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D R N G O V E N D E R 2 4 / 0 5 / 2 0 2 4 APPROACH TO RENAL TUBULAR ACIDOSIS RENAL TUBULAR ACIDOSIS Renal tubular acidosis (RTA) - a group of disorders in which metabolic acidosis develops due to defects of the renal tubules to maintain acid-base balance despite a...

D R N G O V E N D E R 2 4 / 0 5 / 2 0 2 4 APPROACH TO RENAL TUBULAR ACIDOSIS RENAL TUBULAR ACIDOSIS Renal tubular acidosis (RTA) - a group of disorders in which metabolic acidosis develops due to defects of the renal tubules to maintain acid-base balance despite a normal or near normal glomerular filtration rate. All forms of RTA normal anion gap (hyperchloremic) metabolic acidosis-NAGMA Most common cause of a NAGMA in patients without significant renal impairment is diarrhea. Kidneys role in acid base homeostasis Reabsorbs filtered bicarbonate- almost 100% of filtered bicarbonate. Excretion of H+ ions by tubular secretion. Movement of H+ from intracellular space  lumen H+ reacts with HCO3− molecule to form H2CO3 H2CO3 catalyzed by carbonic anhydrases to form CO2 and H2O. HCO−3+H+⇌H2CO3⇌CO2+H2O CO2 enters the cell and with H2O forms H+ and HCO3−. For every H+ secreted, a HCO3− is formed inside the cell. This bicarbonate is reabsorbed back into the bloodstream. 70–80% of bicarb is The kidneys also reabsorbed in generate new proximal bicarbonate. tubules Via 2 mechanisms: ~ 10–15% in - Ammoniagenesis the thick ascending - excretion of limb of the titrable acids. loop of Henle 4–6% in the distal convoluted tubule remaining in the collecting duct. VA LU E S RENAL TUBULAR ACIDOSIS 4 major forms of RTA – Type 1 RTA- Distal RTA (Hypokalemic) defect in distal hydrogen ion excretion Type 2 RTA : Proximal RTA (Hypokalemic)  reduced ability to reabsorb filtered bicarbonate in PCT Type 4 RTA: Hypoaldosteronism RTA (Hyperkalemic) reduced aldosterone secretion/resistance Voltage dependent RTA Subtype of distal RTA (Hyperkalemic)  defects in distal sodium reabsorption affects the negative electric potential difference generated in the distal tubule Note: Type 3 RTA not a well-defined diagnosis; rarely used. When it is used refers to patients with both proximal and distal acidification defects. Genetic or drug-related carbonic anhydrase disorders. RENAL TUBULAR ACIDOSIS D I S TA L R E N A L T U B U L A R A C I D O S I S Type 1- Distal RTA Impaired hydrogen ion secretion in the distal nephron Pathophysiology: the Type A (alpha) intercalated cells of the DISTAL TUBULE are unable to secrete H+ decreased intracellular production of HCO3⁻ decreased HCO3⁻/Cl⁻ exchange decreased serum HCO3-  METABOLIC ACIDOSIS (normal anion gap (or hyperchloremic)) D I S TA L RENAL TUBULAR ACIDOSIS ETIOLOGY C L I N I C A L F E AT U R E S Nephrocalcinosis Calcium phosphate renal stones (increased urine PH) Patients with distal RTA almost always have hypocitraturia and frequently develop kidney calcifications and calcium-containing (frequently calcium phosphate) kidney stones. Polyuria, polydipsia, dehydration Increased bone turnover bone demineralization Growth impairment Hypokalemic features: hyporeflexia, paralysis, muscle weakness, U waves and flat T waves on ECG DIAGNOSIS Serum Hyperchloremic metabolic acidosis NAGMA; Hypokalemia Urine Ph> 5.5, Decreased citrate excretion Decreased NH4+ excretion Hypercalciuria Positive urine anion AG [Urine Na] + [Urine K+] – [Urine Cl-] (normal is -20 to -50) Acid load test: used to induce metabolic acidosis and evaluate whether the kidney is able to excrete hydrogen ions. Administer oral ammonium chloride, if the urine doesn’t acidify, test indicative for Type 1 RTA. T R E AT M E N T Alkalinisation treatment with oral sodium bicarbonate solution or citrate solution (Shohl solution) P R O X I M A L R TA - T Y P E 2 Dysfunctional PCT  unable to reabsorb HCO3increased HCO3- excretion in the urine. H+ secretion from the alpha- intercalated cells in the collecting duct can acidify urine but unable to compensate for the excessive secretion of HCO3- 2 Types: Isolated proximal RTA  Only HCO3- reabsorption is impaired. Fanconi syndrome  impaired reabsorption of HCO3- and other compounds (potassium, glucose, phosphate, amino acid) in the PCT PROXIMAL RTA - T Y P E 2 P R O X I M A L R TA - T Y P E 2 Etiology of Isolated Type Etiology of Fanconi syndrome 2 RTA Inherited disorders Sporadic idiopathic Cystinosis Wilson dz Familial inherited genetic T1 glycogen storage Galactosemia defects Tyrosinemia Drugs: Acetazolamide Light chain nephropathy: multiple myeloma Ischemia- acute tubular necrosis Amyloidosis Vit D deficiency PNH Drugs: TDF, amingoglycosides, ifosfamide, expired tetracyclines, cisplatin C L I N I C A L F E AT U R E S Vitamin D- resistant hypophosphatemic rickets/ osteomalacia--> due to phosphaturia and hypophosphatemia Short stature Polyuria, polydipsia, dehydration Fx of hypokalemia DIAGNOSIS Serum Hyperchloremic metabolic acidosis NAGMA Hypokalemia  worsens with alkali treatment Fanconi syndrome : hypouricemia, hypophosphatemia Urine Urine PH: if serum HCO3- is depleted then pH5.5 Bicarb infusion test: administer IV sodium bicarb; if urine ph rises to > 7.5 or excretion of Bicarb >15%, indicative of T2 RTA Negative urine anion gap Fanconi syndrome: aminoaciduria; glycosuria despite normal or low serum glucose, phosphaturia DIAGNOSIS Alkali therapy with potassium citrate If alkali therapy not tolerated or effective thiazide diuretics. T Y P E 3 R TA  M I X E D Autosomal recessive disease (combination of Type 1 and 2 RTA). Seen in infants and children Etiology: Carbonic anhydrase II deficiency Pathophysiology: Impaired H+ secretion by DCT and HCO3- wasting by PCT Clinical features: Guibaud Vainsel syndrome{osteopetrosis; cerebral calcification, Intellectual disability} Dx Serum: hyperchloremic NAGMA, low K, low Ca Urine: PH>5.5; positive urine anion gap; hypercalciuria, decreased NH4+ excretion, decreased citrate excretion. Rx: Alkali therapy oral sodium citrate (Shohl solution) or potassium citrate. TYPE 4 HYPOALDOSTERONISM R TA Pathophysiology: Aldosterone deficiency and/or resistance in the CD and DCT causes hyperkalemia and MA  NH3+ synthesis is inhibited in the PCT decreased urinary NH4+(ammonium) excretion TYPE 4 HYPOALDOSTERONISM R TA  H Y P E R K A L E M I C Hypoaldosteronism Primary adrenal insufficiency: Addison disease. Hyporeninemic hypoaldosteronism Acute GN Diabetic nephropathy diabetic hyporeninism SLE HIV nephropathy Drugs: NSAIDS, Cyclosporin Drugs: ARBS, ACE-I, heparin Pseudohypoaldosteronism Type 2 Gordon syndrome (autosomal dominant) Aldosterone resistance T Y P E 4 R TA Clinical features Polyuria, polydipsia, dehydration Impaired growth Fx of hyperkalemia Diagnosis Serum : hyperchloremic NAGMA + hyperkalemia Urine: pH

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