Abstract
Various glomerular lesions are described in association with malignancy. We report a rare case of crescentic glomerulonephritis occurring in association with renal cell carcinoma. A granular deposition of immune complexes and complement strongly suggests a tumor associated immune complex glomerulonephritis.
INTRODUCTION
Renal cell carcinoma may be associated on the several secondary complications. These include metastatic spread or infiltration, urinary tract obstruction, electrolyte disturbances, disseminated intravascular coagulation, amyloidosis and glomerulonephritis. Among various types of glomerulonephritis occurring in association with malignant disorders, crescentic glomerulonephritis is rarely described Citation[1-3]. The associated neoplasia described is hematological malignancies and only occasionally carcinomas. We report a 35-year-old female with renal cell carcinoma associated with crescentic glomerulonephritis.
CASE REPORT
A 35-year-old female patient was presented to the Emergency department of Postgraduate Institute of Medical Education and Research, Chandigarh with a history of hematuria and decreased urinary output of 20 days duration. She gradually developed facial puffiness and pedal edema. She also complained of fatigue, anorexia, nausea and vomiting. Two days prior to admission, she had an episode of cough with streaky hemoptysis. There was no history of orthopnea or paroxysmal nocturnal dyspnea. The patient denied any prior history of sore throat, skin rashes or joint pains. She had received isoniazid and rifampicin for 2 years for pulmonary tuberculosis, 10 years ago.
Her physical examination revealed that she had pallor, facial puffiness and pedal edema. Her resting pulse rate was 100 per minute and blood pressure was 120/80 mm of Hg. Mean jugular venous pressure was elevated 12 cm above sternal angle. There were no skin rashes or nodules. Chest examination revealed presence of extensive bilateral crepitations. Cardiovascular examination revealed a gallop rhythm. An 8 cm mass could be palpated in left hypochondrium and lumbar region. The mass was firm, non-tender and it was bimanually palpable. Fundii were normal.
Investigations revealed that her hemoglobin was 8.2 g/dL and total and differential counts were normal. The erythocyte sedimentation rate was 120 mm in first hour. Urinalysis revealed 2+ protein, 8–10 red blood cells and 2–3 white blood cells per high power field. Serum biochemistry revealed sodium 128 mEq/L, potassium 6.2 mEq/L, blood urea 195 mg/dL and serum creatinine 15 mg/dL. Arterial blood gases revealed pH 7.26, PaO2 60 mmHg, PaCO2 25 mmHg and serum HCO3 10.5 mEq/L. Immunological tests including antinuclear antibody antineutrophilic cytoplasmic antibody and anti-glomerular basement antibody were negative. Serum complement (C3) was 86 mg/dL (n = 100 mg/dL). X-ray chest revealed partial collapse of right upper lobe. The veins in the upper lobe were prominent. There were bilateral alveolar shadows in lower zones. A surface electrocardiogram was normal. An ultrasound of abdomen revealed that right kidney was 9.0 cm in length and there was a 9.8×9 cm mass in relation to the upper pole of left kidney. A clinical diagnosis of rapidly progressive renal failure with acute pulmonary edema and left renal cell carcinoma was made. The patient underwent an emergency hemodialysis for fluid overload. However, her respiratory distress persisted and she died during her second session of dialysis.
On autopsy, the left kidney showed a 10 cm diameter tumor in relation to its upper pole. There were areas of necrosis and hemorrhage within this tumor. Right kidney showed multiple petechial hemorrhages on its capsular surface. Upon microscopic examination, the tumor consisted of varying sized tubules that were separated by a loose stroma. The nuclei of the tumor cells had thick nuclear membrane and nucleoli were prominent. Hobnailing of the nuclei was frequently present in the cytoplasm of malignant cell. These features were consistent with those of a collecting duct carcinoma of the kidney.
The rest of the kidney showed that 95% of the glomeruli had cellular crescents. Occasional fibrin thrombi were seen in the blood vessels. The tubules were dilated and filled with red blood cells, hyaline and granular casts. Upon immunoperoxidase staining, granular deposits of immunoglobulins (IgG, IgA) and complement could be demonstrated within the capillaries and mesangium. These findings were consistent with those of immune complex mediated crescentic glomerulonephritis. Right lungs showed calcification in its upper pole with pleural thickening. Sections of lower zones of the lungs showed areas of fresh and old hemorrhages. There was no evidence of arteritis or arteriolitis in the lungs. Liver, spleen and heart were normal.
DISCUSSION
A variety of glomerular lesions have been described in association with renal cell carcinoma. These include membranous nephropathy, mesangiocapillary glomerulonephritis and minimal change nephropathy Citation[[1]]. Crescentic glomerulonephritis has been described only rarely in association with lymphoplasmacytic disorders and other malignancies Citation[[4]]. The association of renal cell carcinoma and crescentic glomerulonephritis makes the present case unique and suggests a cause and effect relationship.
Two reports on patients with crescentic glomerulonephritis have revealed that 7–9% of patients with crescentic glomerulonephritis had a co-existing malignancy Citation[4-5]. However, the strength of the association could not be established firmly. The clinical course of renal disease in these patients is similar to that of idiopathic crescentic glomerulonephritis with the exception that removal of tumor may lead to an improvement in renal function. There are only few cases where an association of crescentic glomerulonephritis and renal cell carcinoma had been described previously Citation[2-3]. Of considerable interest in this patient is the finding of lung hemorrhage with a history of hemoptysis. These findings have described virtually all types of crescentic glomerulonephritis Citation[[6]].
A granular pattern of deposition of immunoglobulins and C3 in the mesangium strongly suggest an immune complex mediated crescentic glomerulonephritis in the present case. Although pathogenesis of glomerulopathy in malignancies is poorly understood, it has been suggested that an antigenic stimulation can occur in these patients. The possible antigens involved may be tumor-associated antigen, re-expressed fetal antigens, viral antigens or autologous nontumour antigen Citation[[1]].
In conclusion, we have demonstrated a rare patient in whom crescentic glomerulonephritis is possibly a paraneoplastic effect of renal cell carcinoma.
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