Role Of Urinary Biomarkers Research Articles

Role of Urinary Biomarkers (Transforming Growth Factor β1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve.

The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients. To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters. This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls. Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 μg/ml, 0.439 μg/ml, and 0.382 μg/ml) than the control group (0.243 μg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 μg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08). The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.

SP3.9 The role of urinary biomarkers in predicting post operative kidney function

Abstract Aims Post-operative Acute Kidney Injury (AKI) has implications on recovery, conferring a significant risk of morbidity and mortality. A previous study of 488 major abdominal surgery patients demonstrated that urinary biomarkers could predict peri-operative AKI. The aim of this follow-up study was to assess the biomarkers (NGAL, KIM-1, DKK-3 and IGFBP-7*TIMP-2) for their ability to predict long-term changes in renal function. Methods Predictive ability for long term renal function derangement was assessed by classifying the participants change in their ‘CKD’ stage from the pre-operative status, determined by the measured eGFR at follow up as per the KDIGO criteria (at least 6 months from their operation). Biomarker performance was assessed utilising AUROC analysis. Biomarkers were also interrogated for their ability to predict mortality at one year. Results Follow up measurement of renal function was obtained in 446 of 488 patients. 40 patients died within 1 year of their operation. Median time of follow up renal function measurement was 398 days post operatively (IQR: 366 – 490 days). 169 patients developed an increase in their CKD stage. No biomarker showed good predictive ability for such a rise – all displayed AUC values of &amp;lt;0.6. Similarly, AUC values for the prediction of mortality within one year were low, with all AUC values &amp;lt;0.65. Discussion This study has determined that urinary AKI biomarkers are poor predictors for long term derangement in renal function and mortality at one year in the surgical patient. Such evidence suggests that biomarkers are best suited to detect changes in the immediate post operative period.

The Role of Urinary Biomarkers as Diagnostic and Prognostic Predictors of Acute Kidney Injury Associated With Vancomycin.

Introduction: The incidence of acute kidney injury (AKI) related to vancomycin is variable, and several risk factors related to the treatment and patients may explain the nephrotoxicity. The role of urinary biomarkers in AKI related to vancomycin is unknown. Objective: The aim of this study was to evaluate the role of urinary IL-18, KIM-1, NGAL, TIMP-2, and IGFBP7 as diagnostic and prognostic predictors of AKI related to vancomycin. Methods: A prospective cohort study of patients receiving vancomycin and admitted to wards of a public university hospital from July 2019 to May 2020 was performed. We excluded patients that had AKI before starting vancomycin, hemodynamic instability, inability to collect urine, and chronic kidney disease stage 5. Results: Ninety-four patients were included, and the prevalence of AKI was 24.5%, while the general mortality was 8.7%. AKI occurred 11 ± 2 days after the first vancomycin dose. The most frequent KDIGO stage was 1 (61%). There was no difference between patients who developed and did not develop AKI due to gender, length of hospital stay, dose, and time of vancomycin use. Logistic regression identified age (OR 6.6, CI 1.16–38.22, p = 0.03), plasmatic vancomycin concentrations between 96 and 144 h (OR 1.18, CI 1.04-1.40, p = 0.04), and urinary NGAL levels between 96 and 144 h (OR 1.123, CI 1.096–1.290, p = 0.03) as predictors of AKI. The time of vancomycin use (OR 4.61, CI 1.11–22.02, p = 0.03), higher plasmatic vancomycin concentrations between 192 and 240 h (OR 1.02, CI 0.98–1.06, p = 0.26), and higher cell cycle arrest urinary biomarkers TIMP-2 multiplied by IGFBP-7 between 144 and 192 h (OR 1.33, CI 1.10–1.62, p = 0.02; OR 1.19, CI 1.09–1.39, p = 0.04, respectively) were identified as prognostic factors for non-recovery of kidney function at discharge. Conclusion: AKI related to vancomycin was frequent in patients hospitalized in wards. Age, plasmatic vancomycin concentrations, and NGAL between 96 and 144 h were identified as predictors of AKI related to vancomycin use. Plasmatic vancomycin concentrations and urinary NGAL were predictors of AKI diagnosis within the next 5 days. The urinary biomarkers of cell cycle arrest TIMP-2 and IGFBP-7 and the duration of vancomycin use were associated with non-recovery of kidney function at hospital discharge moment.

Ureteroscopic biopsy of upper tract urothelial carcinoma and role of urinary biomarkers.

Ureteroscopic biopsy is an integral part of diagnosis of urothelial carcinoma of the upper urinary tract. It can be a technical challenge, but diagnostic rates have improved remarkably with refinements in surgical technique and specimen processing. Cytology aids with diagnosis and other urinary biomarkers continue to evolve, which may help further stratify patients for treatment. The current literature on the ureteroscopic biopsy and role of urinary biomarkers is reviewed and summarized below.

High urinary kidney injury molecule type 1 level is associated with 12-month adverse cardiovascular events in patients with coronary artery disease

INTRODUCTION Contrast‑induced nephropathy is associated with worse prognosis in patients with coronary artery disease (CAD); however, the prognostic role of urinary biomarkers of renal injury has not been fully established. OBJECTIVES We evaluated the clinical utility of urinary biomarkers for the prediction of major adverse cardiac and cerebrovascular events (MACCEs) in patients undergoing coronary angiography. PATIENTS AND METHODS This prospective study included 95 consecutive patients with stable and unstable CAD (men, 69.5%; median age, 65 years), referred for coronary angiography and monitored for MACCEs during 12-month follow-up. MACCEs were defined as cardiovascular death, myocardial infarction, myocardial revascularization, or stroke. Urine samples were collected 24 hours before and 6 hours after coronary angiography and assayed for kidney injury molecule type 1 (KIM-1), interleukin 18, liver fatty acid-binding protein, and renalase, using an enzyme-linked immunosorbent assay. The results were adjusted for urinary creatinine concentration. RESULTS MACCEs occurred in 10 patients (10.5%). These patients had a higher rate of postprocedural contrast‑induced acute kidney injury than patients without MACCEs (30.0% vs 7.1%, P = 0.02), higher median SYNTAX score (25.5 points vs 11.5 points, P = 0.04), higher postprocedural KIM‑1 concentrations (0.45 ng/mg vs 0.21 ng/mg, P = 0.03), and a larger absolute increase of urinary KIM‑1 levels (ΔKIM‑1; 0.41 ng/mg vs 0.10 ng/mg, P = 0.01). Preprocedural values of KI M‑‑1 and other biomarkers were comparable between groups. Patients with ΔKIM‑1 levels above the 75th percentile had worse 12‑month prognosis (P = 0.0004). ΔKIM‑1 levels were an independent predictor of 12‑month MACCEs (P = 0.001). MACCEs were accurately predicted by ΔKIM‑1 levels exceeding 0.093 ng/mg (area under the curve, 0.752; P = 0.0001). CONCLUSIONS Excessive increase of urinary KIM‑1 levels after coronary angiography may help identify CAD patients with poor 12‑month prognosis.

Role of Urinary Biomarkers for Diagnosis of Lupus Nephritis.

Role of Urinary Biomarkers for Diagnosis of Lupus Nephritis.

Nonmuscle-invasive bladder cancer: what's changing and what has changed.

Nonmuscle-invasive bladder cancer (NMIBC) is a challenging disease to manage primarily due to its varied clinical course. The management of NMIBC has witnessed a widespread change with respect to its diagnosis and treatment. Although transurethral resection (TUR) and adjuvant bacillus Calmette-Guerin (BCG) stills remain the cornerstone, newer protocols has come into vogue to achieve optimal care. On the basis of a literature review, we aimed to establish 'what changes has already occurred and what is expected in the future' in NMIBC. A Medline search was performed to identify the published literature with respect to diagnosis, treatment and future perspectives on NMIBC. Particular emphasis was directed to determinants such as the quality of TUR and the newer modifications, Re-TUR, current status of newer macroscopic and microscopic imaging, role of urinary biomarkers, clinical, histologic and molecular predictors of high-risk disease, administration of intravesical agents, salvage therapy in BCG recurrence and the current best practice guidelines were analyzed. Optimal TUR, restaging in select group, incorporation of newer endoscopic imaging and judicious administration of intravesical chemo-immunotherapeutic agents can contribute to better patient care. Although there is a plethora of urinary markers, there is insufficient evidence for their use in isolation. The future probably lies in identification of genetic markers to determine disease recurrence, nonresponders to standard treatment and early institution of alternative/targeted therapy.

Place des biomarqueurs urinaires dans le diagnostic et le suivi des troubles du bas appareil urinaire : une revue de la littérature

To conduct a literature review on the role of urinary biomarkers in the initial assessment and follow-up of lower urinary tract symptoms. A literature review was conducted in August 2014 using the Medline/Pubmed database limiting the search to work in English or French. Most studies were of level of evidence 2 or 3 (prospective cohort, controlled or not) and mainly about overactive bladder and bladder pain syndrome. Nerve Growth Factor (NGF) was the most studied and apparently the most promising in the evaluation of overactive bladder (OAB) and neurogenic detrusor overactivity (NDO). Urinary levels of ATP, prostaglandin E2 (PGE2), Brain-Derived Neurotrophic Factor (BDNF) and some cytokines were also significantly higher in most studies in patients with NDO or OAB. Epidermal Growth Factor (EGF), Heparin-Binding EGF (HBEGF) and Antiproliferative Factor (APF) were the most studied urinary markers in bladder pain syndrome, with a significant increase (EGF APF) or decrease (HBEGF) in cases of interstitial cystitis (compared to healthy controls). The urinary N-terminal-telopeptide (NTx) could be predictive of a failed mid-urethral sling. However, few studies reported the diagnostic values of the markers, their association with urodynamic parameters were rarely evaluated and the existence of a publication bias is likely. No randomized controlled study has so far compared the urinary markers to urodynamic evaluation. In the future, urinary markers could complete or replace urodynamic examination. However, to date, there is no high level of evidence study comparing these markers to urodynamics and their use can therefore not be recommended in daily practice.

Role of urinary biomarkers in the diagnosis of congenital upper urinary tract obstruction

Background:Congenital obstructive uropathy constitutes a significant cause of morbidity in children. Currently, there is no reference standard for the diagnosis of renal obstruction in children. The noninvasive measurement of biomarkers in voided urine has considerable appeal as a potential application in children with congenital obstructive nephropathy. The aim of the present review is to explore the current role of biomarkers in the diagnosis and follow-up of obstructive uropathy in children.Materials and Methods:The literature database (PubMed) was searched from inception to May 2007 regarding the role of urinary biomarkers in the diagnosis and follow-up of children with congenital obstructive uropathy.Results:The review included 23 experimental and 33 prospective controlled clinical studies. Several cytokines, peptides, enzymes and microproteins were identified as major contributors to or ensuing from obstruction-induced renal fibrosis and apoptosis. The most important biomarkers were transforming growth factor-β1 (TGFβ1), epidermal growth factor (EGF), endothelin-1 (ET-1), urinary tubular enzymes [N-acetyl-β-D-glucosaminidase (NAG), γ-glutamyl transferase (GGT) and alkaline phosphatase (ALP)], and microproteins [β2-microglobulin (β2M), microalbumin (M. Alb) and micrototal protein (M.TP)]. All biomarkers showed different degrees of success but the most promising markers were TGFβ1, ET-1 and a panel of tubular enzymes. These biomarkers showed sensitivity of 74.3% to 100%, specificity of 80% to 90% and overall accuracy of 81.5% to 94% in the diagnosis of congenital obstructive uropathy in children. Moreover, some of the markers were valuable in differentiation between dilated non-obstructed kidneys in need of conservative management and obstructed kidneys in need of surgical correction. Some studies demonstrated that urinary biomarkers are helpful in the evaluation of success of treatment of children with congenital renal obstruction. Some limitations of the previous studies include lack of different types of controls and small sample size. Larger studies with variable controls are invited to confirm the clinical usefulness of biomarkers in the diagnosis and follow-up of children with congenital obstructive uropathy.Conclusion:Urinary biomarkers are a promising tool that could be used as a noninvasive assessment of congenital renal obstruction in children.