Studies suggest that the diagnosis of azotaemic chronic kidney disease (CKD) is approximately three times more common in the cat than in the dog. It is generally a disease of the aging cat population with the mean age at presentation being 12 to 13 years. The main focus of this discussion will be the appropriate management of patients with no specific identifiable cause for their CKD, or for which no specific treatment is available. In these patients, treatment has two components: therapies directed at slowing the progression of CKD and therapies that aim to reduce patient morbidity.

Causes of CKD in the Cat

 Pyelonephritis

 FIP

 Hypercalcaemic nephropathy

 Renal lymphoma

 Other renal tumours (primary, metastatic)

 Polycystic kidney disease (PKD)

 Amyloidosis

 Glomerulonephritis

 Ureteral obstruction

 Toxins

 Recovery from ARF

 Tubulointerstitial nephritis

Diagnosing CKD

Although documenting the presence of azotaemia is straightforward (i.e., a blood test abnormality; usually elevation in creatinine), this should be considered the start of the workup rather than its endpoint. In particular, following the documentation of azotaemia, the following questions should be addressed.

 Is the azotaemia (wholly or partially) pre- or postrenal?

 If the azotaemia is renal, is it due to intrinsic disease, or could there be a functional problem?

 If intrinsic renal disease is present, then is this acute or chronic?

 Can a cause for the intrinsic renal disease be identified?

The extent of the diagnostic workup to identify a potential underlying cause for CKD will largely be indicated by the patient's signalment, physical examination findings and the wishes of the owner. A specific cause of the CKD (see above for details) is more likely to be identified in young cats and those with large or asymmetric kidneys. In many instances, particularly in old cats with bilaterally small kidneys, no specific disease is identified. If the kidneys were biopsied (although this is not clinically indicated), the histological description of the lesions would be tubulointerstitial nephritis and fibrosis. This histological lesion may represent the end result of a variety of different initial diseases.

Classification/Subclassification of CKD

A staging system has been proposed for the classification of patients with CKD (www.iris-kidney.com). Assessment is based on the plasma/serum creatinine concentration, proteinuria and blood pressure. Plasma/serum creatinine is a crude index of the glomerular filtration rate (GFR), and more direct methods of measuring GFR may, in the future, replace plasma creatinine in such a classification scheme.

This scheme includes patients that are non-azotaemic. In these cases, the diagnosis of CKD must have been made by some other means than biochemistry; an example would be a young Persian cat with PKD diagnosed ultrasonographically.

Additionally in this scheme, cats are staged for proteinuria and blood pressure.

Intrinsic Disease Progression

The maladaptive mechanisms that are proposed to cause intrinsic progression of kidney disease and have been studied most to date are secondary renal hyperparathyroidism and glomerular hyperfiltration driven by glomerular capillary hypertension. Glomerular hyperfiltration results in proteinuria and management of this condition is the rationale for treating CKD in cats with ACE-inhibitors. This will be discussed in the accompanying lecture on management of proteinuria.

Secondary Renal Hyperparathyroidism

In the early stages of CKD, mildly increased circulating concentrations of PTH could be seen as an appropriate adaptive response, reducing tubular reabsorption of filtered phosphate and stimulating 1-α-hydroxylase activity. However, PTH also results in release of calcium and phosphate from bone and as renal mass declines, increased secretion of PTH is counterproductive, leading to soft tissue mineralisation. If the condition is allowed to go untreated, parathyroid gland hyperplasia ensues. The mechanism of the hyperparathyroidism is thought to be a combination of the direct effect of hyperphosphataemia on the parathyroid gland, the ionized calcium concentration decreasing due to formation of complexes with the retained phosphate and a reduction in production of calcitriol (the active form of vitamin D). The target level for phosphate differs according to the patient's IRIS stage in recognition that more advanced disease will be more difficult to manage. The proposed targets are as follows: Stage 1 and 2, 0.81–1.45; Stage 3, 0.81–1.61; and Stage 4, 0.81–1.94.

The following stages of treatment should be followed:

1.  Dietary phosphate restriction

a.  Generally accomplished by feeding a 'renal care' diet.

b.  In cats with advanced disease, it is usually not possible to normalise phosphate with diet alone.

c.  If the cat will not eat a renal diet, then a 'senior' diet is probably the next-best alternative.

2.  Intestinal phosphate-binding drugs

a.  These should be mixed in the food or at least given at the same time.

b.  Ideally combined with dietary restriction.

c.  Aluminium hydroxide preparations are effective and cheap (60 to 150 mg/kg/day).

d.  Lanthanum carbonate (Renalzin) is a newer alternative.

e.  Sucralfate can be substituted for aluminium hydroxide (it contains half the aluminium, so double the dose).

f.  Calcium carbonate or acetate can be used as a phosphate binder but may worsen hypercalcaemia.

g.  Epakitin/Ipakitine is a mixture of calcium carbonate and chitosan; the fishy smell may make it more palatable.

3.  Calcitriol therapy

a.  Controversial

b.  No evidence that currently recommended dosing protocols reduce PTH in cats.

Results from a study performed some time ago found that the median survival time of cats that ate a renal care diet was 633 days and those cats that continued to eat a maintenance diet was 264 days (Elliott et al 2000). This study was criticised because the groups were self-selecting. However, a more recent study indicated that very similar results were obtained when the study was performed in a randomised controlled manner (Ross et al 2006). Too few cats died during the period of followup to estimate the median survival times for the groups, but there was a significant difference (p = 0.03) in the number of cats that had a uraemic crisis or that died of their renal disease. It can be concluded from these studies that cats that can be successfully transferred onto a restricted phosphate diet will live longer than those that cannot and that the magnitude of this benefit is likely to be greater than anything that is achieved 'pharmacologically.'

Managing Complications of CKD - Reducing Morbidity

It is also important to identify complicating factors that will require treatment or that might alter the prognosis in individual cases. The following are factors of particular importance.

References

1.  Elliott J, et al. Survival of cats with naturally occurring chronic renal failure: effect of dietary management. J Small Anim Pract. 2000;41:235–242.

2.  Ross SJ, et al. Clinical evaluation of dietary modification for treatment of spontaneous chronic kidney disease in cats. J Am Vet Med Assoc. 2006;229:949–957.