Hypokalemia and the kidney

Hypokalemia, especially if persistent, can induce a variety of changes in renal function, impairing tubular transport and possibly inducing chronic tubulointerstitial disease and cyst formation . One function that is not impaired is the ability to appropriately conserve potassium by both decreasing distal potassium secretion and increasing active distal potassium reabsorption
This response is important clinically, since it allows measurement of urinary potassium excretion to distinguish between extrarenal and renal losses as the cause of otherwise unexplained hypokalemia. Potassium excretion should be less than 25 meq/day with extrarenal losses (or with diuretic therapy if the effect of the drug has worn off) . In comparison, a higher value indicates at least some component of renal potassium wasting as might be seen with diuretic therapy, one of the forms of primary hyperaldosteronism (including Bartter's syndrome), or during the bicarbonaturic phase in a patient with vomiting.

The following renal abnormalities, most of which are reversible with potassium repletion, can be induced by hypokalemia .

Impaired urinary concentration — Nocturia, polyuria, and polydipsia all may be seen with chronic hypokalemia (plasma potassium concentration usually ≤3.0 meq/L) . These symptoms appear to be due primarily to diminished urinary concentrating ability, although studies in animals suggest that there may also be a primary stimulus to thirst. The renal defect, which occurs gradually over several weeks, is associated with decreased collecting tubule responsiveness to antidiuretic hormone. How this occurs is incompletely understood, but decreased expression of aquaporin-2, the water channel that fuses with the luminal membrane under the influence of ADH, may play at least a contributory role 

Increased renal ammonia production — Hypokalemia increases the tubular production of ammonia and ammonium, which then enter both the tubular lumen and the peritubular capillary . This effect may be related to a transcellular cation exchange: potassium moves out of the cells to partially replete the extracellular stores, with electroneutrality being maintained by the entry of hydrogen and sodium into the cells. The ensuing intracellular acidosis can then stimulate hydrogen secretion and the production of ammonia from glutamine, a process that is similar to that thought to be responsible for the appropriate increase in ammonium excretion in metabolic acidosis . The associated increase in ammonia entry into the renal vein may be clinically important in patients with advanced cirrhosis, possibly precipitating hepatic encephalopathy .

Measurement of the urine sodium concentration is used in many conditions to distinguish between volume depletion (usually being less than 25 meq/L, unless a diuretic is still acting) and euvolemia (greater than 40 meq/L, being equal to intake). However, metabolic alkalosis represents one of the conditions in which volume depletion may not lead to a low urine sodium concentration. The desire to retain sodium in this setting may be counteracted by the desire to excrete bicarbonate (as the sodium or potassium salt) in an attempt to correct the alkalosis . Both decreased reabsorption and increased secretion of bicarbonate may participate in this response
Sodium wasting is particularly likely to occur during the first few days of vomiting, but can also be seen with chronic metabolic alkalosis if the degree of alkalosis is sufficiently severe that the increase in net bicarbonate reabsorptive capacity induced by volume and chloride depletion is insufficient to reabsorb all of the filtered bicarbonate . Early in the course of vomiting, for example, the plasma bicarbonate concentration and therefore the filtered bicarbonate load are increased; however, the ability to enhance bicarbonate reabsorption takes 3 to 4 days to reach its maximum. Thus, there will be increased NaHCO3 delivery to the collecting tubules; at this site, some of the excess sodium is reabsorbed in exchange for potassium in the collecting tubules. The net effect is that the urine will have the following composition:

• High urine sodium and potassium concentrations. These potassium losses are the major cause of hypokalemia with vomiting, since the concentration of potassium in gastric secretions is only 5 to 10 meq/L.
• Urine pH above 7.0 due to the bicarbonaturia.

The urinary findings change dramatically once NaHCO3 reabsorptive capacity has increased, so that all of the filtered bicarbonate can be reabsorbed. At this time, the excretion of sodium, potassium, and bicarbonate are all low and the urine pH is paradoxically acid (less than 5.5) .