Focal Segmental Glomerulosclerosis: A Need for Caution in Live-Related Renal Transplantation Michelle P. Winn, MD, Ahmed M. Alkhunaizi, MD, William M. Bennett, MD, Ronald L. Garber, MD, David N. Howell, PhD, David W. Butterly, MD, and Peter J. Conlon, MB ● Focal segmental glomerulosclerosis (FSGS) has increasingly been recognized to occur in a familial pattern. We have observed the development of biopsy-confirmed FSGS and subsequent end-stage renal disease (ESRD) in one live related kidney donor and ESRD without biopsy in another. Both donors had family members with ESRD secondary to FSGS. Both donors were apparently healthy by routine physical examination, urinalysis, and serum creatinine at the time of evaluation as live related donors. We believe these cases emphasize the need for great caution when evaluating siblings as potential live related donors.  1999 by the National Kidney Foundation, Inc. INDEX WORDS: FSGS; glomerulonephritis; ESRD; renal transplant; hereditary nephropathy. T HE USE OF live related renal donors (LRD) is an important source of organs for pa- tients with end-stage renal disease (ESRD) and is associated with the longest graft survival com- pared with other sources of organs. 1 In general, a family history of renal disease is not an absolute contraindication to LRD transplantation, al- though in these circumstances extra efforts need to be made to exclude, so far as is possible, that the potential donor is not a latent carrier of the diseased gene. It is important to appreciate that by far the majority of occurrences of focal segmental glo- merulosclerosis (FSGS) are sporadic; however, in recent years the syndrome of FSGS has increas- ingly been recognized to occur in a familial pattern. 2 Recently, a family with autosomal domi- nant FSGS was linked to chromosome 19q13 by Mathis et al. 3 There also has been an association between HLA-DR4 antigens and patients with FSGS. 4 In this report, we describe the develop- ment of ESRD in two kidney donors for LRD renal transplantation in two families afflicted with familial FSGS. CASE REPORTS CASE 1 Patient 1, a 34-year-old white man (Fig 1; Individual 0001), presented with 2.5 g/24h proteinuria and renal insuf- ficiency with a serum creatinine of 2.8 mg/dL. He underwent percutaneous renal biopsy, which showed segmental sclero- sis in one of four glomeruli sampled (Fig 2A) and no evidence of immune complex disease. Five years later he progressed to ESRD and commenced hemodialysis. He underwent successful live related renal transplantation from his sister, patient 2 (Fig 1, Individual 0113). Patient 1 continued to have stable renal transplant function for 6 years, until he discontinued immunosuppression. Percutane- ous renal transplant biopsy showed acute and chronic allo- graft rejection and de novo development of membranous glomerulonephritis, but no evidence of recurrent FSGS. Two years later, he again progressed to ESRD. Patient 2, the kidney donor to patient 1, underwent a thorough medical evaluation before organ donation and was found to be in excellent health, with no significant medical history; she had a normal urinalysis, a serum creatinine of 1.2 mg/dL, and a normal renal arteriogram. She tolerated organ donation without complication and had a stable serum creatinine of 1.2 mg/dL postoperatively. She had two success- ful pregnancies before she presented again 7 years after nephrectomy with nephrotic syndrome, hypertension, and a serum creatinine of 1.8 mg/dL. After showing no improve- ment in level of proteinuria with a trial of prednisone (60 mg/d for 2 months) and cyclophosphamide (2 mg/kg/d for 2 months), she underwent open renal biopsy (Fig 2B), which showed glomerular changes compatible with FSGS. Over subsequent years, she progressed to ESRD and is currently awaiting cadaveric renal transplantation. Patient 3 (Fig 1, Individual 0109), a brother of patient 1 and patient 2, also developed ESRD without ever undergo- ing renal biopsy and received an LRD transplant from another sibling, patient 4 (Fig 1, Individual 0102). This graft continues to function well, and patient 4 has been lost to follow-up. Case 2 Patient 5 presented with advanced renal insufficiency (Fig 3, Individual 0104) and was commenced on hemodialysis From the Department of Medicine, Duke University Medi- cal Center, Durham, NC; the Department of Medicine, Oregon Health Sciences University, Portland, OR; and the Department of Pathology, Duke University Medical Center and Durham Veterans Affairs Hospital, Durham, NC; Caro- lina Kidney Associates, PA, West Wendover Ave, Greens- boro, NC; and the Department of Nephrology, Beaumont Hospital, Dublin, Ireland. Received June 1, 1998; accepted in revised form October 9, 1998. Address reprint requests to Peter J. Conlon, MB, Depart- ment of Nephrology, Beaumont Hospital, Dublin 9, Ireland. E-mail: pjconlon@iol.ie  1999 by the National Kidney Foundation, Inc. 0272-6386/99/3305-0024$3.00/0 970 American Journal of Kidney Diseases, Vol 33, No 5 (May), 1999: pp 970-974