Year : 2009 | Volume
: 20 | Issue : 2 | Page : 274--277
Inherited renal tubular defects with hypokalemia
J Muthukrishnan1, KD Modi1, P Jagdish Kumar2, Ratan Jha2,
1 Department of Endocrinology, Medwin Hospitals, Hyderabad, India
2 Department of Nephrology, Medwin Hospitals, Hyderabad, India
K D Modi
Department of Endocrinology, Medwin Hospitals, Chirag Ali Lane, Abids, Hyderabad-500 001
Bartter«SQ»s and Gitelman«SQ»s syndrome are two ends of a spectrum of inherited renal tubular disorders that present with hypokalemic metabolic alkalosis of varying severity. Clinical features and associated calcium and magnesium ion abnormalities are used to diagnose these cases after excluding other commoner causes. We report on two cases, the first being a young boy, born of pregnancy complicated by polyhydramnios, who had classical dysmorphic features, polyuria, hypokalemia and hypercalciuria and was diagnosed as having Bartter«SQ»s syndrome. The second patient is a lady who had recurrent tetany as the only manifestation of Gitelman«SQ»s syndrome, which is an unusual presentation. Potassium replacement with supplementation of other deficient ions led to satisfactory clinical and biochemical response.
|How to cite this article:|
Muthukrishnan J, Modi K D, Kumar P J, Jha R. Inherited renal tubular defects with hypokalemia.Saudi J Kidney Dis Transpl 2009;20:274-277
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Muthukrishnan J, Modi K D, Kumar P J, Jha R. Inherited renal tubular defects with hypokalemia. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2020 May 30 ];20:274-277
Available from: http://www.sjkdt.org/text.asp?2009/20/2/274/45578
Renal tubular defects leading to hypokalemic metabolic alkalosis are an uncommon group of disorders which include Bartter's and Gitelman's syndromes. Hyper-reninemic hyper-aldosteronism, renal prostaglandin excess, defects in calcium and magnesium homeostasis and urinary concentration ability are seen to a varying extent in patients afflicted with these disorders. We herewith present two patients with the first patient having been born of a pregnancy complicated by polyhydramnios in the mother. He had dysmorphic features, polyuria, short stature and hypokalemia suggestive of classical Bartter's syndrome.  Recurrent tetany was the sole presenting manifestation in the second patient and is seen in less than 10% of cases of Gitelman's syndrome. ,
A nine-year-old boy presented with complaints of polyuria (4-5 liters of urine per day), nocturia and failure to thrive, noted since five months of age. He had delayed mental and motor milestones. His elder brother had died due to an undiagnosed illness at the age of eight years. His mother had polyhydramnios during both the pregnancies. There was no history of muscle weakness, cramps, diuretic intake, excessive vomiting or diarrhea. There was no consanguinity in his parents. On evaluation at the age of eight months, he was detected to have hypokalemia and was advised potassium chloride replacement.
On present evaluation, his height was 118 cm ( 2 31.4 mmHg, PaO2 110 mmHg, HCO 3 36.2 mEq/L). Plasma renin activity (supine) was 4.2 ng/mL/hour (normal 0.15-2.31) and aldosterone was 25.9 ng/dL (normal 2-16). Blood glucose level and renal function were normal. Resting electrocardiogram was within normal limits.
In view of polyhydramnios in the mother, growth retardation, dysmorphic features, polyuria, normal blood pressure, hyper-reninemic hyper-aldosteronism, hypokalemic metabolic alkalosis with high urinary potassium and calcium, in the absence of any other cause, a diagnosis of Bartter's syndrome was made. Potassium replacement with syrup potassium chloride 30 mEq per day and capsule indomethacin 75 mg daily was advised. On follow-up, he was growing at seven cm per year, his serum potassium was 3.3 mEq/L and bicarbonate was 26 mEq/L.
A 20-year-old girl presented with episodes of spontaneous carpopedal spasms and leg cramps since five years of age. She had been repeatedly treated for tetany with parenteral and oral calcium and vitamin D. One year prior to presentation, she was noted to have hypothyroidism for which levothyroxine supplementation was started. She denied history of thyroid surgery, irradiation, prolonged diarrhea, vomiting, diuretic intake, hyperventilation, seizures, and symptoms suggestive of periodic paralysis. There was no similar illness in the family. On examination, trousseau's sign was positive. She was normotensive and had a diffuse grade-2, firm goiter. The remaining part of the general and systemic examination was normal. On investigation, she had hypokalemia (2.9 mEq/L), hypomagnesemia (1.5 mEq/L) and metabolic alkalosis (ABG - pH 7.55, pCO2 36.6 mm Hg, pO2 103 mmHg, HCO3 32.6 mEq/L). Spot urine sodium (175 mEq/L), potassium (36 mEq/ L) and chloride (225 mEq/L) were high. Urinary potassium and magnesium excretion were 38.4 mEq/24 hours and 7.8 mEq/24 hours respectively, both being above normal limits. Urinary calcium was 110 mg/24 hours (N , The pathophysiological and clinical differences between these two conditions are elaborated in [Table 1].
Hyper-reninemic hyper-aldosteronism and increased potassium and hydrogen ion secretion in the collecting tubules leads to hypokalemic metabolic alkalosis in Bartter's syndrome. The renal release of vasodilator prostaglandins (PGE2 and prostacyclins) is increased which may explain normal blood pressure despite hyperaldosteronism.  Urinary calcium excretion is increased and plasma magnesium is within normal limits as seen in our first case.  Gitelman's syndrome is characterized by hypomagnesemia and normal urinary calcium excretion due to magnesium wasting in distal convoluted tubules as a result of inhibition of its uptake in the presence of hypokalemia and metabolic alkalosis as seen in the second case.  Muscle cramps, which are due to hypokalemia and hypomagnesemia, may be severe and are seen frequently. Urinary concentrating ability is maintained, since function of the medullary thick ascending limb is relatively intact.
The tubular defect in Bartter's or Gitelman's syndrome cannot be corrected.  The combination of non-steroidal anti-inflammatory drugs (NSAIDs) to reduce renal PG synthesis, and a potassium-sparing diuretic to raise the plasma potassium concentration towards normal, partially reverse the metabolic alkalosis and corrects the hypomagnesemia. , The main treatment for Gitelman's syndrome is lifelong magnesium and potassium supplementation.
In the first case, onset in intra-uterine period with polyhydramnios, probable occurrence of similar illness in an elder sibling, typical dysmorphic features, growth restriction, hypokalemic metabolic alkalosis with high urinary potassium, hypercalciuria and hyper-reninemic hyper-aldosteronism, in absence of any other underlying cause suggests Bartter's syndrome. The second case differed from the first one in having onset at a later age, recurrent tetany as the sole manifestation, low serum magnesium and normocalciuria.
Bartter's and Gitelman's syndrome are uncommon renal tubular defects with varying degrees of metabolic abnormalities. They present with hyper-reninemic hyper-aldosteronism and hypokalemic metabolic alkalosis. High index of clinical suspicion, history to rule out diuretic abuse and recurrent vomiting and detailed metabolic work up can clinch the diagnosis. Both the conditions respond well to replacement of the deficient ion(s) and use of potassium sparing diuretics.  Anti-prostaglandin therapy with indomethacin has an adjunctive role in these cases.
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