Chronic Kidney Disease in Boys with Posterior Urethral Valves-Pathogenesis, Prognosis and Management

Abstract

Posterior urethral valves (PUV) are the most common form of lower urinary tract obstructions (LUTO). The valves can be surgically corrected postnatally; however, the impairment of kidney and bladder development is irreversible and has lifelong implications. Chronic kidney disease (CKD) and bladder dysfunction are frequent problems. Approximately 20% of PUV patients will reach end-stage kidney disease (ESKD). The subvesical obstruction in PUV leads to muscular hypertrophy and fibrotic remodelling in the bladder, which both impair its function. Kidney development is disturbed and results in dysplasia, hypoplasia, inflammation and renal fibrosis, which are hallmarks of CKD. The prognoses of PUV patients are based on prenatal and postnatal parameters. Prenatal parameters include signs of renal hypodysplasia in the analysis of fetal urine. Postnatally, the most robust predictor of PUV is the nadir serum creatinine after valve ablation. A value that is below 0.4 mg/dl implies a very low risk for ESKD, whereas a value above 0.85 mg/dl indicates a high risk for ESKD. In addition, bladder dysfunction and renal dysplasia point towards an unbeneficial kidney outcome. Experimental urinary markers such as MCP-1 and TGF-β, as well as microalbuminuria, indicate progression to CKD. Until now, prenatal intervention may improve survival but yields no renal benefit. The management of PUV patients includes control of bladder dysfunction and CKD treatment to slow down progression by controlling hypertension, proteinuria and infections. In kidney transplantation, aggressive bladder management is essential to ensure optimal graft survival.

Keywords: bladder dysfunction; chronic kidney disease; end-stage renal disease; lower urinary tract obstruction; posterior urethral valves; vesicoamniotic shunting.

Figure 1

Alterations in the urinary tract due to posterior urethral valves. The subvesical obstruction in the prostatic urethra by posterior urethral valves (PUV) leads to a bladder neck dilation and increased urethral resistance, with the need for increased voiding pressure. As a consequence, bladder wall hypertrophy develops with the morphologic hallmarks of wall thickening and wall irregularity, possibly with diverticula. The obstruction can reach the upper urinary tract and dilate the ureter and the kidney pelvis. The functional tissue of the kidney, the parenchyma, can be reduced in thickness.

Figure 2

Pathophysiology of chronic kidney disease in patients with posterior urethral valves. Posterior urethral valves (PUV) lead to obstructions in the lower urinary tract (LUT) and the upper urinary tract (UUT), with consequent impairment of kidney development as well as bladder dysfunction. Impairment in kidney development may result in hypodysplasia with a reduced nephron mass, and can therefore cause chronic kidney disease (CKD). CKD can progress to end-stage kidney disease (ESKD). Bladder dysfunction can be aggravated by polyuria of the impaired kidneys, and cause secondary vesicoureteral reflux (VUR) and recurrent urinary tract infections (UTI). The latter may cause parenchymal scars in the hypodysplastic kidneys and accelerate CKD progression.

Figure 3

Interventions to prevent and treat chronic kidney disease in posterior urethral valves. Prenatal intervention with vesicoamniotic shunting or fetal cystoscopy yields no renal benefit. Bladder dysfunctions should be treated because they increase the risks of developing chronic kidney disease (CKD). Urinary tract infections (UTI) should be treated, and possibly a prophylaxis should be administered. All boys should be regularly seen by a pediatric nephrologist, in order to assess possible CKD. CKD progression should be slowed down, and CKD symptoms should be treated. In end-stage kidney disease (ESKD), dialysis or preferably transplantation is necessary.