Unilateral renal cell carcinoma with coexistent renal disease: a rare cause of end-stage renal disease
Ramón Peces and
Rafael Alvarez-Navascués
Servicio de Nefrología, Hospital Central de Asturias, Oviedo, Spain
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Abstract
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Background. Renal cell carcinoma (RCC) is a disorder encompassing a wide spectrum of pathological renal lesions. Coexistence of unilateral RCC and associated pathology in the contralateral kidney is an unusual and challenging therapeutic dilemma that can result in renal failure. So far, data on unilateral RCC with chronic renal failure necessitating renal replacement therapy have not been published. The aim of the present study was to evaluate the incidence of end-stage renal disease (ESRD) from unilateral RCC, and to assess the associated pathology and possible pathogenic factors.
Methods. In 1999, a survey of the 350 patients treated by chronic dialysis in Asturias, Spain, was carried out to identify and collect clinical information on patients with primary unilateral RCC whilst on their renal replacement programme.
Results. Seven patients were identified as having ESRD and unilateral RCC, giving an incidence of 2% of patients treated by dialysis. There was a wide spectrum of associated disease and clinical presentation. All patients underwent radical or partial nephrectomy and were free of recurrence 664 months after surgery. Six patients were alive and free of malignancy recurrence for 630 months after the onset of haemodialysis.
Conclusion. ESRD is rare in association with unilateral RCC, but does contribute to significant morbidity. However, the data presented here are encouraging and suggest that cancer-free survival with renal replacement therapy can be achieved in such patients.
Keywords: end-stage renal disease; haemodialysis; nephrectomy; renal carcinoma
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Introduction
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Renal cell carcinoma (RCC) accounts for 23% of all adult cancers, and has many unusual features in its presentation, diagnosis and management [1]. Primary RCC is an unusual cause of end-stage renal disease (ESRD), occurring in only 0.11% of patients treated by dialysis and transplantation [2]. However, ESRD from unilateral RCC is exceptional. Review of the literature reveals only isolated case reports of unilateral RCC and associated pathology in the contralateral kidney [35]. To date, no study has been carried out to look at the incidence of ESRD from unilateral RCC or its clinical presentation, and no study has reported the associated pathology in these patients.
We present our experience in the management of seven patients who had undergone unilateral nephrectomy for RCC and developed ESRD. Before surgery, all patients had clinical and radiological evidence of associated renal disease in the contralateral kidney. The literature is reviewed, and the relationship between RCC and associated renal disease is discussed.
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Subjects and methods
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From February 1999 to January 2000, 350 patients were treated by chronic dialysis in Asturias, Spain. A questionnaire was sent to the dialysis units of Asturias, asking for the following clinical information on any patient with unilateral RCC whilst on their renal replacement programme: sex; age at diagnosis of RCC; age at diagnosis of renal disease; age at onset of ESRD; the reason for diagnosis of RCC; the presenting features of the renal disease; the presence or absence of hypertension; the underlying lesions; the confirmation of diagnosis; renal function at presentation; and treatment received. Patients with bilateral RCC were excluded from this review.
A total of seven patients were identified as having unilateral RCC and associated pathology in the contralateral kidney, necessitating dialysis. The underlying pathology was confirmed by ultrasound, computed tomography (CT), and in some cases arteriography. All patients underwent complete surgical excision of RCC. Six patients underwent radical nephrectomy and one partial nephrectomy. All patients in this study had histopathologically proved RCC. In the non-tumorous parts of the kidney, the presence of other associated lesions was investigated. Tumour stage was determined according to the tumour, nodes and metastases system (TNM), and the cellular grade as G1G4 [1,6]. All patients were evaluated at regular intervals post-operatively by chest radiography and CT.
Over the same period of time, 125 new patients with unilateral RCC without associated pathology in the contralateral kidney were observed in our region (
11/100 000 persons per year). In addition, in the last 2 years, five patients developed unilateral RCC after the start of dialysis, two of them after renal transplantation.
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Results
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Of the 350 chronic haemodialysis patients, seven patients (2%) presented with unilateral RCC and associated renal disease, affecting all of the functioning renal parenchyma or the contralateral kidney. The overall data on the patients and their outcomes are presented in Tables 1
and 2
. There were six males and one female. The mean age of presentation was 58 years (range 3477 years) and the presenting features varied widely. Only two patients (cases 5 and 7) were known to have renal involvement prior to presentation. Two had normal renal function at the time of presentation, four had moderate renal insufficiency and one had advanced renal failure. Three patients presented with renal masses and two complained of flank pain. Four patients presented hypertension. The mean age was 59 years (range 3578 years) at the beginning of dialysis. In cases 1, 2 and 4, radical nephrectomy involved the need for immediate post-operative haemodialysis. Case 3 started haemodialysis 3 weeks before nephrectomy. Cases 5, 6 and 7 needed haemodialysis at 5 years, 6 months and 9 months, respectively, after surgery. There was a wide spectrum of associated pathology. The abnormalities were: renal agenesis (1), post-hydronephrotic atrophy (1), amyloidosis (1), nephrosclerosis (2), diabetic nephropathy (1) and focal segmental glomerulosclerosis (FSGS) (1). On histological examination, all of the resected tumours were identified as nuclear grade G1 (three cases), G2 (three cases) and G4 (one case), and stage T1T3 RCC. In the non-tumorous parts of the kidney there were signs of acquired renal cystic disease (cases 3, 4, 5 and 7). In all four cases, the epithelium of the cyst wall was hyperplastic and the pre-operative CT scan showed multiple cysts in the contralateral kidney. All patients were free of recurrence for 664 months after surgery. One patient (case 3) died of septicaemia after 6 months on haemodialysis with no evidence of malignancy at death. The remaining six patients were alive and free of malignancy recurrence for 630 months after the onset of haemodialysis.
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Table 2. Summary of pathological and prognostic data from patients with renal cell carcinoma and end-stage renal disease
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Discussion
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These seven cases demonstrate the problems associated with unilateral RCC and underlying pathology in the contralateral kidney. The question, of course, arises of whether the occurrence of other renal abnormality in the patients with RCC is an associated feature of unknown causality or is purely coincidental. The patients in our survey represented a wide spectrum of renal disease. In case 1, the contralateral kidney was congenitally absent. In case 2, the contralateral kidney had post-hydronephrotic atrophy secondary to ureteropelvic junction obstruction. Both cases had normal renal function when RCC was diagnosed and may be considered as an anatomically or functionally solitary kidney [7]. Therefore, in these patients the association could be purely coincidental.
Case 3 presented inflammatory bowel disease with chronic suppuration for 14 years, developing nephrotic syndrome and renal failure. Although secondary amyloidosis occurs in 13% of patients with RCC [8], the pathogenesis of amyloidosis in this case was, no doubt, secondary to chronic inflammatory stimulation. In this case, the RCC could be related to stimulation of certain growth factors rather than amyloidosis. Cases 4, 5 and 7 had a long-term history of chronic renal failure associated with hypertension when RCC was diagnosed. Furthermore, pathological study of the non-tumorous parts of the kidney revealed arteriolosclerosis and sclerotic glomerular lesions. Moreover, cases 3, 4, 5 and 7 had acquired renal cystic disease and could have an increased risk of developing RCC. Although it has been considered that patients with chronic renal failure due to hypertension may have an increased risk of developing RCC [3], it is difficult to confirm whether acquired renal cystic disease and RCC are more common in patients with underlying hypertensive renal disease. Whereas the risk of RCC has been reported to be increased in patients with acquired cystic kidney disease associated with chronic renal insufficiency on dialysis [9], reports of RCC developing in patients with chronic renal failure without dialysis treatment are very limited [3,4].
The most common lesion in ESRD is development of variably sized cysts lined by cuboidal epithelium. The epithelial lining of these cysts usually manifests varying degrees of proliferation, subsequently leading to dysplasia, adenoma and carcinoma. The factors responsible for the proliferative changes in renal tubular epithelium are poorly understood. It has been suggested that severely altered microenvironment of the cells in the end-stage kidney may cause the release of certain growth factors. Such factors, acting as ligands for surface receptors on surviving renal cells, could enhance proliferation in the end-stage kidney [1012].
Case 6 presented with nephrotic syndrome and renal failure, and was subsequently found to have an RCC and FSGS. The patient had symptoms of renal disease several months before presenting with RCC. It is possible that in this patient the RCC pre-dated the development of glomerulonephritis, and that the symptoms and signs could constitute a paraneoplastic syndrome. However, there was no evidence of any improvement following removal of the tumour, and haemodialysis was started 6 months after the operation. Several reports exist on the association of unilateral RCC with other renal diseases such as acute and chronic glomerulonephritis [13,14]. Membranous glomerulonephritis is the glomerular lesion that has been described most often in association with RCC [15,16]. Minimal change nephropathy, IgA glomerulonephritis, membranoproliferative glomerulonephritis and rapidly progressive glomerulonephritis have also rarely been described with RCC [13,14,1722]. Other renal lesions, including amyloidosis and renal vasculitis, have been associated with RCC [8,23]. Reports of resolution of the nephrotic syndrome with successful treatment or resection of malignancy, lend support to the theory that tumour-related products are important in pathogenesis [8,17,20]. Although a role of tumour antigens and anti-tumour antibodies in producing glomerular immune deposits has been speculated on, the evidence for this assertion is insufficient.
The management of patients with coexistent RCC and renal disease affecting all of the functioning renal parenchyma presents a challenging clinical problem. Several treatment goals must be balanced, including complete tumour excision and the preservation of renal function. To this end, a variety of factors must be considered, including the size of the tumour, the technical feasibility of a nephron-sparing cancer operation, specific type and severity of renal disease, amount of parenchyma affected by renal disease and level of overall renal function [7]. Because of the size and location of the tumour, the elective treatment in our patients was radical nephrectomy in six cases and partial nephrectomy in one. With this management, all patients were free of recurrence for 664 months after surgery and remained on maintenance haemodialysis for 630 months.
In summary, in some cases of unilateral RCC, a parenchymal preserving procedure as curative treatment is impossible and radical or partial nephrectomy involves the need of post-operative renal replacement therapy. The use of radical surgery to treat RCC in these patients yielded satisfactory results with respect to control of the malignancy. Furthermore, cancer-free survival with renal replacement therapy can be achieved in these patients. These data indicate that in some patients, a reasonable waiting time on dialysis is required to avoid transplanting those with early recurrence.
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Notes
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Correspondence and offprint requests to: Dr R. Peces, Servicio de Nefrología, Hospital Central de Asturias, Celestino Villamil s/n, E-33006 Oviedo, Spain. 
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Received for publication: 18. 3.00
Accepted in revised form: 27. 9.00