Furosemide stress test and interstitial fibrosis in kidney biopsies in chronic kidney disease

Abstract

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.

Kidney Tubulointerstitial Fibrosis and Tubular Secretion

“…29 Additionally, among patients undergoing kidney biopsy for clinical indiciations, the excretion of furosemide was found to be inversely correlated with severity of interstitial fibrosis. 30 Taken together, these findings suggest that the non-invasive assessment of secretory makers may be important in bridging the gap between functional and J o u r n a l P r e -p r o o f anatomical changes in the setting of kidney injury. Our findings add to this knowledge by demonstrating that secretory solutes, reflecting proximal tubule function, are lower in the urine relative to plasma in the setting of greater histologic tubule damage, independent of GFR.…”

The Promise of Tubule Biomarkers in Kidney Disease: A Review

“…Additional functions of the kidney tubules are not routinely measured clinically but are measurable by research assays. These include assessment of the proximal tubules' capacity to reabsorb filtered smallmolecular-weight proteins (eg, α 1 -microglobulin [A1M]), 8 the capacity of the proximal tubule to secrete endogenous metabolites (eg, hippurate) 9 or exogenous compounds (eg, furosemide), 10 the production of proteins required to maintain impermeability of water to distal tubule segments and to protect against infection (eg, uromodulin), 11 and ammonium production as a marker of the kidney tubules' ability to excrete acid. 12 These tubule biomarkers should have direct relevance to the prognosis for kidney-specific end points and also for CKD complications such as CVD, heart failure, and mortality.…”

Furosemide stress test as a predictive marker of acute kidney injury progression or renal replacement therapy: a systemic review and meta-analysis

“…Of the 29 articles, two [32,33] were suspected of using a duplicate cohort from another study [8], five were focused on child populations [11,12,[34][35][36], and three were based on kidney transplant outcomes [9,10,37]. Meanwhile, five studies reported different outcomes of interest and the remaining three did not report sufficient information for analysis [38][39][40][41][42][43][44][45] (Additional profile 1: Supplementary Table 2). As such, eleven studies were ultimately included in this meta-analytic study (Fig.…”