TY - JOUR
T1 - A case report of adrenocorticotropic hormone to treat recurrent focal segmental glomerular sclerosis post-transplantation and biomarker monitoring
AU - Anwar, Siddiq
AU - Larson, Derek S.
AU - Naimi, Nima
AU - Ashraf, Muhammad
AU - Culiberk, Nancy
AU - Liapis, Helen
AU - Wei, Changli
AU - Reiser, Jochen
AU - Brennan, Daniel C.
N1 - Funding Information:
This research was supported in part by NIH/NIDDK P30 DK079333 and K24DK002886-11, the Alan A. and Edith L. Wolff endowment, the generous support of Eileen M. Brooks and Donald F. Roach to DB and DK089394, DK073495, and DK101350 to JR. The authors would also like to acknowledge the laboratory expertise of Mukut Sharma and Dr. Virginia Savin at the Veterans Administration Hospital in Kansas City and Drs. Sian Eng and Nada Alachkar at Johns Hopkins University School of Medicine.
Publisher Copyright:
© 2015 Anwar, Larson, Naimi, Ashraf, Culiberk, Liapis, Wei, Reiser and Brennan.
PY - 2015
Y1 - 2015
N2 - Background: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies. Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure, requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb), soluble urokinase-type plasminogen activator receptor (suPAR) serum level with suPAR-ß3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab) titer. Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, ß3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance), and high dose steroids, the Palb and suPAR-ß3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation, we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel), 80 units subcutaneously twice weekly. Four-weeks later, he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria. Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.
AB - Background: Recurrent focal segmental glomerular sclerosis (rFSGS) in renal transplant recipients (RTR) is difficult to predict and treat. Early rFSGS is likely from circulating factors and preformed antibodies. Methods: We present the case of a 23-year-old white man who presented with rFSGS and acute renal failure, requiring dialysis 9-months after a 1-haplotype matched living-related transplant. We retrospectively analyzed serum samples from various clinical stages for rFSGS biomarkers: serum glomerular albumin permeability (Palb), soluble urokinase-type plasminogen activator receptor (suPAR) serum level with suPAR-ß3 integrin signaling on human podocytes, and angiotensin II type I receptor-antibody (AT1R-Ab) titer. Results: All biomarkers were abnormal at 1-year pre-transplant prior to initiation of dialysis and at the time of transplant. After initiation of hemodialysis, ß3 integrin activity on human podocytes, in response to patient serum, as well as AT1R-Ab were further elevated. At the time of biopsy-proven recurrence, all biomarkers were abnormally high. One week after therapy with aborted plasmapheresis (secondary to intolerance), and high dose steroids, the Palb and suPAR-ß3 integrin activity remained significantly positive. After 12-weeks of treatment with high-dose steroids, rituximab, and galactose, the patient remained hemodialysis-dependent. Three-months after his initial presentation, we commenced adrenocorticotropic hormone (ACTH, Acthar® Gel), 80 units subcutaneously twice weekly. Four-weeks later, he was able to discontinue dialysis. After 8-months of maintenance ACTH therapy, his serum creatinine stabilized at 1.79 mg/dL with <1 g of proteinuria. Conclusion: ACTH therapy was associated with improvement in renal function within 4 weeks. The use of rFSGS biomarkers may aid in predicting development of rFSGS.
KW - Acute kidney injury
KW - Albumin permeability factor
KW - Angiotensin 1 receptor antibody
KW - Podocyte
KW - Recurrent focal segmental glomerular sclerosis
KW - Soluble urokinase plasminogen activator receptor
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U2 - 10.3389/fmed.2015.00013
DO - 10.3389/fmed.2015.00013
M3 - Article
AN - SCOPUS:84974592821
SN - 2296-858X
VL - 2
SP - 13
JO - Frontiers in Medicine
JF - Frontiers in Medicine
IS - MAR
ER -