This document discusses renal tubular acidosis (RTA). It begins by explaining the different types of RTA, including proximal (Type 1), distal (Type 2), and combined (Type 3). It then covers the clinical presentation, diagnostic evaluation, and management of RTA. Key points include that children with RTA often present with failure to thrive, polyuria, and polydipsia. Diagnosis involves assessing for a normal anion gap metabolic acidosis along with electrolyte abnormalities. Treatment focuses on bicarbonate replacement and addressing complications like hypercalciuria. With early diagnosis and treatment, most children can see improved growth and development.

1. Presentor- Dr. Bikramjit Singh Jafra
Moderator- Dr. V.R. Anand
Co-Moderator- Dr. Ankit Mangla

3.  Water and electrolytes are freely filtered at
glomerulus
 The electrolyte content of ultrafiltrate
“At the beginning of the PCT = that of plasma”
 Tubular reabsorption vs tubular secretion determine
the final water content and electrolyte composition
of urine
 Movement of solute in nephron
 Bulk movement in proximal portions
 Fine adjustments in distal portions

4.  Responsible for the reabsorption of more than 99% of the
water and sodium in the ultrafiltrate.
 65% of sodium and water is reabsorbed by the proximal
tubule
 25% by thick ascending limb of Loop of Henle
 5% by distal convoluted tubule
 2-3% by the cortical collecting tubule
 Regulate acid-base balance
 Mineral homeostasis
 Excretion of organic acids and drugs
 Has specialized transporters and channels located in the
 Tubular cell membranes
 Apical memb.
 Basolateral side (interstitial side)

8.  Kidneys contribute to acid–base balance by
 Reabsorption of filtered HCO3
 Excretion of H+
 Because loss of filtered HCO3 − is equivalent to
addition of H+ to the body, all filtered bicarbonate
should be absorbed before dietary H+ can be
excreted.
 Reabs. of filtered bicarbonate
 85% in PCT
 15% in the distal segments (thick ascending limb and
outer medullary collecting tubule)

10.  The renal acid-base homeostasis may be broadly
divided into two processes:
1. Reabsorption of filtered HCO3
 In the proximal convoluted tubule
2. Excretion of fixed acids
 Through the titration of urinary buffers and the
excretion of ammonium, which takes place primarily
in the distal nephron

11. H+ from water is secreted by
the Na+-H+ exchanger on the
luminal membrane
H+ combines with filtered
HCO3- resulting in the
formation of H2CO3, which
splits into H2O and CO2 in
the presence of carbonic
anhydrase IV
CO2 diffuses freely back into
the cell, combines with OH−
(from H2O) to form HCO3−
in the presence of carbonic
anhydrase II, and returns
to the systemic circulation via
a Na+-HCO3− cotransporter
situated at the basolateral
membrane of the cell

12. In the collecting tubule,
H+ is secreted into lumen
by H+ATPase
HCO3− is returned to the
systemic circulation by the
HCO3–-Cl− exchanger
located on the basolateral
membrane
The H+ secreted
proximally and distally in
excess of the filtered
HCO3− is excreted in the
urine either as titratable
acid or as NH4+

14.  Comprises a gp of tubular transport defects charac. by
inability to appropriately acidify the urine with resultant
met. ac.
 Normal anion gap (hyperchloremic) metabolic acidosis in
the setting of normal or near-normal glomerular
filtration rate
 In contrast, the term “UREMIC ACIDOSIS” is
applied to patients with low GFR in whom
metabolic acidosis is accompanied by normo- or
hypochloremia and an increased plasma
anion gap

15.  Type 1 (Distal)
 Type 2 (Proximal) isolated
 Multiple/Global tubular dysfunction (Fanconi syn.)
 Type 3 (Combined)
 Type 4 (Hyperkalemic)

16.  Prox tubule defect
 Type 2= Bicarbonate reabs defect
 Loss in urine of
 Na
 K
 HCO3
 Cl
 Uric acid
 PO4 (Rickets)
 B’cause distal acidification mech is intact, so H+ is sec in
urine
 pH of urine <5.5 (acidic)

18. Primary
 Sporadic
 Inherited
 Inherited renal disease (idiopathic
Fanconi)
 Sporadic (mc), AD,AR
 X-linked (Dent disease)
 Inherited syndromes
 Cystinosis
 Tyrosinemia type 1
 Galactosemia
 Oculocerebral dystrophy (Lowe
syndrome)
 Wilson disease
 Hereditary fructose intolerance
Secondary
 Intrinsic renal disease
 Autoimmune diseases (Sjögren
syndrome)
 Hypokalemic nephropathy
 Renal transplant rejection
 Hematologic disease (Myeloma)
 Drugs
 Gentamicin
 Cisplatin
 Ifosfamide
 Sodium valproate
 Heavy metals
 Lead
 Cadmium
 Mercury
 Organic compounds (Toluene)
 Nutritional (Kwashiorkor)
 Hormonal (Primary hyperparathyroidism)

19.  Charac. by global dysfunc. of prox. tub.
 Glycosuria
 Phosphaturia
 Gen. aminoaciduria
 In addition impaired abs. of
 Water
 HCO3-
 Na
 K
 Organic acids
 Plasma conc of Glucose & aa are within N range, but
those of PO4- are low
 Cystinosis & use of Ifosamide are common causes among
children

20.  Extremely rare, AR
 Features of both type I and type II (juvenile RTA)
 Term Type 3 RTA was abandoned as the charac of prox
RTA were transient & acidosis was primarily d/t distal
acidification defect
 d/t Inherited carbonic anhydrase II deficiency (k/a
Guibaud-Vainsel syn.)
 CF
 Osteopetrosis
 Renal tubular acidosis
 Cerebral calcification
 Mental retardation

21.  Distal tub defect
 Type 1= Acid excretion defect
 B’cause distal tubule defective, so H+ not sec in lumen
 pH of urine >5.5
 Kidney sec K+ in place of H+ l/t hypokalemia
 As no H+ in lumen to bind to HCO3, so NaHCO3 is lost
in urine
 As HCO3 lost, so kidney reabs. Cl- l/t hyperchloremia
 Hypercalciuria l/t stone
 Hypocitraturia
 Bone buffer (CaCO3) starts to combat chronic acidosis l/t
bone disease

23. Primary
 Sporadic
 Inherited
 Inherited renal diseases
 AD/AR
 AR with early-onset hearing
loss
 AR with later-onset hearing
loss
 Inherited syndromes associated
with type I renal tubular acidosis
 Marfan syndrome
 Wilson syndrome
 Ehlers-Danlos syndrome
 Familial hypercalciuria
Secondary
 Intrinsic renal
 Interstitial nephritis
 Pyelonephritis
 Transplant rejection
 Sickle cell nephropathy
 Lupus nephritis
 Nephrocalcinosis
 Medullary sponge kidney
 Urologic
 Obstructive uropathy
 Vesicoureteral reflux
 Cirrhosis
 Toxins or medications
 Amphotericin B
 Lithium
 Toluene
 Cisplatin

24.  RTA + HyperK + Ability to appropriately acidify urine
 Defect
 Impaired aldosterone poduction
 Unresponsiveness to aldosterone
 Aldosterone
 Stimulates H+ ATPase
 Stmulates K+ sec. in exchange for Na reabs by CD
 Effects
 Na lost in urine
 H2O lost in urine
 K+ not sec. (Hyperkalemia)
 H+ not sec. (Acidosis)

26. Primary
 Sporadic
 Genetic
 Hypoaldosteronism
 Addison disease
 Congenital adrenal hyperplasia
 Pseudohypoaldosteronism (type I
or II)
Secondary
 Urologic
 Obstructive uropathy
 Intrinsic renal
 Pyelonephritis
 Interstitial nephritis
 Systemic
 Diabetes mellitus
 Sickle cell nephropathy
 Drugs
 Trimethoprim/sulfamethoxazole
 Angiotensin-converting enzyme
inhibitors
 Cyclosporine
 Prolonged heparinization
 Addison disease

28. Pointers towards renal tubulopathy
 Failure to thrive
 Delayed physical milestones and weakness
 Polyuria
 Polydypsia
 Resistant rickets (RTA type 2)
 Unexplained hypertension
 Constipation
 Craving for salt & savory foods

29. History
 m/c complain:“my child is not growing”
 Other specific complaints include:
 Polyuria
 Polydipsia
 Constipation
 Episodic weakness
 Gross hematuria and recurrent UTI’s
 Seizures and recurrent fevers
 Antenatal and birth history
 Polyhydroaminos
 Premature delivery
 Family history
 Similar complaints in siblings, renal stones and hearing
impairment

30. Physical examination:
 General appearance
 “dehydrated” or malnourished
 Weight and height percentiles (often below 5th percentile)
 Blood pressure
 Low/normal- exception hypertension (monogenic) such as
Liddle’s syndrome will have hypertension (Stage II)
 Rickets
 P/A
 Renal /abdominal mass
 Ambiguous genitalia/ hyperpigmentation
 Generalized hypotonia

31. 1st step= Complete urine exm.
 Specific gravity
 Most children with salt wasting tubulopathy have sp.gr. of <1010
(dilute urine, corresponding to urine osm. of <300 mOsm/kg)
 Children who can conc. their urine have sp. gr. of >1020 (Renal
tubulopathy can be ruled out)
 Urine pH
 <5.5 = distal tub. acidification mech. is intact
 Proteinuria
 Even 1+ pr. in a dilute urine is significant
 Glycosuria
 In abscense of Hypergycemia indicates Fanconi syn
 Microscopy
 RBCs & Ca oxalate (as in hypercalciuria)

33.  Confirm the presence of a normal anion gap metabolic
acidosis
 Identify electrolyte abnormalities
 Assess renal function
 R/o other causes of bicarbonate loss such as diarrhea
 Blood anion gap
[Na+] − [Cl− + HCO3−]
 <12 = Absence of an anion gap
 >20 =Presence of an anion gap
 If such an anion gap is found, then R/O other diagnoses
 Lactic acidosis
 IEM
 Toxins

35. Urinary anion gap (uAGAP)
(U Na+ + U K+) - U Cl-
 Normal uAGAP is 0 +/- 5 mΣq/L and reflects the urinary
concentration of ammonium
 In distal acidification defect of dRTA, urinary ammonium
excretion is decreased and hence, the uAGAP will be
positive
 In contrast, a negative uAGAP indicates presence of
ammonium and an intact distal acidification mechanism
as seen with diarrhea (urinary chloride excretion is
higher than the sum of sodium and potassium since the
increased urinary ammonium in urine has to bind with
negatively charged chloride ions to be excreted)

37. Spot urine for calcium and creatinine ratio
 Assist in evaluation of hypercalciuria in
 dRTA
 Some forms of Bartter’s syndrome
 Dent’s disease
 Normal ratio is age dependant
 < 0.8 in infants below 6 months
 <0.5 in 6 months – 18 months
 < 0.20 in >18 months age

38.  Abdominal ultrasonography:
 Nephrocalcinosis
 Hydronephrosis
 Hydroureter
 Post void residual urine
 S. magnesium concentration
 S. PTH assay (for Rickets)
 Urinary acidification tests

40.  The mainstay of therapy in all forms of RTA is
bicarbonate replacement
Patients with pRTA
 Often require large quantities of bicarbonate, up to
20 mEq/kg/24 hr, in the form of sodium bicarbonate
or sodium citrate solution
Patients with Fanconi syndrome
 Usually require phosphate supplementation

41. Patients with dRTA
 Base requirement is generally in the range of 2-4
mEq/kg/24 hr, although patients’ requirements vary
 Should be monitored for the development of
hypercalciuria
 Pt with symptomatic hypercalciuria (recurrent episodes
of gross hematuria), nephrocalcinosis, or nephrolithiasis
can require thiazide diuretics to decrease urine calcium
excretion
Patients with type IV RTA
 Require chronic treatment for hyperkalemia with sodium
potassium exchange resin (Kayexalate)

42.  Depends on associated disease
 Good with therapy
 Patients with treated isolated proximal or distal RTA
generally demonstrate improvement in growth,
provided serum bicarbonate levels can be maintained
in the normal range.
 Patients with systemic illness and Fanconi syndrome
can have ongoing morbidity

43.  Nephrocalcinosis, nephrolithiasis (type I)
 Hypercalciuria (type I)
 Hypokalemia (type I, type II if given bicarbonate)
 Hyperkalemia (type IV, some causes of type I)
 Osteomalacia (type II due to phosphate wasting)

47.  Children with RT disorders present with polyuria,
polydipsia, delayed physical milestones and
inadequate growth
 Detailed h/o along with appropriate investigations
can often lead to a specific diagnosis
 Majority of children can be treated with simple
medications
 Early diagnosis (preferably before 2 years age) can
minimize the morbidity and improve growth of
these children