PURPOSE: To report the occurrence of focal segmental glomerulosclerosis (FSGS) in children with acute lymphocytic leukemia (ALL), discuss pathogenesis and problems in management. PATIENTS AND METHODS: Progressive renal dysfunction developed in two adolescent black girls with high-risk ALL who underwent renal biopsies that were consistent with FSGS. In both patients, no known etiologic factors, such as systemic lupus erythematosus, poststreptococcal glomerulonephritis, sickle cell anemia, or acquired immunodeficiency syndrome, were evident. FSGS induced by Adriamycin (Pharmacia & Upjohn, Columbus, OH) has been observed experimentally in rats. The patients had received anthracyclines and methotrexate, a known nephrotoxic chemotherapeutic agent. RESULTS: One patient progressed to chronic renal failure and required prolonged dialysis followed by renal transplantation, though the leukemia remained in remission. The other patient is also in remission and on maintenance treatment for leukemia. She has persistent proteinuria and is currently undergoing a trial of high-dose steroid therapy. CONCLUSION: The combination of FSGS with leukemia poses a management challenge to the clinician in terms of further treatment with potentially nephrotoxic drugs, complications of nephrotic syndrome (including infections), and timing of renal transplantation. Future studies should address whether FSGS represents a glomerular response to anthracycline-induced injury in susceptible black persons.
PURPOSE: To report the occurrence of focal segmental glomerulosclerosis (FSGS) in children with acute lymphocytic leukemia (ALL), discuss pathogenesis and problems in management. PATIENTS AND METHODS: Progressive renal dysfunction developed in two adolescent black girls with high-risk ALL who underwent renal biopsies that were consistent with FSGS. In both patients, no known etiologic factors, such as systemic lupus erythematosus, poststreptococcal glomerulonephritis, sickle cell anemia, or acquired immunodeficiency syndrome, were evident. FSGS induced by Adriamycin (Pharmacia & Upjohn, Columbus, OH) has been observed experimentally in rats. The patients had received anthracyclines and methotrexate, a known nephrotoxic chemotherapeutic agent. RESULTS: One patient progressed to chronic renal failure and required prolonged dialysis followed by renal transplantation, though the leukemia remained in remission. The other patient is also in remission and on maintenance treatment for leukemia. She has persistent proteinuria and is currently undergoing a trial of high-dose steroid therapy. CONCLUSION: The combination of FSGS with leukemia poses a management challenge to the clinician in terms of further treatment with potentially nephrotoxic drugs, complications of nephrotic syndrome (including infections), and timing of renal transplantation. Future studies should address whether FSGS represents a glomerular response to anthracycline-induced injury in susceptible black persons.
Authors: Zongyu Zheng; Kai M Schmidt-Ott; Streamson Chua; Kirk A Foster; Rachelle Z Frankel; Paul Pavlidis; Jonathan Barasch; Vivette D D'Agati; Ali G Gharavi Journal: Proc Natl Acad Sci U S A Date: 2005-02-07 Impact factor: 11.205