A Model of Reversible Uremia Employing Isogenic Kidney Transplantation in the Rat

Abstract

Kidney transplanted patients with normalized kidney function may still exhibit a variety of problems such as bone problems, vasculary problems, and hormonal dysfunctions. A part of the symptoms may be persisting uremic symptoms, secondary to the pretransplanted period of chronic uremia. An experimental rat model, designed to the study of the reversibility of the chronic uremic implications is therefore described. A stable, severe chronic uremia was induced by 5/6 nephrectomy to inbred Lewis rats. Ten weeks later uremia was reverted by a successful isogenic rat kidney transplantation. During the period of chronic uremia the p-urea was elevated to an average of 21.8±0.9 mmol/l and p-creatinine to 105.7±5.7 μM/l. The isogenic kidney transplantation resulted in reestablishment of normal kidney function with an average level of p-urea of 7.6±0.2 mmol/l and p-creatinine 42.5±1.9 μM/l perfectly corresponding to the sham-operated rats, i.e. one-kidney rats. Reversibility of the secondary hyperparathyroidism due to chronic uremia was investigated in the model. In rats with chronic renal failure PTH increased from 52±4.9 pg/ml to 152±12.2 pg/ml and was normalized after transplantation. It is therefore concluded that the present described technique of introducing long term uremia followed up by a successful kidney transplantation in the rat may be a useful model to study the reversibility of different uremic manifestations.