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

Characterization of proteinuria in dogue de bordeaux dogs, a breed predisposed to a familial glomerulonephropathy: A retrospective study

Dogue de Bordeaux dog has been reported to be predisposed to a familial glomerulonephropathy that displays some morphological modifications reported in focal and segmental glomerulosclerosis. Prevalence of quantitatively abnormal renal proteinuria was recently reported to be 33% in this breed. The nature of the proteinuria was assessed by sodium dodecyl sulfate-agarose gel electrophoresis and determinations of urinary markers (urinary retinol-binding protein, urinary N-acetyl-beta-glucosaminidase, urinary albumin and urinary immunoglobulin G) on stored specimens. Diagnostic performances of sodium dodecyl sulfate-agarose gel electrophoresis to identify dogs with elevated urinary biomarkers were assessed. Samples from 102 adult Dogue de Bordeaux dogs (47 non-proteinuric [urine protein-to-creatinine ratio 0.5]) were used, of which 2 were suffering from familial glomerulonephropathy. The electrophoretic protein patterns, for all but one proteinuric dog, were indicative of a glomerular origin and, in all dogs, the urinary albumin concentration related to creatinine concentration and the urinary immunoglobulin G concentration related to creatinine concentration were above the upper limit of the reference interval established for the breed. Sensitivity and specificity of sodium dodecyl sulfate-agarose gel electrophoresis identifying dogs with elevated urinary albumin concentration were 94% and 92%, respectively, while diagnostic performance of sodium dodecyl sulfate-agarose gel electrophoresis in detecting dogs with elevated urinary immunoglobulin G concentration yielded sensitivity and specificity of 90% and 74%, respectively. These results suggest that all proteinuric and some borderline-proteinuric Dogue de Bordeaux dogs likely have underlying glomerular lesions and that sodium dodecyl sulfate-agarose gel electrophoresis and urinary markers might be useful to screen dogs with borderline-proteinuria. Additional investigations are warranted to assess if these findings are related to the familial glomerulonephropathy

Tubular and interstitial lesions in the hydrocortisone (n = 6 dogs) and control group (n = 5 dogs).

<p>T0, baseline; T16 wks, end of the 16 weeks hydrocortisone treatment period; T24 wks, 4 weeks after complete cessation of hydrocortisone treatment; HC, hydrocortisone. Score:</p><p>1 = rare lesion, 2 = mild, 3 = moderate, 4 = severe.</p

Glomerular filtration rate and routine renal markers in the control and hydrocortisone group.

<p>T0, baseline; T16 wks, end of the 16 weeks hydrocortisone treatment period; T24 wks, 4 weeks after complete cessation of hydrocortisone treatment; HC, hydrocortisone group; controls, control group; Cl_creat, plasma clearance of creatinine; Cl_exo, plasma clearance of exo-iohexol, Cl_endo, plasma clearance of endoiohexol; sCr, serum creatinine; USG, urinary specific gravity; UPC, urinary protein-to-creatinine ratio. The asterisk indicates in which group results are significantly increased (<i>p</i><0.05) compared to the other group at that timepoint.</p

Glomerular lesions.

<p>(A) Glomerulus, Dog 8 at T16 weeks. Obsolescent glomerulus. Periodic acid-Schiff staining (×400). (B) Glomerulus, Dog 5 at T24 weeks. Accentuated lobulation, increase of mesangial and endothelial cellularity of the tuft, and synechiae. Splitting of Bowman's capsule is visible. Periodic acid-Schiff staining (×400).</p

Light microscopic lesions.

<p>(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).</p

Urinary markers.

<p>Median and 75-25^th 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.</p

Plasma concentration versus time curves.

<p>Plasma creatinine (A1, A2), exo-iohexol (B1, B2) and endo-iohexol concentration (C1, C2) versus time curves in the hydrocortisone (HC) group (6 dogs) and the control group (5 dogs) at T0, T16 wks and T24 wks. Mean ± standard deviation is displayed. The asterisk indicates a statistically significant difference (<i>p</i><0.001) in plasma clearance between groups at T16 wks, for creatinine and exo-iohexol clearance.</p

Glomerular lesions in the hydrocortisone (n = 6 dogs) and control group (n = 5 dogs).

<p>Endocap., endocapillary; Prim.mesang., primary mesangial; T0, baseline; T16 wks, end of the 16 weeks hydrocortisone treatment period; T24 wks, 4 weeks after complete cessation of hydrocortisone treatment; HC, hydrocortisone. Score: 1 = rare lesion, 2 = mild, 3 = moderate, 4 = severe.</p

Electron microscopic glomerular lesions.

<p>(A) Glomerulus, Dog 10 at T16 weeks. Sub-endothelial widening and rarefaction of the glomerular basement membrane associated with foot process effacement. EM ×5000; (B) Glomerulus, Dog 9 at T24 weeks. Multifocal foot process effacement (arrow) and endothelial cell swelling with reduction of the capillary lumens and mesangial interposition (asterisk). EM ×4000; (C) Glomerulus, Dog 11 at T24 weeks. Diffuse and severe foot process effacement (arrows). EM ×4000.</p