Renal tubular acidosis

Renal tubular acidosis topic is clearly explained for the benefit of both UG and PG students of medicine and biochemistry students.

1. Renal tubular acidosis Dr.S.Sethupathy,M.D.,Ph.D ., Professor of Biochemistry, Rajah Muthiah Medical College, Annamali University

2. Renal tubular acidosis Renal tubular acidosis (RTA) is due either inherited or acquired kidney’s inability to reabsorb bicarbonate or secrete H + secretion. It is characterized by normal anion gap metabolic acidosis ( Hyperchloremic ) GFR will be normal or near normal.

3. Types of RTA

4. Type 1 RTA (Distal) Classical form Inability to acidy urine maximum Distal defect – decreased H+ secretion Metabolic acidosis K+ secreted in stead of H+ - hypokalemia Urine pH > 5.5 Hypercalciuria Renal stones

5. Pathophysiology

6. Genetic defect

7. Type 1 Recessive form in infancy

8. Hypokalemia and Nephrocalcinosis Urinary loss of sodium causes volume contraction Increased aldosterone section Increased tubular secretion and decreased reabsorption of potassium in proximal tubules Resulting in hypokalemia Chronic acidosis leads to decreased reabsorption of Ca 2+ - Hypercalciuria Acidosis and hypokalemia cause increased reabsorption of citrate – hypocitraturia Hypercalciuria , hypocitraturia , alkaline urine – leads to Calcium phosphate stone formation - nephrocalcinosis

9. Clinical features Failure to thrive, growth retardation Polyuria , polydipsia Nephrolithiasis Weakness, transient paralysis- hypokalemia

10. Nephrolithiasis

11. Nephrocalcinosis

12. Treatment –Type 1 RTA Bicarbonate administration – initially 2-3 meq / Kg/day Then increased till serum bicarbonate level becomes normal Usually maintenance dose will be 5-10 meq /kg/day Continued Life long

13. Type 2 RTA (proximal) defect

14. Treatment

15. Bicarbonate loading test

16. Fractional excretion of bicarb %

17. Causes of Fanconi syndrome

18. Investigations Hypochloremic metabolic acidosis Decreased serum PO4 Hypokalemia Proteinuria Urine anion gap = Na +  + K +  − Cl. where the concentrations are expressed in units of milliequivalents /liter ( mEq /L). low urinary AG = GI loss of base no change in urinary AG = renal loss of base negative urinary AG = severe diarrhea positive urinary AG = altered urinary acidification

19. Type 4 RTA The underlying defect is the impaired cation exchange in the distal tubules with reduced excretion of H+ and K+ Hyperkalemic acidosis present Hypoaldosteronism or decreased response to aldosterone Type 3 RTA no longer used.

20. Type 4 RTA -causes Hypoaldosteronism (low renin ) - Hyporeninemic hypoaldosteronism (diabetes mellitus/mild renal impairment, chronic interstitial nephritis, non-steroidal anti-inflammatory drugs, beta-blockers) Hypoaldosteronism (high renin ) – Primary adrenal defect (congenital hypoaldosteronism ; Addison disease, adrenalectomy , AIDS) inhibition of aldosterone secretion (heparin, ACE inhibitors, AT1 receptor blockers)

21. Type 4 RTA -causes Aldosterone resistance (drugs) \- Diuretics ( amiloride , triamterene , spironolactone ), calcineurin inhibitors (cyclosporine, tacrolimus ), antibiotics ( trimethoprim , pentamidine ) Aldosterone resistance (genetic) - Pseudohypoaldosteronism (PHA) types I and II

22. Clinical features

23. Type 4 RTA treatment

24. Follow up

25. Thank you