Current conventional tests of kidney damage and function in blood (serum creatinine and urea nitrogen) and urine (urine protein creatinine ratio and urine specific gravity) are widely used for diagnosis and monitoring of kidney disease. However, they all have important limitations, and additional markers of glomerular filtration rate and glomerular and tubular damage are desirable, particularly for earlier detection of renal disease when therapy is most effective. Additionally, urinary markers of kidney damage and function may help localize damage to the affected portion of the kidney. In general, the presence of high- and intermediate-molecular weight proteins in the urine are indicative of glomerular damage, while low-molecular weight proteins and enzymes in the urine suggest tubular damage due to decreased reabsorption of proteins, direct tubular damage, or both. This review aims to discuss many of these new blood and urinary biomarkers in domestic veterinary species, focusing primarily on dogs and cats, how they may be used for diagnosis of renal disease, and their limitations. Additionally, a brief discussion of serum creatinine is presented, highlighting its limitations and important considerations for its improved interpretation in domestic species based on past literature and recent studies.
BackgroundUrine protein loss is common in dogs with chronic kidney disease (CKD).Hypothesis/ObjectivesTo evaluate new biomarkers of glomerular and tubulointerstitial (TI) damage compared with histology and as survival indicators in dogs with naturally occurring, proteinuric CKD.AnimalsOne hunderd and eighty dogs with naturally occurring kidney disease.MethodsRetrospective study using urine, serum, and renal biopsies from dogs with kidney disease, 91% of which had proteinuric CKD. Biomarkers were evaluated and correlated with pathologic renal damage, and significant associations, sensitivities, and specificities of biomarkers for renal disease type were determined.ResultsFractional excretions of immunogloblin M (IgM_FE) and immunoglobulin G (IgG_FE) correlated most strongly with glomerular damage based on light microscopy (r = 0.58 and 0.56, respectively; P < .01). Serum creatinine (SCr) correlated most strongly with TI damage (r = 0.70, P < .01). Urine IgM/creatinine and urine NAG/creatinine had the highest sensitivity (75%) and specificity (78%) for detection of immune complex‐mediated glomerulonephritis. Although individually most biomarkers were significantly associated with decreased survival time (P < .05), in a multivariate analysis, SCr, IgM_FE, and glomerular damage based on transmission electron microscopy (TEM) were the only biomarkers significantly associated with survival time (SCr: P = .001; IgM_FE: P = .008; TEM: P = .017).Conclusions and Clinical ImportanceNovel urine biomarkers and FEs are useful for detection of glomerular and TI damage in dogs with proteinuric CKD and might predict specific disease types and survival.
Dogs with X-linked hereditary nephropathy (XLHN) have a glomerular basement membrane defect that leads to progressive juvenile-onset renal failure. Their disease is analogous to Alport syndrome in humans, and they also serve as a good model of progressive chronic kidney disease (CKD). However, the gene expression profile that affects progression in this disease has only been partially characterized. To help fill this gap, we used RNA sequencing to identify differentially expressed genes (DEGs), over-represented pathways, and upstream regulators that contribute to kidney disease progression. Total RNA from kidney biopsies was isolated at 3 clinical time points from 3 males with rapidly-progressing CKD, 3 males with slowly-progressing CKD, and 2 age-matched controls. We identified 70 DEGs by comparing rapid and slow groups at specific time points. Based on time course analysis, 1,947 DEGs were identified over the 3 time points revealing upregulation of inflammatory pathways: integrin signaling, T cell activation, and chemokine and cytokine signaling pathways. T cell infiltration was verified by immunohistochemistry. TGF-β1 was identified as the primary upstream regulator. These results provide new insights into the underlying molecular mechanisms of disease progression in XLHN, and the identified DEGs can be potential biomarkers and therapeutic targets translatable to all CKDs.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.