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An Urban Experience
R. Jepson1
1Royal Veterinary College, Clinical Science and Services, London, United Kingdom
Rosanne E. Jepson BVSc MVetMed PhD DipACVIM DipECVIM
Royal Veterinary College, London (UK)
The management of any condition in veterinary medicine should always be undertaken with consideration of
the currently available evidence base. Studies that are performed may include a variety of levels of evidence base (See Figure 1) ranging from the strongest levels of evidence such as a systematic review or meta-analysis down to the weakest forms of evidence such as case reports and expert opinion. evidence-based-veterinary-medicine/ebvm-toolkit/
Figure 1: Levels of supporting evidence base
Today in feline medicine and specifically for chronic kidney disease (CKD) we are fortunate to have guidelines that
are generated by the International Renal Interest Society (IRIS) which focus on the available evidence base for stage specific management.
CKD in cats is considered an irreversible condition. Therefore any treatment or management that is used
is aimed at trying to slow the progression of disease, counteract the clinical manifestations and homeostatic derangements that are identified with reducing renal function whilst at the same time trying to ensure, maintain and improve the welfare and wellbeing of the cat and the relationship between cat and owner. There are certain management factors that are general to all cats with CKD irrespective of age such as trying to avoid exposure to nephrotoxins, episodes of acute kidney injury (AKI) or periods of pre- or post-renal azotaemia. But other areas of management can be considered in a stage specific manner.(1) The main areas of management in relation to preventing progression of CKD have focused on control of CKD-mineral and bone disorder (CKD-MBD; previously referred to as renal secondary hyperparathyroidism), proteinuria and systemic hypertension.
With declining renal function, the kidneys are less able to excrete phosphorus leading to phosphate retention and stimulation of homeostatic mechanisms to try and maintain phosphate regulation, including increased production of hormones such as parathyroid hormone
and recently identified phosphaturic factor, Fibroblast growth factor 23.(2) These adaptations to phosphate regulation are termed CKD-MBD and whilst initially beneficial ultimately may be detrimental in terms of progression of disease by increasing the risk of soft tissue mineralisation including the kidneys and altering calcium:phosphate release from bones which may
result in renal osteodystrophy. For cats with azotaemic IRIS stage 2-4 CKD there are both case control and randomized controlled trials that support the use of a phosphate restricted renal diet and that use of such diets significantly increases survival and reduces uremic episodes. (3, 4) Targets for phosphate control, as used in the IRIS staging have been based on the outcomes from these studies. However, as we begin to understand better the differences that exist between cats and the different stages of CKD particular for early stage disease, it is possible that further improvements will be made
in the optimal dietary management for cats with CKD. (5) It must also be remembered that these studies have utilized complete renal diets which frequently have modifications beyond just phosphate restriction and
that therefore it could be the combination of different adjustments that are made to renal diet that bring about the survival advantage not just the phosphate restriction.
Proteinuria has been implicated as a factor that it likely to be associated with progression of CKD. Experimental data supports that protein handling by the kidney and specifically the proximal tubule cells may promote a pro-inflammatory and pro-fibrotic environment within the tubulointerstitium. Retrospective cohort studies have indicated that in cats the development of azotaemia, survival and a more progressive phenotype of CKD
is associated with proteinuria despite the overall
severity of proteinuria being relatively low in cats with tubulointerstitial nephritis. (6-8) Persistent proteinuria that is considered significant (urine protein:creatinine >0.4)
is typically managed by administration of drugs that inhibit angiotensin II with the goal of reducing glomerular capillary pressure. Whilst randomized placebo controlled studies have demonstrated significant reduction in proteinuria in cats with CKD to date the only study
that evaluated the effect of an angiotensin converting enzyme inhibitor, benazepril, failed to demonstrate a survival advantage although there was a trend towards improved survival in cats that were more markedly proteinuric.(9) Equivalency has been demonstrated for the more recently released angiotensin receptor blocker, telmisartan, in terms of anti-proteinuric therapy. (10)
Systemic hypertension is widely accepted to be detrimental to target organs including the kidney, eye, cardiovascular system and central nervous system and to be implicated in progression of renal disease due to

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