EFFECT OF RECURRENT PREGNANCIES ON THE EVOLUTION OF ADRIAMYCIN NEPHROPATHY

Background. In rats with incipient adriamycin nephropathy, pregnancy increases urine protein excretion and mean arterial pressure, with no changes in the glomerular filtration rate. Renal histology is normal and the glomerular TxB(2)/PGE(2) ratio is increased. Methods. In the present study we evaluated the influence of repeated pregnancies on the evolution of adriamycin nephropathy. Two weeks after a first delivery, rats were mated again and were followed till 35 days after the second delivery. Results. In pregnant rats with adriamycin nephropathy, urine protein excretion and mean arterial pressure returned to values identical to those found in age-sex-matched virgin rats with adriamycin nephropathy. At the end of the second pregnancy, mean arterial pressure and urine protein excretion were again elevated, compared with virgin rats with adriamycin nephropathy. Thirty-five days after the second delivery, urine protein excretion and mean arterial pressure remained elevated, 296+/-50 mg/day vs 115+/-26 and 121+/-4 vs 110+/-1 mmHg respectively, P<0.05. Glomerular filtration rate remained unchanged 0.84+/-0.09 vs 0.79+/-0.09 ml/min in virgin rats with adriamycin nephropathy. The glomerular TxB(2)/PGE(2) ratio was decreased, contrasting with the first pregnancy. At the end of the second pregnancy, histological examination of the kidneys in rats with adriamycin nephropathy revealed a significant increase in mesangial expansion. It was even more marked 35 days later, at the last follow-up, with a semiquantitative score of 162+/-29 vs 81+/-20 in virgin adriamycin nephropathy rats, P<0.05. Conclusions. In rats with adriamycin nephropathy, repetitive pregnancies seem to aggravate the natural course of the disease in an irreversible fashion. The earlier changes in glomerular prostanoid synthesis, particularly on thromboxane, may play a pathogenic role by activating mesangial cell matrix synthesis.