Metabolic Acidosis--What It Means and What To Do
ACVIM 2008
Jonathan Elliott, MA, Vet MB, PhD, Cert SAC, DECVPT
London, UK


Metabolic acidosis is said to be an inevitable consequence of chronic kidney disease (CKD) and, therefore, part of the uraemic syndrome. The adverse effects of metabolic acidosis to the kidney disease patient are wide-ranging and serious. Even mild metabolic acidosis stimulates protein catabolism and reduces protein synthesis and so contributes to the chronic wasting characteristic of renal failure. Severe metabolic acidosis (arterial pH <7.2) has haemodynamic effects, reducing myocardial contractility, causing arteriolar vasodilation and peripheral venoconstriction. Gastrointestinal abnormalities occur in the uraemic syndrome, leading to vomiting, nausea and gastric atony. Metabolic acidosis may contribute to these abnormalities. With sustained acidosis, perhaps the most important effects in human medicine are on the skeletal system because a negative calcium balance ensues. Increased bone resorption occurs and is coupled with reduced bone formation thus contributing to uraemic osteodystrophy [1]. In children, effects on bone turnover can be striking leading to marked stunting of growth, effects which can be reversed by alkali therapy. Excessive dietary acidification in normal cats can cause increased urinary loss of calcium and reduced bone mineral density [2]. Finally, metabolic acidosis has been suggested to be one of the factors which may play a role in the progression of CKD because increased ammonia production within the tubular cells has been linked to complement fixation and tubulo-interstitial damage [3,4]. By altering dietary intake of certain acidifying amino acids, providing a source of bicarbonate and modifying the ash content of the diet, it may be possible to correct the acid-base disturbances that occur in CKD patients, improve their quality of life and, possibly, slow the progression of their disease. It is important, however, to recognise which CKD patients would in fact benefit from such treatment by understanding the degree and severity of disturbances in acid-base balance which occur in naturally occurring feline CKD patients.

Acid Base Balance and the Role of the Kidney

The cat, an obligate carnivore, is generally fed a diet that is rich in protein. As a consequence, its kidneys are required to excrete a non-volatile acid load each day in order that acid-base balance is maintained. In blood and extracellular fluid, the non-volatile acid is buffered leading to a decrease in plasma bicarbonate concentration and reduction in buffering capacity of other important buffers such as haemoglobin. The kidneys reverse this process by excreting the excess acid and in the process, regenerating the bicarbonate used to buffer it. In addition, the kidney must reabsorb all the bicarbonate it filters (sometimes termed 'reclamation of bicarbonate'). Finally, bicarbonate losses occur in the faeces and the kidneys need to regenerate bicarbonate to replace faecal losses if acid-base balance is to be maintained.

Reclamation of filtered bicarbonate occurs predominantly in the proximal tubule the cells of which possess both intracellular and apical brush border carbonic anhydrase enzymes to facilitate this process. The distal nephron is largely responsible for regenerating bicarbonate. Although quantitatively this is a much smaller amount than that reclaimed by the proximal tubule, distal tubular acidification of the urine is the final regulator of acid-base balance. The tubular cells also contain intracellular carbonic anhydrase, which through the hydration of carbon dioxide and the formation of carbonic acid, produces hydrogen ions and bicarbonate ions. Bicarbonate ions return to the blood stream whereas the hydrogen ions are secreted into the tubular fluid. Secretion of hydrogen ions occurs independently of, but is functionally linked to, sodium ion reabsorption. Large pH gradients can be generated in the distal parts of the tubule. Excretion of hydrogen ions is assisted, however, by the presence of urinary buffers enhancing the number of protons that can be excreted by the distal tubular cells. Phosphate and ammonia are the two major urinary buffers.

Acid Base Balance in Feline Chronic Kidney Disease

With a reduction in functioning nephrons the ability to excrete the acid taken in the diet is compromised because net acid excretion falls. Some renal diseases may have a disproportionate effect on tubular function initially, reducing the ability to reclaim or regenerate bicarbonate thus increasing urine bicarbonate loss and decreasing titratable acid excretion. However, with loss of nephrons adaptation of the remaining functioning nephrons may compensate to allow acid-base balance to be achieved until the disease reaches a severe stage. This would involve reclaiming all the filtered bicarbonate (provided an active disease process does not affect the ability of the remaining tubules to do this) and regenerating sufficient bicarbonate to remain in balance by increasing the generation of ammonia by the distal tubules. However, the ability of the feline kidney to respond to metabolic acidosis by increasing its production of ammonia has been questioned [5]. In addition, as the number of functioning nephrons falls in CKD one might expect the capacity of the kidney to produce ammonia in response to increased urine acidity to be reduced.

Another way the animal with CRF could remain in acid-base balance would be by chronically buffering the dietary excess of acid by the release of carbonate and bicarbonate from bone, allowing balance to be maintained but at the expense of progressive bone demineralisation [2]. Lulich et al., [6] reported that 36 of 41 cats with CRF had a blood pH of <7.30, 33 of which had blood bicarbonate concentrations of <17 mmol/l and 22 had a raised anion gap (>25 mmol/l). In another study, total venous CO2 concentrations were measured in 59 cases of CRF presenting for treatment at another second opinion hospital and 37 of these had concentrations <15 mmol/l [7]. These studies suggest that metabolic acidosis is commonly associated with feline CKD.

In first opinion practice, however, cases of feline CKD can present at many different stages of their disease [8] and the management regimens necessary to treat these animals effectively differ according to the severity of the disease. From the two studies referred to above, animals admitted to hospitals when their kidney disease had recently deteriorated have metabolic acidosis and many may benefit from alkali therapy to stabilise their condition. We conducted a cross-sectional study involving fifty nine cases of naturally occurring feline CRF was conducted to determine the prevalence of acid-base disturbances [9]. Cases were categorised on the basis of their plasma creatinine concentrations as stage II (mild), stage III (moderate) and stage IV (severe) CKD based on the IRIS Classification. A low venous blood pH (<7.270) was found in 10 of the 19 stage IV cases (52.6%), three of the 20 stage III cases (15%) and none of the 20 mild cases. Acidaemia was associated with an increased anion gap contributed to by both low plasma bicarbonate and chloride ion concentrations. Biochemical analysis of urine samples showed urine pH to decrease with increasing severity of renal failure. Urinary loss of bicarbonate was not associated with the occurrence of acidaemia and there was a trend for urinary ammonium ion excretion to decrease as the severity of renal failure increased. A subsequent longitudinal study demonstrated that metabolic acidosis became evident when kidney function deteriorated to Stage IV CKD but there was no evidence that metabolic acidosis preceded or predicted a deterioration in kidney function [10].

The Effects of Providing Bicarbonate Precursors in the Diet

Many clinical diets used in the management of CKD provide more bicarbonate precursor and are less acidifying than standard maintenance feline diets. It is possible that cats adapt to reduced kidney function by buffering metabolic acid within bone in stages II and III CKD. If this were the case then feeding extra bicarbonate precursor might be beneficial in reducing demineralisation of bone. We conducted a double blind placebo controlled cross-over study to examine the effect of supplementing the diet with potassium gluconate (2 mEq twice daily) for 12 weeks [11]. This regimen had no effect on venous blood pH or bicarbonate ion concentrations although it did result in an increase in urinary pH. Our ability to assess urinary calcium excretion in this study was hampered by the low concentration of calcium in many urine samples collected. Measurement of markers of bone turnover (Osteocalcin, serum alkaline phosphatase and fragments of type I collagen) did not change significantly during the period of potassium gluconate supplementation, suggesting that adding extra bicarbonate precursor to the diet of a cat with CKD does not appear to influence bone turnover in these patients.


Metabolic acidosis is a common finding in later stages of feline CKD where alkali supplementation is required to improve the quality of life of the patient and reduce protein anabolism. In the earlier stages of feline CKD, renal adaptations appear to prevent the plasma pH and bicarbonate concentrations falling. We have found no evidence to suggest bone demineralisation is occurring as a means of maintaining a stable blood pH and the benefit of additional alkali supplementation over and above that provided by renal clinical diets in stage II and stage III CKD remains to be determined.


1.  Bushinsky DA. The contribution of metabolic acidosis to renal osteodystrophy. Kidney International, 1995, 47, 1816-1832;

2.  Fettman MJ, Coble JM, Hamar DW, Norridin RW, Seim HB, Kealy RD, Rogers QR, McCrea K, Moffat K. Effect of dietary phosphoric acid supplementation on acid-base balance and mineral and bone metabolism in adult cats. Am. J. Vet. Res., 1992, 53, 2125-2135;

3.  Nath KA, Hostetter MK, Hostetter TH. Pathophysiology of chronic tubulo-interstitial disease in rats. Interactions of dietary acid load , ammonia, and complement component C3. Journal of Clinical Investigation, 1985, 76, 667-675;

4.  Tolins JP, Hostetter MK, Hostetter TH. Hypokalaemic nephropathy in the rat. Role of ammonia in chronic tubular damage. Journal of Clinical Investigation, 1987, 79, 1447-1458;

5.  Lemieux G, Lemieux C, Duplessis S, Berkofsky J. (1990) Metabolic characteristics of cat kidney: failure to adapt to metabolic acidosis. American Journal of Physiology, 259, R277-R281;

6.  Lulich JP, Osborne CA, O'Brien TD, Polzin DJ. Feline renal failure: questions, answers, questions. Compendium on Continuing Education for the Practising Veterinarian, 1992, 14, 127-152;

7.  DiBartola SP, Rutgers HC, Zack PM,d Tarr MJ. Clinicopathologic findings associated with chronic renal disease in cats: 74 cases (1973-1984). Journal of the American Veterinary Medical Association1987, 190, 1196-1202;

8.  Elliott J, Barber PJ. Feline chronic renal failure: clinical findings in 80 cases diagnosed between 1992 and 1995. Journal of Small Animal Practice, 1998, 39, 78-85;

9.  Elliott J, Syme HM, Reubens E, Markwell PJ. Assessment of acid-base status of cats with naturally occurring chronic renal failure. J Small Anim Pract. 2003, 44:65-70;

10. Syme HM, Markwell PJ, Elliott J. Acid-base balance of cats with chronic renal failure: effect of deterioration in renal function. J Small Anim Pract. 2003; 44:261-8;

11. Elliott J, Syme HM. Response of cats with chronic renal failure to dietary potassium supplementation. J Vet Intern Med2003; 17: 418 (abstract 156);

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Jonathan Elliott, MA, Vet MB, PhD, Cert SAC, DECVPT
Royal Veterinary College-University of London
London, United Kingdom