Bartter- and Gitelman-like syndromes: salt-losing tubulopathies with loop or DCT defects

Salt-losing tubulopathies with secondary hyperaldosteronism (SLT) comprise a set of well-defined inherited tubular disorders. Two segments along the distal nephron are primarily involved in the pathogenesis of SLTs: the thick ascending limb of Henle’s loop, and the distal convoluted tubule (DCT). The functions of these pre- and postmacula densa segments are quite distinct, and this has a major impact on the clinical presentation of loop and DCT disorders – the Bartter- and Gitelman-like syndromes. Defects in the water-impermeable thick ascending limb, with its greater salt reabsorption capacity, lead to major salt and water losses similar to the effect of loop diuretics. In contrast, defects in the DCT, with its minor capacity of salt reabsorption and its crucial role in fine-tuning of urinary calcium and magnesium excretion, provoke more chronic solute imbalances similar to the effects of chronic treatment with thiazides. The most severe disorder is a combination of a loop and DCT disorder similar to the enhanced diuretic effect of a co-medication of loop diuretics with thiazides. Besides salt and water supplementation, prostaglandin E2-synthase inhibition is the most effective therapeutic option in polyuric loop disorders (e.g., pure furosemide and mixed furosemide–amiloride type), especially in preterm infants with severe volume depletion. In DCT disorders (e.g., pure thiazide and mixed thiazide–furosemide type), renin–angiotensin–aldosterone system (RAAS) blockers might be indicated after salt, potassium, and magnesium supplementation are deemed insufficient. It appears that in most patients with SLT, a combination of solute supplementation with some drug treatment (e.g., indomethacin) is needed for a lifetime

Thrombolysis After Protamine Reversal of Heparin for Acute Ischemic Stroke After Cardiac Catheterization: Case Report and Literature Review

BACKGROUND: Patients with an acute ischemic stroke (AIS) following cardiac catheterization (CC) generally do not receive intravenous thrombolysis [intravenous tissue plasminogen activator (IV-tPA)] as it is contraindicated due to the coagulopathy related to the heparin used during the procedure. We report a case of AIS successfully treated with IV thrombolysis following protamine reversal of heparin effect. CASE REPORT: An 87-year-old man with diabetes mellitus, hypertension, neurofibromatosis, and hyperlipidemia underwent elective transradial CC following an abnormal stress test. He had 2 drug-eluting stents for severe stenosis of mid-circumflex and right coronary arteries and received heparin 13,000 IU during procedure. He developed acute left hemiparesis with initial NIH stroke scale (NIHSS) of 4. Computed tomographic scan of the brain and computed tomographic angiogram of head and neck were unremarkable. Bedside activated clotting time was 181. Protamine 40 mg was administered and 30 minutes later, the activated clotting time level was normalized. IV-tPA was administered at 4 hours 25 minutes from his last known well. Within 15 minutes, his NIHSS was 0. Magnetic resonance imaging of brain showed no acute infarction 24 hours after stroke. CONCLUSIONS: There are limited reports of protamine reversal of heparin before IV-tPA administration. To our knowledge, there are only 6 AIS cases including ours. Three cases received 0.6 mg/kg of tPA dose. All have favorable outcomes and no intracranial hemorrhage was reported. Protamine reversal of heparin for AIS after CC seems to be safe. Further studies are needed to confirm the therapeutic safety and efficacy of this strategy