Quantitative and qualitative evaluation of proteinuria in non human primates recipients of porcine xenografts

Introduction: Immunological and histopathological features in pig-to-primate renal xenotransplantation are widely studied. However, only limited data have been reported on clinical-pathological findings in primate recipients of life supporting renal xenografts. In human medicine, proteinuria represents a common complication in kidney transplantation and is associated with impaired patient and graft survival. The detection of low molecular weight proteins of tubular origin such as α1-microglobulin, β2-microglobulin, retinol-binding protein, lysozime, is considered an early marker for predicting potential graft rejection. In the present study the presence and significance of quantitative and qualitative proteinuria were evaluated in xenotransplanted non-human primates in which kidney function is supported only by the transplanted organ. Material and methods: Eight captive-bred, bilaterally nephrectomized cynomolgus monkeys (Macaca fascicularis), recipient of a life-supporting transgenic porcine kidney, were included in the present study. Quantitative and qualitative analysis of proteinuria, evaluated with urinary protein to creatinine ratio (UPC ratio) and sodium dodecyl sulphate-agarose gel electrophoresis (SDSAGE) respectively, have been performed. Results: In urine samples, the measurement of UPC ratio was low before transplantation and increased after transplantation. Similarly, SDS-AGE was negative before transplantation but evidenced bands consistent with mixed (i.e. tubular and glomerular) proteinuria in all the samples collected posttransplantation. Proteinuria and presence of LMW proteins was consistently found in urine after transplantation, independently of the fluctuations of creatinine values and/or of the status of renal functions. Conclusions: The evaluation of UPC ratio and the use of SDS-AGE technique in urine samples of cynomolgus monkey recipients of a life-supporting renal xenograft, may be considered a valid, cheap and rapid technique to monitor proteinuria in the post-transplanted period.