Skip to main content

Advertisement

SpringerLink
Log in

Increased risk for kidney sequelae surrogates in survivors of Wilms tumor

  • Original Article
  • Published:
Pediatric Nephrology Aims and scope Submit manuscript

Abstract

Background

There is evidence of increased risk of hypertension, albuminuria, and development of chronic kidney disease (CKD) in long-term follow-up of survivors of Wilms tumor (WT). However, most studies were conducted in heterogeneous groups, including patients with solitary kidney. In addition, little is known about tubular dysfunction. This study aimed to investigate kidney sequelae, including CKD development, hypertension, and glomerular and tubular damage in WT survivors.

Methods

This cross-sectional, single-center study included 61 patients treated for WT. Surrogates for kidney sequelae were defined as presence of at least one of the following: decrease in GFR for CKD, hypertension detected by ambulatory blood pressure monitoring, albuminuria (albumin-to-creatinine ratio [ACR] > 30 mg/g), or increase in at least one tubular biomarker (beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, kidney injury marker-1, and liver fatty acid-binding protein) in 24-h urine.

Results

Median age of patients was 11.7 years, with median follow-up of 8.8 years. Thirty-eight patients (62%) had at least one surrogate for kidney sequelae. Twenty-four patients (39%) had CKD, 14 patients (23%) had albuminuria, 12 patients (21%) had hypertension, and 11 patients (18%) had tubular damage. Urine ACR was significantly higher in patients with advanced tumor stage and patients with nephrotoxic therapy than their counterparts (p < 0.05), but neither eGFR nor tubular biomarkers showed any association with tumor- or treatment-related factors.

Conclusions

A considerable number of patients with WT have kidney sequelae, especially early-stage CKD with a high prevalence. Albuminuria emerges as a marker associated with tumor stages and nephrotoxic treatment.

Graphical abstract

A higher resolution version of the Graphical abstract is available as Supplementary information

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Howlader N NA, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds) (2021) SEER Cancer Statistics Review, 1975–2018, National Cancer Institute., Bethesda, MD, https://seer.cancer.gov/csr/1975_2018/, based on November 2020 SEER data submission, posted to the SEER web site.

  2. Armstrong GT, Chen Y, Yasui Y, Leisenring W, Gibson TM, Mertens AC, Stovall M, Oeffinger KC, Bhatia S, Krull KR, Nathan PC, Neglia JP, Green DM, Hudson MM, Robison LL (2016) Reduction in late mortality among 5-year survivors of childhood cancer. N Engl J Med 374:833–842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Lange J, Peterson SM, Takashima JR, Grigoriev Y, Ritchey ML, Shamberger RC, Beckwith JB, Perlman E, Green DM, Breslow NE (2011) Risk factors for end stage renal disease in non-WT1-syndromic Wilms tumor. J Urol 186:378–386

    Article  PubMed  PubMed Central  Google Scholar 

  4. Interiano RB, Delos Santos N, Huang S, Srivastava DK, Robison LL, Hudson MM, Green DM, Davidoff AM (2015) Renal function in survivors of nonsyndromic Wilms tumor treated with unilateral radical nephrectomy. Cancer 121:2449–2456

    Article  PubMed  Google Scholar 

  5. Ritchey ML, Green DM, Thomas PR, Smith GR, Haase G, Shochat S, Moksness J, Breslow NE (1996) Renal failure in Wilms’ tumor patients: a report from the National Wilms’ Tumor Study Group. Med Pediatr Oncol 26:75–80

    Article  CAS  PubMed  Google Scholar 

  6. Breslow NE, Collins AJ, Ritchey ML, Grigoriev YA, Peterson SM, Green DM (2005) End stage renal disease in patients with Wilms tumor: results from the National Wilms Tumor Study Group and the United States Renal Data System. J Urol 174:1972–1975

    Article  PubMed  PubMed Central  Google Scholar 

  7. de Graaf SS, van Gent H, Reitsma-Bierens WC, van Luyk WH, Dolsma WV, Postma A (1996) Renal function after unilateral nephrectomy for Wilms’ tumour: the influence of radiation therapy. Eur J Cancer 32A:465–469

    Article  PubMed  Google Scholar 

  8. Stefanowicz J, Kosiak M, Romanowicz G, Owczuk R, Adamkiewicz-Drozynska E, Balcerska A (2011) Glomerular filtration rate and prevalence of chronic kidney disease in Wilms’ tumour survivors. Pediatr Nephrol 26:759–766

    Article  PubMed  PubMed Central  Google Scholar 

  9. Romao RL, Lorenzo AJ (2016) Renal function in patients with Wilms tumor. Urol Oncol 34:33–41

    Article  PubMed  Google Scholar 

  10. Janeczko M, Niedzielska E, Pietras W (2015) Evaluation of renal function in pediatric patients after treatment for wilms’ tumor. Adv Clin Exp Med 24:497–504

    Article  PubMed  Google Scholar 

  11. Bailey S, Roberts A, Brock C, Price L, Craft AW, Kilkarni R, Lee RE, Skillen AW, Skinner R (2002) Nephrotoxicity in survivors of Wilms’ tumours in the North of England. Br J Cancer 87:1092–1098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Kern W, Braess J, Kaufmann CC, Wilde S, Schleyer E, Hiddemann W (2000) Microalbuminuria during cisplatin therapy: relation with pharmacokinetics and implications for nephroprotection. Anticancer Res 20:3679–3688

    CAS  PubMed  Google Scholar 

  13. Stefanowicz J, Owczuk R, Kaluzynska B, Aleksandrowicz E, Owczarzak A, Adamkiewicz-Drozynska E, Balcerska A (2012) Renal function and solitary kidney disease: Wilms tumour survivors versus patients with unilateral renal agenesis. Kidney Blood Press Res 35:174–181

    Article  PubMed  Google Scholar 

  14. Chu DI, Ehlayel AM, Ginsberg JP, Meyers KE, Benton M, Thomas M, Carlson C, Kolon TF, Tasian GE, Greenberg JH, Furth SL, Denburg MR (2021) kidney outcomes and hypertension in survivors of Wilms tumor: A prospective cohort study. J Pediatr 230:215-220 e211

    Article  CAS  PubMed  Google Scholar 

  15. Neu MA, Russo A, Wingerter A, Alt F, Theruvath J, El Malki K, Kron B, Dittrich M, Lotz J, Stein R, Beetz R, Faber J (2017) Prospective analysis of long-term renal function in survivors of childhood Wilms tumor. Pediatr Nephrol 32:1915–1925

    Article  PubMed  Google Scholar 

  16. Green DM, Wang M, Krasin MJ, Davidoff AM, Srivastava D, Jay DW, Ness KK, Shulkin BL, Spunt SL, Jones DP, Lanctot JQ, Shelton KC, Brennan RC, Mulrooney DA, Ehrhardt MJ, Gibson TM, Kurt BA, Robison LL, Hudson MM (2020) Long-term renal function after treatment for unilateral, nonsyndromic Wilms tumor. A report from the St Jude Lifetime Cohort Study. Pediatr Blood Cancer 67:e28271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Akyuz C, Yalcin B, Yildiz I, Hazar V, Yoruk A, Tokuc G, Akici F, Buyukpamukcu N, Kale G, Atahan L, Buyukunal C, Dervisoglu S, Atkovar GA, Melikoglu M, Karpuzoglu G, Olgun N, Ayan I, Oguz A, Yaris N, Dagdemir A, Darendeliler E, Sander S, Kuyumcuoglu U, Ozseker N, Corapcioglu F, Tanyeli A, Duzovali O, Aydin GB, Buyukpamukcu M (2010) Treatment of Wilms tumor: a report from the Turkish Pediatric Oncology Group (TPOG). Pediatr Hematol Oncol 27:161–178

    Article  CAS  PubMed  Google Scholar 

  18. Neyzi O, Bundak R, Gokcay G, Gunoz H, Furman A, Darendeliler F, Bas F (2015) Reference Values for Weight, Height, Head Circumference, and Body Mass Index in Turkish Children. J Clin Res Pediatr Endocrinol 7:280–293

    Article  PubMed  PubMed Central  Google Scholar 

  19. Schwartz GJ, Schneider MF, Maier PS, Moxey-Mims M, Dharnidharka VR, Warady BA, Furth SL, Munoz A (2012) Improved equations estimating GFR in children with chronic kidney disease using an immunonephelometric determination of cystatin C. Kidney Int 82:445–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Inker LA, Eckfeldt J, Levey AS, Leiendecker-Foster C, Rynders G, Manzi J, Waheed S, Coresh J (2011) Expressing the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) cystatin C equations for estimating GFR with standardized serum cystatin C values. Am J Kidney Dis 58:682–684

    Article  PubMed  PubMed Central  Google Scholar 

  21. Flynn JT, Kaelber DC, Baker-Smith CM, Blowey D, Carroll AE, Daniels SR, de Ferranti SD, Dionne JM, Falkner B, Flinn SK, Gidding SS, Goodwin C, Leu MG, Powers ME, Rea C, Samuels J, Simasek M, Thaker VV, Urbina EM, Subcommittee on Screening and Management of High Blood Pressure In Children (2017) Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 140:e20171904

    Article  PubMed  Google Scholar 

  22. Duzova A, KarabayBayazit A, Canpolat N, Niemirska A, Kaplan Bulut I, Azukaitis K, Karagoz T, Oguz B, Erdem S, Anarat A, Ranchin B, Shroff R, Djukic M, Harambat J, Yilmaz A, Yildiz N, Ozcakar B, Buscher A, Lugani F, Wygoda S, Tschumi S, Zaloszyc A, Jankauskiene A, Laube G, Galiano M, Kirchner M, Querfeld U, Melk A, Schaefer F, Wuhl E, 4C Study Consortium (2019) Isolated nocturnal and isolated daytime hypertension associate with altered cardiovascular morphology and function in children with chronic kidney disease: findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease study. J Hypertens 37:2247–2255

    Article  PubMed  CAS  Google Scholar 

  23. Flynn JT, Daniels SR, Hayman LL, Maahs DM, McCrindle BW, Mitsnefes M, Zachariah JP, Urbina EM, American Heart Association Atherosclerosis, Hypertension and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young (2014) Update: ambulatory blood pressure monitoring in children and adolescents: a scientific statement from the American Heart Association. Hypertension 63:1116–1135

    Article  CAS  PubMed  Google Scholar 

  24. Dinkel E, Ertel M, Dittrich M, Peters H, Berres M, Schulte-Wissermann H (1985) Kidney size in childhood. Sonographical growth charts for kidney length and volume. Pediatr Radiol 15:38–43

    Article  CAS  PubMed  Google Scholar 

  25. Kern AJ, Inouye B, Ko JS, Gorin MA, Allaf ME, Goldstein S, DiCarlo HN, Shah BB, Wang MH (2014) Impact of nephrectomy on long-term renal function in non-syndromic children treated for unifocal Wilms tumor. J Pediatr Urol 10:662–666

    Article  PubMed  Google Scholar 

  26. Huff V (1996) Genotype/phenotype correlations in Wilms’ tumor. Med Pediatr Oncol 27:408–414

    Article  CAS  PubMed  Google Scholar 

  27. Habib R, Loirat C, Gubler MC, Niaudet P, Bensman A, Levy M, Broyer M (1985) The nephropathy associated with male pseudohermaphroditism and Wilms’ tumor (Drash syndrome): a distinctive glomerular lesion–report of 10 cases. Clin Nephrol 24:269–278

    CAS  PubMed  Google Scholar 

  28. Cozzi DA, Ceccanti S, Frediani S, Mele E, Cozzi F (2013) Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross-sectional and longitudinal study. Pediatr Blood Cancer 60:1534–1538

    Article  PubMed  Google Scholar 

  29. Romao RL, Pippi Salle JL, Shuman C, Weksberg R, Figueroa V, Weber B, Bagli DJ, Farhat WA, Grant R, Gerstle JT, Lorenzo AJ (2012) Nephron sparing surgery for unilateral Wilms tumor in children with predisposing syndromes: single center experience over 10 years. J Urol 188:1493–1498

    Article  PubMed  Google Scholar 

  30. Millar AJ, Davidson A, Rode H, Numanoglu A, Hartley PS, Desai F (2011) Nephron-sparing surgery for bilateral Wilms’ tumours: a single-centre experience with 23 cases. Afr J Paediatr Surg 8:49–56

    Article  CAS  PubMed  Google Scholar 

  31. Cozzi DA, Zani A (2006) Nephron-sparing surgery in children with primary renal tumor: indications and results. Semin Pediatr Surg 15:3–9

    Article  PubMed  Google Scholar 

  32. Simon J, Zamora I, Mendizabal S, Castel V, Lurbe A (1982) Glomerulotubular balance and functional compensation in nephrectomized children. Nephron 31:203–208

    Article  CAS  PubMed  Google Scholar 

  33. Aperia A, Broberger O, Wikstad I, Wilton P (1977) Renal growth and function in patients nephrectomized in childhood. Acta Paediatr Scand 66:185–192

    Article  CAS  PubMed  Google Scholar 

  34. Mavinkurve-Groothuis AM, van de Kracht F, Westland R, van Wijk JA, Loonen JJ, Schreuder MF (2016) Long-term follow-up of blood pressure and glomerular filtration rate in patients with a solitary functioning kidney: a comparison between Wilms tumor survivors and nephrectomy for other reasons. Pediatr Nephrol 31:435–441

    Article  PubMed  Google Scholar 

  35. Kishore SS, Oberoi S, Bhattacharya A, Prasad R, Trehan A, Bansal D, Marwaha RK (2015) Function and size of the residual kidney after treatment of Wilms tumor. Pediatr Hematol Oncol 32:11–17

    Article  PubMed  Google Scholar 

  36. Di Tullio MT, Casale F, Indolfi P, Polito C, Giuliano M, Martini A, Cimmaruta E, Morgera C, Cioce F, Greco N (1996) Compensatory hypertrophy and progressive renal damage in children nephrectomized for Wilms’ Tumor. Med Pediatr Oncol 26:325–328

    Article  PubMed  Google Scholar 

  37. Shirzai A, Yildiz N, Biyikli N, Ustunsoy S, Benzer M, Alpay H (2014) Is microalbuminuria a risk factor for hypertension in children with solitary kidney? Pediatr Nephrol 29:283–288

    Article  PubMed  Google Scholar 

  38. Elli M, Sungur M, Genc G, Ayyildiz P, Dagdemir A, Pinarli FG, Acar S (2013) The late effects of anticancer therapy after childhood Wilm’s tumor: the role of diastolic function and ambulatory blood pressure monitoring. Jpn J Clin Oncol 43:1004–1011

    Article  PubMed  Google Scholar 

  39. Levitt GA, Yeomans E, Dicks Mireaux C, Breatnach F, Kingston J, Pritchard J (1992) Renal size and function after cure of Wilms’ tumour. Br J Cancer 66:877–882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Stefanowicz J, Owczuk R, Aleksandrowicz E, Owczarzak A, Kurylak A, Adamkiewicz-Drozynska E, Balcerska A (2012) Renal function and low-molecular-weight proteins (cystatin C, beta2-microglobulin, neutrophil gelatinase-associated lipocalin) in child and young adult cancer survivors. J Pediatr Hematol Oncol 34:461–466

    Article  CAS  PubMed  Google Scholar 

  41. Susantitaphong P, Siribamrungwong M, Doi K, Noiri E, Terrin N, Jaber BL (2013) Performance of urinary liver-type fatty acid-binding protein in acute kidney injury: a meta-analysis. Am J Kidney Dis 61:430–439

    Article  CAS  PubMed  Google Scholar 

  42. Parikh CR, Thiessen-Philbrook H, Garg AX, Kadiyala D, Shlipak MG, Koyner JL, Edelstein CL, Devarajan P, Patel UD, Zappitelli M, Krawczeski CD, Passik CS, Coca SG, TRIBE-AKI Consortium (2013) Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery. Clin J Am Soc Nephrol 8:1079–1088

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Mishra J, Mori K, Ma Q, Kelly C, Barasch J, Devarajan P (2004) Neutrophil gelatinase-associated lipocalin: a novel early urinary biomarker for cisplatin nephrotoxicity. Am J Nephrol 24:307–315

    Article  CAS  PubMed  Google Scholar 

  44. Mishra J, Dent C, Tarabishi R, Mitsnefes MM, Ma Q, Kelly C, Ruff SM, Zahedi K, Shao M, Bean J, Mori K, Barasch J, Devarajan P (2005) Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery. Lancet 365:1231–1238

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This study was supported by the Scientific Research Projects Coordination Unit of Istanbul University-Cerrahpasa, Istanbul, Turkey (research number 30034).

Author information

Authors and Affiliations

  1. Department of Pediatrics, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Emrullah Arslan

  2. Department of Pediatric Nephrology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Seha Saygili, Salim Caliskan, Lale Sever & Nur Canpolat

  3. Department of Pediatric Hematology Oncology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Tülin Tiraje Celkan & Hilmi Apak

  4. Department of Radiology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Sebuh Kurugoglu

  5. Department of Pediatric Surgery, Division of Pediatric Urology, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Mehmet Elicevik

  6. Department of Public Health, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Abdulhamit Enes Camcioglu

  7. Department of Biochemistry, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Dildar Konukoglu

Authors
  1. Emrullah Arslan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seha Saygili
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tülin Tiraje Celkan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sebuh Kurugoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mehmet Elicevik
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abdulhamit Enes Camcioglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dildar Konukoglu
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Hilmi Apak
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Salim Caliskan
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Lale Sever
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Nur Canpolat
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

EA: Study design, data acquisition, data analysis/interpretation, data visualization, drafting and editing the manuscript.

SS: Data acquisition, data analysis/interpretation, data visualization.

TC, SK, HE, ME, SC, LS: Data acquisition, subsequent critical revisions.

NC: Research formulation, study design, data analysis/interpretation, drafting and editing the manuscript, and subsequent critical revisions.

Corresponding author

Correspondence to Nur Canpolat.

Ethics declarations

Ethics approval

The Ethical Committee of Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, approved the study (approval number 89555).

Conflict of interest

The authors declare no competing interests.

Additional information

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Graphical Abstract 5460 (PPTX 230 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arslan, E., Saygili, S., Celkan, T.T. et al. Increased risk for kidney sequelae surrogates in survivors of Wilms tumor. Pediatr Nephrol 37, 2415–2426 (2022). https://doi.org/10.1007/s00467-022-05460-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00467-022-05460-1

Keywords

Search

Navigation