Pediatric Nephrology

, Volume 34, Issue 2, pp 283–294 | Cite as

A clinical predictive model of chronic kidney disease in children with posterior urethral valves

  • Mariana A. Vasconcelos
  • Ana Cristina Simões e Silva
  • Izabella R. Gomes
  • Rafaela A. Carvalho
  • Sergio V. Pinheiro
  • Enrico A. Colosimo
  • Peter Yorgin
  • Robert H. Mak
  • Eduardo A. OliveiraEmail author
Original Article
Part of the following topical collections:
  1. What’s New in Chronic Kidney Disease



Posterior urethral valves (PUVs) are associated with severe consequences to the urinary tract and are a common cause of chronic kidney disease (CKD). The aim of this study was to develop clinical predictive model of CKD in a cohort of patients with PUVs.


In this retrospective cohort study, 173 patients with PUVs were systematically followed up at a single tertiary unit. The primary endpoint was CKD ≥ stage 3. Survival analyses were performed by Cox regression proportional hazard models with time-fixed and time-dependent covariables.


Mean follow-up time was 83 months (SD, 70 months). Sixty-five children (37.6%) developed CKD stage ≥ 3. After adjustment by the time-dependent Cox model, baseline creatinine, nadir creatinine, hypertension, and proteinuria remained as predictors of the endpoint. After adjustment by time-fixed model, three variables were predictors of CKD ≥ stage 3: baseline creatinine, nadir creatinine, and proteinuria. The prognostic risk score was divided into three categories: low-risk (69 children, 39.9%), medium-risk (45, 26%), and high-risk (59, 34.1%). The probability of CKD ≥ stage 3 at 10 years age was estimated as 6%, 40%, and 70% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). The main limitation was the preclusion of some relevant variables, especially bladder dysfunction, that might contribute to a more accurate prediction of renal outcome.


The model accurately predicts the risk of CKD in PUVs patients. This model could be clinically useful in applying timely intervention and in preventing the impairment of renal function.


Posterior urethral valves Fetal hydronephrosis Vesicoureteral reflux Urinary tract infection Hypertension Proteinuria Chronic kidney disease 


Funding information

R.H.M. is supported by NIH grants U01 DK-03012 and R24HD050837. E.A.O. is supported by CAPES grant 2746-15-8. This study was partially supported by CNPq (Brazilian National Research Council, Grant 481649/2013-1, Grant 460334/2014-0), FAPEMIG (Fundação de Amparo à Pesquisa do Estado de Minas Gerais, Grant PPM-00228-15, Grant PPM-00555-15), and the INCT-MM Grant (FAPEMIG: CBBAPQ-00075-09/CNPq 573646/2008-2).

Compliance with ethical standards

Ethical aspects

The study was approved by the Ethics Committee of UFMG.

Conflicts of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Dinneen MD, Duffy PG (1996) Posterior urethral valves. Br J Urol 78:275–281CrossRefGoogle Scholar
  2. 2.
    Lloyd JC, Wiener JS, Gargollo PC, Inman BA, Ross SS, Routh JC (2013) Contemporary epidemiological trends in complex congenital genitourinary anomalies. J Urol 190:1590–1595CrossRefGoogle Scholar
  3. 3.
    Clayton DB, Brock JW 3rd (2014) Lower urinary tract obstruction in the fetus and neonate. Clin Perinatol 41:643–659CrossRefGoogle Scholar
  4. 4.
    Stanasel I, Gonzales ET (2015) Posterior urethral valves. Curr Bladder Dysfunct Rep 10:250–255CrossRefGoogle Scholar
  5. 5.
    Deshpande AV (2017) Current strategies to predict and manage sequelae of posterior urethral valves in children. Pediatr Nephrol.
  6. 6.
    Heikkila J, Holmberg C, Kyllonen L, Rintala R, Taskinen S (2011) Long-term risk of end stage renal disease in patients with posterior urethral valves. J Urol 186:2392–2396CrossRefGoogle Scholar
  7. 7.
    Aulbert W, Kemper MJ (2016) Severe antenatally diagnosed renal disorders: background, prognosis and practical approach. Pediatr Nephrol 31:563–574CrossRefGoogle Scholar
  8. 8.
    Lopez Pereira P, Martinez Urrutia MJ, Espinosa L, Jaureguizar E (2013) Long-term consequences of posterior urethral valves. J Pediatr Urol 9:590–596CrossRefGoogle Scholar
  9. 9.
    Coelho GM, Bouzada MC, Pereira AK, Figueiredo BF, Leite MR, Oliveira DS, Oliveira EA (2007) Outcome of isolated antenatal hydronephrosis: a prospective cohort study. Pediatr Nephrol 22:1727–1734CrossRefGoogle Scholar
  10. 10.
    Quirino IG, Silva JM, Diniz JS, Lima EM, Rocha AC, Simoes e Silva AC, Oliveira EA (2011) Combined use of late phase dimercapto-succinic acid renal scintigraphy and ultrasound as first line screening after urinary tract infection in children. J Urol 185:258–263CrossRefGoogle Scholar
  11. 11.
    Oliveira EA, Rabelo EA, Pereira AK, Diniz JS, Cabral AC, Leite HV, Silva JM, Fagundes TA (2002) Prognostic factors in prenatally-detected posterior urethral valves: a multivariate analysis. Pediatr Surg Int 18:662–667PubMedGoogle Scholar
  12. 12.
    Quirino IG, Diniz JS, Bouzada MC, Pereira AK, Lopes TJ, Paixao GM, Barros NN, Figueiredo LC, Cabral AC, Simoes ESAC, Oliveira EA (2012) Clinical course of 822 children with prenatally detected nephrouropathies. Clin J Am Soc Nephrol 7:444–451CrossRefGoogle Scholar
  13. 13.
    Coelho GM, Bouzada MC, Lemos GS, Pereira AK, Lima BP, Oliveira EA (2008) Risk factors for urinary tract infection in children with prenatal renal pelvic dilatation. J Urol 179:284–289CrossRefGoogle Scholar
  14. 14.
    Schwartz GJ, Brion LP, Spitzer A (1987) The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clin N Am 34:571–590CrossRefGoogle Scholar
  15. 15.
    Schwartz GJ, Munoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637CrossRefGoogle Scholar
  16. 16.
    Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, Hogg RJ, Perrone RD, Lau J, Eknoyan G (2003) National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Ann Intern Med 139:137–147CrossRefGoogle Scholar
  17. 17.
    (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576Google Scholar
  18. 18.
    Rubin DB, Schenker N (1991) Multiple imputation in health-care databases: an overview and some applications. Stat Med 10:585–598CrossRefGoogle Scholar
  19. 19.
    Youden WJ (1950) Index for rating diagnostic tests. Cancer 3:32–35CrossRefGoogle Scholar
  20. 20.
    van Dijk PC, Jager KJ, Zwinderman AH, Zoccali C, Dekker FW (2008) The analysis of survival data in nephrology: basic concepts and methods of Cox regression. Kidney Int 74:705–709CrossRefGoogle Scholar
  21. 21.
    Sullivan LM, Massaro JM, D'Agostino RB Sr (2004) Presentation of multivariate data for clinical use: the Framingham Study risk score functions. Stat Med 23:1631–1660CrossRefGoogle Scholar
  22. 22.
    Nunez E, Steyerberg EW, Nunez J (2011) Regression modeling strategies. Rev Esp Cardiol 64:501–507CrossRefGoogle Scholar
  23. 23.
    Moons KG, Kengne AP, Grobbee DE, Royston P, Vergouwe Y, Altman DG, Woodward M (2012) Risk prediction models: II. External validation, model updating, and impact assessment. Heart 98:691–698CrossRefGoogle Scholar
  24. 24.
    Moons KG, Kengne AP, Woodward M, Royston P, Vergouwe Y, Altman DG, Grobbee DE (2012) Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker. Heart 98:683–690CrossRefGoogle Scholar
  25. 25.
    Harrell FE Jr, Lee KL, Mark DB (1996) Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med 15:361–387CrossRefGoogle Scholar
  26. 26.
    Steyerberg EW, Vickers AJ, Cook NR, Gerds T, Gonen M, Obuchowski N, Pencina MJ, Kattan MW (2010) Assessing the performance of prediction models: a framework for traditional and novel measures. Epidemiology 21:128–138CrossRefGoogle Scholar
  27. 27.
    Steyerberg EW, Bleeker SE, Moll HA, Grobbee DE, Moons KG (2003) Internal and external validation of predictive models: a simulation study of bias and precision in small samples. J Clin Epidemiol 56:441–447CrossRefGoogle Scholar
  28. 28.
    Otukesh H, Sharifiaghdas F, Hoseini R, Fereshtehnejad SM, Rabiee N, Kiaiee MF, Javadi R, Mojtahedzadeh M, Simfroosh N, Basiri A, Hooman N, Nasiri J, Delshad S, Farhood P (2010) Long-term upper and lower urinary tract functions in children with posterior urethral valves. J Pediatr Urol 6:143–147CrossRefGoogle Scholar
  29. 29.
    Kousidis G, Thomas DF, Morgan H, Haider N, Subramaniam R, Feather S (2008) The long-term outcome of prenatally detected posterior urethral valves: a 10 to 23-year follow-up study. BJU Int 102:1020–1024CrossRefGoogle Scholar
  30. 30.
    Caione P, Nappo SG (2011) Posterior urethral valves: long-term outcome. Pediatr Surg Int 27:1027–1035CrossRefGoogle Scholar
  31. 31.
    Tikkinen KA, Heikkila J, Rintala RJ, Tammela TL, Taskinen S (2011) Lower urinary tract symptoms in adults treated for posterior urethral valves in childhood: matched cohort study. J Urol 186:660–666CrossRefGoogle Scholar
  32. 32.
    Ylinen E, Ala-Houhala M, Wikstrom S (2004) Prognostic factors of posterior urethral valves and the role of antenatal detection. Pediatr Nephrol 19:874–879PubMedGoogle Scholar
  33. 33.
    Sarhan OM, El-Ghoneimi AA, Helmy TE, Dawaba MS, Ghali AM, Ibrahiem el HI (2011) Posterior urethral valves: multivariate analysis of factors affecting the final renal outcome. J Urol 185:2491–2495CrossRefGoogle Scholar
  34. 34.
    DeFoor W, Clark C, Jackson E, Reddy P, Minevich E, Sheldon C (2008) Risk factors for end stage renal disease in children with posterior urethral valves. J Urol 180:1705–1708 discussion 1708CrossRefGoogle Scholar
  35. 35.
    Denes ED, Barthold JS, Gonzalez R (1997) Early prognostic value of serum creatinine levels in children with posterior urethral valves. J Urol 157:1441–1443CrossRefGoogle Scholar
  36. 36.
    Engel DL, Pope JC, Adams MC, Brock JW 3rd, Thomas JC, Tanaka ST (2011) Risk factors associated with chronic kidney disease in patients with posterior urethral valves without prenatal hydronephrosis. J Urol 185:2502–2506CrossRefGoogle Scholar
  37. 37.
    Lopez Pereira P, Espinosa L, Martinez Urrutina MJ, Lobato R, Navarro M, Jaureguizar E (2003) Posterior urethral valves: prognostic factors. BJU Int 91:687–690CrossRefGoogle Scholar
  38. 38.
    Matsell DG, Yu S, Morrison SJ (2016) Antenatal determinants of long-term kidney outcome in boys with posterior urethral valves. Fetal Diagn Ther 39:214–221CrossRefGoogle Scholar
  39. 39.
    Reinberg Y, de Castano I, Gonzalez R (1992) Prognosis for patients with prenatally diagnosed posterior urethral valves. J Urol 148:125–126CrossRefGoogle Scholar
  40. 40.
    Pulido JE, Furth SL, Zderic SA, Canning DA, Tasian GE (2014) Renal parenchymal area and risk of ESRD in boys with posterior urethral valves. Clin J Am Soc Nephrol 9:499–505CrossRefGoogle Scholar
  41. 41.
    Odeh R, Noone D, Bowlin PR, Braga LH, Lorenzo AJ (2016) Predicting risk of chronic kidney disease in infants and young children at diagnosis of posterior urethral valves: initial ultrasound kidney characteristics and validation of parenchymal area as forecasters of renal reserve. J Urol 196:862–868CrossRefGoogle Scholar
  42. 42.
    Fathallah-Shaykh SA, Flynn JT, Pierce CB, Abraham AG, Blydt-Hansen TD, Massengill SF, Moxey-Mims MM, Warady BA, Furth SL, Wong CS (2015) Progression of pediatric CKD of nonglomerular origin in the CKiD cohort. Clin J Am Soc Nephrol 10:571–577CrossRefGoogle Scholar
  43. 43.
    Locatelli F, Marcelli D, Comelli M, Alberti D, Graziani G, Buccianti G, Redaelli B, Giangrande A (1996) Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian cooperative study group. Nephrol Dial Transplant 11:461–467CrossRefGoogle Scholar
  44. 44.
    Staples AO, Greenbaum LA, Smith JM, Gipson DS, Filler G, Warady BA, Martz K, Wong CS (2010) Association between clinical risk factors and progression of chronic kidney disease in children. Clin J Am Soc Nephrol 5:2172–2179CrossRefGoogle Scholar
  45. 45.
    Warady BA, Abraham AG, Schwartz GJ, Wong CS, Munoz A, Betoko A, Mitsnefes M, Kaskel F, Greenbaum LA, Mak RH, Flynn J, Moxey-Mims MM, Furth S (2015) Predictors of rapid progression of glomerular and nonglomerular kidney disease in children and adolescents: the chronic kidney disease in children (CKiD) cohort. Am J Kidney Dis 65:878–888CrossRefGoogle Scholar
  46. 46.
    Wong CS, Pierce CB, Cole SR, Warady BA, Mak RH, Benador NM, Kaskel F, Furth SL, Schwartz GJ, Investigators CK (2009) Association of proteinuria with race, cause of chronic kidney disease, and glomerular filtration rate in the chronic kidney disease in children study. Clin J Am Soc Nephrol 4:812–819CrossRefGoogle Scholar
  47. 47.
    Ardissino G, Testa S, Dacco V, Vigano S, Taioli E, Claris-Appiani A, Procaccio M, Avolio L, Ciofani A, Dello Strologo L, Montini G, Ital Kid P (2004) Proteinuria as a predictor of disease progression in children with hypodysplastic nephropathy. Data from the Ital Kid Project. Pediatr Nephrol 19:172–177CrossRefGoogle Scholar
  48. 48.
    Wuhl E, Trivelli A, Picca S, Litwin M, Peco-Antic A, Zurowska A, Testa S, Jankauskiene A, Emre S, Caldas-Afonso A, Anarat A, Niaudet P, Mir S, Bakkaloglu A, Enke B, Montini G, Wingen AM, Sallay P, Jeck N, Berg U, Caliskan S, Wygoda S, Hohbach-Hohenfellner K, Dusek J, Urasinski T, Arbeiter K, Neuhaus T, Gellermann J, Drozdz D, Fischbach M, Moller K, Wigger M, Peruzzi L, Mehls O, Schaefer F (2009) Strict blood-pressure control and progression of renal failure in children. N Engl J Med 361:1639–1650CrossRefGoogle Scholar
  49. 49.
    Larkins NG, Craig JC, Teixeira-Pinto A (2018) A guide to missing data for the pediatric nephrologist. Pediatr Nephrol.
  50. 50.
    Greenberg JH, Kakajiwala A, Parikh CR, Furth S (2018) Emerging biomarkers of chronic kidney disease in children. Pediatr Nephrol 33:925–933CrossRefGoogle Scholar

Copyright information

© IPNA 2018

Authors and Affiliations

  • Mariana A. Vasconcelos
    • 1
  • Ana Cristina Simões e Silva
    • 1
  • Izabella R. Gomes
    • 1
  • Rafaela A. Carvalho
    • 1
  • Sergio V. Pinheiro
    • 1
  • Enrico A. Colosimo
    • 2
  • Peter Yorgin
    • 3
  • Robert H. Mak
    • 3
  • Eduardo A. Oliveira
    • 1
    • 4
    Email author return OK on get
  1. 1.Pediatric Nephrourology Division, Department of Pediatrics, National Institute of Science and Technology (INCT) of Molecular Medicine, School of MedicineFederal University of Minas Gerais (UFMG)Belo HorizonteBrazil
  2. 2.Department of StatisticsUFMGBelo HorizonteBrazil
  3. 3.Division of Pediatric Nephrology, Rady Children’s Hospital San DiegoUniversity of California, San DiegoLa JollaUSA
  4. 4.Visiting Scholar, Division of Pediatric Nephrology, Rady Children’s Hospital San DiegoUniversity of California, San DiegoLa JollaUSA

Personalised recommendations