Slide Seminar Drugs and Kidney Case 3

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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. Clinical history. First renal transplant lost in 1995 due to infectious complications 4 weeks after TX - PowerPoint PPT Presentation

Transcript of Slide Seminar Drugs and Kidney Case 3

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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