Effect of recurrent pregnancies on the evolution of adriamycin nephropathy

BACKGROUND.: In rats with incipient adriamycin nephropathy, pregnancy increasesurine protein excretion and mean arterial pressure, with nochanges in the glomerular filtration rate. Renal histology isnormal and the glomerular TxB₂/PGE2 ratio is increased. METHODS.: In the present study we evaluated the influence of repeatedpregnancies on the evolution of adriamycin nephropathy. Twoweeks after a first delivery, rats were mated again and werefollowed till 35 days after the second delivery. RESULTS.: In pregnant rats with adriamycin nephropathy, urine proteinexcretion and mean arterial pressure returned to values identicalto those found in age-sex-matched virgin rats with adriamycinnephropathy. At the end of the second pregnancy, mean arterialpressure and urine protein excretion were again elevated, comparedwith virgin rats with adriamycin nephropathy. Thirty-five daysafter the second delivery, urine protein excretion and meanarterial pressure remained elevated, 296±50 mg/day vs115±26 and 121±4 vs 110±1 mmHg respectively,P<0.05. Glomerular nitration rate remained unchanged 0.84±0.09vs 0.79±0.09 ml/min in virgin rats with adriamycin nephropathy.The glomerular TxB₂/PGE₂ ratio was decreased, contrasting withthe first pregnancy. At the end of the second pregnancy, histologicalexamination of the kidneys in rats with adriamycin nephropathyrevealed a significant increase in mesangial expansion. It waseven more marked 35 days later, at the last follow-up, witha semiquantitative score of 162±29 vs 81±20 invirgin adriamycin nephropathy rats, P<0.05. CONCLUSIONS.: In rats with adriamycin nephropathy, repetitive pregnanciesseem to aggravate the natural course of the disease in an irreversiblefashion. The earlier changes in glomerular prostanoid synthesis,particularly on thromboxane, may play a pathogenic role by activatingmesangial cell matrix synthesis.