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Nephrotic syndrome and renal failure as an unusual presentation of solid tumour

Nephrotic syndrome and renal failure as an unusual presentation of solid tumour NDT Plus (2010) 3: 51–53 doi: 10.1093/ndtplus/sfp119 Advance Access publication 3 September 2009 Case Report Nephrotic syndrome and renal failure as an unusual presentation of solid tumour 1 2 3 4 1 Florence Bonkain , Graziella Ena , Michel Depierreux ,Frederic D. Debelle and Joelle L. Nortier ´ ´ ¨ 1 2 3 4 Departments of Nephrology, Gynaecology, Pathology, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels and Department of Nephrology and Dialysis, RHMS Baudour Hospital, Baudour, Belgium Correspondence and offprint requests to:Fred ´ eric ´ Debelle; E-mail: fdebelle@ulb.ac.be Abstract Case report Glomerular diseases may occur as primary manifestation of cancer, especially in patients older than 60 years. Among A 79-year-old woman was referred by her family doctor glomerulopathies, membranous nephropathy is preferen- for dyspnoea, ascites and lower limb oedema that appeared tially associated with respiratory and gastrointestinal tract a few weeks previously and rapidly worsened. Her past adenocarcinomas, whereas minimal change disease is most medical history consisted in essential hypertension well often seen in haematological malignancies. Though breast controlled by barnidipine and bumetanide, and osteoporotic cancer is one of the most frequent malignancies in women, fractures treated by alendronate. She had no personal or paraneoplastic glomerular disease is rarely observed. We familial history of kidney disease. A recent determination describe the case of a 79-year-old female patient who pre- of serum creatinine was within the normal range. She had sented with nephrotic syndrome and renal failure. Breast no known atopy. cancer was found. Pathological studies of kidney and breast Upon admission, the physical examination revealed biopsy revealed a minimal change disease and an infiltrat- widespread oedema and wet rales on auscultation of the ing ductal carcinoma, respectively. chest. Blood and urine tests demonstrated a functional acute kidney injury (serum creatinine: 256.4 μmol/l; blood urea: Keywords: acute kidney injury; minimal change disease; nephrotic 34.9 mmol/l, fractional excretions of sodium: 0.14% and syndrome; paraneoplastic glomerulopathy; solid tumour of urea: 4.6%) with hypoalbuminaemia (24 g/l) and hyper- cholesterolaemia (6.9 mmol/l). Nephrotic syndrome was further confirmed on a 24-h urine collection with a pro- tein/creatinine ratio at 1338 mg/mmol. Neither haematuria Introduction nor casts were found in voided urine sample. Serologi- cal studies for antinuclear antibodies, antineutrophil cyto- Nephrotic syndrome may occur in a wide variety of clin- plasmic antibodies, rheumatoid factors, antistreptolysin-O, ical settings such as diabetes mellitus, amyloidosis, sys- HBC, HCV, HIV and complement levels were all nega- temic lupus erythematosus, membranous nephropathy, fo- tive. Blood and urine protein electrophoreses were unre- cal glomerulosclerosis, as well as minimal change disease markable. No pulmonary opacities were observed on the (MCD). It is generally recognized that MCD accounts for chest x-ray. A transthoracic echocardiography revealed a up to 15% of all cases of adult nephrotic syndrome and is normal cardiac anatomy and function. The renal Doppler most often of idiopathic origin [1]. However, drugs, infec- ultrasonography displayed normal-sized kidneys without tions, atopy and neoplasms may be associated with MCS. any sign of obstruction or renal veins thrombosis. A re- The paraneoplastic minimal change nephrotic syndrome, nal biopsy was performed. Histopathological examination generally defined by a close time relationship between the demonstrated optically normal glomeruli, mild tubular atro- glomerular disease and the malignancy, is mainly secondary phy and the absence of complement or immunoglobulin de- to haematological malignancies [2]. Occasionally, solid tu- posits by immunofluorescence microscopy, consistent with mours are associated with MCD and therefore should be a diagnosis of MCD (Figure 1A and B). Drugs, infection, searched, especially in older patients [3,4]. We report on a atopy and haematological malignancies were reasonably case of a woman who presented with acute kidney injury ruled out as possible causal factors of MCD on the basis of and nephrotic syndrome secondary to MCD as the inaugu- biological and clinical findings. ral manifestation of a breast cancer. The patient came off During the first days, the patient’s outcome was marked dialysis after a 4-week course of steroids combined with by a pulmonary oedema uncontrolled by high doses of di- enalapril, and surgical removal of the breast tumour. uretics, and requiring haemodialysis. A few days later, the C The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org 52 F. Bonkain et al. Fig. 1. (A) Representative photomicrographs of renal biopsy showing glomerulus of the normal size and no segmental lesions. Mild tubular atrophy is found, probably as a result of ischaemic and protein overload processes (silver stain, 400×). (B) At higher magnification, the glomerular basement membrane is thin without any spikes (silver stain, 1000×). Fourteen glomeruli were observed on the renal biopsy specimen. Fig. 2. Time course evolution of renal functional parameters (serum creatinine and proteinuria) along with major clinical events. Nephrotic syndrome and renal failure as an unusual presentation of solid tumour 53 patient received prednisolone (1 mg/kg per day, orally) and (improvement, remission, recurrence) [4]. In about half of the angiotensin-converting enzyme inhibitor enalapril. A cases, the diagnosis of nephrotic syndrome precedes those progressive reduction of proteinuria was observed and re- of cancer while the simultaneous presentation of both dis- nal function parameters improved, allowing us to taper the eases occurs in ∼30% [4]. Renal improvement is mainly steroid dosage (Figure 2). observed after complete clinical remission of the cancer. Careful physical examination revealed a suspect mass However, the two conditions can independently evolve [4]. (20 × 15 mm) in the inner quadrant of her right breast that Taking together, the firm causal link is often missing as in was further confirmed by mammography and ultrasonogra- many similar cases, which makes the formal diagnosis of phy. Histopathological examination of a breast biopsy tissue paraneoplastic glomerulopathies uneasy. sample demonstrated a moderately differentiated infiltrat- Finally, the beneficial effect of steroid therapy observed ing ductal carcinoma (grade II) expressing oestrogen and in our patient cannot distinguish idiopathic form from progesterone hormones receptors but not the erb-2 protein. cancer-associated MCD since pathophysiology of parane- The supraclavicular and axillar areas were free of enlarged oplastic glomerulopathies involves numerous immunologi- lymph nodes and no distant metastasis was found. Serum cal processes (cytokines, growth factors or tumour antigens) markers CA 15-3 and CEA were at 27 U/ml (<25 U/ml) susceptible to be efficiently reduced by immunosuppressive and 6.2 ng/ml (<4.5 ng/ml), respectively. treatment [4]. In conclusion, the diagnosis of idiopathic One month later, the patient was dialysis free and the MCD may be firmly assessed only after exclusion of all surgical removal of the breast cancer was performed (final possible causes such as drugs, infections, allergies and neo- staging pT1cN1cM0 according to the WHO classification). plasms, among others solid tumours. Our case highlights the The immediate postoperative period resulted in the nearly fact that a cancer as common as a breast malignancy may complete remission of the renal disease with a serum cre- have an uncommon inaugural manifestation such as a MCD atinine level at 114.9 μmol/l (Figure 2). Unfortunately, the nephrotic syndrome. patient developed a fulminant septic shock due to Staphy- lococcus aureus and died 48 h later. Conflict of interest statement. None declared. Discussion References The present case draws the physician’s attention to the pos- 1. Cameron JS. The nephrotic syndrome and its complications. Am J sible presentation of MCD nephrotic syndrome and acute Kidney Dis 1987; 10: 157–171 2. Audard V, Larousserie F, Grimbert P et al. Minimal change nephrotic kidney injury as inaugural manifestations of solid tumour. syndrome and classical Hodgkin’s lymphoma: report of 21 cases and Cancer-related MCD is preferentially linked to haemato- review of the literature. Kidney Int 2006; 69: 2251–2260 logical malignancies whereas membranous nephropathy is 3. Martinez-Vea A, Panisello JM, Garcia C et al. Minimal-change mostly associated with solid tumours such as respiratory glomerulopathy and carcinoma. Report of two cases and review of and gastrointestinal tract adenocarcinomas [4,5]. The asso- the literature. Am J Nephrol 1993; 13: 69–72 ciation between MCD and solid tumours is extremely rare, 4. Bacchetta J, Juillard L, Cochat P et al. Paraneoplastic glomeru- especially those associated with breast cancer [3,6,7]. lar diseases and malignancies. Crit Rev Oncol Hematol 2009; 70: 39–58 In this case, the simultaneous presentation of the 5. Lee JC, Yamauchi H, Hopper J Jr. The association of cancer and the nephrotic syndrome and the breast cancer is in favour nephrotic syndrome. Ann Intern Med 1966; 64: 41–51 of an association between those two entities. Moreover, 6. Meyrier A, Delahousse M, Callard P et al. Minimal change nephrotic alternative causes of MCD such as non-steroidal anti- syndrome revealing solid tumors. Nephron 1992; 61: 220–223 inflammatory agents or antibiotics were excluded. Rare 7. Macanovic M, Peat D. Minimal change nephropathy with adenocar- cases of biphosphonate-induced nephrotic syndrome have cinoma of breast. J R Soc Med 2000; 93: 539 been reported in the literature; most of them were collaps- 8. Markowitz GS, Appel GB, Fine PL et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. ing focal glomerulosclerosis due to pamidronate and ex- J Am Soc Nephrol 2001; 12: 1164–1172 ceptionally to alendronate [8,9]. On the other hand, Barry 9. Pascual J, Torrealba J, Myers J et al. Collapsing focal segmen- et al. observed two cases of biphosphonate-related MCD tal glomerulosclerosis in a liver transplant recipient on alendronate. but both after i.v. administration of pamidronate [10]. Osteoporos Int 2007; 18: 1435–1438 The term paraneoplastic glomerulopathy generally refers 10. Barri YM, Munshi NC, Sukumalchantra S et al. Podocyte injury as- to a glomerular disease without specific aetiology and sociated glomerulopathies induced by pamidronate. Kidney Int 2004; which develops in parallel with cancer evolution phases 65: 634–641 Received for publication: 26.1.09; Accepted in revised form: 7.8.09 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Clinical Kidney Journal Oxford University Press

Nephrotic syndrome and renal failure as an unusual presentation of solid tumour

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Publisher
Oxford University Press
Copyright
© The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Subject
Case Report
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2048-8505
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2048-8513
DOI
10.1093/ndtplus/sfp119
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25949405
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Abstract

NDT Plus (2010) 3: 51–53 doi: 10.1093/ndtplus/sfp119 Advance Access publication 3 September 2009 Case Report Nephrotic syndrome and renal failure as an unusual presentation of solid tumour 1 2 3 4 1 Florence Bonkain , Graziella Ena , Michel Depierreux ,Frederic D. Debelle and Joelle L. Nortier ´ ´ ¨ 1 2 3 4 Departments of Nephrology, Gynaecology, Pathology, Erasme Hospital, Universite´ Libre de Bruxelles, Brussels and Department of Nephrology and Dialysis, RHMS Baudour Hospital, Baudour, Belgium Correspondence and offprint requests to:Fred ´ eric ´ Debelle; E-mail: fdebelle@ulb.ac.be Abstract Case report Glomerular diseases may occur as primary manifestation of cancer, especially in patients older than 60 years. Among A 79-year-old woman was referred by her family doctor glomerulopathies, membranous nephropathy is preferen- for dyspnoea, ascites and lower limb oedema that appeared tially associated with respiratory and gastrointestinal tract a few weeks previously and rapidly worsened. Her past adenocarcinomas, whereas minimal change disease is most medical history consisted in essential hypertension well often seen in haematological malignancies. Though breast controlled by barnidipine and bumetanide, and osteoporotic cancer is one of the most frequent malignancies in women, fractures treated by alendronate. She had no personal or paraneoplastic glomerular disease is rarely observed. We familial history of kidney disease. A recent determination describe the case of a 79-year-old female patient who pre- of serum creatinine was within the normal range. She had sented with nephrotic syndrome and renal failure. Breast no known atopy. cancer was found. Pathological studies of kidney and breast Upon admission, the physical examination revealed biopsy revealed a minimal change disease and an infiltrat- widespread oedema and wet rales on auscultation of the ing ductal carcinoma, respectively. chest. Blood and urine tests demonstrated a functional acute kidney injury (serum creatinine: 256.4 μmol/l; blood urea: Keywords: acute kidney injury; minimal change disease; nephrotic 34.9 mmol/l, fractional excretions of sodium: 0.14% and syndrome; paraneoplastic glomerulopathy; solid tumour of urea: 4.6%) with hypoalbuminaemia (24 g/l) and hyper- cholesterolaemia (6.9 mmol/l). Nephrotic syndrome was further confirmed on a 24-h urine collection with a pro- tein/creatinine ratio at 1338 mg/mmol. Neither haematuria Introduction nor casts were found in voided urine sample. Serologi- cal studies for antinuclear antibodies, antineutrophil cyto- Nephrotic syndrome may occur in a wide variety of clin- plasmic antibodies, rheumatoid factors, antistreptolysin-O, ical settings such as diabetes mellitus, amyloidosis, sys- HBC, HCV, HIV and complement levels were all nega- temic lupus erythematosus, membranous nephropathy, fo- tive. Blood and urine protein electrophoreses were unre- cal glomerulosclerosis, as well as minimal change disease markable. No pulmonary opacities were observed on the (MCD). It is generally recognized that MCD accounts for chest x-ray. A transthoracic echocardiography revealed a up to 15% of all cases of adult nephrotic syndrome and is normal cardiac anatomy and function. The renal Doppler most often of idiopathic origin [1]. However, drugs, infec- ultrasonography displayed normal-sized kidneys without tions, atopy and neoplasms may be associated with MCS. any sign of obstruction or renal veins thrombosis. A re- The paraneoplastic minimal change nephrotic syndrome, nal biopsy was performed. Histopathological examination generally defined by a close time relationship between the demonstrated optically normal glomeruli, mild tubular atro- glomerular disease and the malignancy, is mainly secondary phy and the absence of complement or immunoglobulin de- to haematological malignancies [2]. Occasionally, solid tu- posits by immunofluorescence microscopy, consistent with mours are associated with MCD and therefore should be a diagnosis of MCD (Figure 1A and B). Drugs, infection, searched, especially in older patients [3,4]. We report on a atopy and haematological malignancies were reasonably case of a woman who presented with acute kidney injury ruled out as possible causal factors of MCD on the basis of and nephrotic syndrome secondary to MCD as the inaugu- biological and clinical findings. ral manifestation of a breast cancer. The patient came off During the first days, the patient’s outcome was marked dialysis after a 4-week course of steroids combined with by a pulmonary oedema uncontrolled by high doses of di- enalapril, and surgical removal of the breast tumour. uretics, and requiring haemodialysis. A few days later, the C The Author 2009. Published by Oxford University Press [on behalf of ERA-EDTA]. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org 52 F. Bonkain et al. Fig. 1. (A) Representative photomicrographs of renal biopsy showing glomerulus of the normal size and no segmental lesions. Mild tubular atrophy is found, probably as a result of ischaemic and protein overload processes (silver stain, 400×). (B) At higher magnification, the glomerular basement membrane is thin without any spikes (silver stain, 1000×). Fourteen glomeruli were observed on the renal biopsy specimen. Fig. 2. Time course evolution of renal functional parameters (serum creatinine and proteinuria) along with major clinical events. Nephrotic syndrome and renal failure as an unusual presentation of solid tumour 53 patient received prednisolone (1 mg/kg per day, orally) and (improvement, remission, recurrence) [4]. In about half of the angiotensin-converting enzyme inhibitor enalapril. A cases, the diagnosis of nephrotic syndrome precedes those progressive reduction of proteinuria was observed and re- of cancer while the simultaneous presentation of both dis- nal function parameters improved, allowing us to taper the eases occurs in ∼30% [4]. Renal improvement is mainly steroid dosage (Figure 2). observed after complete clinical remission of the cancer. Careful physical examination revealed a suspect mass However, the two conditions can independently evolve [4]. (20 × 15 mm) in the inner quadrant of her right breast that Taking together, the firm causal link is often missing as in was further confirmed by mammography and ultrasonogra- many similar cases, which makes the formal diagnosis of phy. Histopathological examination of a breast biopsy tissue paraneoplastic glomerulopathies uneasy. sample demonstrated a moderately differentiated infiltrat- Finally, the beneficial effect of steroid therapy observed ing ductal carcinoma (grade II) expressing oestrogen and in our patient cannot distinguish idiopathic form from progesterone hormones receptors but not the erb-2 protein. cancer-associated MCD since pathophysiology of parane- The supraclavicular and axillar areas were free of enlarged oplastic glomerulopathies involves numerous immunologi- lymph nodes and no distant metastasis was found. Serum cal processes (cytokines, growth factors or tumour antigens) markers CA 15-3 and CEA were at 27 U/ml (<25 U/ml) susceptible to be efficiently reduced by immunosuppressive and 6.2 ng/ml (<4.5 ng/ml), respectively. treatment [4]. In conclusion, the diagnosis of idiopathic One month later, the patient was dialysis free and the MCD may be firmly assessed only after exclusion of all surgical removal of the breast cancer was performed (final possible causes such as drugs, infections, allergies and neo- staging pT1cN1cM0 according to the WHO classification). plasms, among others solid tumours. Our case highlights the The immediate postoperative period resulted in the nearly fact that a cancer as common as a breast malignancy may complete remission of the renal disease with a serum cre- have an uncommon inaugural manifestation such as a MCD atinine level at 114.9 μmol/l (Figure 2). Unfortunately, the nephrotic syndrome. patient developed a fulminant septic shock due to Staphy- lococcus aureus and died 48 h later. Conflict of interest statement. None declared. Discussion References The present case draws the physician’s attention to the pos- 1. Cameron JS. The nephrotic syndrome and its complications. Am J sible presentation of MCD nephrotic syndrome and acute Kidney Dis 1987; 10: 157–171 2. Audard V, Larousserie F, Grimbert P et al. Minimal change nephrotic kidney injury as inaugural manifestations of solid tumour. syndrome and classical Hodgkin’s lymphoma: report of 21 cases and Cancer-related MCD is preferentially linked to haemato- review of the literature. Kidney Int 2006; 69: 2251–2260 logical malignancies whereas membranous nephropathy is 3. Martinez-Vea A, Panisello JM, Garcia C et al. Minimal-change mostly associated with solid tumours such as respiratory glomerulopathy and carcinoma. Report of two cases and review of and gastrointestinal tract adenocarcinomas [4,5]. The asso- the literature. Am J Nephrol 1993; 13: 69–72 ciation between MCD and solid tumours is extremely rare, 4. Bacchetta J, Juillard L, Cochat P et al. Paraneoplastic glomeru- especially those associated with breast cancer [3,6,7]. lar diseases and malignancies. Crit Rev Oncol Hematol 2009; 70: 39–58 In this case, the simultaneous presentation of the 5. Lee JC, Yamauchi H, Hopper J Jr. The association of cancer and the nephrotic syndrome and the breast cancer is in favour nephrotic syndrome. Ann Intern Med 1966; 64: 41–51 of an association between those two entities. Moreover, 6. Meyrier A, Delahousse M, Callard P et al. Minimal change nephrotic alternative causes of MCD such as non-steroidal anti- syndrome revealing solid tumors. Nephron 1992; 61: 220–223 inflammatory agents or antibiotics were excluded. Rare 7. Macanovic M, Peat D. Minimal change nephropathy with adenocar- cases of biphosphonate-induced nephrotic syndrome have cinoma of breast. J R Soc Med 2000; 93: 539 been reported in the literature; most of them were collaps- 8. Markowitz GS, Appel GB, Fine PL et al. Collapsing focal segmental glomerulosclerosis following treatment with high-dose pamidronate. ing focal glomerulosclerosis due to pamidronate and ex- J Am Soc Nephrol 2001; 12: 1164–1172 ceptionally to alendronate [8,9]. On the other hand, Barry 9. Pascual J, Torrealba J, Myers J et al. Collapsing focal segmen- et al. observed two cases of biphosphonate-related MCD tal glomerulosclerosis in a liver transplant recipient on alendronate. but both after i.v. administration of pamidronate [10]. Osteoporos Int 2007; 18: 1435–1438 The term paraneoplastic glomerulopathy generally refers 10. Barri YM, Munshi NC, Sukumalchantra S et al. Podocyte injury as- to a glomerular disease without specific aetiology and sociated glomerulopathies induced by pamidronate. Kidney Int 2004; which develops in parallel with cancer evolution phases 65: 634–641 Received for publication: 26.1.09; Accepted in revised form: 7.8.09

Journal

Clinical Kidney JournalOxford University Press

Published: Feb 3, 2010

Keywords: Keywords acute kidney injury minimal change disease nephrotic syndrome paraneoplastic glomerulopathy solid tumour

There are no references for this article.