Hatem AL-Nasser 8 March 2010

Proximal Tubule Reabsorption: HCO3- (90%) – carbonic anhydrase calcium glucose Amino acids NaCl, water Distal Tubule Na+ reabsorbed H+ (NH4+ or phosphate salts) excreted molar competition between H+ and K+ Aldosterone

Type 2 RTAType 1 RTA Type 4 RTA

 First described, classical form  Distal defect  decreased H+ secretion  H+ builds up in blood (acidotic)  K+ secreted instead of H+ (hypokalemia)  Urine pH > 5.5  Hypercalciuria  Renal stones

Causes:  Primary  Idiopathic, sporadic  Familial – AD, AR  Secondary –  Autoimmune (SLE, Sjogren’s, RA)  Hereditary hypercalciuria, hyperparathyroidism, Vit D intoxication  Hypergammaglobulinemia  Drugs (Amphotericin B, Ifosfamide, Lithium)  Chronic hepatitis  Obstructive uropathy  Sickle cell anemia  Renal transplantation

Treatment:  Alkali replacement:  1-3mmol/kg/day bicarbonate  Sodium citrate tolerated better than sodium bicarb  Potassium citrate if hypokalemia

 Proximal defect  Decreased reabsorption of HCO3-  HCO3- wasting, net H+ excess  Urine pH < 5.5, although high initially  K+: low to normal

Causes:  Primary  Idiopathic, sporadic  Familial: Cystinosis, Tyrosinemia, Hereditary Fructose intolerance, Galactosemia, Glycogen storage disease (type 1), Wilson’s disease, Lowe’s syndrome  Fanconi’s Syndrome  Generalized proximal tubule dysfunction  Proximal loss of phos, uric acid, glucose, AA  Acquired  Multiple Myeloma  Carbonic anhydrase inhibitors (Acetazolamide)  Other drugs (Ampho B, 6- mercaptopurine)  Heavy Metal Poisonings (Lead, Copper, Mercury, Calcium)  Amyloidosis  Disorders of protein, Carb, AA metabolism  Hypophosphatemia, hypouricosuria, renal glycosuria with normal serum glucose

Treatment:  Alkali therapy:  5-15mmol/kg/day bicarbonate  Supplemental potassium  Vit D

 Aldosterone deficiency or distal tubule resistance to Aldosterone   Impaired function of Na+/K+-H+ (cation) exhange mechanism  Decreased H+ and K+ secretion  plasma buildup of H+ and K+ (hyperkalemia)  Urine pH < 5.5

Type 2 RTAType 1 RTA LOW serum K+ Type 4 RTA HIGH serum K+

Acquired Causes   Renin:  Diabetic nephropathy  NSAIDS  Interstitial Nephritis  Normal renin,  Aldo:  ACEs, ARBs  Heparin  Primary adrenal response   response to Aldo:  Medications: K+ sparing drugs (Sprinolactone), TMP-SMX, pentamidine, tacrolimus  Tubulointerstitial ds: sickle cell, SLE, amyloid, diabetes

Treatment:  Dietary restriction of sodium  Furosemide

 Very rare  Used to designate mixed dRTA and pRTA of uncertain etiology  Now describes genetic defect in Type 2 carbonic anhydrase (CA2), found in both proximal, distal tubular cells and bone

Primary defectSerum K+ Urine pH OtherCauses Type 1 distal H+ secretion decreased Low-nl> 5.5Renal stones Autoimmune (SLE, Sjogrens) Hypercalciuria Drugs (Ampho B, Ifosfamide, lithium) Hypergammaglobulinemia Type 2 proximal HCO3- reab decreased Low-nl< 5.5, although high initially Multiple Myeloma Acetazolamide Heavy Metal Poisonings (Lead, Copper, Mercury, Calcium) Amyloidosis Disorders of protein, Carb, AA metabolism Type 4 Aldosterone deficiency, cation exchange decreased High< 5.5 Aldosterone deficiency Diabetic nephropathy Spirinolactone Interstitial nephritis Obstructive uropathy Renal transplant

 Thank you