Multicentric Carpal-Tarsal Osteolysis With Nephropathy Treated Successfully With Cyclosporine A: A Case Report and Literature Review Andrew Connor, MBBS, MRCP, John Highton, MD, FRACP, Noelyn Anne Hung, MBChB, FRCPA, John Dunbar, MBChB, FRACS, Robert MacGinley, FRACP, and Robert Walker, MBChB, MD, FRACP Multicentric carpal-tarsal osteolysis is a rare skeletal disorder characterized by osteolysis of the metacarpal, carpal, and tarsal bones and leading to crippling joint deformities. Progressive nephropathy occurs in more than half the cases. All previously reported series with renal biopsies showed only end-stage renal disease on histological examination because of the late presentation to nephrologists. Accurate diagnosis of the underlying renal pathological state therefore has not been possible. We report the first case in which early and sequential renal biopsies were performed. These show the renal lesion to be focal and segmental glomerulosclerosis, which was treated successfully with cyclosporine A. Am J Kidney Dis 50:649-654. © 2007 by the National Kidney Foundation, Inc. INDEX WORDS: Multicentric carpal-tarsal osteolysis; osteolysis nephropathy; focal segmental glomer- ulosclerosis (FSGS); cyclosporine A. M ulticentric carpal-tarsal osteolysis (MCTO) is characterized by crippling deformities resulting from osteolysis of the carpal and tarsal bones and associated with a poorly defined ne- phropathy. We report the first case in which the renal pathological state was defined by early and sequential renal biopsies as a focal segmental glomerulosclerosis (FSGS) and describe its suc- cessful treatment with cyclosporine A. CASE REPORT Our patient was born to unrelated parents with no family history of bone or renal disease. At the age of 2 years, his left foot was noted to be smaller than his right. Radiographs showed an apparent delay in the development of the bones of the left foot. Deformities of his wrists and ankles developed over the following years. Radiographs at 5 years of age showed osteolysis of the carpal and tarsal bones and proximal ends of the metacar- pals. The bones were diffusely osteoporotic. Comparison with previous radiographs showed the progressive nature of this process, and a diagnosis of carpal-tarsal osteolysis was made. Later radiographs showed complete dissolution of the carpal bones (Fig 1). Laboratory investigations, including renal, bone, liver, and lipid profiles, had normal results. A bone scan showed normal growth plates. At the age of 6 years, urinary protein excretion was increased at 0.076 g/dL (0.76 g/L). The patient was normo- tensive. Renal tract ultrasonographic findings were unremark- able. Proteinuria persisted, and at the age of 10 years, the patient underwent renal biopsy (Fig 2). Twelve glomeruli and a long section of medulla were available for evaluation. Three glomeruli were globally sclerosed. One glomerulus showed segmental sclerotic change (Fig 2, arrow) adjacent to normal glomerular segments. Another glomerulus had an attachment of a sclerotic segment of the glomerular tuft to Bowman capsule, around 60% of its circumference. One other glomerulus showed 2 synechiae, whereas others showed increased collagen within the mesangial matrix. Tubules and surrounding interstitium appeared normal, and there was no evidence of malignancy or inflammation. Renal vessels appeared normal, with no changes to suggest hypertension. Electron microscopy showed changes typical of glomeru- losclerosis, with distortion, fusion, and effacement of foot processes of epithelial cells (Fig 3). Epithelial cells also were vacuolated and possessed microvillous processes, but epithelial detachment was not obvious in the glomeruli examined. Immunofluorescence staining for immunoglobulin M and C3 showed segmental localization and nonspecific linear staining. There was no specific staining pattern with immu- noglobulin A, immunoglobulin G, or other complement reagents. Light and immunofluorescence appearances were consistent with FSGS. Cyclosporine A therapy was started at a dose of 75 mg twice daily (5 mg/kg/d). An angiotensin-converting enzyme (ACE) inhibitor was initiated simultaneously (cilazapril, 1 mg/d). Improvement in albumin-creatinine ratio (ACR) was apparent within 6 months (Fig 4). After 20 months of treatment, mean ACR decreased to 155.6 mg/g (17.6 mg/ mmol). However, the osteolysis progressed, with worsening of erosions at the elbows and knees. By age 13 years, after nearly 2 years of cyclosporine A therapy, control of the renal pathological state appeared to have been established; ACR had remained at less than 176.8 mg/g (20 mg/mmol) for 12 months. However, side effects of From the Department of Medical and Surgical Sciences, University of Otago School of Medicine, Dunedin, New Zealand. Received October 21, 2006. Accepted in revised form June 1, 2007. Originally published online as doi: 10.1053/j.ajkd.2007.06.014 on August 1, 2007. Address correspondence to Andrew Connor, MRCP, 1 Vineyard Rd, Hereford, HR1 1TT, UK. E-mail: andrewconnor1974@hotmail.co.uk © 2007 by the National Kidney Foundation, Inc. 0272-6386/07/5004-0017$32.00/0 doi:10.1053/j.ajkd.2007.06.014 American Journal of Kidney Diseases, Vol 50, No 4 (October), 2007: pp 649-654 649