Indian Pediatrics 1999; 36:1224-1227 

Hyperkalemic Renal Tubular Acidosis

From the Departments of Pediatrics and Medicine, PD. Hinduja Hospital and Medical Research Centre, Veer Savarkar Marg, Mahim, Mumbai400 016, India.

Reprint requests: Dr. Snehlal Shah, 51, Jashoda Nivas, Nehru Road, Vile Parle (East), Mumbai 400 057, India.

Manuscript Received: January 22, 1998; Initial review completed: March 7, 1998;
Revision Accepted: July 4, 1998.

Renal tubular acidosis (RTA) is a rare cause of acidosis and growth failure in infants. Most of these are hypokalemic RTAs. Hyperkalemic RT A is still a rarer clinical entity. Because of its rarity and difficult diagnostic and therapeutic problems it poses to the clinician, we report here our experiences with two cases of hyperkalemic RTA.

Case Reports

Case 1: A 2^1/2months-old male infant weighing 3^1/2 kg presented with breathlessness, refusal to take feeds and failure to gain weight. He was admitted to another hospital with similar complaints on 7th day and 25th day of life. Both the times he was found to have severe metabolic acidosis, but he was not investigated and was discharged on alkali therapy.

Examination on admission revealed an ill-looking tachypneic infant with respiratory rate of 88/min, heart rate of 140/min and normal temperature. Auscultation of chest revealed normal breath sounds and absence of any adventitious sounds. Rest of the sytemic examination was normal.

Investigations on admission were as follows: Arterial blood gases-pH-7.25, PaCO₂-24.5 mm Hg, PaO₂-93.1 mm Hg, bicarbonate-13.3 mEq/L, serum sodium-135 mEq/L, serum potassium-6.2 mEq/L, serum chloride-108 mEq/L, anion gap-13.7 mEq/L; blood urea nitrogen-30 mg/dl serum creatinine-1.6 mg/ dl, serum ammonia-71 mg/dl, serum calcium-9.6 mg/dl and serum phosphorus 4.8 mg/dl. Urinalysis revealed pH 5.0, specific gravity 1.018, white cells 2-3/HPF-and red blood cells 2-3/HPF. Urine pH was measured by pH meter by collecting urine under mineral oil and sending it to laboratory immediately. The hemoglobin level was 9.3 g/dl white cell count 13,900/cu mm and platelet count 315000/cu mm. Differential white cell count was normal. An ultrasound abdomen showed hypoplastic left kidney in left illac fossa and normal fight kidney. There was no evidence of obstructive uropathy. Urinary bladder and ureters were normal. In view of hyperkalemic hyperchloremic metabolic acidosis with normal anion gap, urine investigations were carried out. Urinary sodium was 24 mEq/L, potassium-30 mEq/L and chloride-34 mEq/L. The urinary anion gap (Sodium + Potassium - Chloride) was therefore 20 mEq/L. Plasma renin activity was elevated at 25.3 ng/ml/hr (normal < 16.6 ng/ml/hr). Plasma aldosterone level was elevated at 9791 pg/ml (normal 10-1600 pg/ml). Urine for metabolic screen was negative. Sickling test was negative. Renal scan showed normal function of right kidney and 80% function of left kidney. Thus, this child had hyperkalmic, hyperchloremic acidosis with an ability to acidify urine pH. below 5.5. This was considered consistent with acidosis associated with hyporeninemia and hypoaldosteronism(1). However, the in- creased renin and aldosterone levels in our case suggested the diagnosis of type IV RTA with pseudohypoaldosteronism(2).

The child was put on daily alkali therapy and kayexalate enema. The acidosis was corrected and potassium came down to normal. The child was discharged on sodium bicarbonate 12 mEq/ day in 3 divided doses orally, oral kayexalate powder in dose of 1 g/kg/ dose 6 hourly and oral calcium supplement of 60 mg/kg/day. On follow up, the child was feeding well and had a weight gain of 1.5 kg over 2 months period. His serum electrolytes were normal, serum bicarbonate was 20 mEq/L and pH was 7.32

Case 2: A SVz-months-old male infant, one of the triplet, weighing 3.5 kg was brought with complaints of failure to thrive, excessive crying and refusal to take feeds. On examination, the child was malnourished and tachypneic with a respiratory rate of 68/min. The temperature was 101^oF. The lungs were clear on examination. The rest of systemic examination was normal.

The investigations revealed serum pH- 7.29, PaCO₂-33.3 mm Hg, PaO₂-78 mm Hg, serum bicarbonate-12 mEq/L, sodium-133 mEq/L, potassium-6.0 mEq/L, chloride- 110 mEq/L, serum anion gap [Sodium- (Chloride + Bicarbonate)]-11 mEq/L, blood urea nitrogen-16 mg/dl serum creatinine- 0.4 mg/dl serum ammonia-88 mg/dl serum calcium-8.3 mg/dl and serum phosphorus-3.2 mg/dl. Routine urinalysis revealed pH of 6.8, specific gravity of 1.010, no red cells or white cell. The hemoglobin was 9.6 g/dl, white cell count was 10,100/ cu mm and platelets were 2,57,000/cu mm.

The differential white cell count was normal. The sickling test was negative. Urinary sodium was 60 mEq/L, potassium was 44. mEq/L and chloride was 61 mEq/L. The urinary anion gap therefore was 43 (Sodium + Potassium - Chloride). Urine for metabolic screen was negative. Plasma renin activity and aldosterone levels were normal.

Urine pH was measured by pH meter after collecting urine under mineral oil and sending it to laboratory immediately. Thus, this child had hyperkalemic metabolic acidosis with normal anion gap and failure to acidify urine (Urine pH >6.8) with normal level of renin and aldosterone. The findings are consistent with a diagnosis of hyperkalemic distal RTA.

The child was put on daily alkali therapy, sodium bicarbonate orally in dose of 12 mEq/ day and kayexalate powder orally in a dose of 1 g/kg/ dose 6 hourly. On follow up, the child weighed 6 kg at the age of 7 months and had no further episode of acidosis. His electrolytes and acid base values were normal.

Discussion

Both the cases were brought with severe metabolic acidosis with hyperkalemia with normal plasma anion gap (8-16 mEq/L). The normal plasma anion gap rules out acidosis due to overproduction of endogneous acids or underexcretion of fixed acids as in case of inborn errors of metabolism or acute or chronic renal failure(1). A normal anion gap acidosis results from the net loss of bicarbonate either from kidney (e.g., renal tubular acidosis or nephrotoxin related) or gastrointestinal tract, mainly from diarrhea(1). As there was no gastrointestinal loss, renal etiology was suspected in both cases.

In the first case, urine pH of < 5.8, ruled out distal RTA as etiology. The elevated urinary anion gap and hyperkalemia also ruled out proximal RTA, which is usually associated with normal or negative urinary anion gap and hypokalemia(2). Hence type IV RTA was suspected. Type IV RTA can be anyone of the three sub-types which can be identified on the basis of plasma aldosterone and renin levels (Table I). As our case had increased levels of both renin and aldosterone, it obviously is of the subtype caused by psuedohypoaldosteronism(l). In this cases, there is resistance to aldosterone action due to receptor defect. It is usually seen in young boys, and has autosomal recessive mode of inhritance(3). Aldosterone has a direct effect on sodium channel causing active transport of sodium from the interior of the tubular epithelial cell into the interstitial fluid at the lateral intercellular spaces. This Na+ transport out of the cell creates a very low concentration of sodium inside cell and negative electrical potential of -70 mv within cell, which attracts positively charged potassium ion into the cell. Once potassium enters the cell, it diffuses into tubular lumen leading to K+ secretion(4). Aldosterone also stimulates proton pump directly leading to H+ excretion(5). In state of deficiency of aldosterone or in a state resistance to aldostorone, the electronegative potential required for potassium and hydrogeh ion excretion does not develop, leading to impaired H+ and K+ excretion and thus causing hyperkalemic metabolic acidosis(5). In second case, elevated urine anion gap ruled out proximal RTA and urine pH of >5.8 ruled out type IV RTA. Hence diagnosis of distal RTA was made. Associated hyperkalemia suggested diagnosis of hyperkalemic distal RTA due to 'voltage dependent defect'(3).
 

The principal cells constitute 60% of cells in the distal tubule and collecting tubules. The entry of luminal Na+ into these cells occurs primarily down a concentration gradient through non-specific Na+ channel in luminal membrane. In comparison with the electroneutral Na+K+-2Cl- and Na+-CI- entry mechanism in thick ascending limb and early distal tubule, movement through this N a + channel is electrogenic in that it creates lumen negative potential difference, which promotes H+ and K+ secretion. In hyperkalemic distal RT A, there is a defect in Na+ reabsorption via renal collecting tubule through Na+ channels described above. Due to this Na+ channel defect, lumen -ve voltage gradient required for H+ and K+ secretion does not develop. Hence this defect is called "Voltage dependent defect"(4). This is reflected by inability to secrete hydrogen and potassium ion, which results in an inability to both lower urine pH and to excrete potassium. Thus it leads to hyperkalemic metabolic acidosis(5). The decrease in net acid excretion is also due to decrease in ammonia synthesis secondary to hyperkalemia in both cases(6).

The mainstay of treatment in both cases are sodium bicarbonate supplementation to correct acidosis, potassium exchange resin for hyperkalemia and calcium supplementation(7). Some of the patients of type IV RTA may outgrow their defect with age(8).


 

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