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Judy Savige

Publications and source records attributed to Judy Savige.

23 records · Page 2Linked to original sources
PubMed2002

Correlation of histopathological features and renal impairment in autosomal dominant Alport syndrome in Bull terriers.

BACKGROUND: Bull terrier hereditary nephritis represents a model for autosomal dominant Alport syndrome, as affected dogs have the characteristically lamellated glomerular basement membrane and demonstrate vertical male-to-male disease transmission. METHODS: This study compared the histopathological features in kidneys from affected Bull terrier neonates, puppies, and adult dogs with normal or impaired renal function, with the histopathological appearance of kidneys from age- and size-matched normal dogs. RESULTS: There were fewer glomeruli per unit area of cortex in kidneys from affected neonatal kidneys (P<0.05), increased numbers of fetal glomeruli in affected puppy kidneys (P<0.05), and a separate population of glomeruli with larger renal corpuscles and glomerular tufts in kidneys from affected adult dogs with normal renal function (both P<0.0001) compared with normal dogs. Other histological features that are characteristic of human X-linked and autosomal recessive Alport syndrome and that were present included hypercellular glomeruli, occasional crescents, segmental and global glomerular sclerosis, periglomerular fibrosis, interstitial fibrosis without significant cellular infiltrates and cystic dilatation of Bowman's capsular space and tubules. In dogs with renal impairment, the tubular index was the best predictor of increased urinary protein:creatinine (r=0.92) compared with glomerular, interstitial and vascular indices (r=0.77, 0.88 and 0.81), and medullary fibrosis correlated best with serum creatinine (r=0.72, P=0.0002). CONCLUSIONS: The demonstration in Bull terrier kidneys of fewer nephrons in neonates increased fetal glomeruli, and a separate population of glomeruli with larger corpuscles and tufts reflects the effects of the underlying genetic mutation that are first manifest antenatally. The major determinant of renal impairment in adult affected Bull terriers is, however, progressive tubulointerstitial damage after birth.

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PubMed2002

A novel model of autosomal dominant Alport syndrome in Dalmatian dogs.

BACKGROUND: Autosomal dominant Alport syndrome is a rare inherited disease characterized clinically by haematuria, renal failure and deafness, and ultrastructurally by a lamellated glomerular basement membrane (GBM). It is usually caused by mutations in the COL4A3 or COL4A4 genes which code for the alpha3 and alpha4 chains of type IV collagen. We describe here a novel spontaneous model of autosomal dominant Alport syndrome in Dalmatian dogs. METHODS: Affected dogs were identified by a urinary protein creatinine >/=0.3. A total of 10 affected adult Dalmatians and eight unaffected age- and sex-matched dogs from breeds other than Dalmatians were examined. In addition, kidneys from five Dalmatian fetuses from affected mothers were examined histologically and ultrastructurally. RESULTS: All affected dogs were purebred Dalmatians and had a common progenitor. Successive generations were affected, and males and females were affected equally often and equally severely, consistent with autosomal dominant inheritance. The median age at onset of renal failure was 18 months (range 8 months to 7 years). Affected dogs were not clinically deaf, and did not have the ocular abnormalities seen in human X-linked or autosomal recessive Alport syndrome. In addition, they did not have the leucocyte inclusions, low platelet counts or large platelets seen in autosomal dominant hereditary nephritis due to MYH9 mutations. The renal histology and ultrastructural appearance of the GBM appeared to be normal in utero. However, affected adult kidneys demonstrated segmental glomerular hyalinosis and sclerosis with tubulo-interstitial inflammation and fibrosis, and on ultrastructural examination the GBM was lamellated with subepithelial frilling, vacuolation and occasional intramembranous deposits. All alpha1(IV)-alpha5(IV) type IV collagen chains were present in the affected GBM and Bowman's capsule. CONCLUSIONS: Autosomal dominant Alport syndrome in Dalmatians resembles the disease in Bull terriers but has arisen independently. These models will enable us to determine how genetic mutations affect the corresponding proteins and overall membrane structure in autosomal dominant Alport syndrome.

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