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Page 22 - VETcpd - Vol 5 - Issue 2 VET cpd - Feline Peer Reviewed Dr Rosanne Jepson BVSc (Dist) MVetMed PhD DipACVIM DipECVIM MRCVS Senior Lecturer in Small Animal Internal Medicine Rosanne is a Senior Lecturer and recognised RCVS, ACVIM and ECVIM Specialist in Small Animal Internal Medicine. Her particular areas of interest include canine and feline nephrology and urology. She is a member of the RVC GFR Service, co-director of the extracorporeal therapies unit and is one of two clinicians offering minimally invasive urological procedures including laser lithotripsy and laser ablation of ectopic ureters at the Queen Mother Hospital for Animals (QMHA). She has an active research profile in feline and canine renal disease and hypertension. As well as lecturing both nationally and internationally, Rosanne is involved in both undergraduate and postgraduate (Royal Veterinary College CertAVP Medicine Module leader and ACVIM/ECVIM residency training) level education. She is also co-director of the Infection Control Committee at the QMHA. E-mail: [email protected] Chronic kidney disease (CKD) implies that there is a loss of structure or function by the kidneys which has been present for at least 2-3 months. For most geriatric cats, when CKD is discussed we are referring to the development and progression of tubulointerstitial nephritis which is characterised by progressive inflammation, fibrosis and loss of nephrons. There has been considerable interest in recent years in optimising early diagnosis of CKD in the ageing cat given that the histopathological changes, once present, are irreversible; an early diagnosis therefore gives the greatest opportunity for slowing both development and progression of disease. The relatively new surrogate marker of glomerular filtration rate (GFR), symmetric dimethylarginine, has been reported to allow the earlier identification of cats with CKD. This article will explore the current knowledge base on the utility of this marker in cats and highlight areas where continued study is required. Key words: SDMA, feline chronic kidney disease, cats, GFR Feline chronic kidney disease and symmetric dimethylarginine SUBSCRIBE TO VETCPD JOURNAL Call us on 01225 445561 or visit www.vetcpd.co.uk Introduction Feline chronic kidney disease (CKD) is a common condition in both general and referral practice. From a clinical perspective it is recognised that many cats with CKD due to tubulointerstitial nephritis have stable disease for many years whilst others show clinical and biochemical evidence of progression of disease. This article will discuss CKD and examine the current understanding of symmetric dimethylarginine (SDMA), a surrogate biomarker of glomerular filtration rate (GFR). SDMA is a serum test that is commercially available via IDEXX laboratories and is considered a more sensitive marker of declining renal function than creatinine. The pathogenesis of CKD In recent years there has been much interest in the pathogenesis of CKD and factors that may promote progression of disease such as altered renal haemodynamics, activation of the renin- angiotensin-aldosterone system, mineral and bone disorder, proteinuria, systemic hypertension, hypoxia and oxidative stress (Jepson 2016). Renal fibrosis, is considered the final common pathway to which many of these progression factors contribute (Lawson et al. 2015). Healthy renal interstitium is composed of sparse cells (fibroblasts and dendritic cells) embedded in an extracellular matrix composed of collagen (I, III, VII), fibronectin and extracellular matrix glycoproteins e.g. tenascin. Renal fibrosis usually begins with focal areas of inflammation secondary to an inciting injury and activation of mesenchymal cells, progressing to generate expanding areas of fibrosis and scarring (Prunotto et al. 2011). Initially after injury, the recruitment of activated fibroblasts, termed myofibroblasts, is a beneficial response and forms part of the normal repair mechanism. However, in CKD, an excessive or maladaptive response occurs leading to the continuation of mechanisms that promote renal fibrosis (Kramann et al. 2013). Renal fibrosis is characterised by excessive accumulation of matrix proteins, e.g. collagen IV and laminin and myofibroblasts, in association with a secondary inflammatory component (Figure 1). In feline CKD, the inciting injury that drives the development of CKD is often unknown. Historically, studies have evaluated potential triggers including vaccination, infectious aetiologies (e.g. feline immunodeficiency virus, leptospirosis, morbillivirus), ageing and environmental and lifestyle factors (Jepson 2016). A recent concept that is gaining interest is the association between acute kidney injury (AKI) insults and the development of CKD (Cowgill et al. 2016). Experimental feline models of renal ischaemia have demonstrated similarities in the development of renal inflammation and fibrosis and may provide interesting models in which to explore further the pathways involved in progression of disease, with the potential of novel therapeutics if these pathways can be exploited (Schmiedt et al. 2016; Dickerson et al. 2017).
