Chronic renal failure (CRF) is a common condition in geriatric cats.(1,2) CRF is characterised by the presence of irreversible structural lesions, and is generally considered, at least in clinical cases, to be progressive and ultimately result in the death of the cat. Therapy is thus aimed at ameliorating the clinical signs and systemic complications associated with CRF, and slowing the progressive decline of renal function.
Research into the progression of CRF in cats is limited, particularly in cats with naturally occurring disease. Postulated causes of progression can broadly be grouped into three categories:
Continuation of the primary cause of renal disease.
Systemic and metabolic abnormalities associated with loss of renal function, e.g. hyperphosphataemia, hyperparathyroidism, dyslipoproteinaemias, systemic hypertension, and oxidative stress.
Adaptive anatomical and functional changes in surviving nephrons (hypertrophy, hypertension and hyperfiltration) to compensate for loss of renal function.
Dietary therapy has long been considered a cornerstone in the management of CRF. It is, however, only one aspect of medical management and additional therapeutic measures may be required to control urinary tract infections, systemic hypertension, anorexia, metabolic acidosis, hypokalaemia, and anaemia.
Dietary factors potentially of importance in the management of CRF include protein, phosphate, potassium, sodium, fat, and water-soluble vitamins. Independent studies have evaluated phosphate restriction,(3) or protein and energy restriction in renal ablation models of CRF in cats.(4,5) Controlled studies have also been conducted in cats with naturally occurring CRF. These studies have shown that diets restricted in phosphate and protein can provide clinical benefits (improved physical condition and haematological parameters, and decreased azotaemia) in cats with naturally occurring CRF.(6,7) More recent studies have demonstrated that dietary modification can help control hyperphosphataemia and renal secondary hyperparathyroidism (RHPTH) and significantly increase life-span in cats with naturally occurring CRF.(8-12) These data are discussed in the sections below.
Dietary phosphate restriction has been shown to slow the progression of induced renal failure in dogs.(13) Ross et al., did not find an effect of dietary phosphate restriction on renal function or survival in a one year study in cats, however, phosphate restriction largely inhibited renal mineralisation, fibrosis, and mononuclear cell infiltration.(3) The mechanism(s) underlying these observations remain unexplained. Nevertheless, it seems reasonable to assume that these effects resulted from one or more consequences of reducing the phosphate retention (not always manifest as hyperphosphataemia) that results from reduced renal function.
Increased extracellular fluid phosphate concentration can result in the deposition of calcium phosphate complexes in various tissues, including the kidney. Metastatic soft tissue calcification can cause a reduction in plasma ionised calcium concentration, which stimulates parathyroid hormone (PTH) production, thus representing one mechanism for the development of RHPTH. Phosphate retention also inhibits the activity of the enzyme 1-µ-hydroxylase in the kidney, contributing towards a decrease in production of 1,25-dihydroxycholecalciferol (calcitriol), the most active form of vitamin D3. In turn, decreased calcitriol concentration stimulates PTH synthesis and release, leading to RHPTH. Early in the course of renal failure this probably represents a more important mechanism for RHPTH than do changes in plasma ionised calcium concentration.(14,15)
RHPTH is common in cats with CRF. The prevalence varies from 47% in clinically normal cats with only biochemical evidence of CRF, to 100% of cats with end-stage renal failure.(14) The severity of RHPTH increases with declining renal function, but it may also be present in cats that have normal plasma phosphate concentrations.(14) Renal osteodystrophy is a well recognised adverse effect of RHPTH in various species, which has also been demonstrated in cats with advanced CRF.(16) It has been suggested that PTH may act as an uraemic toxin exerting adverse effects on a range of body systems.(17) PTH may also play a role in the progression of CRF by promoting a rise in cytosolic calcium in renal cells leading to their death.(15) These potential roles of PTH as an uraemic toxin and in the progression of CRF remain controversial.
Restriction of phosphate intake and absorption, using phosphate restricted diets in conjunction with oral phosphate binding agents, is recommended as the mainstay of therapy for RHPTH, with calcitriol therapy also advocated by some authors.(14,15) The efficacy of a management regimen aimed at controlling RHPTH and hyperphosphataemia has been evaluated recently in a prospective controlled study of cats with naturally-occurring CRF. This regimen used a commercial dieta restricted in phosphate and protein, together with oral phosphate binders where appropriate.(8-12) The effect of the restricted phosphate diet on plasma phosphate and PTH was initially evaluated alone. Therapy was adjusted if plasma phosphate concentration increased markedly, if a slight increase was maintained over a number of visits, or if PTH concentrations failed to decrease or started increasing. The adjustment to therapy was the introduction of aluminium hydroxide gel, either in liquid b or dried formulationc, to the treatment regimen. The initial dose was approximately 60 mg/kg/day (liquid formulation). This regimen was evaluated in 29 cats (RPD group). Its efficacy was compared with a group of 21 cats whose owners were offered the same regimen, but who were either not able or not willing to introduce the diet (NPD group). Other complications of CRF, such as hypokalaemia, hypertension and urinary tract infections, were managed as and when they were recognised in both groups of cats.
Plasma phosphate and PTH concentrations did not differ significantly between the two groups at initial diagnosis. Plasma phosphate concentration had decreased significantly in the RPD group by the mid-survival time point; it tended to increase in the NPD group. PTH increased significantly in the NPD group by the mid-survival time point, whereas it tended to decrease in the RPD group. Control of plasma PTH was initially achieved using the diet alone in 25 of the 29 cats (86%) in the RPD group; phosphate binders were used at a later stage in a further six cats to maintain the control of PTH secretion that had originally been achieved by diet alone.(11,12)
The most important observations from this study concerned survival time from diagnosis. At the time of analysis of the data 76.2% of the NPD group and 72.4% of the RPD group had died. Median survival time for the NPD group was 264 days, compared with 633 days in the RPD group (P=0.0036).(11) These data indicate that this treatment regimen, using a phosphate and protein restricted diet together with phosphate binders in some cats, not only brought about decreases in plasma phosphate and PTH concentrations, but also significantly increased survival time in cats with naturally occurring CRF. The study did not determine the mechanism of these clinical benefits, as the diet was considered restricted in phosphate, protein and sodium compared with typical cat foods, and was supplemented with water-soluble vitamins. In addition, the canned formulation was higher in fat and energy (on an as fed basis) than typical cat foods. Which of these factors, either alone or in combination with the use of phosphate binders in some cats, resulted in the beneficial effects seen, remains speculative. The observations of Ross et al.,(3) and Brown et al.(13) (if the latter are in any way applicable to cats) suggest that restriction of dietary phosphate may have been of considerable importance.
Restriction of dietary protein has been recommended for patients with CRF based primarily on the premise that protein catabolites, retained because of excretory failure, contribute to uraemic signs. The potential risks of protein restriction in the cat’s diet are, however, considerably greater than for the dog. The cat is unable to down-regulate hepatic enzyme activity associated with protein catabolism even when dietary protein intake is low,(18) thus it is particularly at risk of protein malnutrition. A dietary protein content of 25.8 g/400 kcal was shown in a clinical study to be adequate for the maintenance of cats with naturally occurring CRF, whilst bringing about improvements in uraemic signs and azotaemia.(6,7) Dietary protein should probably not be restricted to less than 20–22 g/400 kcal in feline diets for the management of CRF.
Whilst protein restriction for the control of uraemic signs is well established, the suggestion that it may slow progression of renal damage is much more controversial. Dietary protein intake has been evaluated in two studies of induced renal failure conducted at North American universities.(4,5) Adams et al., showed that restriction of dietary protein (to approximately 2.7 g/kg/day) and energy intake (to approximately 56 kcal/d) resulted in fewer renal lesions in cats with induced renal failure, than consumption of approximately 6.8 g protein/kg/d and 75 kcal/d.(4) Finco et al., did not find an effect of different protein intakes (approximately 5.3 or 9.0 g/kg/d) and showed only minor effects of energy intake on the development of renal lesions.(5)
It is not clear how the data from the studies of induced renal failure relate to the observations from cats with naturally occurring disease that are discussed in the section on phosphate restriction. If comparisons can be drawn, the data suggest that phosphate restriction may have been more important than protein restriction in the increased life span that was observed in the clinical cases; nevertheless, protein restriction may also have been of value in the uraemic cats. Whilst further studies may help in understanding the underlying mechanisms, management of cats with naturally occurring CRF using a phosphate and protein restricted diet, in combination with oral phosphorus binding agents in those cats where control of hyperphosphataemia and RHPTH was not achieved by diet alone, resulted in more than doubling of average survival time from the commencement of treatment.
a) WALTHAM Feline Renal Support DietTM: Masterfoods, Bruck, Austria (canned) and Effem, Minden, Germany (dry)
b) Aludrox®, Wyeth Laboratories, Maidenhead, UK
c) Alu-Cap®, Riker Laboratories, Loughborough, UK
1. Lulich J, Osborne C, O’Brien T, et al: Feline renal failure: Questions, answers, questions. Comp Contin Educ Small Anim Pract 14:127-153, 1992.
2. Krawiec DR, Gelberg HB: Chronic renal disease in cats, in Kirk RW (ed): Current Veterinary Therapy X. Philadelphia, WB Saunders Co, 1989, pp 1170-1173.
3. Ross LA, Finco DR, Crowell WA: Effect of dietary phosphorus restriction on the kidneys of cats with reduced renal mass. Am J Vet Res 43:1023-1026, 1982.
4. Adams LG, Polzin DJ, Osborne CA, et al: Influence of dietary protein / calorie intake on renal morphology and function in cats with 5/6 nephrectomy. Lab Invest 70:347-357, 1994.
5. Finco DR, Brown SA, Brown CA, et al: Protein and calorie effects on progression of induced chronic renal failure in cats. Am J Vet Res 59:575-582, 1998.
6. Harte JG, Markwell PJ, Moraillon R: Dietary management of feline renal disease. Feline Medicine Symposium (Proceedings of a Symposium held in association with the North American Veterinary Conference). Vernon, Waltham Inc, 1993, pp 27-36.
7. Harte JG, Markwell PJ, Moraillon RM, et al: Dietary management of naturally occurring chronic renal failure in cats. J Nutr 2124:2660S-2662S.
8. Barber PJ: Parathyroid gland function in the ageing cat. PhD thesis, University of London, 1998.
9. Barber PJ, Rawlings JM, Markwell PJ, Elliott J: Treatment of hyperparathyroidism in feline chronic renal failure. J Vet Intern Med 10:166 (A), 1996.
10. Barber PJ, Rawlings JM, Markwell PJ, Elliott, J: Effect of conventional dietary management on renal secondary hyperparathyroidism in the cat. J Small Anim Pract 40:62-70, 1999.
11. Elliott J, Rawlings JM, Barber PJ, Markwell PJ: Survival of cats with naturally occurring chronic renal failure: effect of dietary management. J Small Anim Pract 41:235-242, 2000.
12. Markwell PJ, Elliott J, Barber PJ: Recent research in the dietary management of chronic renal failure in cats. Rec Res Anim Nutr Aust, 12:115-119, 1999.
13. Brown SA, Crowell WA, Barsanti JA, et al: Beneficial effects of dietary mineral restriction in dogs with marked reduction of functional mass. J Am Soc Nephrol 1: 1169-1179, 1991.
14. Barber PJ, Elliott J: Feline chronic renal failure: calcium homeostasis in 80 cases diagnosed between 1992 and 1995. J Small Anim Pract 39:108-116, 1998.
15. Nagode LA, Chew DJ, Steinmeyer BS, Carothers MA: Renal secondary hyperparathyroidism: Toxic aspects, mechanisms of development, and control by oral calcitriol treatment. Proceedings of the Eleventh Annual Veterinary Medical Forum, 1993, pp 154-157.
16. Lucke VM: Renal disease in the domestic cat. J Pathol Bacteriol 95:67-91, 1968.
17. Slatapolsky E, Martin K, Hruska K: Parathyroid hormone metabolism and its potential as a uraemic toxin. Am J Physiol 264:H1998-H2006, 1980.
18. Rogers QR, Morris JG, Friedland RA: Lack of hepatic enzyme adaptation to low and high levels of dietary protein in the adult cat. Enzyme 22:348-356, 1977.