Intrarenal Distributions and Changes of Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 in Feline and Canine Chronic Kidney Disease

Abstract

Angiotensin-converting enzyme (ACE) is a key enzyme in the renin-angiotensin system (RAS). ACE2 is a newly identified member of the RAS. The present immunohistochemical study focused on changes in intrarenal ACE and ACE2 immunoreactivity in feline and canine chronic kidney disease (CKD). ACE immunoreactivity was predominantly observed in the brush border of the proximal tubules in dogs and cats. ACE immunoreactivity was lower in CKD kidneys than in normal kidneys, and quantitative analysis demonstrated negative correlations between ACE and renal tissue damage in dogs. ACE2 immunoreactivity was also detected in the proximal tubules; it increased or decreased with CKD in dogs, depending on the renal region assessed. The changes in ACE and ACE2 in CKD were associated with the plasma creatinine concentration in dogs. Findings from dogs with glomerulonephritis were similar to those from dogs with non-glomerulonephritis. The present study suggests that changes in the intrarenal expression of ACE and ACE2 contribute to the pathological mechanisms of canine CKD, but not to the mechanisms of feline CKD.

ACE and ACE2 in kidney disease

“…In dogs, Mitani et al [24] found that chronic kidney disease (CKD) kidneys exhibited weaker ACE immunoreactivity than normal kidneys and detected a negative association between ACE expression and renal tissue damage. However, both upregulated and downregulated ACE2 expression were detected in dogs with CKD, and ACE/ ACE2 immunoreactivity did not exhibit a close relationship with renal tissue damage [24] .…”

“…In dogs, Mitani et al [24] found that chronic kidney disease (CKD) kidneys exhibited weaker ACE immunoreactivity than normal kidneys and detected a negative association between ACE expression and renal tissue damage. However, both upregulated and downregulated ACE2 expression were detected in dogs with CKD, and ACE/ ACE2 immunoreactivity did not exhibit a close relationship with renal tissue damage [24] . Burrell et al [25] suggested 76 February 6, 2015|Volume 4|Issue 1| WJN|www.wjgnet.com [30] 2003 Type 2 DM Mice ND ↓ ND ↑ 1 Ye et al [9] 2004 [14] 2006 [31] 2008 [32] 2013 Type 2 DN Humans ND ND ↑ ↑ Lely et al [34] 2004 Type 2 DN Humans ↑ ↑ ↓ ↓ Mizuiri et al [15] 2007 Type 2 DN Humans ↑ ↑ ↓ ↓ Reich et al [16] 2007 Primary glomerulopathy Humans ND ND ↑ -Lely et al [34] 2004 IgA nephropathy Humans ↑ ↑ ↓ ↓ Mizuiri et al [36] 2011 Hypertension Rats ND ND ↓ 1 Prieto et al [41] 2011 Hypertension…”

Current Understanding of the Pathogenesis of Progressive Chronic Kidney Disease in Cats

“…[146][147][148] The first study by 147 The second study by Mitani and colleagues evaluated ACE and ACE2 (mediates production of Ang1-7/Mas pathway) expression. ACE was identified predominantly in the proximal tubules whilst ACE2 was identified in proximal tubules and weaker staining in the distal nephron.…”

“…Unlike in dogs, there was no association between immunostaining of ACE or ACE2 with histopathology scores although sample numbers were small. 148 Further work and larger studies are required to confirm the association between altered expression of these components of RAAS with severity and progression of CKD.…”

ACE2 in the Era of SARS-CoV-2: Controversies and Novel Perspectives

“…High levels of ACE2 protein expression have been detected in mammalian, including human, kidney (Gembardt et al, 2005;Koka et al, 2008;Reich et al, 2008;Giani et al, 2012;Mitani et al, 2014;Grobe et al, 2015;Shi et al, 2015;Larouche-Lebel et al, 2019;Alawi et al, 2020). Strong signals were reported in the brush border of the proximal tubular cells, whereas weak to moderate signals could be found in the glomeruli, Henle's loop, distal tubules, and collecting duct (Hamming et al, 2004;Lely et al, 2004;Kamilic et al, 2010;Giani et al, 2012;Bae et al, 2015;Cao et al, 2017;Errarte et al, 2017).…”