Urinary Biomarkers for The Prediction of Reversibility in Acute-on-Chronic Renal Failure

Abstract

Abstract. BACKGROUND:There is no reliable clinical test to predict the reversibility of acute-on-chronic renal failure. We study whether urinary biomarkers could be used as a noninvasive prognostic marker in patients with acute-on-chronic renal failure. METHODS:We studied 39 adult patients with pre-existing chronic renal impairment presenting to us with acute-on-chronic renal failure. Urinary neutrophil gelatinase-associated lipocalin (NGAL) level was measured. The mRNA of kidney injury molecule-1 (KIM-1), interleukin-18 (IL-18), alpha-1-microglobulin (α1M), sodium/hydrogen exchanger-3 (NHE3), beta-2 microglobulin (β2M), and N-acetyl-β-D-glucosaminidase (NAG) in urinary sediment were quantified. RESULTS: Urinary NGAL level significantly correlated with the serum creatinine at presentation (r = 0.762, p < 0.0001) but not baseline serum creatinine. Urinary sediment β2M expression significantly correlated with baseline glomerular filtration rate (GFR) (r = −0.400, p = 0.012). Urinary α1M and NHE3 expressions were significantly higher in ischemic acute tubular necrosis than other causes of acute kidney injury (p < 0.0001 and p = 0.006, respectively). Urinary α1M expression significantly correlated with the degree of improvement in renal function (r = 0.387, p = 0.026), as well as the estimated GFR 6 months later (r = 0.386, p = 0.027). CONCLUSION: In patients with acute-on-chronic renal failure, urinary NGAL level correlates with the severity of renal failure, while urinary α1M expression correlates with the degree of renal function recovery. Quantification of urinary α1M mRNA may be developed as an non-invasive tool for risk stratification of this group of patients.

MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets

“…Recently, miRNAs have become of great interest as sensitive, noninvasive, and precise stage‐specific diagnostic biomarkers for DN, especially because of their stability in biofluids (such as urine and plasma) and in exosomes, and because of established techniques for reliable detection and quantification by sequencing, quantitative PCR, and microarrays . Several reports now demonstrate comprehensive profiles in patient urine, urinary sediment, and serum of miRNAs that could be correlated with specific stages of DN, fibrosis, and renal function decline (estimated by glomerular filtration rate, GFR) . In particular, exosomes in urine are an extremely valuable source for miRNA profiling in renal disorders because they originate from most renal cells .…”

“…[122][123][124][125] Several reports now demonstrate comprehensive profiles in patient urine, urinary sediment, and serum of miRNAs that could be correlated with specific stages of DN, fibrosis, and renal function decline (estimated by glomerular filtration rate, GFR). 83,[126][127][128][129][130][131][132][133][134][135] In particular, exosomes in urine are an extremely valuable source for miRNA profiling in renal disorders because they originate from most renal cells. 132 For example, miR-145 was reported to be enriched in urinary exosomes from type-1 diabetic patients showing microalbuminuria and in HG-treated MCs.…”

Biomarkers of renal recovery after acute kidney injury

“…Recently, Luk et al (77) recruited 39 adult patients with pre-existing CKD who presented to the hospital with acute-on-chronic renal failure in stages I or F of the RIFLE classification (excluding patients with anuria) and collected, within the first 24 hours of admission, urine samples to examine neutrophil gelatinase-associated lipocalin (NGAL) and the mRNA expressions of kidney injury molecule-1, interleukin-18 (IL-18), alpha-1-microglobulin (α-1-M), sodium/hydrogen exchanger-3, beta-2 microglobulin and N-acetyl-β-D-glucosaminidase. During the 6-month follow-up, 24 patients experienced complete recovery (defined by authors as the plasma creatinine concentrations falling below 110% of the baseline), 7 experienced partial recovery (defined as plasma creatinine remaining above 110% of the baseline and below 90% of the plasma creatinine at presentation), and 8 experienced no recovery (defined as plasma creatinine remaining above 90% of the plasma creatinine at presentation or whenever the patient became dialysis dependent).…”

Effects of Unilateral Nephrectomy on Renal Function in Male Spontaneously Diabetic Torii Fatty Rats: A Novel Obese Type 2 Diabetic Model

“…Proteinuria has been considered a strong predictor of kidney disease outcome [24]. In addition, urinary biomarkers such as kidney injury molecule-1 (KIM-1) and N-acetyl- β -D-glucosaminidase (NAG) have been reported [25, 26]. In the further study, measuring these biomarkers may be useful to assess the severity of diabetic kidney damage.…”