Renal Tubular Acidosis

Dr.Pramod Kamble; MBBS,MD

Specialist (Nephrology)

Introduction

• Lungs and Kidneys are responsible for Normal acid base balance

• Alveolar ventillation removes CO2 • Kidneys reabsorb filtered Bicarbonate and

excrete a daily quantity of Hydrogen ion equal to that produced by the metabolism of dietary proteins

Introduction(contd)

• Normal renal response to Acidemia is to reabsorb all of the filtered biacrbonate and to increase hydrogen ion excretion primarily by enhancing the excretion of ammonium ions in the urine

RTA-Defination

• Renal tubular acidosis refers to the development of metabolic acidosis because of a defect in the ability of the renal tubules to perform these functions.

• All forms of RTA are characterised by--• Metabolic acidosis,Normal anion gap, Hyperchloremia• Usually results from ----• Net retention of hydrogen chloride or its equivalent

( ammonium chloride)or• Net loss of sodium bicarbonate or its equivalent

Classification/Subgroup

• Distal or Type 1 RTA• Proximal or type 2 RTA• Type 4 RTA( Hyperaldosternism)• Type 3RTA??----features of both type 1 and

type 2RTA. RARE autosomal recessive syndrome ( due to carbonic anhydrase II deficiency).Other features include Osteopetrosis,cerebral calcification and mental retardation

Renal role in Acid-Base Balance

• To maintain acid –base balance• Reabsorption of Filtered bicarbonate• Excretion of Daily Acid load

Renal acid base balance

• Reabsorption of Bicarbonate• Predominantly occurs in proximal Tubules

primarily by Na-H exchange• Approximately 85-90% filtered load is

reabsorbed proximally.• 10-15% is reabsorbed in Distal Nephron via H

ion secretion by a proton pump(H-ATPase)• Under normal conditions, virtually no

bicarbonate is present in the final urine

Acid excretion• The excretion of daily H ion load is a function of distal tubules• It requires sufficient buffering compounds to bind H ions , to

be excreted in urine• The principal buffers in urine are Ammonia ( excreted as

ammonium) and phosphate ( ref to as titrable acidity).Ammonium excretion requires the renal synthesis of ammonia and the secretion of hydrogen ion by the collecting duct cells into the tubular lumen which serves to trap the ammonia in the urine as ammonium( ammonia diffuses freely across cell memb while ammonium does not)

• Renal production of NH4 is stimulated by intracellular acidosis• Hence when syst acid load is modestly increased , near normal

balnce occurs via increasing NH3 production and excretion• Failure to excrete sufficient ammonium leads to retention of

net H ion and devpt of Metabolic acidosis

Acid excretion-consequences• Impaired H ion secretion is the primary defect

in Distal RTA • Impaired ammoniagenesis is the primary

defect in Type 4 RTA and renal failure.• These disorders are associated with different

abnormalities of plasma potassium conc• Distal RTA—hypokalemia • RTA type 4 and renal failure in late stages

with hyperkalemia.

Acid excretion-consequences• Degree of acidosis may be different in different types

of RTA• Type 1-Plasm HCO3 may fall below 10

meQ/L(inability to excrete daily acid load leading to progressive ion retention)

• Type 2Plasma HCO3 12—20 meQ/L(HCO3 wasting only when plasma HCO3 above the reabsorptive threshhold and the more disrtal seg have substantial HCO3 reabsorptive capacity )

• Type 4RTA-Hyperkalemia is prominent .Plasma HCO3 usually above 17 meQ/L

Proximal RTA(type2)• Occasionally present as Isolated defect• More commonly associated with generalised

proximal dysfunction- Fanconi Syndrome—bicarbonaturia,glucosuria,phosphaturia,uricosuria,aminoaciduria and tubular proteinuria.

• Most common causes in Adults—Multiple myeloma,carbonic anhydrase inhibitor(acetazolamide),ifsofamide

• In children-several forms of genetically inherited diseases are responsible,Cystinosis is most common

Proximal RTA type 2

• The diagnosis of proximal RTA is made by measurement of urine pH and fractional bicarbonate excretion during a bicarbonate infusion. The hallmark is a urine pH above and appearance of > 15 % of filtered bicarb in the urine when a serum bicarb is raised to a normal level.

Complications of type 2 RTA

• Poor growth in children• Osteomalacia due to hypoPO4• Treatment may be difficullt as large amount of alkali may be

required to correct acidosis which may increase hypokalemia.Hence empirically determined fraction of alkali given as potassium salt( usually K citrate)

• Thiazide diuretic( associated mild vol depletion depletion enhances proximal Na reabsorption ans Secondarily HCO3

• Po4 and Vit D supllement• Serial monitoring of Electrolytes • Type 2 RTA is transient in some children

Distal RTA

• Distal type 1RTA is charcterised by an impaired capacity for H ion and therefore NH3 secretion in the collecting tubules

• This manifest as an abnrmally high Urine pH (. 5.5 Normal urine pH 4.5-5)during systemic acidosis

• Results from one of several defects in distal hydrogen ion secretion---1) Decreased proton pump activity 2)Increased luminal membrane permaebility with backleak of hydrogen ions 3) Diminished distal tubular Na reabsorption which reduces the electrical gradient for proton secretion

Distal RTA-causes

• Primary-idiopathic/ sporadic• familial-autosomal domonant/ recessive• Secondary-Sjogren’s syndrome,

hypercalciuria, rheumatoid arthritis,hypreglobulinemia, ifosfamide,amphotericin B,cirrhosis,SLE,sickle cell anemia,obstructive uropathy,lithium carbonate,Toluene exposure due to glue-sniffing(in recreational drug abuser)renal transplntation

Distal RTA -Presentation

• Hyperchloremic acidosis with an appropriately high urine pH( > 5.5 in p of acidosis)

• Hypercalciuria due to chronic acidosis on bone resorption and renal tubular Reabsorption of Ca

• Nephrolithiasis and nephrocalcinosis• Hypokalemia( due to K wasting due to proton pump defect) is

frequent –muscle weakness.• Hyperkalemia can be seen esp. when RTA is associated with

obstructive uropathy or Sickle cell disease. Here the defect in Na reabsorption interferes with both K and hydrogen ion secretion

Treatment• Correction of acidemia—with alkali therapy• Advantages—minimize new stone

formation,nephrocalcinosis,diminished Ca losses and hence osteopenia and help in correction of hypokalemia

• Bicarb 1-2 meq/kg- sodabicarb/ or sodium citrate.Children will require more

• Potassium citrate or Na citrate is indicated for persistent Hypokalemia or Ca Stone disease

• High Na ,Low K diet with thiazide or loop diuretic in pt with Hyperkalemic distal RTA

Type 4 RTA• Due to either Aldosterone deficiency or tubular resistance to the action of

aldosterone.• Major causes of Aldosterone deficiency• Primary-1)Primary adrenal insufficiency 2)congenital hyperplasia(21

hydroxylase def),3)Isolated aldosterone synthase def ,4)Heparin and LMWH

• Hyporeninemic hypoaldosteronism—1) renal disease-Diabetic nephropathy, volume expansion as inGN,ACEI,NSAIDS,Cyclosporin,HIV inf,some cases of obstructive uropathy

• Aldosterone Resistance—1)Drugs which close the collecting tubule Na channel—Amiloride,Spironolactone,triamterene,Trimethoprim,pentamidine,2)Tubulointerstitial disease ,3)Pseudohypoaldosteronism,4)Distal chloride shunt

Presentation RTA4

• Hyperkalemia (hypoaldosterone) associated with mild to moderate acidosis( due to suppression of NH4 excretion)

• Appropriate urine acid pH below 5.3 in p of acidosis and plasma HCO3 above 17 meq/L

• Diagnosis can be made by measuring plasma renin and aldosterone level

• Many pts are treated empirically with low K diet, diuretics and Ion excahange resins.

• Fludrocortisone ( 0.05-0.2mg/d)for pt with primary aldosterone def.But often it is NOT used due to HTN, heart failure and edema