Reduced renin expression and altered gene transcript profiles in multicystic dysplastic kidneys.
OBJECTIVE
Some patients with multicystic dysplasia experience hypertension in infancy which can be clinically improved with simple nephrectomy. Little is known of the role of renin in multicystic dysplasia and therefore, we studied renin expression in nonhypertensive multicystic dysplasia and compared it with hypertensive multicystic dysplasia. Additionally, global gene transcript profiles were studied in nonhypertensive multicystic dysplasia.


METHODS
Tissue from 12 patients with multicystic dysplasia without hypertension and 2 patients with hypertensive multicystic dysplasia were compared to normal metanephric mid-term and neonatal kidneys. Renin expression was studied by immunohistochemistry. CD-68, a marker for macrophages, was applied to slides previously stained with renin. GeneChip (Affymetrix, Southern Oaks, California) microarray analysis was performed using total RNA from 2 nonhypertensive multicystic dysplastic kidneys and normal newborn kidney as control.


RESULTS
Strong renin staining was present in arteries and arterioles in normal early metanephric kidneys and concentrated in juxtaglomerular cells in neonatal kidneys. Renin was variably decreased in arterioles in multicystic dysplasia and was ectopically expressed in interstitial cells. Renin positive interstitial cells co-expressed CD-68 antigen identifying these cells as macrophages. Ectopic renin production was more pronounced in hypertensive multicystic dysplasia. GeneChip hybridization showed a 60 to 200-fold decrease in expression of renin transcript in multicystic dysplasia relative to normal kidney, concordant with immunohistochemical results. Altered expression of several other candidate transcripts was also identified.


CONCLUSIONS
Dramatic renin decrease in multicystic dysplasia suggests that it may participate in the development of dysplastic vessels. Pronounced ectopic renin expression by macrophages in multicystic dysplasia associated with hypertension may be linked to hypertension in multicystic dysplasia. Several other candidate genes whose altered expression may be associated with the pathophysiology of multicystic dysplasia provide intriguing molecular targets for future study.
D015703:Antigens, CD / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics; D005260:Female; D006801:Humans; D006977:Hypertension, Renal / Q000235:genetics* / Q000473:pathology; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000473:pathology; D008264:Macrophages / Q000473:pathology; D008297:Male; D021782:Multicystic Dysplastic Kidney / Q000235:genetics* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D012083:Renin / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D012083:Renin; C067980:CD68 antigen, human; D000097382:CD68 Molecule