HIGH RELIABILITY IN USING BANFF CLASSIFICATION TO MONITOR RENAL ALLOGRAFT REJECTION IN CYNOMOLGUS MACAQUES.


Grazyna Wieczorek1, Sabine Riesen1, Antje Marcantonio
1, Klaus Menninger1, Michael J Mihatsch2, Volker Nickeleit3 and Marc Bigaud1

 

1Transplantation Research, Novartis Pharma AG, Basel, Switzerland and 2Institute for Pathology, University of Basel, Basel, Switzerland and 3Nephropathology Laboratory, University of North Carolina, Chapel Hill, USA.

 

BACKGROUND: The monitoring of renal allografts following transplantation (TX) is often difficult, and graft biopsies are considered the standard to evaluate renal dysfunction. The Banff schema is widely used in humans to define and score histological changes. In the present study, we applied the Banff 97 working classification in protocol biopsies in order to monitor non-human primate kidney transplant recipients.

 

METHODS: Twenty six percutaneous ultrasound-guided biopsies were obtained by one radiologist in 6 cynomolgus macaques (Macaca fascicularis: #236, #240, #248, #264, #277 and #284, ranged 3.2-6.8 kg body weight). All monkeys were subjected to an allograft TX followed by unilateral nephrectomy (non-life supporting graft) and their post-TX monitoring was performed by regular sonographical examinations. Due to the presence of one native kidney, clinical monitoring of graft dysfunction was not possible and serial protocol biopsies were performed, starting 20-22 days post-TX. Ten glass slides with 2 mm-thick sequential sections (each slide containing at least two sections) were prepared for histochemical stainings with HE, PAS, AFOG (trichrome staining) and Verhoeff (elastic fibers). For semiquantitative assessment of histological changes, each of the major parenchymal components of the kidney interstitium, tubules, glomeruli, and vessels were assessed.

 

RESULTS: 84.7 % of biopsies (22 out of 26) were defined as adequate specimens (at least 10 glomeruli and 2 arteries), 7.7% (2 out of 26) met the minimal requirements (at least 7 glomeruli and 1 artery) whereas 7.7% (2 out of 26) did not reach the minimal requirements. Acute and chronic rejection was diagnosed based on the extent of interstitial inflammation, tubulitis, intimal arteritis and glomerulitis, and interstitial fibrosis, tubular atrophy, sclerosing vascular changes and glomerulopathy, respectively. Observations were noted in the individual scoring sheets. No transmural arteritis, necrotizing arteritis or thrombosis were detected.

 

CONCLUSION: Ultrasound-guided biopsies of renal allografts can be performed with a high degree of safety and reliability in cynomolgus monkeys and provide a valuable tool for renal transplantation research. Semiquantitative assessment of histological findings according to one schema provides a consistent way of recording such findings. Our schema based on Banff classification, provides valuable data concerning the graft function, progression of lesions, response to treatment and finally, helps defining the experimental end points, particularly in situations when clinical monitoring of graft dysfunction is not sufficient such as presence of native kidney, toxicity, etc.

 

 

 

 

 

 

 

 

HIGH RELIABILITY IN USING BANFF CLASSIFICATION TO MONITOR RENAL ALLOGRAFT REJECTION IN CYNOMOLGUS MACAQUES.


Grazyna Wieczorek1, Sabine Riesen1, Antje Marcantonio1, Klaus Menninger1, Michael J Mihatsch2, Volker Nickeleit3 and Marc Bigaud1

 

1Transplantation Research, Novartis Pharma AG, Basel, Switzerland and 2Institute for Pathology, University of Basel, Basel, Switzerland and 3Nephropathology Laboratory, University of North Carolina, Chapel Hill, USA.

 

Contact person:

Grazyna Wieczorek, Dr.med.vet.

Novartis Pharma AG

NIBR Basel

Transplantation Research

WSJ-386.5.57

CH-4002 Basel

Switzerland

Tel.+41-61-3241317

Fax +41-61-3247534

E-mail: grazyna.wieczorek@pharma.novartis.com