves the accuracy in predicting RRT necessity.MethodsIn this prospective, multicenter study 100 patients with sepsis (diagnosed < 48h), AKI stage ≥ 2, and an indication for negative fluid balance were included between 02/2020 and 12/2022. All patients received a standardized FST and urinary biomarkers TIMP-2*IGFBP-7 were serially measured immediately before and up to 12 h after the FST. The primary outcome was the RRT requirement within 7 days after inclusion.Results32% (n = 32/99) of SA-AKI patients eventually required RRT within 7 days. With the FST, urine TIMP-2*IGFBP-7 decreased within 2 h from 3.26 ng2/mL2/1000 (IQR: 1.38-5.53) to 2.36 ng2/mL2/1000 (IQR: 1.61-4.87) in RRT and 1.68 ng2/mL2/1000 (IQR: 0.56-2.94) to 0.27 ng2/mL2/1000 (IQR: 0.12-0.89) and non-RRT patients, respectively. While TIMP-2*IGFBP-7 concentrations remained low for up to 12 h in non-RRT patients, we noted a rebound in RRT patients after 6 h. TIMP-2*IGFBP-7 before FST (accuracy 0.66; 95%-CI 0.55-0.78) and the FST itself (accuracy 0.74; 95%-CI: 0.64-0.82) yielded moderate test accuracies in predicting RRT requirement. In contrast, a two-step approach, utilizing FST as an upstream screening tool followed by TIMP-2*IGFBP-7 quantification after 2 h improved predictive accuracy (0.83; 95%-CI 0.74-0.90, p = 0.03) compared to the FST alone, resulting in a positive predictive value of 0.86 (95%-CI 0.64-0.97), and a specificity of 0.96 (95%-CI 0.88-0.99).ConclusionsThe combined application of an upstream FST followed by urinary TIMP-2*IGFBP-7 measurements supports highly specific identification of SA-AKI patients requiring RRT. Upcoming interventional trials should elucidate if this high-risk SA-AKI subgroup, identified by our predictive enrichment approach, benefits from an early RRT initiation.

Project description: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.

Project description:Incomplete distal renal tubular acidosis is a well known cause of calcareous nephrolithiasis but the prevalence is unknown, mostly due to lack of accepted diagnostic tests and criteria. The ammonium chloride test is considered as gold standard for the diagnosis of incomplete distal renal tubular acidosis, but the furosemide/fludrocortisone test was recently proposed as an alternative. Because of the lack of rigorous comparative studies, the validity of the furosemide/fludrocortisone test in stone formers remains unknown. In addition, the performance of conventional, nonprovocative parameters in predicting incomplete distal renal tubular acidosis has not been studied.We conducted a prospective study in an unselected cohort of 170 stone formers that underwent sequential ammonium chloride and furosemide/fludrocortisone testing.Using the ammonium chloride test as gold standard, the prevalence of incomplete distal renal tubular acidosis was 8%. Sensitivity and specificity of the furosemide/fludrocortisone test were 77% and 85%, respectively, yielding a positive predictive value of 30% and a negative predictive value of 98%. Testing of several nonprovocative clinical parameters in the prediction of incomplete distal renal tubular acidosis revealed fasting morning urinary pH and plasma potassium as the most discriminative parameters. The combination of a fasting morning urinary threshold pH <5.3 with a plasma potassium threshold >3.8 mEq/L yielded a negative predictive value of 98% with a sensitivity of 85% and a specificity of 77% for the diagnosis of incomplete distal renal tubular acidosis.The furosemide/fludrocortisone test can be used for incomplete distal renal tubular acidosis screening in stone formers, but an abnormal furosemide/fludrocortisone test result needs confirmation by ammonium chloride testing. Our data furthermore indicate that incomplete distal renal tubular acidosis can reliably be excluded in stone formers by use of nonprovocative clinical parameters.

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Role of the Furosemide Stress Test in Renal Injury Prognosis.

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Role of the Furosemide Stress Test in Renal Injury Prognosis.

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