Total body potassium in healthy adults is around 3700 mmol and most of it is located in the intracellular compartment, especially in muscles1,2,3. Conversely, the extracellular space contains only 50 to 70 mmol of this cation. In Western societies an adult eats about 1 mmol/kg/day of potassium4.
Potassium retention is one of the alarming signs that accompany chronic renal failure, specially when glomerular filtration rate falls toward 20 % of normal. The low rate of potassium excretion in such patients is due to the rapid rate of flow in the remaining cortical collecting ducts (CCDs), thus potassium concentration in each CCD cannot rise to 10 times that in plasma, as it happens in normal kidneys5.
Various mechanisms help patients with renal failure to adapt to changes in plasma potassium level and thus to avoid hyperkalemia: restriction of dietary potassium to 40-60 mmol/day6, increase in renal and intestinal potassium excretion and redistribution of this cation into the intracellular space.
Renal Adaptation Mechanisms
The main renal adaptation against hyperkalemia occurs in the renin-aldosterone system through its influence on the distal tubules4. As chronic renal failure progresses, the patient undergoes potassium adaptation by increasing the amount of potassium excreted by each nephron unit7. Hyperkalemia stimulates aldosterone secretion while this hormone increase renal fractional excretion of potassium, then in end stage renal disease patients there is a direct relationship between renal potassium excretion and plasma aldosterone levels. Hene et al have demonstrated that, when glomerular filtration rate is less than 50 ml/minute, the level of plasma aldosterone begins to increase progressively8. On the other hand, there is also an inverse relationship between glomerular filtration rate and the fractional excretion of potassium9
Also intrinsic changes in the renal tubular epithelial cells are associated with increased potassium excretion, particularly increased Na-K-ATPase activity4. This local increase in enzyme activity is stimulated by hyperkalemia itself or by increased a1dosterone secretion10,11.
Intestinal Adaptation Mechanisms
Intestinal potassium excretion rises during chronic renal failure and the body can eliminate an additional 10-20 mmol of this cation by this route3. Colonic potassium secretion begins to adapt when glomerular filtration is reduced to around one-third of normality and when renal failure is severe, this route may account for as much as 30 to 70% of total potassium excretion3,12 The colon is the chief site of aldosterone action.10,12. This hormone increases luminal membrane sodium permeability by activating new sodium channels, and also it increases the number and activity of the Na-K.-ATPase pumps.13,14,15,16. Also hyperkalemia itself may increase Na-K-ATPase activity in the bowel3,4.
Intracellular Redistribution of Potassium
Although patients with severe end stage renal disease are at increased risk of hyperkalemia, their total body potassium content and cellular potassium concentration often are below normal. The decrease in total body potassium may be explained by an abnormality in cellular potassium regulation4. In peritoneal dialysis, the intracellular potassium content is normal or even high, especially in CAPD patients. Perhaps this phenomenon is related to glucose and its stimulus of intracellular uptake of potassium mediated by insulin release17,18,19.
Potassium Excretion by Dialysis
Potassium has a dialytic clearance disproportionally low for its molecular size and this is because of its charge20,21. It is removed mainly by diffusion (85%) and, its removal by convection generally is around 15% 22.
Its clearance is similar to that of creatinine, but its rate of removal varies with the potassium gradient between plasma and dialysate. The reduction is greater for patients with hyperkalemia than in those with normal potassium levels predialysis, and when one uses sodium "profiling" to make sequential changes in the dialysate sodium concentration from hypertonic to normal levels17 and with glucose-free dialysate23.
Approximately 60 % of the potassium removed during dialysis is lost from the intracellular compartment (ICC). Such removal follows at least a two-compartment kinetic model: external transfer - from ICC to extracellular compartment (ECC), and internal transfer - from ECC to ICC. The latter is slower than the former and, as a consequence, the net amount of potassium entering the ECC from the cells is less than the amount of potassium leaving the ECC to enter the dialysis fluid. Movement of potassium from ICC to ECC continues even after the end of dialysis, until a steady state is re-established between the spaces22. Therefore, after the end of a highly efficient hemodialysis, one should expect an increase in plasma potassium of 0.5 to 1 mmol, within 1 to 3 hours17.
Although the same general principles apply in chronic peritoneal dialysis as in hemodialysis, the rate of potassium removal in the former is markedly slower17. During the first hour of a dwell, the potassium clearance value is 24 ml/minute. The most probable explanation for these high values is the release of potassium from the cells that line the peritoneal cavity. This release may be promoted by the initial low pH and/ or by the hyperosmolality of the instilled dialysate20. In patients with severe hyperkalemia and total body potassium excess, peritoneal dialysis has a low efficiency for potassium removal, therefore, hemodialysis is recommended if it is available17. During the first one to two hours, there is a more rapid fall in plasma potassium concentration which is due chiefly to a shift of potassium into the cells. This initial shift is due to the correction of acidosis and probably is also related to the transfer of glucose from the dialysate17. Hyperkalemia. is considerably less common in stable CAPD than in those on chronic hemodialysis. The incidence of hyperkalemia with CAPD is 0.8 % as contrasted to 10 % with chronic hemodialysis6.
Oreopoulos et al, in 1982 reported that 10% - 15% of CAPD patients required potassium supplementation for hypokalemia24,25, while Spital and Sterns noted that 36% of their CAPD patients had a serum potassium less than 3.5 mmol/l at some time during their course26. In a recent study, Oreopoulos et al. have found that hypokalemic patients on peritoneal dialysis were younger, had been on CAPD for longer periods, had a high Kt/V, had a lower urine creatinine clearance and urine volume, and they had a lower weight respect to the normokalemic ones27.
Potassium metabolism in chronic renal failure is the result of several factors, such as a low potassium diet, an increase in renal and colonic potassium excretion, and a shift of this cation into the intracellular space. When these mechanisms begin to fail, dialytic potassium removal contributes to maintain its balance in end-stage renal disease patients.
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