Renal Tubular Acidosis

Dr.Anurag FursuleDNB Resident II yr

JLNHRC,Bhilai

Renal tubular acidosis (RTA) is a disease state characterized by a normal anion gap (hyperchloremic) metabolic acidosis in the setting of normal or near-normal glomerular filtration rate.

Definition

Anion Gap = Serum(Na+ + K+ )-(Cl- + HCO3-) Purpose of using anion gap: metabolic

acidosis resulting from bicarbonate loss can be differentiated from accumulation of non volatile acis

Normal value : 14 – 18 mEq/L >20 is highly suggestive of presence of anion

gap For every mEq of bicarb loss there is equal

increase in serum chloride levels so anion gap remains within normal range

What is anion gap?

Mostly reabsorped in PCT 80-85% Remainder in initial part of distal tubule

Bicarbonate reabsorption

Normal Urinary Acidification

Proximal (type II ) RTA is characterized by impairment of PCT reabsorption of bicarbonate.

So at normal plasma HCO3 levels 15%(30% or mor in fanconi) or more HCO3 is excreted in urine and during sustained acidosis excessive HCO3 excretion is reduced and increased reabsorption of HCO3 from proximal tubule.

Distal acidification mechanisms are intact.

Proximal (type II ) RTA

Common Causes of TYPE I RTA

Primary isolated proximal RTA secondary to defective HCO3 reabsorption is rare,may occur as sporadic or inherited(AR).

In children RTA II is usually part of global proximal tubular dysfunction i.e Fanconi syndrome.

Proximal RTA is mc caused by sporadic Fanconi syndrome

Among inherited conditions cystinosis is commonly identified

Clinical Features

Hypophosphatemia,acidosis,low 1,25(OH)3 D3

A detailed history, with particular attention to growth and development recent or recurrent diarrheal illnesses family history of mental retardation failure to thrive end-stage renal disease infant deaths miscarriages is essentialPhysical examination should determine growth parameters volume status dysmorphic features suggesting an

underlying syndrome

Lab Findings

•Urine pH should be assesed during state of metabolic acidosis

•Urine and blood pCO2 difference is more than 20mmHg

Correction of acidosis: 5-20mEq/kg of alkali Prudent to give 5-8 mEq/kg bicarbonate

(shohl solution,polycitra) Part of alkali is given in form of potassium

citrate Dietary Na restriction Hydrochlorthiazide : contraction of ECF and

increased proximal HCO3 reabsorption Supplements of phosphate (neutral

phosphate , joulie solution)are necessary in Fanconi syndrome. Dose: 1-3gm/day

Small doses of vit D may enable healing of rickets(though rare)

Treatment

Mutation in CTNS gene(17p)--encodes novel protein:cystinosin(H+ driven cystine transporter)

Defect in metabolism of cystine

Accumulation of cystine crystals in major organsKidney, brain ,liver,eye,others

Cystinosis

1.Infantile /Nephropathic cystinosis-1st 2 years of life-severe tubular dysfuntion-if no t/t then ESRD till first decade 2.Adoloscents-mild-slower progression to ESRD 3.Benign adult form with no kidney

involvement

Forms

Diminished pigmentation: fair and blond Fanconi syndrome: polyuria, polydipsia Growth failure Rickets Fever: dehydration and decreased sweat production Ocular: photophobia, retinopathy, impaired visual

acuity Hepatosplenomegaly, delayed sexual maturation,

hypothyroidism Complications: CNS abnormalities, muscle weakness,

swallowing dysfunction, pancreatic insufficiency.

Clinical Features and Complications

Diagnosis:1.Detection of cystine crystals in cornea2.Increased leukocyte cystine content3.Prenatal diag by CVS,amniocentesis

Early initiation of therapy is important. correcting the metabolic abnormalities associated

with Fanconi syndrome or chronic renal failure. cysteamine,which binds to cystine and converts it

to cysteine: facilitates lysosomal transport and decreases tissue cystine.

cysteamine eyedrops is required growth hormone for growth failure

Diagnosis & Treatment

Mutation in OCRL1 of X chromosome(XLR)

Encodes PIBPase in golgi network

Accumulation of PIBP

1.Changes in protein trafficking2.Defective actin cyctosleleton polymerization

3.Altered cell signalling for endocytosis

Lowe Syndrome

Clinical Features

•Hypotonia with hyporeflexia•Severe psychomotor retardartion•Bilateral cong Cataract•Strabismus•Infantile onset Glaucoma•cheloids

•Frontal bossing•Deep set eyes•Chubby cheeks•Fair complexion

Rachitic rosary

Fanconi syndrome

Diagnosis is clinical,molecular testing for OCLR gene is available.

Prenatal Dx: slit lamp examination of mother(punctate white opacities)

Treatment is symptomatic-cataract extraction-glaucoma control-physical and speech therapy-drugs to address behavioral problem

Diagnosis & Treatment

Defects in one or more of following:-H+ ATPase-HCO3/Cl anion exchanger-Components of aldosterone pathway Due to impaired H+ excretion urine pH cannot be reduced to

<5.5 Inability to secrete H+ distally is compensated by secreting K+

leading to hypokalemia Lack of NaHCO3 distally, owing to lack of H+ to bind to tubuLar

lumen, leads to chloride absorption leading to hyperchloremia. Chronic metabolic acidosis: impairs citrate excretion leading

hypocitraturia Hypercalciuria:-Increased calcium release from bone to buffer systemic acidosis-Acidosis induced downregulation of renal Calcium transport

protein-Increased distal sodium delivery

Distal (Type I) RTA

Secretory defects causing Distal RTA

Clinical Features

•Urine and blood pCO2 difference is <10mmHg provided urine pH >7.5 and bicarbonate >23mEq/L

Radiology

Base requirement for distal RTA is generally 2-4mEq/kg/24hr.(requirement decreases after age of 5 yrs)

Patient should b monitored for development of hypercalciuria

Some patients may require K+ replacement Symptomatic hypercalciuria: gross

hematuria, nephrocalcinosis, nephrolithiasis — treated with thiazide diuretics

Vit D should be used in case of severe rickets

Treatment

aldosterone -direct effect on the H+/ATPase responsible for

hydrogen secretion-potent stimulant for potassium secretion in

the collecting tubule Type IV RTA occurs as the result of -impaired aldosterone production

(hypoaldosteronism)-impaired renal responsiveness to

aldosterone (pseudohypoaldosteronism).

Type IV RTA

Etiology

Type IV RTA

ACUTE CHRONIC

OBSTRUTIVE UROPATHY

•ACUTE PYELONEPHRITIS•ACUTE URINARY OBSTRUCTION

ALDOSTERONE UNRESPONSIVENESS

ACIDOSISHYPERKALEMIA

Growth failure Polyuria Dehydration with salt wasting Life threatning hyperkalemia

Clinical Features

PHA ISalt loss Hypotensionhyperkalemia PHA IIHypertensionAcidosisHyperkalemiaHyporeninemic hypoaldosteronism

hyperkalemic non–anion gap metabolic acidosis Urine may be alkaline or acidic Elevated urinary sodium levels with

inappropriately low urinary potassium levels reflect the absence of aldosterone effect.

require chronic treatment for hyperkalemia with sodium-potassium exchange resin (Kayexalate).

PHA I- Kayexelate PHA II-thiazides Addisons- fludrocortisone

Lab investigation and treatment

Approach to RTA

Nelson Textbook of Pediatrics 19th edition IAP Textbook of Pediatrics 5th edition Pediatric Nephrology by RN Srivastava,A

Bagga 5th edition

References