From PUV to Renal Insufficiency: A Meta-analysis and A Single Centre Experience

(CONTINUATION) Of the identified prognostic factors 1/7 had primary urinary diversion, 4/6 had elevated initial serum creatinine (1mg/dL) and 4/7 had bilateral VUR, renal outcomes were not available. Conclusion: Poor renal outcome is the major cause of morbidity in children with PUV. Methods of predicting chronic renal failure, warrant further assessment. Patients undergoing primary urinary diversion, elevated serum creatinine, nadir creatine, and presence of VUR may benefit from closer monitoring. At small centers it is almost impossible to assess the significance of predictive/prognostic/risk factors for renal outcome, however, using large scale assessment for their identification showed us that little more than half our patients had at least one negative prognostic factor. Limitations include biases inherent to retrospective and relatively small sized of studies included in the meta-analysis and, especially, in our clinical experience. Longer follow-up and larger studies or multicenter studies are necessary to identify prognostic factors of progression of renal disease.

Background: Posterior urethral valves (PUV) may cause a subclinical to severe obstruction of the urethra, resulting in a broad clinical spectrum, with PUVs as the most common cause of chronic kidney disease in young males. The mortality associated with posterior urethral valves has decreased significantly in the past decades, but morbidity and ongoing disability continue to be significant in the pediatric age and long-term. The aim of this study is two-fold, one is at a broader level understanding the association of PUV and renal function by a meta-analysis reporting 39 studies. This was done through identification of prevalence and significant prognostic factors of a poor renal outcome in patient previously diagnosed with PUV. The second aimed to understand the clinical experience with PUV at a local level through retrospective analysis of the clinical cases from the past 8 years in our single center - Ospedale Policlinico San Matteo, and identify the possibilities and limitations of small-scale investigation of this malformation. In this way we were able to compare our experience at a local level and identify possible prognostic factors in our patients, and understand how tailored our clinical approach is in relation to patient’s outcome is. Materials and Methods: Primarily, a systematic review of the literature was performed for studies comparing posterior urethral valves and renal outcome. The main endpoint was renal failure (CKD>2). Between-study heterogeneity was assessed. Meta-analysis of high quality studies, identified using the Newcastle–Ottawa Scale, was performed using fixed or random models in order to identify significant prognostic factors, within those already proposed in the literature (time of diagnosis, primary intervention, initial serum creatinine, nadir serum creatinine, pop-off mechanism and VUR). Secondarily a retrospective analysis of the clinical files of all children followed at the pediatric surgery department of the Policlinico San Matteo between March 2013 and May 2020 with a mean follow-up time of 19.5 months (7-48), previously diagnosed with PUV. The variables analyzed were time of diagnosis, clinical presentation, surgical treatment, image evaluation and follow up methods. Results: In our meta-analysis 39 retrospective studies were included. From 3950 unselected patients, 1232 experienced kidney failure (31%, range 10–70%). Meta-analysis of the high quality studies revealed that renal failure was significantly higher in patients with urinary diversion as primary intervention (odds ratio 0.70, 95% confidence interval 0.50-0.96, p=0.03, I2 = 13%), elevated initial serum creatinine ((OR 9.21, 95% CI 5.94-14.28, p <0.00001, I2 = 45%,), elevated nadir serum creatinine ((OR 8.99, 95% CI 5.43-14.90, p <0,0001, I2 = 68%) and bilateral vesicoureteral reflux (OR 2.25, 95% CI 1.22-4.17, p=0,02, I2 = 56%), no significant values was given to the remaining tested prognostic factors. At our single center experience, seven patient diagnosed with PUV were identified during the study period. The diagnosis was suggested by ultrasound in 5 patients, the other had diagnosis within the first months of life. The initial clinical manifestations were urinary tract infection and abnormal upper urinary US findings. Four patients presented an initial serum creatinine >1mg/dL. All patients presented hydroureteronephrosis at postnatal ultrasound (1 unilateral). All patients also presented with renal parenchyma alterations and stress bladder signs. Voiding cystourethrogram revealed presence of bilateral VUR in 4 patients. All children underwent endoscopic valve ablation one had a primary vesicostomy. Some cases required other surgical interventions, including removal of residual valves in 2 patients and circumcision in 3. Five patients required at least one hospitalization for pyelonephritis post-treatment. (CONTINUES)