Long-Term Follow-Up Study of Remnant Kidney Function and Volume after Nephron-Sparing Surgery for Unilateral Renal Tumor in Children  

Project location: ITALY, Rome
Project start date: December 2015 - Project end date: December 2016
Project number: 2015-048
Beneficiary: Dipartimento di Pediatria e Neuropsichiatria Infantile, Sapienza Università di Roma

Renal tumors are infrequently encountered during childhood. Of these, nephroblastoma or Wilms tumor (WT) represents the most frequent primary renal tumor, accounting for 6% to 7% of childhood cancer.
The remaining renal tumors account for less than 1%.
Clinical onset occurs before 5 years of age in 75% of cases.  Rarely, this malignancy affects also young adults. Most patients with WT can be cured with treatment and subsequently lead normal life. The multidisciplinary management of WT has resulted striking improvement in survival of more than 85% nowadays and has become a paradigm for successful cancer therapy.
Amongst the well standardized multimodal treatment of WT, surgery still plays a pivotal role. Radical nephrectomy (RN) is currently considered as the procedure of choice, because it allows excision of the primary tumor with a wide surgical margin and most of the patients are believed to have another good kidney.
Nephron-sparing surgery (NSS) plays instead a lesser role and is predominantly confined to patients with bilateral Wilms tumor (bWT). Indeed, the rationale for NSS is to limit potential long-term morbidity by maximizing the preservation of functional renal parenchyma.
Whether NSS is a reasonable alternative to nephrectomy in non-syndromic patients with WT in the setting of a normal contralateral kidney remains a matter of debate. The main issue against such approach is that there is no convincing evidence that 50% reduction of renal mass is associated with increased risk of renal failure.
In an attempt to answer this question, in 1992 we started a prospective study investigating whether NSS was feasible and effective in select children with WT and a normal contralateral kidney. Our study protocol was then revised few years later. Preoperative chemotherapy was routinely administered, except in select instances. NSS was considered only for patients with stage I disease, which was established at surgery on frozen section of specimens from renal and periaortic lymph nodes, specimens from perirenal fat and resection margin. Since the initiation of our study to May 2015, 49 children with unilateral primary renal tumor have been treated at our Institution. Of these, 35 patients underwent RN and 14 received NSS. Notably, our ongoing pilot study is one of the few existing that provides a treatment protocol of NSS as an alternative to radical nephrectomy in children with unilateral primary renal tumor and normal contralateral kidney.
The research team has already reported some interesting results on renal function in patients receiving radical nephrectomy, demonstrating that more than 50% of nephrectomised children develops a moderate renal dysfunction. Additionally, we found that aging is associated with a mild-to-moderate renal function loss in many adult patients following nephrectomy during childhood for unilateral renal tumor.
The purpose of the present study project will be mainly focusing on the oncologic and nephrological outcomes of NSS in our cohort of patients.

References  1. Pizzo PA, Poplack DG (eds). Principles and Practice of Pediatric Oncology. 3rd Edition, Lippincott-Raven, Philadelphia, 1997;733-59.  2. Cozzi F, Schiavetti A, Bonanni M, et al. Enucleative surgery for stage I nephroblastoma with a normal contralateral kidney. J Urol. 1996;156:1788-91; discussion 1791-3.  3. Cozzi DA, Schiavetti A, Morini F,et al. Nephron-sparing surgery for unilateral primary renal tumor in children. J Pediatr Surg. 2001;36:362-5.  4. Cozzi F, Schiavetti A, Morini F, et al. Renal function adaptation in children with unilateral renal tumors treated with nephron sparing surgery or nephrectomy. J Urol. 2005; 174:1404-8.  5. Cozzi DA, Ceccanti S, Frediani S, et al. Chronic kidney disease in children with unilateral renal tumor. J Urol. 2012;187:1800-5.  6. Cozzi DA, Ceccanti S, Frediani S, et al. 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. 2013;60:1534-8.

In the proposed study all patients with unilateral kidney tumor treated at the center will be recruited. An electronically maintained database will be set up, including both patients enrolled prospectively from 1992 and those treated during the previous decades, collecting patients since the establishment of our center in 1939.
The Municipal Archives of the city of Rome will be also searched to trace patients born during the initial decades of activity of our center. The Research Team estimates to recruit about 80 patients.  The database will be filled with all available patients’ clinical information, including laboratory and imaging studies data. The following parameters will be analyzed for the study: demographics including age at diagnosis and at surgery, pre- and post-operative renal function, type of surgery performed, neo-adjuvant and adjuvant chemotherapy, radiotherapy, tumor staging and histological findings. 
To assess renal function, the Team will calculate the estimated glomerular filtration rate (eGFR), which is widely accepted as the best surrogate marker of overall renal function. eGFR is actually calculated from serum creatinine values indexed not only to age and gender, but also to body size. Measurements of eGFR will be made using either the revised Schwartz equation or the equation from the Modification of Diet in Renal Disease study, as appropriate for age. A renal dysfunction will be defined as eGFR  150 mg/24 hours. Systemic blood pressure measurements will be also taken and values will be indexed by gender and age, and expressed as standard deviation scores, utilizing available values of systolic and diastolic pressure in the normal population. An ultrasonography, if not recently performed, will be repeated for kidney volume quantification. Standard deviations will be calculated using available nomograms of renal volumes in both pediatric and adult population. Notably, while collecting data for the main purpose of our study  project, the designed Research Fellow will be actively involved in other ongoing research activities, as well as clinical activities, conducted at the research center.

The intended beginning of this Fellowship is January 2016 and the expected end will be December 2016. During the period of the Fellowship, the designed fellow will be also involved  in a busy clinical practice in general pediatric surgery and neonatal surgery, attached to the Pediatric Surgery Unit of the Policlinico Umberto I, University Hospital of Rome.

The Nando and Elsa Peretti Foundation has awarded a grant for this project. The aims of this study can be summarized as follows: 

1.    To determine the oncologic outcomes of our cohort of patients treated with nephron-sparing surgery (NSS) for primary unilateral renal tumor.

2.    To determine residual renal function and relative renal volume of the kidney remnants after NSS.

3.    To compare oncologic and nephrological outcomes of patients with primary renal tumor receiving either radical nephrectomy or NSS.  The obtained results from the proposed study will be very innovative and will contribute to expand the currently limited role of NSS for select children with unilateral primary renal tumor and normal opposite kidney.

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