slide seminar drugs and kidney case 3 heinz regele department of pathology
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Slide Seminar
Drugs and Kidney
Case 3
Heinz Regele
Department of Pathology
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Clinical history
•First renal transplant lost in 1995 due to infectious complications 4 weeks after TX
•Second allograft in October 1999. During the first post-transplantation year serum creatinine (sCr) ranged from 2.2-2.5 mg/dl (194-221 μmol/l).
•Maintenance immunosuppression: Cy-A, MMF, and low-dose steroids mg/day).
•Fourteen months after TX recruitment to a clinical trial of cyclosporine withdrawal in patients with chronic allograft dysfunction. Conversion to rapamycin was performed after ruling out rejection or glomerular disease (protocol biopsy).
•After 9 months of rapamycin therapy (12- 20 ng/ml), sCr increased from 2.5 mg/dl to 4.0 mg/dl (221-354 μmol/l), and proteinuria of 2.5 g/ 24 h developed.
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Differential diagnosis
•Chronic TX Glomerulopathy
•Immune complex mediated GN
•Thrombotic microangiopathy
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C4d
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C4d C3
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C4dC4d C4d
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Diagnosis
•De novo IC mediated Glomerulonephritis (likely related to the switch from CNI to rapamycin)
•No convincing evidence of acute rejection (C4d negative)
•Medullary only mononuclear inflammatory infiltrate
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IC GN after rapamycin switch
MGN IgA-GN IgA-GN
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Clinical course
Dittrich E, Transpl Int 2004
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C4d
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Evidence for pro-inflammatory properties of rapamycin
Recurrent or de-novo GN develops in allografts after conversion to sirolimus and recovery can be achieved by re-introducing of CNI
Säemann MD, AJT 2009
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Immunosuppression and transplant glomerulonephritis
A USRDS analysis of 41272 transplant recipients found recurrent GN causing graft loss in 2,6% of patients
The likelihood of developing a recurrent GN was not associated with a specific type of immunosuppressive regimen
Any change of immunosuppression however increased the risk of developing recurrent GN
Mulay AV, AJT 2009
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Evidence for pro-inflammatory properties of rapamycin
Drug dependent occurrence of fever and inflammation (unrelated to infection) in different organs
Recurrent or de-novo GN in allografts after conversion to sirolimus and recovery after re-introduction of CNI
Sirolimus treatment leads to exacerbation of lesions in some experimental models of autoimmune disease.
Säemann MD, AJT 2009
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Different effects of rapamycin in innate and adaptive immunity
Säemann MD, AJT 2009