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 reduction and the method of renal mass reduction accelerate the course of ADPKD. Studies were conducted in male heterozygous cystic Han:SPRD rats and unaffected littermate controls. Control and cystic rats were subjected to 50% renal mass reduction by uninephrectomy, 50% renal mass reduction by infarction of half of each kidney, or sham operation. Most groups were followed up to the age of 20 weeks, with serial measurements of blood pressure and proteinuria. At 20 weeks, glomerular filtration rate (GFR) and renal plasma flow (RPF) rate were measured. Similar studies to 12 weeks of age were performed in additional groups of control and cystic rats with either sham operation or 50% renal infarction. In noncystic rats, uninephrectomy led to minimal effects on blood pressure and proteinuria and to substantial compensatory renal hypertrophy, hyperfiltration, and hyperperfusion. Similar renal mass reduction by segmental infarction led to greater values for blood pressure and proteinuria and significant compensatory hyperfiltration. In contrast, the cystic rats showed a significant reduction in baseline renal blood flow, more profound increases in blood pressure and proteinuria, and no compensatory increases in GFR and RPF after reduction of renal mass. These studies 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 additional renal injury is superimposed.
Kang
S H
SH
Department of Medicine, Division of Nephrology and Hypertension, Oregon Health Sciences University, Portland 97201-2940, USA.
Oyama
T T
TT
Kennefick
T M
TM
Thompson
M M
MM
Anderson
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S
D000818:Animals; D001794:Blood Pressure; D005919:Glomerular Filtration Rate; D008297:Male; D016891:Polycystic Kidney, Autosomal Dominant / Q000601:surgery*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D012079:Renal Circulation