Alendronate-associated focal segmental glomerulosclerosis
نویسندگان
چکیده
Alendronate-associated focal segmental glomerulosclerosis Sir, Alendronate sodium, a bisphosphonate and commonly used pharmacologic agent for postmenopausal osteoporosis, has been rarely linked to renal toxicity [1] but not in association with focal segmental glomerulosclerosis (FSGS). A 55-year-old Caucasian woman developed proteinuria and hypertension. Nine years earlier, she had been diagnosed with breast cancer treated with lumpectomy, radio-therapy and chemotherapy without evidence of recurrence. Two years later, she was diagnosed with osteoporosis and started on alendronate sodium 10 mg once daily for 3 years followed by 70 mg once weekly for 4 years and calcium plus vitamin D supplements. Other medications were mul-tivitamins, primrose oil and venlafaxine for hot flushes. She had no other significant past medical history. Blood pressure was 160/90 mmHg, with ankle oedema present. Serum creatinine was 106 mmol/dl with protein-uria of 10 g/day. HIV infection and viral hepatitis were ruled out. Computed tomography of the head, chest, abdomen and pelvis was negative for malignancy or metastatic disease. A renal biopsy contained 36 glomeruli present, none of which were globally sclerotic. Few glomeruli demonstrated mesangial hypercellularity with segmental areas of sclerosis with hyperplasia of visceral epithelial cells (podocytes) (Figure 1). A background of chronic interstitial inflammation and interstitial fibrosis was present. IgA, IgM, C3 and C1q were demonstrated on immunofluorescence in a globu-lar segmental distribution. Electron microscopy supported this impression of FSGS with diffuse podocyte foot process effacement without immune-complex-type deposits (Figure 2). Alendronate was discontinued, and prednisone 1 mg/kg/day and lisinopril were started. Six weeks later, she went into partial remission (proteinuria 1.1 g/day). Alendronate has an estimated terminal half-life in bone of >10 years, and only ∼50% of a systemic dose is ex-creted unchanged in the urine within 3 days. Long-term drug excretion may cause renal toxicity through disruption of the podocyte cytoskeleton, a mechanism similar to that described in osteoclasts [2]. This beneficial effect of bis-phosphonates on bone resorption has led to extensive use in several bone diseases. Pamidronate that is structurally almost identical to alendronate has been linked to FSGS. Studies in primary and recurrent FSGS implicate podocyte injury [3] and increased production of T-cell-derived lym-phokines or 'permeability factors' [4] in the pathogenesis of segmental glomerular scarring. Drug dose and duration of treatment may influence the patient susceptibility to in-Fig. 1. PAS stain (400× magnification)—glomerulus with focal segmen-tal sclerosis in the upper-left aspect of the glomerulus associated with visceral epithelial cell hyperplasia. Fig. 2. Electron …
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