Lupus After Kidney Donation to an Affected Male Relative

One poorly defined aspect of the evaluation of potential kidney donors concerns the degree to which there is increased future risk of developing systemic lupus erythematosus (SLE) and lupus nephritis (LN) for those who have a family history. We report the case of a female donor given a clinical diagnosis of SLE following kidney donation to her brother who had end-stage renal disease (ESRD) due to LN. Studies assessing the genetics of familial SLE have provided new insights into genetic susceptibility.1 As highlighted by this case, one scenario of particular relevance to the evaluation of living related kidney donors is when the intended recipient is a man and has ESRD due to LN. In this situation, the risk of familial LN may be increased substantially.2 A 50-year-old woman was evaluated for possible kidney donation. She had previously been in good health and was on no medications. Her family history was significant for a brother with SLE and LN resulting in ESRD. She also had a male first cousin who had been diagnosed with SLE but no other family history of autoimmune or connective tissue disease. Physical examination and imaging studies were normal. The patient proceeded to donate her left kidney to her brother without perioperative complications. When seen in clinic 1 year after donation, she reported feeling well. Serum creatinine was 1.1 mg/dL (96 μmol/L), and there was no proteinuria. Two years after donation, the patient developed malar rash, fatigue, and morning stiffness. She reported no fevers or other constitutional symptoms. Her blood pressure was 130/75 mm Hg. No additional abnormalities were noted on physical examination. Her antinuclear antibody was found to be negative but she was found to persistently test positive for anti–double-stranded DNA and had low C4 levels with normal C3. There was no evidence of LN on the basis of blood and urine testing. Table 1 details the results of selected laboratory investigations before, and 2 years after, kidney donation.TABLE 1: Serologic test results before kidney donation and 2 years afterNow, over 1 year after a clinical diagnosis of SLE by her rheumatologist (in the absence of meeting formal American College of Rheumatology SLE classification criteria, which were formulated as research, not clinical-diagnostic, criteria3), her renal function remains stable, and she has not had further manifestations of autoimmune disease after starting treatment with Plaquenil 400 mg daily. Although our patient has no evidence of renal involvement at this time, she is now at increased risk of developing LN. While LN is not traditionally considered an inherited renal condition, the risk is increased in family members.1 Although women are more likely to be diagnosed with SLE by a factor of approximately 10:1,4 men are more likely to have severe disease including LN.5 A study by Stein et al2 demonstrated that women with SLE who have at least one affected first-degree relative who is male are also more likely to have severe disease with kidney involvement. In addition, this study showed that the prevalence of renal disease (with or without a formal diagnosis of SLE using American College of Rheumatology diagnostic criteria) is significantly increased in female family members of men with SLE as compared to that of female family members with an affected female relative (68% vs 43%; P = 0.002). Subsequent studies suggest that, for families with only affected male relatives, the etiology of SLE occurrence relates to a relatively greater genetic predisposition than is present in families with familial SLE but no (or relatively fewer) affected males.6 Although not studied directly, based on the current evidence, it can be inferred that the future risks of developing SLE and LN may be especially elevated for potential kidney donors who are first-degree relatives of SLE-affected men. In conclusion, to our knowledge, this is the first case report of a patient developing clinical features of SLE after donation of a kidney to a relative with ESRD secondary to SLE. Given that first-degree relatives of men with SLE may be at especially increased risks of future SLE and LN,2,6,7 added caution is indicated when assessing potential kidney donors with this particular family history. ACKNOWLEDGMENTS The authors thank the patient who is the subject of this report for providing additional history and for reviewing and agreeing to submission of this letter. The authors also thank Ms. Mary Rada, Ms. Brenda Cyr-Mockler and Ms. Marjetka Sawchyn who assisted with data collection.

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