Impaired adaptation to renal mass reduction in the polycystic rat

Autosomal dominant polycystic kidney disease (ADPKD) is a serious cause of renal failure, In many renal-disease models, surgical renal mass reduction accelerates disease progression. We explored whether surgical renal mass re duction and the method of renal mass reduction accelerate the course of ADP KD, Studies were conducted in mate heterozygous cystic Han:SPRD rats and un affected littermate controls. Control and cystic rats were subjected to 50% renal mass reduction by uninephrectomy, 50% renal mass reduction by infarc tion of half of each kidney, or sham operation. Most groups were followed u p to the age of 20 weeks, with serial measurements of blood pressure and pr oteinuria. At 20 weeks, glomerular filtration rate (GFR) and renal plasma f low (RPF) rate were measured, Similar studies to 12 weeks of age were perfo rmed in additional groups of control and cystic rats with either sham opera tion or 50% renal infarction, In noncystic rats, uninephrectomy led to mini mal effects on blood pressure and proteinuria and to substantial compensato ry renal hypertrophy, hyperfiltration, and hyperperfusion, Similar renal ma ss reduction by segmental infarction led to greater Values for blood pressu re and proteinuria and significant compensatory hyperfiltration. In contras t, the cystic rats showed a significant reduction in baseline renal blood f low, more profound increases in blood pressure and proteinuria, and no comp ensatory increases in GFR and RPF after reduction of renal mass. These stud ies suggest that the ability of cystic kidneys to respond to acquired loss of nephrons is impaired and that these kidneys are at greater risk when add itional renal injury is superimposed, (C) 2000 by the National Kidney Found ation, Inc.