Doctoral thesis, 2018
Chronic kidney disease in the dogPelander, Lena
AbstractAbstract Chronic kidney disease (CKD) is a contributor to morbidity and mortality in dogs. The general aim of this thesis was to increase knowledge regarding pathophysiologic mechanisms and early diagnosis of canine CKD by identifying dogs with increased risk of disease, and by exploring the value of various biomarkers in blood and urine. Dogs are comparably commonly diagnosed with kidney-related disease (KD), but neither incidence nor mortality rates of KD have previously been reported. In paper I, incidence and mortality rates of KD were calculated in a population of >600,000 dogs. The total incidence rate of KD in this population was 15.8 cases per 10,000 dog years at risk (DYAR, representing one dog insured for one year). The mortality rate of KD was 9.7 deaths per 10,000 DYAR. The breeds with the highest incidence rates in this study were the Bernese mountain dog, miniature schnauzer and boxer. The Swedish elkhound, Siberian husky and Finnish spitz were the breeds with the lowest rates. Increased concentrations of two cardiovascular biomarkers, B-type natriuretic peptide (NT-proBNP) and cardiac troponin I (cTnI), have been reported in dogs with decreased renal function. The aim of paper II was to investigate if NT-proBNP and cTnI accumulate in the circulation of dogs with CKD, as GFR declines. The results did not support passive accumulation, and the conclusion was that these markers identify increased blood volume and damage to cardiac cells, respectively, in dogs with CKD. Symmetric dimethyl arginine (SDMA) and cystatin C are two potential biomarkers of decreased GFR in the dog. In paper III, the aim was to investigate overall diagnostic value of SDMA and cystatin C as markers of decreased GFR, compared to the current marker, creatinine. The overall value of SDMA was equivalent to that of creatinine, but cystatin C performed less well as a marker of decreased renal function in this study. In human medicine, a specific urinary peptide pattern that detects CKD has been developed. Changes in the canine urinary peptide pattern may represent a completely new opportunity for early diagnosis of canine CKD as well. In paper IV, a CE-MS-based urinary peptidome model, 133P, was constructed and shown to be able to discriminate healthy dogs from dogs with CKD in a separate cohort. This model, although in need of further investigation and validation, represents an exciting new diagnostic modality in that it may prove to be able to detect chronic progressive CKD in a single urine sample.
KeywordsCKD, renal, canine, biomarker, GFR, cardiovascular-renal disorder, nephrology
Published inActa Universitatis Agriculturae Sueciae
2018, number: 2018:34
ISBN: 978-91-7760-208-8, eISBN: 978-91-7760-209-5
Publisher: Department of Clinical Sciences, Swedish University of Agricultural Sciences