Hyporeninemic hypoaldosteronism in a patient with multiple myeloma

A patient with progressive renal failure due to multiple myeloma presented with a mixed acid-base disorder (non-anion gap acidosis and respiratory alkalosis) with persistent severe hyperkalemia. Studies revealed an intact ability to lower urine pH during acid loading, markedly decreased plasma renin and aldosterone concentrations despite volume depletion, and an inappropriately low fractional excretion of potassium. Renal biopsy demonstrated plasma cell infiltration of the renal interstitium and typical proteinaceous intratubular casts. Both proximal and distal renal tubular acidification defects have been described previously in patients with multiple myeloma, but this is the first report of hyporeninemic hypoaldosteronism, hyperkalemia, and hyperchloremic metabolic acidosis in association with renal involvement in multiple myeloma.     

Primary role of hyperkalemia in the acidosis of hyporeninemic hypoaldosteronism

A 65-year-old woman with mild renal insufficiency had persistent hyperkalemia and hyperchloremic acidosis. Her plasma aldosterone level was relatively low for her hyperkalemia, and her urine pH was low. Fludrocortisone acetate administration corrected both hyperkalemia and acidosis by increasing urinary excretion of potassium and net acid, implicating deficient mineralocorticoid activity in the distal renal tubule in this patient. During this medication urinary ammonium excretion increased, but urine pH remained low, so that urinary titratable acid excretion did not decrease. On the other hand, correction of hyperkalemia by administration of a potassium-calcium exchange resin alone also resolved the acidosis by increasing urinary ammonium excretion. This increment exceeded the decrement of urinary titratable acid excretion, which was caused by raised urine pH secondary to increased urinary ammonium excretion, and resulted in increase of net acid excretion. Thus, in this patient, hyperkalemia appears to be a decisive causative factor in the acidosis, with deficient mineralocorticoid effect only contributing in part to the reduction of net acid excretion and the acidosis.     

On the mechanism of impaired distal acidification in hyperkalemic renal tubular acidosis: evaluation with amiloride and bumetanide.

It has been postulated that a distinctive type of hyperkalemic distal renal tubular acidosis (DRTA), referred to as voltage-dependent DRTA, results from diminished potassium and hydrogen ion secretion in the distal nephron, which is due to a suboptimal voltage (lumen negative) as a result of impaired sodium reabsorption. To test for the presence of a voltage-dependent DRTA, we used amiloride (20 mg oral, single dose) and bumetanide (2 mg oral, single dose) to inhibit and to stimulate voltage-dependent potassium and hydrogen ion secretion, respectively. Eighteen patients with hyperkalemic DRTA and seven controls with a comparable degree of renal impairment were studied. Patients were subdivided in two groups on the basis of their ability to lower their urine pH during spontaneous acidosis. Patients in Group I lowered their urine pH to the level of controls (5.29 +/- 0.06 and 5.37 +/- 0.11, respectively) whereas patients in Group II could not lower their urine pH below 5.5 (6.38 +/- 0.11). Patients in Group I and Group II had a similar degree of metabolic acidosis and hyperkalemia whereas controls had neither acidosis or hyperkalemia. Most patients in Group II and all patients in Group I had low plasma aldosterone levels. The administration of amiloride resulted in an increase in urine pH and a decrease in potassium excretion in all three groups. The finding that amiloride, presumably by obliterating the transtubular voltage as a result of blockade of sodium transport, inhibited potassium excretion to about the same extent in both groups of patients and in controls argues against the existence of a voltage-dependent defect. Bumetanide produced a fall in urine pH below 5.5 and an increase in potassium excretion in controls and Group I patients. In Group II patients, bumetanide failed to elicit a fall in urine pH below 5.5 but resulted in an increase in potassium excretion similar to that seen in controls and Group I patients. These findings suggest that a derangement other than a voltage-dependent defect is responsible for the inability, characteristic of Group II patients, to lower their urine pH. It was concluded that the impairment in urinary acidification observed in patients with this subtype of hyperkalemic DRTA is due to a defect in collecting tubule hydrogen secretion that results from H+ ATPase dysfunction rather than from a voltage-dependent defect.     

The Spitzer-Weinstein syndrome: one form of type IV renal tubular acidosis and its response to hydrochlorothiazide

A twelve-year-old girl with persistent hyperkalemia, metabolic acidosis, normal blood pressure and glomerular filtration rate, and short stature (first percentile for height) was studied using metabolic balance techniques. Prior to therapy with hydrochlorothiazide (HCTZ), urinary potassium and acid excretion were low and urine pH was inappropriately high at 5.8. HCTZ (25 mg orally per day) (1 mg/kg) was then started and rapidly corrected her serum electrolytes. The therapy with HCTZ was associated with a diuresis, a decrease in urine pH to 4.8, and concomitant increases in potassium, titratable acid (TA) and ammonium excretion. The increase in TA excretion was explicable, in part, to the decrease in urine pH and, in part, to the considerable increase in phosphate excretion (from 56 to 81 mmol/d). Plasma renin activity and plasma aldosterone increased markedly following HCTZ but urinary prostaglandin E (PGE) excretion was unchanged. These observations suggest that administration of HCTZ in this setting increases hydrogen ion secretion. It is unclear whether this effect is a direct consequence of HCTZ at the level of the tubule or is secondary to some other action of HCTZ. However, it is clear that this effect is not related to an alteration in PGE excretion.     

Acute increase in plasma osmolality as a cause of hyperkalemia in patients with renal failure

These studies were performed in patients with chronic renal failure to understand the mechanism(s) of hyperkalemia secondary to hypertonic NaCl infusion. In 10 patients, after intravenous infusion of either 5% or 2.5% NaCl (6 mEq per kg body wt for 120 minutes in both solutions), the maximum increase in plasma potassium averaged 0.6 (range 0.3 to 1.3) mmol/liter (P less than 0.01) or 0.3 (range 0.2 to 0.6) mmol/liter (P less than 0.01), respectively. The rise of both plasma potassium and osmolality was significantly higher during 5% NaCl than during 2.5% NaCl infusion (P less than 0.01). A significant linear correlation (P less than 0.01) between plasma potassium and osmolality was observed. Urinary potassium excretion was increased to a similar extent by 5% NaCl and 2.5% NaCl infusion. The observed hyperkalemia, secondary to NaCl infusion, was independent of venous pH, plasma bicarbonate, anion gap, insulin levels, and urinary norepinephrine and epinephrine excretion, and was associated with a fall in plasma aldosterone concentration. In separate studies, nine patients were treated with desoxycorticosterone acetate (DOCA; 20 mg i.m. for three days) before receiving saline (5%) infusion. DOCA did not prevent the level increase in plasma potassium that remained significantly correlated with plasma osmolality (P less than 0.01). In conclusion, hypertonic NaCl infusion in patients with renal failure causes a clinically relevant hyperkalemia despite increased renal excretion of potassium. This hyperkalemia is independent of acid-base or hormonal mechanisms known to regulate extrarenal homeostasis of potassium, and is strictly correlated with a rise in plasma osmolality.     

Recurrent hyperkalemia in the course of rheumatoid arthritis--a case report]

A 69-year-old woman with advanced rheumatoid arthritis (RA) suffered two episodes of hyperkalemic hyperchloremic metabolic acidosis (HCMA). Plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were markedly suppressed in the first episode occurring in paralell with the administration of metoprolol during piroxicam and lobenzarit (CCA) therapy. Rechallenge with diclofenac sodium and CCA lead to the second hyperkalemia, but no significant suppression of the renin-aldosterone axis was seen at that time. This suggests that the different mechanisms contribute to the development of these episodes, including the tubulo-interstitial injury which is not uncommon in RA. The combined use of nonsteroidal anti-inflammatory drugs (NSAIDs) and beta-adrenergic blockers may increase the risk of life-threatening hyperkalemia through their suppressive effect on the renin-aldosterone system, whereas the concomitant administration of CCA with NSAIDs through the impairment in the renal tubular function. These drugs should be most carefully given to patients with a latent defect in renal potassium excretion.     

The plasma potassium concentration in metabolic acidosis: a re-evaluation

The purpose of these investigations was to describe the mechanisms responsible for the change in the plasma [K] during the development and maintenance of hyperchloremic metabolic acidosis. Acute metabolic acidosis produced by HCI infusion resulted in a prompt rise in the plasma [K], whereas no change was observed during acute respiratory acidosis in the dog. After 3 to 5 days of acidosis due to NH4Cl feeding, dogs became hypokalemic; this fall in the plasma [K] was due largely to increased urine K excretion. Despite hypokalemia, aldosterone levels were not low, and the calculated transtubular [K] gradient was relatively high, suggesting renal aldosterone action. Thus, rather than anticipating hyperkalemia in patients with chronic metabolic acidosis due to a HCl load, the finding of hyperkalemia should suggest that the rate of urinary K excretion is lower than expected (ie, there are low aldosterone levels or failure of the kidney to respond to this hormone).     

Correction of hyperkalemia by bicarbonate despite constant blood pH.

Patients having hyperkalemia often are given bicarbonate to raise blood pH and shift extracellular potassium into cells. Blood pH in many hyperkalemic patients, however, is compensated. To determine whether bicarbonate, independent of its pH action, affects plasma potassium, 14 hyperkalemic patients were treated with bicarbonate in 5% dextrose. In five patients (changed pH group), blood pH rose at least 0.08, while in nine (constant pH group), it changed less than 0.04. In the first group, pH rose 0.12, bicarbonate rose 5.9 mEq/liter, and plasma potassium fell 1.6 mEq/liter, and plasma potassium fell 1.4 mEq/liter. The correlation between changes in plasma potassium and bicarbonate was identical in the two groups and independent of urinary potassium excretion. Four additional patients, who were treated with 5% dextrose alone, did not significantly lower their plasma potassium, although subsequent treatment with bicarbonate in 5% dextrose lowered their plasma potassium. Thus, bicarbonate lowers plasma potassium, independent of its effect on blood pH, and despite a risk of volume overload, should be used to treat hyperkalemia in compensated acid-base disorders, even in the presence of renal failure, provided the plasma bicarbonate concentration is decreased.     

Hyperkalemia in the elderly

Physiologic and pathologic events that occur in patients as they grow older may result in distal renal tubular dysfunction, as well as decreased levels of plasma renin activity and plasma aldosterone. Such alterations result in a tendency toward hyperkalemia. A syndrome termed hyporeninemic hypoaldosteronism, associated with hyperkalemia, has been frequently described in elderly patients. The common occurrence of hyperkalemia in the elderly may be aggravated by the use of drugs that either further suppress renin and/or aldosterone or interfere with distal tubular potassium excretion. Some patients with hyporeninemic hypoaldosteronism respond to diuretic therapy. The recognition of the possible development of severe hyperkalemia in the elderly patient may avoid serious and even fatal complications of this electrolyte disorder.     

Mechanism of the metabolic acidosis of selective mineralocorticoid deficiency.

The mechanism of generation of metabolic acidosis in selective mineralocorticoid deficiency was investigated in bilaterally adrenalectomized (ADX) rats treated with dexamethasone and in sham-operated (S) rats. ADX rats had significantly lower plasma sodium and bicarbonate concentrations and significantly higher plasma potassium concentrations than S rats did. ADX rats developed negative sodium balance when fed a "zero" sodium diet. The minimum urine pH achieved during sodium sulfate infusion and during ammonium chloride administration was not significantly different between ADX and S rats. Bicarbonate reabsorption and urine minus blood PCO2 gradient were not different between ADX and S rats. For any given urine pH, absolute ammonium excretion was significantly lower in ADX than it was in S rats, both during sodium sulfate infusion and during chronic ammonium chloride administration. Glomerular filtration rate (GFR) was significantly lower in ADX than it was in S rats; ammonium excretion corrected for GFR was not different between the two groups. To determine the role of decreased distal sodium delivery (secondary to decrease in GFR and enhanced proximal sodium reabsorption which resulted from distal sodium chloride wastage) on ammonium excretion, ADX rats were fed 0.9% sodium chloride in an effort to keep body weight constant. Salt-loaded ADX rats had a plasma bicarbonate concentration higher than did S rats. Salt-loading also led to a significant increase in GFR; absolute ammonium excretion was significantly higher than that of other ADX rats with the same degree of acidosis. At comparable levels of GFR, there was no difference in ammonium excretion between ADX and S rats. Ammonium excretion was linearly related to GFR. ADX rats fed a zero potassium diet had significantly greater ammonium excretion than did all other groups of ADX or S rats receiving a normal potassium intake. These data suggest that volume contraction is a major factor responsible for the acidosis of selective mineralocorticoid deficiency.     

Pseudohypoaldosteronism type II: proximal renal tubular acidosis and dDAVP-sensitive renal hyperkalemia

The mechanisms of metabolic acidosis and hyperkalemia were investigated in a patient with chronic mineralocorticoid-resistant renal hyperkalemia (5.3-6.9 mmol/l), metabolic acidosis (arterial blood pH 7.27, total CO2 17 mmol/l), arterial hypertension, undetectable plasma renin activity (less than 0.10 ng/ml/h), high plasma aldosterone level (32-100 ng/dl), and normal glomerular filtration rate (131 ml/min/1.73 m2). During the hyperkalemic period, urine was highly acidic (pH 4.6-5.0), urinary NH4 excretion (10-13 microEq/min) and urinary net acid excretion (19-24 microEq/min) were not supernormal as expected from a chronic acid load. During NaHCO3 infusion, the maximal tubular HCO3 reabsorption was markedly diminished (19.8 mmol/l glomerular filtrate), and the fractional excretion of HCO3 (FE HCO3) when plasma HCO3 was normalized was 20%. Urine minus blood PCO2 increased normally during NaHCO3 infusion (31 mm Hg), and the urinary pH remained maximally low (less than 5.3) when the buffer urinary excretion sharply increased after NH4Cl load. When serum K was returned toward normal limits, metabolic acidosis disappeared, urinary NH4 excretion rose normally after short NH4Cl loading while the urinary pH remained maximally low (4.9-5.2), the maximal tubular HCO3 reabsorption returned to normal values (24.8 mmol/l glomerular filtrate), and FE HCO3 at normal plasma HCO3 was 1%. Nasal insufflation of 1-desamino-8-D-Arginine Vasopressin (dDAVP) resulted in an acute normalization of the renal handling of K and in an increase in net urinary acid excretion. We conclude that: the effect of dDAVP on renal handling of K may be explained by the reversal of the distal chloride shunt and/or an increase in luminal membrane conductance to K; the distal acidification seems to be normal which in the event of distal chloride shunt impairing distal hydrogen secretion might be explained by the presence of systemic acidosis which is a potent stimulus of hydrogen secretion, and metabolic acidosis in the steady state was accounted for by the diminution of bicarbonate reabsorption and ammonia production in the proximal tubule secondary to chronic hyperkalemia.     

Hyperkalemia in patients infected with the human immunodeficiency virus: involvement of a systemic mechanism.

BACKGROUND: The appearance of hyperkalemia has been described in human immunodeficiency virus (HIV)-positive patients treated with drugs with amiloride-like properties. Recent in vitro data suggest that individuals infected with HIV have alterations in transcellular K+ transport. METHODS: With the objective of examining the presence of alterations in transmembrane K+ equilibrium in HIV-positive patients, we designed a prospective, interventional study involving 10 HIV-positive individuals and 10 healthy controls, all with normal renal function. An infusion of L-arginine (6%, intravenously, in four 30-min periods at 50, 100, 200, and 300 ml/hr) was administered, and plasma and urine electrolytes, creatinine, pH and osmolality, total and fractional sodium and potassium excretion, transtubular potassium gradient, plasma insulin, renin, aldosterone, and cortisol were measured. RESULTS: A primary disturbance consisting of a significant rise in plasma [K+] induced by L-arginine was detected in only the HIV patients but not in the controls (P < 0.001 between groups). A K+ redistribution origin of the hyperkalemia was supported by its rapid development (within 60 min) and the lack of significant differences between HIV-positive individuals and controls in the amount of K+ excreted in the urine. The fact that the HIV-positive individuals had an inhibited aldosterone response to the increase in plasma K+ suggested a putative mechanism for the deranged K+ response. CONCLUSIONS: These results reveal that HIV-infected individuals have a significant abnormality in systemic K+ equilibrium. This abnormality, which leads to the development of hyperkalemia after the L-arginine challenge, may be related, in part, to a failure in the aldosterone response to hyperkalemia. These results provide a new basis for understanding the pathogenesis of hyperkalemia in HIV individuals, and demonstrate that the risk of HIV-associated hyperkalemia exists even in the absence of amiloride-mimicking drugs or overt hyporeninemic hypoaldosteronism.     

Atrial natriuretic peptide and response to changing plasma volume in diabetic nephropathy.

We evaluated the renal and hormonal responses to volume expansion induced by water immersion in subjects with diabetic nephropathy (n = 12) and in healthy control subjects (n = 9). Immersion induced similar average increments in sodium excretion (+/- 223 vs. 176 mumol/min) and comparable decrements in renovascular resistance (RVR; -15 vs. -16 U). However, whereas the control subjects responded uniformly, the response among diabetic subjects was highly variable, with a subset of patients exhibiting paradoxical antinatriuresis and vasoconstriction. Immersion was associated with marked elevation of atrial natriuretic peptide (ANP) in plasma of diabetic versus control subjects (61 +/- 9 vs. 19 +/- 2 pM, respectively; P less than 0.001). Yet for each picomolar increment in plasma ANP during immersion, the corresponding increases in urinary excretion of cyclic guanosine monophosphate (26 vs. 279 pmol/min) and sodium (9 vs. 47 mumol/min) and the reciprocal lowering of RVR (0.7 vs. 1.9 U) were blunted in the diabetic versus control group. Volume contraction in the postimmersion period was associated with disproportionate antinatriuresis and renal vasoconstriction in the diabetic group, despite a persistent elevation of ANP (29 +/- 2 vs. 16 +/- 2 pM, P less than 0.01). We propose that renal insensitivity to ANP in diabetic nephropathy could contribute to altered vasoreactivity and abnormal excretory responsiveness to changing plasma volume. Blunted natriuresis in response to ANP release and enhanced sodium retention during volume contraction could account for the expanded extracellular fluid volume that has consistently been reported to accompany the development of diabetic nephropathy.     

Vasoactive hormones in the renal response to systemic sepsis

The pathophysiology of renal dysfunction in generalized sepsis remains unknown. In this study, 24 hours after surgical induction of peritonitis in 20 volume-loaded sheep, three patterns of renal function were seen. In group 1 (n = 8), glomerular filtration rate (GFR) decreased by 70%, urine volume by 85%, absolute sodium excretion by 95%, and fractional sodium excretion by 83%. Group 2 (n = 4) exhibited similar sodium retention but GFR did not fall. Group 3 (n = 8) showed no change in GFR or urine volume and only minimally reduced sodium excretion. Mean arterial pressure fell 17% in group 1 only; central venous pressure, pulmonary capillary wedge pressure, and plasma volume were maintained at or above presepsis values in all groups. Cardiac index was either increased or unchanged, and renal plasma flow was maintained in all groups; there was thus no hemodynamic evidence to suggest volume contraction. Histologic examination showed only minor changes with no consistent pattern. Renal functional changes correlated with other manifestations of severe sepsis--GFR and sodium retention correlated significantly with increased cardiac index, decreased systemic vascular resistance, pulmonary arterial hypertension, leukopenia, hypoproteinemia, and hypoglycemia. All of these changes were most marked in group 1. In groups 1 and 2, plasma renin activity (PRA) increased and urinary kallikrein excretion decreased. PRA correlated inversely with GFR, urine volume, and sodium excretion; urinary kallikrein excretion correlated positively with urine volume and sodium excretion. Urinary excretion of 6-keto-PGF1 alpha was increased in groups 1 and 2 and correlated inversely with mean arterial pressure in group 1 animals. During sepsis, urinary thromboxane B2 excretion continued at presepsis values in all groups. The results suggest that unusual reciprocal changes in activity of the renin-angiotensin and renal kallikrein-kinin systems may play a role in the renal response to sepsis. PGI2 synthesis is increased and may affect systemic hemodynamics and renal function; the role of thromboxane A2 in this context is unknown.     

Hyperkalemic renal tubular acidosis: effect of furosemide in humans and in rats

Furosemide increases urinary acidification in control subjects and in certain patients with normokalemic or hypokalemic distal renal tubular acidosis (RTA). We studied the effect of furosemide in 14 patients with hyperkalemic distal RTA. In a group of patients with pure selective aldosterone deficiency, furosemide increased net acid and K excretion in a fashion indistinguishable from controls. This effect of furosemide was observed both in the presence and in the absence of acute mineralocorticoid administration. In another group of patients with hyperkalemic distal RTA, furosemide failed to decrease urine pH and to increase net acid excretion despite acute mineralocorticoid administration. Plasma aldosterone was variable in this group in that some patients had appropriate levels of aldosterone for the degree of hyperkalemia, whereas in the other patients the levels were low. The failure of these patients to respond to furosemide, despite pharmacologic doses of mineralocorticoid, suggests that these patients had a defect in H+ secretion other than that attributable to aldosterone deficiency alone. To gain insight into the mechanism whereby furosemide increases urinary acidification, we studied control and amiloride-treated rats pretreated with mineralocorticoid. In response to furosemide, control rats had a significantly lower urine pH and higher net acid and K excretion than that observed in amiloride-treated rats. These data suggest that furosemide increases H+ and K excretion, at least in part, by creating a favorable electric gradient for secretion of these ions since these effects were blunted in presence of inhibition of distal Na transport by amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)     

A case of lupus nephritis with hyporeninemic hypoaldosteronism]

We report a case of 67-year-old woman with systemic lupus erythematosus presenting hyporeninemic hypoaldosteronism. She admitted because of anasarca in March, 1990. She manifested nephrotic syndrome, and hyperkalemia and hyperchloremic metabolic acidosis. The hyperkalemia was disproportionate to the degree of renal insufficiency. Basal levels of plasma renin activity and plasma aldosterone concentration were low. Renal tubular function studies revealed normal hydrogen ion secretion. Renal biopsy demonstrated diffuse proliferative lupus nephritis and prominent interstitial cell infiltration. There was no vasculitis of glomerular vascular poles. After treatment of lupus nephritis with prednisolone, levels of plasma renin activity and plasma aldosterone concentration were elevated. Hyperkalemia and metabolic acidosis were normalized and renal function improved. We conclude that the heperkalemia and metabolic acidosis could be attributed to hyporeninemic hypoaldosteronism.     

A comparison of the effects of potassium citrate and sodium bicarbonate in the alkalinization of urine in homozygous cystinuria

For many years, urine alkalinization has been one of the cornerstones in the treatment of homozygous cystinuria. Because of the relationship found between the excretion of urinary sodium and cystine, potassium citrate has emerged as the preferred sodium-free alkalizing agent. To evaluate the usefulness of potassium citrate for urine alkalization in cystinuric patients, sodium bicarbonate and potassium citrate were compared in 14 patients (10 on tiopronin treatment and four without treatment with sulfhydryl compounds). The study started with 1 week without the use of any alkalizing agents (Period 0) followed by 2 weeks with sodium bicarbonate (Period 1) and 2 weeks with potassium citrate (Period 2). Urinary pH, volume, excretion of sodium, potassium, citrate and free cystine, as well as the plasma potassium concentration, were recorded. Potassium citrate was shown to be effective as an alkalizing agent and, in this respect, not significantly different from sodium bicarbonate. Even though a normal diet was used, a significant increase in urinary sodium excretion was observed with sodium bicarbonate (Period 1). Urinary potassium and citrate excretion increased with potassium citrate (Period 2). A significant correlation was found between urinary sodium and cystine in the tio-pronin-treated patients. No significant differences in cystine excretion were recorded in Periods 0, 1 and 2. Plasma potassium was significantly higher during Period 2, but only one patient developed a mild hyperkalemia (5.0 mmol/l). The use of potassium citrate for urine alkalization in homozygous cystinuria is effective and can be recommended in the absence of severe renal impairment.     

Reversible suppression of the renin-aldosterone axis after unilateral adrenalectomy for adrenal adenoma

Reduced adrenocortical (aldosterone and cortisol) and adrenomedullary (adrenaline) secretory mass after unilateral adrenalectomy for aldosterone-producing adenoma has been associated with long-term hypotension (more than 2 years) in some studies. In these patients, cortisol and aldosterone levels are low, whereas plasma renin activity is high. Other studies suggest that normotension and normal plasma renin activity and serum aldosterone and cortisol levels are achieved in 60% to 87% of the patients without evidence of decreased adrenal mass, whereas the remaining patients may continue to have hypertension. We report a unique case in which unilateral adrenalectomy for adrenal adenoma was followed by severe hyperkalemia, marked volume depletion and undetectable plasma renin activity, and serum aldosterone, suggesting marked, chronic suppression of the renin-aldosterone axis. One year later, a gradual return to normokalemia, normotension, and normal plasma renin activity and aldosterone levels was achieved, indicating resolution of the suppression of the renin-aldosterone axis. Patients undergoing unilateral adrenalectomy for aldosteronoma should be followed up closely after unilateral adrenalectomy of adrenal adenoma to avoid life-threatening hyperkalemia and severe intravascular volume depletion.     

The effect of trimethoprim on potassium and uric acid metabolism in normal human subjects

BACKGROUND: Trimethoprim used in combination with other antibiotics, has been implicated in causing hyperkalemia and hypouricemia in patients with acquired immune deficiency syndrome (AIDS). In experimental animal models, trimethoprim has been demonstrated to block sodium channels and Na+-K+-ATPase in the distal nephron and thus impair potassium excretion. Although the data from the experimental models suggest that trimethoprim reduces urinary potassium excretion, the retrospective clinical studies have confounding factors that prevent a rigorous demonstration that the hyperkalemia and hypouricemia are due solely to the effects of trimethoprim on solute excretion. AIM: The purpose of this study was to evaluate the effect of trimethoprim on potassium and uric acid balance in normal human subjects. METHODS: Five normal human subjects were admitted to the general clinical research center and placed on a fixed metabolic diet. After a 4-day control period, the subjects were given trimethoprim (15 mg/kg/day) orally for 5-7 days followed by a 4-day recovery period. Free-flow blood samples and 24-hour urine collections were obtained daily. RESULTS: Treatment with trimethoprim resulted in a significant increase in plasma potassium concentration (4.5 +/- 0.1 versus 3.7 +/- 0.1 mmol/l, p < 0.005) and significant decrease in serum uric acid concentration (3.8 +/- 0.4 versus 5.6 +/- 0.5 mg/dl, p < 0.001). Treatment with trimethoprim significantly increased the urinary excretion of uric acid, but did not significantly decrease potassium excretion during the 7-day treatment period. There was, however, a significant decrease in potassium excretion observed during the first 48 hours of trimethoprim treatment. In one subject where repeat studies were performed using different dosages, the effect on potassium and uric acid levels appeared to be dose-dependent. CONCLUSIONS: Trimethoprim increases plasma potassium concentration probably by reducing urinary potassium excretion. Trimethoprim decreases serum uric acid levels by augmenting urinary uric acid excretion. This uricosuric effect may be due to the ability of trimethoprim to impair urate reabsorption by the urate-anion exchanger in the proximal tubule.     

Isohydric regulation of plasma potassium by bicarbonate in the rat.

pH and bicarbonate affect many metabolic reactions but each may change independently. To study bicarbonate's effect onplasma potassium, blood bicarbonate in normal, hypokalemic or hyperkalemic rats was either maintained constant, lowered by hydrochloric acid or raised by sodium bicarbonate administraion. Blood pH was maintained constant by changing PCO2. In normokalemia lowering bicarbonate increased plasma potassium 2.0mEq above values obtained in the other groups. To eliminate urinary potassium losses, experiments were also performed in rats with bilateral ureteral ligation. Again, plasma potassium concentration rose significantly more in the lowered bicarbonate group. Similarly, in hypokalemia, plasma potassium rose 1.2 and 0.4mEq in the lowered and unchanged groups, but fell 0.2mEq/liter in the elevated group. Differences could not be ascribed to renal potassium losses as potassium excretion was essentially zero in each group. In hyperkalemia, plasma potassium concentration remained elevated for 150 min in the lowered bicarbonate group but fell 1.3 and 2.0mEq in the unchanged and elevated groups, respectively. Urinary potassium losses in the three groups were statistically identical. In all experiments blood pH was maintained unchanged during the experiment. The data show that bicarbonate, independent of blood pH, alters transcellular potassium distribution suggesting the usefulness of bicarbonate therapy in hyperkalemia even at a compensated blood pH.