A 33-year-old male farmer presented with a history of excessive thirst, weight loss, and increased urine output over the preceding two months. He then developed generalized body weakness, associated with vomiting which occurred 3-5 times a day, over the past 2 weeks prior to admission. The weakness, which was predominantly in the limbs and the neck, worsened over the course of the next two weeks, and on admission he was bed bound. At the time of presentation his motor power was grade 2 in all limbs (unable to move against gravity, movement possible with gravity eliminated[6]), and he was unable to move his neck. The limbs were hypotonic with absent reflexes, and muscle tenderness was present. However, there was no respiratory difficulty, diplopia or dysarthria. He retained his bladder and bowel control. His height was 156 cm and weight was 52 kg (BMI of 21.4 kg/m2). Cardiovascular, respiratory and abdominal examination did not reveal any abnormalities. While this acute episode was dramatic in onset, it was also noted that over the last 2 years he had intermittently complained of ill health, pain in the legs, backache and body pains, and had been off work frequently.
He had no history of any other significant medical or psychiatric comorbidities. There was no other significant illness that required hospitalization or long term treatment during his neonatal period or childhood. He had not been on any long term medication or indigenous medicine. There was no significant family history. He had not used any addictive substances.
His serum potassium level was less than 1 mEq/l (3.5-5.1) at that time of peak paralysis; serum sodium was 135 mEq/l (135-148), chloride 96 mEq/l (95-105). The electrocardiogram at this stage showed flattened P waves, and U waves. His serum creatinine readings were between 80 - 120 μmol/l (60-120) and the random blood sugar was 102 mg/dl (<200). The estimated glomerular filtration rate (eGFR) was between 64-90 ml/min/m2 based on these values. He had neutrophil leucocytosis (total count 18,800 cells/μl with 90% neutrophils). The hemoglobin and platelet counts were within the reference range.
The priority at this stage was correction of his serum potassium. With intravenous replacement of potassium, the muscle power and the overall clinical condition of the patient improved rapidly.
We investigated him for a cause of hypokalemia. The main reasons for hypokalemia are excessive losses (renal or gastrointestinal loss) or redistribution within body compartments. This patient had vomiting and polyuria, hence loss through the gastrointestinal tract or kidneys was considered. Given the protracted history for 2 years, associated with polyuria, polydipsia and weight loss, we considered renal potassium loss to be more likely. Spot urine analysis showed urinary potassium of 24 mEq/l(13-62) and sodium of 120 mEq/l. The patient had a 24 hour urine volume of 3500 ml, and despite severe hypokalemia he was losing potassium in his urine. A subsequent 24-hour urinary potassium level confirmed an abnormally excessive urinary potassium loss of 80 mmol/24 hours despite severe hypokalemia (reference range: 40-100).
Urinalysis revealed a urine pH of 6.5 and 7.5 on two occasions. There were a few calcium oxalate crystals and 2-4 red cells per high power field. There was also a mild hypercalciuria, with a 24-hour urinary calcium excretion of 0.134 mmol/kg (upper limit 0.1 mmol/kg/day). The rest his urinalysis was normal and there was no glycosuria or proteinuria.
At the time of peak paralysis, the arterial blood gas showed a pH of 7.45 (7.35-7.45), pCO2 of 22.4 mmHg (36-44), pO2 of 129 mmHg (80-100), Oxygen saturation of 99%, Bicarbonate of 15.6 mmol/l (22-28), and a base excess of (-)8.6 mEq/l. This picture was suggestive of a compensated metabolic acidosis. He was admitted to the intensive care unit and daily arterial blood gases were performed. These continued to show metabolic acidosis (pH: 7.20-7.25). Plasma anion gap was 12.2 mEq/l (10-14). Thus this patient had normotensive hypokalemia with a normal anion gap (hyperchloremic) metabolic acidosis, and persistently alkaline urine (his urine pH was >5.5 despite metabolic acidosis). The urine anion gap was positive (UNa 120 + UK 24 - UCl 116 = 28). These findings are compatible with renal tubular acidosis (RTA), most likely distal/type 1 RTA (dRTA 1).
While further investigating for a cause for the RTA, renal ultrasound showed bilaterally enlarged kidneys with multiple cysts of varying sizes. Cortical echogenicity was increased with altered cortico-medullary demarcation.
This was investigated further with a computed tomography-intravenous urogram (CT IVU) which revealed enlarged (right -125 mm, left -123 mm) kidneys with variable sized multiple thin walled medullary cysts with no septae in both kidneys (figure 1). The largest cyst measured 30 mm × 25 mm. Fine calcified foci of 1-2 mm were seen in cortices of both kidneys. Similar cysts were not observed in the liver, pancreas or in any other solid organ.
The creatine kinase level in this patient was high (initially 704 IU/l and increased to 1262 IU/L subsequently, reference range: 60-300) probably due to rhabdomyolysis associated with hypokalemia and RTA [5, 7], although this did not result in acute kidney injury (AKI).
Liver transaminases were elevated [AST -151 U/l (10-40) and ALT - 208 U/l (10-40), which could be due to many reasons, related or unrelated to renal tubular acidosis. The possibility of Wilsons disease was considered as it may also present as renal tubular acidosis[7]. However, ophthalmological assessment excluded Kaiser-Fleisher (KF) rings in this patient. Chronic active hepatitis is also known to be associated with renal tubular acidosis and hypokalemia[8].
