Type 3 renal tubular acidosis
A 44-year-old man presented with flaccid paralysis of all four limbs, and tetanic spasm of the hand. He had a history of a similar episode 1 year ago that progressed to respiratory paralysis, needing assisted ventilation. The past episode was attributed to hypokalemia and hypocalcemia. He received treatment outside, under an empirical diagnosis of familial periodic paralysis (FPP), with oral potassium and calcium supplementation, with acetazolamide to combat muscle weakness. The patient was stringently taking the drugs.\nHe was normotensive (120/80 mmHg ± 8/4 mmHg), with normal blood sugar (fasting 86 mg/dL, post prandial 112 mg/dL), and normal renal function (urea 11 mg/dL and creatinine 0.6 mg/dL). The present episode was also associated with persistent hypokalemia (K+ 1.8 (±0.45) mmol/L) and hypocalcemia []. Arterial blood gas showed hyperchloremic metabolic acidosis (plasma HCO 3\n- 12.0 mEq/L, pH 7.21, anion gap 12 mEq/L). Abdominal ultrasonography revealed bilateral nephrocalcinosis. Routine urinalysis showed glycosuria and 3+ proteinuria by dipstick.\nHistorically, we excluded important extrarenal causes of hypokalemia such as chronic diarrhea or laxative abuse. Documented normotension excluded aldosteronism, Cushing's syndrome, congenital adrenal hyperplasia, renovascular hypertension, and Liddle syndrome.[]\nNext, urinary electrolytes were measured with calculation of the following parameters []:\nUK/UCr = Urine potassium (mmol/day) divided by urine creatinine (mmol/day) Trans tubular potassium gradient (TTKG) = (UK/PlasmaK)/(UOsmolarity/POsmolarity) Urine anion gap (UAG) = UNa + UK – UCl\nThe high UK/UCr (>1.5) and TTKG (>5) with positive UAG suggested renal potassium loss and acidification defect.[–] Urine pH was 6.7 in the face of systemic acidosis (arterial blood pH = 7.21). These along with bilateral nephrocalcinosis suggested a diagnosis of distal or type 1 RTA (dRTA). His liver (bilirubin – 0.4 mg/dL, alanine aminotransferase 23 IU/L, aspartate aminotransferase 27 IU/L) and thyroid function tests (thyroid stimulating hormone level 1.2 μIU/mL, free thyroxine level 0.9 ng/dL) were normal. Serum vitamin D level was 23.45 (normal 8-40) ng/mL and serum parathormone level was 55 (normal 10-65) pg/mL. Serum protein electrophoresis, antinuclear antibody, anti-dsDNA, anti-Ro, and anti-La; antimitochondrial antibodies; and antithyroid peroxidase and antithyroglobulin antibodies were all negative.\nNext, we measured beta-2 microglobulin concentration in a 24-h urinary sample and urinary albumin to creatinine ratio (UACR). High beta-2 microglobulin and low UACR levels established proximal tubular dysfunction.[]\nTo further consolidate the diagnosis, we put the patient on oral Shohl's solution (custom-made by in-house biochemistry department providing 1 mEq/mL of alkali) at a dose of 10 mEq/Kg body weight of HCO3- for 2 weeks, which restored arterial potassium level to 22 mEq/L. We then estimated fractional excretion of HCO3-, which came out to be 24%. Tubular reabsorption of phosphate was determined to be 78%. These, along with qualitative demonstration of glycosuria by Benedict's method, established a proximal tubular origin of acidosis as well.\nThus, we finally determined that the patient was suffering from combined or type 3 RTA, presumably from inappropriate acetazolamide therapy.\nThe patient was weaned from acetazolamide. He was put on oral Shohl's solution with potassium supplementation. Muscle weakness improved and he was finally discharged. He has been on follow-up for 6 months without any further episode of muscle weakness.