Novel Allelic Variants in the Canine Cyclooxgenase-2 (Cox-2) Promoter Are Associated with Renal Dysplasia in Dogs

Renal dysplasia (RD) in dogs is a complex disease with a highly variable phenotype and mode of inheritance that does not follow a simple Mendelian pattern. Cox-2 (Cyclooxgenase-2) deficient mice have renal abnormalities and a pathology that has striking similarities to RD in dogs suggesting to us that mutations in the Cox-2 gene could be the cause of RD in dogs. Our data supports this hypothesis. Sequencing of the canine Cox-2 gene was done from clinically affected and normal dogs. Although no changes were detected in the Cox-2 coding region, small insertions and deletions of GC boxes just upstream of the ATG translation start site were found. These sequences are putative SP1 transcription factor binding sites that may represent important cis-acting DNA regulatory elements that govern the expression of Cox-2. A pedigree study of a family of Lhasa apsos revealed an important statistical correlation of these mutant alleles with the disease. We examined an additional 22 clinical cases from various breeds. Regardless of the breed or severity of disease, all of these had one or two copies of the Cox-2 allelic variants. We suggest that the unusual inheritance pattern of RD is due to these alleles, either by changing the pattern of expression of Cox-2 or making Cox-2 levels susceptible to influences of other genes or environmental factors that play an unknown but important role in the development of RD in dogs

α-thalassaemia

Alpha-thalassaemia is inherited as an autosomal recessive disorder characterised by a microcytic hypochromic anaemia, and a clinical phenotype varying from almost asymptomatic to a lethal haemolytic anaemia

Juvenile Nephropathy in a Boxer, a Rottweiler, a Collie and an Irish Wolfhound

Juvenile nephropathy was diagnosed in a Boxer, a Rottweiler, a Collie and an Irish Wolfhound dog, each presenting with signs compatible with chronic renal failure. The diagnosis in each case was based on the presence of persistence of poorly differentiated tissue (immature glomeruli and/or tubules, persistent mesenchyme) on histopathologic examination. Although juvenile nephropathy has been reported in many breeds of dog, this is the first report of the condition in the Collie and the Irish Wolfhound and only the second description in the Boxer and the Rottweiler. The possibility of an inherited origin of the condition in these four breeds is at present unknown

Development and validation of a nomogram for urothelial cancer in patients with chronic kidney disease

Abstract Urothelial cancer (UC) is a common kidney cancer in Taiwan and patients with chronic kidney disease (CKD) are more at risk for UC than the general population. The diagnostic value of urine analysis and urine cytology is limited, especially in CKD patients. The aim of the study is to develop a nomogram to predict the risk of UC in CKD patients. We enrolled 169 UC patients and 1383 CKD patients from 9 hospitals in Taiwan between 2012 and 2015. CA125, HE4, clinical characteristics, and medical history were analyzed using multivariable logistic regression for its association with UC. A nomogram was developed to predict the risk of UC and was validated using Bootstrap. CA125 was associated with UC in CKD patients (OR: 5.91, 95% CI: 3.24–10.77) but HE4 was not (OR: 1.29, 95% CI: 0.67–2.35). A nomogram based on patients’ age, estimated glomerular filtration rate, CA125 (log transformed), smoking, exposure of environmental toxin, use of nonsteroid anti-inflammatory drugs, and use of traditional Chinese medicine was conducted. The AUC of the nomogram was 0.90 (95% CI: 0.86–0.92, p < 0.01). Serum CA125 may identify UC patients from CKD patients but has limited diagnostic value due to low sensitivity. The diagnostic value of serum CA125 level can be improved by the combination with clinical characteristics including age, renal function, and medical history