Posterior urethral valve in children: Using novel biomarkers as an early predictive tool for the onset and progression of chronic kidney disease

Abstract

This narrative review aims to appraise the current evidence on using biomarkers of obstructive nephropathy to predict the onset and progression of chronic kidney disease (CKD) in infants with posterior urethral valves (PUV). PUV is the most frequently reported congenital anomaly of the kidney and urinary tract (CAKUT) associated with bladder outlet obstruction in male children. It contributes significantly to the CKD burden in childhood. Despite different approaches for its postnatal repair, evidence-based data still suggest a high risk of CKD and end-stage kidney disease (ESKD) later in childhood. In obstructive nephropathy, glomerular and tubulointerstitial lesions contribute to renal impairment. Although it may be difficult to predict these adverse renal outcomes in repaired PUV, detecting and monitoring future CKD appears enhanced using the combination of serum creatinine- or cystatin C-based estimated glomerular filtration rate (eGFR) and albuminuria. Given the drawbacks of these conventional biomarkers, there is a paradigm shift to novel biomarkers as tools for the early identification of glomerular and tubulointerstitial lesions seen in obstructive nephropathy. Most novel biomarkers are yet to be fully applied to routine clinical practice globally. Nevertheless, there is substantial evidence showing that they form part of the emerging diagnostics for obstructive nephropathy. From the reviewed studies, urine transforming growth factor-beta 1 (TGF-β1) is the most prominent biomarker among the novel biomarkers of obstructive nephropathy. However, other novel approaches like the machine learning (ML) model (a form of health-related artificial intelligence) and urodynamic parameters like bladder contractility index hold promise for PUV outcomes prediction (PUVOP). Because of the association of urine TGF-β1 with urine angiotensin level (a biomarker of the renin-angiotensin-aldosterone system [RAAS]), early angiotensin-converting enzyme inhibitor (ACEI) therapy in patients with PUV may potentially retard the progression of CKD and improve renal outcomes. Thus, future research directions will be to explore the role of ACEI as a pre-emptive treatment for poor renal outcomes in post valve-ablation patients and to conduct longitudinal studies that would properly demonstrate these biomarkers as predictors of these outcomes.

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

“…In the absence of any tubular dysfunction, notwithstanding anything that filters across is catabolized by the proximal tubules and does not appear in urine. It is only when there is a proximal tubular malfunction, the uCysC will rise[ 15 , 34 , 35 ] It is expected that the uncatabolized uCysC in a similar concentration might not reach the urinary bladder due to an obstruction present at the ureteropelvic junction Thus, this hypothesis explains the reason for similar levels of uCysC observed between the cases and controls by Madsen et al . [ 11 ] and Karakus et al .…”

“…[ 34 ] found a significantly higher mean uCysC in patients with renal tubular diseases (4.13 ± 3.85 mg/l) than that of the controls (0.096 ± 0.044 mg/l), whereas Uwaezuoke et al . [ 35 ] suggested that a higher the serum CysC will be observed in patients with glomerular diseases [ Figure 3 ].…”

“…In the absence of any tubular dysfunction, notwithstanding anything that filters across is catabolized by the proximal tubules and does not appear in urine. It is only when there is a proximal tubular malfunction, the uCysC will rise[ 15 , 34 , 35 ]…”

Renal Papillary Necrosis (RPN) in an African Population: Disease Patterns, Relevant Pathways, and Management

“…Despite the very limited published data available on the pattern and pathways of RPN in African population, the hallmark of the disease depends on geographical location, environmental hazards and the quality of basic health care system [7][8][9]. The most morbid risk factors are unknown and underdiagnosed genetic diseases such as congenital obstructive nephropathy (posterior urethral valves) [10], and sickle cell nephropathy [11]. The primary defect of sickle cell disease results from the replacement of glutamate for valine at the sixth amino acid of the beta globin chain.…”