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Hemolytic-uremic syndrome after kidney transplantation
Hemolytic-Uremic Syndrome After Kidney Transplantation E. Piovesan, C. Castilhos, R. Pozza, T.F. Michelon, D.C. Seelig, A.F. Santos, E. Bittar, E. Keitel, J.C. Goldani, C.D. Garcia, J. Neumann, and V.D. Garcia
T
HE HEMOLYTIC-UREMIC syndrome (HUS) is a severe, albeit infrequent, complication after kidney transplantation that has been associated with drug therapy and infections. The aim of this paper was to assess the prevalence of HUS in our center and to evaluate possible factors related to its pathogenesis. PATIENTS AND METHODS This is a retrospective analysis of 885 kidney transplants performed at Santa Casa of Porto Alegre from January 1990 to December 2000. HUS was defined as impairment of renal function, hemolytic anemia, thrombocytopenia, and histologic evidence of thrombotic microangiopathy in a renal biopsy specimen. HUS was the cause of original renal disease in four patients (0.4%).
RESULTS
The prevalence of HUS was 1.1% (11 episodes in 10 patients). The affected subjects included six women and 5 recipients of cadaveric kidney grafts. The mean age was 30-years old (7- to 39-years old). All but one received initial triple immunosuppression with prednisone, azathioprine, and cyclosporine. The renal biopsy samples showed a predominance of arteriolar thrombosis and necrosis, with less compromise of the glomerular capillary. The syndrome occurred during cytomegalovirus (CMV) disease in six patients (60%), two of whom also had shigilosis at the same time and, four of whom lost their grafts. Acute rejection previous to HUS was observed in four (40%) patients, three of whom had CMV disease and two E. coli urinary tract infections associated with the syndrome. Development of HUS after the third month posttransplant was observed in two special clinical situations: first as a recurrence of original renal disease in a child under cyclosporine immunosuppression, who lost the graft; second, following pre-eclampsia in a pregnant patient receiving prednisone plus azathioprine, who recovered renal function completely. The rejection episodes were treated with methylprednisolone, and one patient needed OKT3 due to steroidresistant rejection. The infectious episodes were treated according to the causal agent.
The cyclosporine was withdrawn in all cases. One patient, converted to tacrolimus with recurrence of HUS, showed partial recovery after conversion to mofetil mycophenolate plus prednisone. We did not use plasmapheresis therapy. There were no deaths, but five (50%) patients lost their grafts. Only in the pregnancy-associated HUS did graft function recover completely; the other four patients showed partial return with a mean serum creatinine value of about 3.0 mg/dL.
COMMENTS
The prevalence of HUS ranges from 0.5% to 5% in literature reports, with a high rate of graft lost.1,2 The majority of our cases occurred during the first trimester after transplantation under cyclosporine immunosuppression. Because the differential diagnosis between vascular rejection and HUS may be difficult, we only considered patients to display HUS if all renal, hematologic, and histologic criteria were present. The histologic pattern observed in these cases was similar to those described by Neild, namely, a predominance of preglomerular pathology as opposed to cases with special involvement of glomerular capillaries.3,4 HUS presents as recurrence of the original disease in about 28% of patients who also experience a high rate (77%) of graft loss.5 In our series of one of four patients presented with recurrence of HUS and lost his graft. Older age at onset of HUS, short interval between HUS and transplantation, short interval between HUS and end-stage renal disease, living related donor, and calcineurin inhibitor therapy have been associated with recurrence.5 Although a few reports claim successful conversion to tacrolimus after induction of HUS during cyclosporine treatment our patient had remission of disease upon experienced recurrence of HUS after conversion from cyclosporine to tacrolimus.2,6 All cases associated with CMV infection were treated with ganciclovir; cyclosporine was From the Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, Brazil. Address reprint requests to V.D. Garcia, Rua Correa Lima, 1493, 90850-250 Porto Alegre, Brazil. E-mail: cdgarcia@ terra.com.br
© 2002 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/02/$–see front matter PII S0041-1345(02)03410-3
Transplantation Proceedings, 34, 2779 –2780 (2002)
2779
2780
stopped. Four of six lost their grafts, suggesting a poor prognosis of HUS associated with CMV disease, especially if a previous rejection episode was present. The worst graft survival and patient mortality has been described among cases of HUS associated with rejection, 35% and 24%, respectively, and the best prognosis for associations with cyclosporine-induced HUS.2 The concomitant presence of an immunologic event, mainly CMV infection, rejection, or bacterial infection, seems to be related to the triggering of HUS. The prognosis for the patient and graft seems to depend on the associated events.
PIOVESAN, CASTILHOS, POZZA ET AL
REFERENCES 1. Ruggenenti P, Schieppati A, Bertani T, et al: In Schrier R, Gottschalk W (eds): Disease of the Kidney 6th ed. Boston: Little, Brown; 1997, p 1832 2. Asaka M, Ishikawa I, Nakazawa T, et al: Nephron 84:258, 2000 3. Neild GH: Lancet 343:398, 1994 4. Mor E, Lustig S, Tovar A, et al: Transplant Proc 32:686, 2000 5. Ducloux D, Rebibou J, Semhoun-Ducloux S, et al: Transplantation 65:1405, 1998 6. Kaufman DB, Kaplan B, Kanwar YS, et al: Transplantation 59:1737, 1995
T
HE HEMOLYTIC-UREMIC syndrome (HUS) is a severe, albeit infrequent, complication after kidney transplantation that has been associated with drug therapy and infections. The aim of this paper was to assess the prevalence of HUS in our center and to evaluate possible factors related to its pathogenesis. PATIENTS AND METHODS This is a retrospective analysis of 885 kidney transplants performed at Santa Casa of Porto Alegre from January 1990 to December 2000. HUS was defined as impairment of renal function, hemolytic anemia, thrombocytopenia, and histologic evidence of thrombotic microangiopathy in a renal biopsy specimen. HUS was the cause of original renal disease in four patients (0.4%).
RESULTS
The prevalence of HUS was 1.1% (11 episodes in 10 patients). The affected subjects included six women and 5 recipients of cadaveric kidney grafts. The mean age was 30-years old (7- to 39-years old). All but one received initial triple immunosuppression with prednisone, azathioprine, and cyclosporine. The renal biopsy samples showed a predominance of arteriolar thrombosis and necrosis, with less compromise of the glomerular capillary. The syndrome occurred during cytomegalovirus (CMV) disease in six patients (60%), two of whom also had shigilosis at the same time and, four of whom lost their grafts. Acute rejection previous to HUS was observed in four (40%) patients, three of whom had CMV disease and two E. coli urinary tract infections associated with the syndrome. Development of HUS after the third month posttransplant was observed in two special clinical situations: first as a recurrence of original renal disease in a child under cyclosporine immunosuppression, who lost the graft; second, following pre-eclampsia in a pregnant patient receiving prednisone plus azathioprine, who recovered renal function completely. The rejection episodes were treated with methylprednisolone, and one patient needed OKT3 due to steroidresistant rejection. The infectious episodes were treated according to the causal agent.
The cyclosporine was withdrawn in all cases. One patient, converted to tacrolimus with recurrence of HUS, showed partial recovery after conversion to mofetil mycophenolate plus prednisone. We did not use plasmapheresis therapy. There were no deaths, but five (50%) patients lost their grafts. Only in the pregnancy-associated HUS did graft function recover completely; the other four patients showed partial return with a mean serum creatinine value of about 3.0 mg/dL.
COMMENTS
The prevalence of HUS ranges from 0.5% to 5% in literature reports, with a high rate of graft lost.1,2 The majority of our cases occurred during the first trimester after transplantation under cyclosporine immunosuppression. Because the differential diagnosis between vascular rejection and HUS may be difficult, we only considered patients to display HUS if all renal, hematologic, and histologic criteria were present. The histologic pattern observed in these cases was similar to those described by Neild, namely, a predominance of preglomerular pathology as opposed to cases with special involvement of glomerular capillaries.3,4 HUS presents as recurrence of the original disease in about 28% of patients who also experience a high rate (77%) of graft loss.5 In our series of one of four patients presented with recurrence of HUS and lost his graft. Older age at onset of HUS, short interval between HUS and transplantation, short interval between HUS and end-stage renal disease, living related donor, and calcineurin inhibitor therapy have been associated with recurrence.5 Although a few reports claim successful conversion to tacrolimus after induction of HUS during cyclosporine treatment our patient had remission of disease upon experienced recurrence of HUS after conversion from cyclosporine to tacrolimus.2,6 All cases associated with CMV infection were treated with ganciclovir; cyclosporine was From the Complexo Hospitalar Santa Casa de Porto Alegre, Porto Alegre, Brazil. Address reprint requests to V.D. Garcia, Rua Correa Lima, 1493, 90850-250 Porto Alegre, Brazil. E-mail: cdgarcia@ terra.com.br
© 2002 by Elsevier Science Inc. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/02/$–see front matter PII S0041-1345(02)03410-3
Transplantation Proceedings, 34, 2779 –2780 (2002)
2779
2780
stopped. Four of six lost their grafts, suggesting a poor prognosis of HUS associated with CMV disease, especially if a previous rejection episode was present. The worst graft survival and patient mortality has been described among cases of HUS associated with rejection, 35% and 24%, respectively, and the best prognosis for associations with cyclosporine-induced HUS.2 The concomitant presence of an immunologic event, mainly CMV infection, rejection, or bacterial infection, seems to be related to the triggering of HUS. The prognosis for the patient and graft seems to depend on the associated events.
PIOVESAN, CASTILHOS, POZZA ET AL
REFERENCES 1. Ruggenenti P, Schieppati A, Bertani T, et al: In Schrier R, Gottschalk W (eds): Disease of the Kidney 6th ed. Boston: Little, Brown; 1997, p 1832 2. Asaka M, Ishikawa I, Nakazawa T, et al: Nephron 84:258, 2000 3. Neild GH: Lancet 343:398, 1994 4. Mor E, Lustig S, Tovar A, et al: Transplant Proc 32:686, 2000 5. Ducloux D, Rebibou J, Semhoun-Ducloux S, et al: Transplantation 65:1405, 1998 6. Kaufman DB, Kaplan B, Kanwar YS, et al: Transplantation 59:1737, 1995