AZOTEMIA AND EXTRARENAL MANIFESTATIONS IN OLD FEMALE HAN-SPRD (CY +) RATS/

In humans suffering from polycystic kidney disease (PKD) a gender diff erence is seen with males exhibiting a faster rate of progression of c hronic renal failure than females. The aim of this study was to examin e renal function in female rats suffering from autosomal dominant PKD [Han:SPRD (cy/+)] and to look for the occurrence of extrarenal organ m anifestations of PKD. In young (2 months) as well as in old female rat s (21 months) relative kidney weight was greater in affected than unaf fected animals. In contrast, only the old affected female rats develop ed azotemia (serum urea 95 +/- 124 mg/dl) and severe cystic kidney tra nsformation. Furthermore, old affected female rats exhibited liver cys ts (affected 42%; unaffected 3%) and pancreatic cysts (affected 69%; u naffected 15%). Liver cyst epithelia stained positive for cytokeratin 19, a marker for bile duct epithelia. By immunohistochemistry liver cy sts exhibited a similar extracellular matrix composition as observed i n renal cysts of the same animals (staining positive for laminin, fibr onectin and heparan sulfate proteoglycan, but not collagen I). This st udy proves PKD in the Han:SPRD (cy/+) rat model to be a truly multiorg an disease with a close resemblance of the human disease.