Renal Function and Morphology in Aged Beagle Dogs Before and after Hydrocortisone Administration
Objectives of this study were to evaluate glomerular filtration rate (GFR), renal structural changes and proteinuria in aged Beagle dogs before and after hydrocortisone (HC) administration. Eleven Beagle dogs ≥10 years old were treated with either hydrocortisone (HC group, n = 6) or placebo (control group, n = 5). Urinary markers, GFR and kidney biopsies were evaluated before (T0), during (T16 wks) and after discontinuing HC administration (T24 wks). Results indicate that HC administration causes a significant increase in GFR. At all time points except T16 wks, proteinuria was higher in the control group than in the HC group, and there was no significant difference in urinary markers between groups. At T16 wks, proteinuria, urinary albumin-to-creatinine (c) ratio, immunoglobulin G/c and retinol-binding protein/c were higher compared to baseline in the HC group. At T0, rare to mild renal lesions were detected in all HC dogs and rare to moderate changes in all control dogs. Glomerulosclerosis progressed in both groups until T24 wks. Tubular atrophy was detected in three HC dogs at T16 wks and T24 wks, but also in five control dogs throughout the study. At every time point, five HC dogs and all control dogs had rare to moderate interstitial inflammation. Rare to mild interstitial fibrosis was found in up to three HC dogs at T16 wks and T24 wks, and severe fibrosis in one HC dog at T24 wks. Up to four control dogs had rare to mild fibrosis at all time points. These findings indicate that clinically healthy, aged Beagle dogs may have considerable renal lesions and proteinuria, which could have implications for experimental or toxicological studies. Additional research is needed to elucidate glucocorticoid effects on renal structure, but functional changes such as hyperfiltration and proteinuria warrant attention to kidney function of canine patients with Cushing's syndrome or receiving exogenous glucocorticoids.
Figure 3. Light microscopic lesions.
(A) Glomerulus, Dog 11 at T0. Early glomerular lesions including minimal increase of mesangial matrix. Periodic acid-Schiff staining (×400); (B) Glomerulus, Dog 11 at T16 weeks. Moderate hypercellularity of mesangial and endothelial cells and one synechia. There is segmental to global increase of mesangial matrix and Bowman's capsule is symmetrically thickened with proliferation of parietal epithelial cells. Periodic acid-Schiff staining (×400); (C) Glomerulus, Dog 11 at T24 weeks. Moderate hypercellularity of mesangial and endothelial cells associated with global increase of mesangial matrix. Visceral epithelial cells are hypertrophic. Periodic acid-Schiff staining (×400); (D) Tubulo-interstitium, Dog 11 at T24 weeks. Moderate inflammation widely separating tubules and atrophic tubules. Periodic acid-methenamine silver staining (×400).
Figure 2. Urinary markers.
Median and 75-25th percentiles of urinary albumin-to-creatinine ratio (uALBc) (A), immunoglobulin G-to-creatinine ratio (uIgG/c) (B), retinol-binding protein-to-creatinine ratio (uRBP/c) (C) and N-acetyl-β-D-glucosaminidase ratio (uNAG/c) (D) at T0, T4 wks, T16 wks, T20 wks and T24 wks in the hydrocortisone (HC) group (black circles) and in the control (C) group (white squares). The grey area indicates the hydrocortisone administration period.