Rosanne E. Jepson, BVSc, MVetMed, PhD, DACVIM, DECVIM
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 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. http://knowledge.rcvs.org.uk/evidence-based-veterinary-medicine/ebvm-toolkit/.
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. www.iris-kidney.com
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 is 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 proinflammatory 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 transfer of high systemic pressures to the glomerular capillaries, development of glomerular hypertension, glomerulosclerosis and exacerbation of proteinuria.11 However, hypertension per se has not been identified as a risk factor for survival in cats with CKD and indeed it was proteinuria that was associated with the survival of cats with systemic hypertension.12 Nevertheless, management of systemic hypertension, due to the known effect on target organs is considered an important part of management of CKD when identified and there is good evidence from both experimental and clinical cohort studies that amlodipine besylate is an effective antihypertensive agent.13-15
Other management and treatment strategies that are advocated in cats with CKD are dependent largely on the individual patient and include addressing hypokalaemia and anaemia when identified, maintaining hydration and consideration for subcutaneous fluid therapy or oesophageal feeding tube placement when indicated. Historically there has been anecdotal support for the use of antacid products. However, recent data indicates that gastric ulceration is an infrequent finding in cats with CKD with gastric fibrosis being a more common histopathological abnormality.16 This raises questions regarding the routine use of either H2 blockers or proton pump inhibitors. For those cats where appetite is poor then new evidence supports that both mirtazapine and antiemetics such as maropitant may be of clinical utility.17,18 There is no current evidence base for the use of treatments such as anabolic steroids or vitamin B12.
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17. Quimby JM, Lunn KF. Mirtazapine as an appetite stimulant and anti-emetic in cats with chronic kidney disease: a masked placebo-controlled crossover clinical trial. Vet J. 2013;197(3):651–5. PubMed PMID: 23838205.
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