Upregulation of angiotensin II receptors in reflux nephropathy.
OBJECTIVE
Reflux nephropathy (RN) is the cause of end-stage renal failure in 3% to 25% of children and in 10% to 15% of adults. Angiotensin II (Ang II) is a biologically active peptide of the renin-angiotensin system (RAS), which has a profound role not only in the urinary tract-development, but also in the response of the urinary tract to injury. The actions of Ang II are mediated through 2 receptors, angiotensin type 1 receptor (AT(1)R) and angiotensin type 2 receptor (AT(2)R). The aim of this study was to examine the expression of AT(1)R and AT(2)R in severe reflux nephropathy.


METHODS
The kidney specimens from 8 patients (age range, 6 months to 14 years) with severe reflux nephropathy secondary to primary high-grade vesicoureteral reflux (VUR) were obtained at the time of nephrectomy. Control material included normal kidney specimens obtained from 3 adult patients during partial nephrectomy for an incidentaloma. Soluble enzyme immunohistochemistry was carried out using polyclonal antibodies to AT(1)R and AT(2)R. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to evaluate the relative amount of AT(1)R and AT(2)R mRNA.


RESULTS
In the refluxing kidney there was strong AT(1)R immunoreactivity in the glomerulus and proximal tubules and moderate to weak immunoreactivity in the distal tubules. There was strong AT(2)R immunoreactivity in the distal tubules with absent or weak staining in the glomerulus and proximal tubules. In the control kidneys, homogeneous weak AT(1)R immunoreactivity was shown in the proximal and AT(2)R in the distal tubules, respectively. RT-PCR showed strong AT(1)R and AT(2)R expression in the refluxing kidneys compared with controls.


CONCLUSIONS
Upregulation of angiotensin II receptors in reflux nephropathy suggests that Ang II is involved in the pathogenesis of the renal parenchymal damage in patients with RN. Pharmacologic blockade of angiotensin II receptors may be helpful in preventing renal fibrosis associated with reflux nephropathy.
Chertin
Boris
B
Dublin, Ireland and Jerusalem, Israel.
Rolle
Udo
U
Cascio
Salvatore
S
McDermot
Michael
M
O'Briain
Sean
S
Farkas
Amicur
A
Puri
Prem
P
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007668:Kidney / Q000737:chemistry / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism*; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D014718:Vesico-Ureteral Reflux / Q000378:metabolism*
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin