Pediatr Blood Cancer 2015;62:1637–1644
Long-term Renal Function in Unilateral Non-Syndromic Renal Tumor Survivors Treated According to International Society of Pediatric Oncology Protocols Amalia Schiavetti,
1 MD, *
Pierluigi Altavista, MD,2 Laura De Luca, MD,1 Gianmarco Andreoli, Giacomina Megaro, MD,1 and Paolo Versacci, MD1
Background. The risk of renal impairment among survivors of childhood unilateral non-syndromic renal tumors (RTs) is not well defined. We evaluated the prevalence of and possible risk factors for renal impairment by estimating Glomerular Filtration Rate (eGFR) categories and chronic kidney disease (CKD) according to Kidney Disease: Improving Global Outcomes guidelines. Procedure. Since 1978, 82 patients were treated for RT, according to the International Society of Pediatric Oncology protocols in a single oncology unit. Of the 67 survivors, those who underwent nephron sparing surgery, those with short-term follow-up or those who had bilateral and/or syndromic disease or a second malignancy were excluded. Thirtyfive adult survivors (14 M/21F; mean age 25 years; mean follow-up 20 years) were studied by chemistry, kidney ultrasound, blood pressure measurement, urinanalysis. Correlations were investigated
1 MD,
between the prevalence of eGFR categories and CKD and gender, age at diagnosis, radiotherapy, chemotherapy, body mass index, time of follow-up, and age at study. Results. Eight (22.9%) survivors presented a mildly decreased eGFR (G2 category), the mean value was 80 9.78 ml/min/1.73m2 (median 84.5, range 63–89). Three (8.6%) survivors had CKD and a fourth (2.9%) hypertension. No significant correlations between G2 category and clinical variables were found. Conclusions. A small percentage of survivors had CKD or hypertension after two decades. It is not yet clear whether a mildly decreased eGFR that does not constitute CKD in the absence of other markers (albuminuria and/or kidney ultrasound abnormalities) is likely to progress to CKD. Health promotion programs to avoid comorbidities are required. Pediatr Blood Cancer 2015;62:1637– 1644. # 2015 Wiley Periodicals, Inc.
Key words: children; comorbidities; renal function; uninephrectomy
INTRODUCTION Renal disease had not until recently been considered a major issue for uncomplicated unilateral renal tumor (RT). End-stage renal disease (ESRD), defined as the need for dialysis and/or renal transplantation and/or glomerular filtration rate (GFR) 60 ml/min/1.73 m2) fulfill the criteria for chronic kidney disease (CKD) according to the recent Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [27] (Fig. 1). Moreover, the late decrease in the eGFR reflects treatments given over many decades, before the current generation of treatment protocols was introduced.[25–26] Finally, the studies do not take into consideration comorbidities: though high blood pressure (BP), hyperglycemia, dyslipidemia, smoking, obesity, and cardiac function assessment are all relevant in cases with very long follow-up.[24–26] C
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25558 Published online 20 April 2015 in Wiley Online Library (wileyonlinelibrary.com).
In view of the conflicting data available on long-term renal function, we decided to evaluate the prevalence of and possible risk factors for renal dysfunction defined both by means of the eGFR categories and of CKD, in adult long-term survivors of childhood unilateral non-syndromic RT, treated in a single oncology unit, according to the International Society of Pediatric Oncology (SIOP) protocols.
METHODS We performed a retrospective cross-sectional single-center study. Demographic and clinical data were collected from the medical files of patients treated for a RT from 1978 to 2014 at the Pediatric Oncology Unit of ”Sapienza” University of Rome. Eligibility criteria for the current study were as follows: diagnosis and treatment for a primary RT since 1978; age 17 years. All eligible survivors were invited to the outpatient clinic to receive specialized screening. Written informed consent was obtained from the survivors, as appropriate. Survivors underwent a physical examination, chemistry, kidney ultrasound, blood pressure (BP) measurement, and urinanalysis. They were matched for body
1
Department of Pediatrics, “Sapienza” University, Rome, Italy; Technical Unit for Radiation, Biology and Human Health, Casaccia ENEA Research Center, Rome, Italy
2
Conflict of interest: Nothing to declare.
Correspondence to: Amalia Schiavetti, Department of Pediatrics, Viale Regina Elena 324, 00161 Rome, Italy. E-mail: [email protected] Received 10 November 2014; Accepted 20 March 2015
1638
Schiavetti et al.
Fig. 1. CKD by GFR and Albuminuria Categories. CKD, chronic kidney disease; GFR, glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes. White, low risk (if no other markers of kidney disease, no CKD); Gray, moderately increased risk; Striped, high risk; Black, very high risk. Adapted with the permission from the copyright holder (KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Inter, Suppl. 2013; 3: pg9.).
mass index (BMI), because of the potential influence of body composition on renal function and BP.
Patients Eighty-two patients with RT completed their treatment according to the protocols SIOP 5, SIOP 6, SIOP 9, SIOP 93-01, and SIOP 2001 between 1978 and 2014. Twenty-three of the 82 patients underwent surgery in other surgical centers, but received pre/post operative therapy in our oncology unit. The histology was renal cell carcinoma (RCC) in 6, clear cell sarcoma in 1, WT in 73, oncocytoma in 1, congenital mesoblastic nephroma in 1. Fifteen patients died before the present study: 12 died of disease (2 of these affected by RCC), 1 of renal failure (WAGR syndrome in bilateral case) and 2 in accidents. The overall-survival is 81.7% for all renal tumors and 86.4% for WT at a mean follow-up of 18.8 years. Of the 64 five-year survivors, we excluded from the present study those who received NSS and/or had syndromic and/or bilateral disease (n15), those whose age at the time of study was
Long-term Renal Function in Unilateral Non-Syndromic Renal Tumor Survivors Treated According to International Society of Pediatric Oncology Protocols Amalia Schiavetti,
1 MD, *
Pierluigi Altavista, MD,2 Laura De Luca, MD,1 Gianmarco Andreoli, Giacomina Megaro, MD,1 and Paolo Versacci, MD1
Background. The risk of renal impairment among survivors of childhood unilateral non-syndromic renal tumors (RTs) is not well defined. We evaluated the prevalence of and possible risk factors for renal impairment by estimating Glomerular Filtration Rate (eGFR) categories and chronic kidney disease (CKD) according to Kidney Disease: Improving Global Outcomes guidelines. Procedure. Since 1978, 82 patients were treated for RT, according to the International Society of Pediatric Oncology protocols in a single oncology unit. Of the 67 survivors, those who underwent nephron sparing surgery, those with short-term follow-up or those who had bilateral and/or syndromic disease or a second malignancy were excluded. Thirtyfive adult survivors (14 M/21F; mean age 25 years; mean follow-up 20 years) were studied by chemistry, kidney ultrasound, blood pressure measurement, urinanalysis. Correlations were investigated
1 MD,
between the prevalence of eGFR categories and CKD and gender, age at diagnosis, radiotherapy, chemotherapy, body mass index, time of follow-up, and age at study. Results. Eight (22.9%) survivors presented a mildly decreased eGFR (G2 category), the mean value was 80 9.78 ml/min/1.73m2 (median 84.5, range 63–89). Three (8.6%) survivors had CKD and a fourth (2.9%) hypertension. No significant correlations between G2 category and clinical variables were found. Conclusions. A small percentage of survivors had CKD or hypertension after two decades. It is not yet clear whether a mildly decreased eGFR that does not constitute CKD in the absence of other markers (albuminuria and/or kidney ultrasound abnormalities) is likely to progress to CKD. Health promotion programs to avoid comorbidities are required. Pediatr Blood Cancer 2015;62:1637– 1644. # 2015 Wiley Periodicals, Inc.
Key words: children; comorbidities; renal function; uninephrectomy
INTRODUCTION Renal disease had not until recently been considered a major issue for uncomplicated unilateral renal tumor (RT). End-stage renal disease (ESRD), defined as the need for dialysis and/or renal transplantation and/or glomerular filtration rate (GFR) 60 ml/min/1.73 m2) fulfill the criteria for chronic kidney disease (CKD) according to the recent Kidney Disease: Improving Global Outcomes (KDIGO) guidelines [27] (Fig. 1). Moreover, the late decrease in the eGFR reflects treatments given over many decades, before the current generation of treatment protocols was introduced.[25–26] Finally, the studies do not take into consideration comorbidities: though high blood pressure (BP), hyperglycemia, dyslipidemia, smoking, obesity, and cardiac function assessment are all relevant in cases with very long follow-up.[24–26] C
2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25558 Published online 20 April 2015 in Wiley Online Library (wileyonlinelibrary.com).
In view of the conflicting data available on long-term renal function, we decided to evaluate the prevalence of and possible risk factors for renal dysfunction defined both by means of the eGFR categories and of CKD, in adult long-term survivors of childhood unilateral non-syndromic RT, treated in a single oncology unit, according to the International Society of Pediatric Oncology (SIOP) protocols.
METHODS We performed a retrospective cross-sectional single-center study. Demographic and clinical data were collected from the medical files of patients treated for a RT from 1978 to 2014 at the Pediatric Oncology Unit of ”Sapienza” University of Rome. Eligibility criteria for the current study were as follows: diagnosis and treatment for a primary RT since 1978; age 17 years. All eligible survivors were invited to the outpatient clinic to receive specialized screening. Written informed consent was obtained from the survivors, as appropriate. Survivors underwent a physical examination, chemistry, kidney ultrasound, blood pressure (BP) measurement, and urinanalysis. They were matched for body
1
Department of Pediatrics, “Sapienza” University, Rome, Italy; Technical Unit for Radiation, Biology and Human Health, Casaccia ENEA Research Center, Rome, Italy
2
Conflict of interest: Nothing to declare.
Correspondence to: Amalia Schiavetti, Department of Pediatrics, Viale Regina Elena 324, 00161 Rome, Italy. E-mail: [email protected] Received 10 November 2014; Accepted 20 March 2015
1638
Schiavetti et al.
Fig. 1. CKD by GFR and Albuminuria Categories. CKD, chronic kidney disease; GFR, glomerular filtration rate; KDIGO, Kidney Disease Improving Global Outcomes. White, low risk (if no other markers of kidney disease, no CKD); Gray, moderately increased risk; Striped, high risk; Black, very high risk. Adapted with the permission from the copyright holder (KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Inter, Suppl. 2013; 3: pg9.).
mass index (BMI), because of the potential influence of body composition on renal function and BP.
Patients Eighty-two patients with RT completed their treatment according to the protocols SIOP 5, SIOP 6, SIOP 9, SIOP 93-01, and SIOP 2001 between 1978 and 2014. Twenty-three of the 82 patients underwent surgery in other surgical centers, but received pre/post operative therapy in our oncology unit. The histology was renal cell carcinoma (RCC) in 6, clear cell sarcoma in 1, WT in 73, oncocytoma in 1, congenital mesoblastic nephroma in 1. Fifteen patients died before the present study: 12 died of disease (2 of these affected by RCC), 1 of renal failure (WAGR syndrome in bilateral case) and 2 in accidents. The overall-survival is 81.7% for all renal tumors and 86.4% for WT at a mean follow-up of 18.8 years. Of the 64 five-year survivors, we excluded from the present study those who received NSS and/or had syndromic and/or bilateral disease (n15), those whose age at the time of study was
