Hatem AL-Nasser8 March 2010

Proximal TubuleReabsorption: • 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 RTA Type 1 RTAType 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 RTA Type 1 RTALOW serum K+

Type 4 RTAHIGH 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 defect Serum K+

Urine pH

Other Causes

Type 1distal

H+ secretion decreased

Low-nl > 5.5 Renal stones

Autoimmune (SLE, Sjogrens)HypercalciuriaDrugs (Ampho B, Ifosfamide, lithium)Hypergammaglobulinemia

Type 2proximal

HCO3- reab decreased

Low-nl < 5.5, although high initially

Multiple MyelomaAcetazolamideHeavy Metal Poisonings (Lead, Copper, Mercury, Calcium)AmyloidosisDisorders of protein, Carb, AA metabolism

Type 4 Aldosterone deficiency, cation exchange decreased

High < 5.5 Aldosterone deficiencyDiabetic nephropathy SpirinolactoneInterstitial nephritisObstructive uropathyRenal transplant

Thank you