This document provides a case summary and presentation on renal tubular acidosis (RTA). It summarizes the case of a 10-month-old male child admitted with poor urinary stream, straining on urination, recurrent fever, abdominal swelling, and vomiting. Initial investigations revealed metabolic acidosis. The child was diagnosed with posterior urethral valve with obstructive uropathy and bilateral renal parenchymal disease. The document then provides an overview of renal acidification physiology, the different types of RTA including proximal and distal RTA, their characteristics and causes, laboratory diagnosis of RTA, and general treatment approaches.

1. RENAL TUBULAR ACIDOSIS
Presented by
IRENE OBUZOR
Senior Registrar, Nephrology Unit,
Department of Paediatrics UPTH
21st April 2022

2. Case Summary
• I. E, 10 month old male admitted with complaints of:
• Poor urinary stream – noticed 1 week after birth
• Straining on micturition – noticed 1 week after birth
• Recurrent Fever – 2 months
• Abdominal Swelling – 1 week
• Vomiting - 2 days

3. – Poor urinary stream was evidenced by child’s urine not forming
an arch. It dribbled.
– Straining was evidenced by writhing and discomfort before
passing urine.
– Fever was high grade, intermittent, worse at night, transiently
relieved by paracetamol. Child had fever everyday.
– Abdominal swelling was noticed by mother. It started in the
lower abdomen and progressively increased in size. No history
of trauma prior to onset. First episode in child’s life.
– Vomiting was non-projectile, non-billous, non-bloody. Child
vomited about 5 times a day. He vomited 5 times on the day of
presentation.

4. • At onset of symptoms, child was taken to a health centre
in Omagwa where mother was reassured. With onset of
fever, he received syrup paracetamol for 6 weeks and
was subsequently taken to a health centre where he was
investigated.
• MP was done which was positive +. He received IM
meds on outpatient basis daily for 3 days. He also
received Syrup Augmentin for 7 days. With persistence of
vomiting, he was brought to UPTH.

5. • No previous hospital admissions or surgeries. No
previous blood transfusion.
• Pregnancy was supervised at Omagwa HC at 5 months.
Obstetric USS at 5months and 9 months revealed no
abnormality.Pregnancy was carried to term. Delivery was
by SVD at term. No PROM, No peripartum pyrexia. Child
cried well at birth. BW 4.2kg
• He was exclusively breastfed for 1 month following which
NAN was commenced. He was commenced on pap at 7
months. Child is still being breastfed.

6. • Attained neck control at 3 months. Sat at 7 months.
Crawled at 8 months. Yet to walk.
• He is the 4th child of 4 children in a monogamous setting.
• Siblings are 11 and 9 year old male and 6 year old
female.
• ROS
• Cough+, no change in urine colour, fast breathing0,
convulsion0

7. Examination
• Ill looking, in respiratory distress with IC/SCR, Deep
sighing respiration, moderately pale, febrile 37.5c, had dry
buccal mucosa, cap refill 3secs, weight 5.9kg (62% of
expected)
Abdomen
• Distended, MWR
• Abdominal girth 44.5, 2cm above umbilicus
• Tense. Organs difficult to palpate
• Bowel sounds present but normoactive

8. Respiratory System
• RR =50 cpm
• BS Vesicular
CVS
• Pulse moderate volume
and regular
• HR 160bpm
CNS
• Conscious and alert
• AF slightly depressed
• OFC = 43.5cm
• Normal tone in limbs

9. Admitting Diagnosis
• Bladder Outlet Obstruction secondary to ?PUV with ?CKD
• Persistent vomiting with Moderate Dehydration
• PCV 22% then 15% for which was transfused with
sedimented cells
• Post transfusion PCV 27%
• Moderate dehydration was corrected with normal saline.
• Urine output 4mls/kg/hr
• Placed on maintenace 500mls/day

10. E/U/Cr
16/11/2021 20/11/2021 25/11/21 26/11/21 5/12/2021
Sodium 124 133 151 143
Potassium 4.2 4.2 5.1 4.5
Bicarbonate 11 15 11 16
Urea 32.6 66.6 33 14.4
Creatinine 1160 500 730 70
Calcium 2.1
Phosphate 1.4

11. Urinalysis
16/11/21 18/11/21 23/11/21 30/11/21 8/12/21 9/12/21 13/12/21
Leucocyte
s
Negative Large 500cells/ul 125
cells/ul
Trace Trace Trace
Nitrites Negative Positive Negative Negative Negative Negative Negative
Urobilinog
en
Normal + Normal Normal Normal Normal Normal
Protein ++ + ++ Negative ++ + +
pH 6.0 6.0 6.5 6.0 6.0 6.0 6.0
Blood ++ Trace ++
(>200cells/
ul)
80 cells/ul Large Large Large
Specific
Gravity
1.020 1.020 1.015 1.015 1.025 1.025 1.010
Ketones + Negative Negative Negative Negative Negative ++
Bilirubin Nil Negative Negative Negative Negative Negative Negative
Glucose Negative Negative Negative Negative Negative Negative 0.5

12. Abdominal USS
• Kidneys were both enlarged and echogenic with reduced
cortico medullary differentiation. There is moderate utero-
pelvicalyceal dilatation bilaterally.
• Liver is enlarged 9.5 cm
• Urinary bladder contains debritic urine with thickened
walls 7.6mm and trabeculations.
• The posterior urethra is dilated.
• Impression: Findings are in keeping with posterior urethral
valve with obstructive uropathy and bilateral renal
parenchymal disease. Hepatomegaly ?cause

13. Urine MCS
• Moderate growth of E.Coli sensitive to Piperacilin-
Tazobactam and resistant to Cefuroxime, Meropenem,
Ciprofloxacin, Erythromycin and Nitrofurantoin
• He received sodium bicarbonate 1/2 teaspoon bd
• IV Cefuroxime was changed to piperacillin tazobactam
following which he was discharged to do MCUG after
becoming fever free.

14. Renal Tubular Acidosis

15. OBJECTIVES
• Physiology of Renal acidification
• Types of RTA and characteristics
• Laboratory diagnosis of RTA
• Approach to a patient with RTA
• Treatment

16. INTRODUCTION
• The term "renal tubular acidosis" (RTA) refers to a group
of disorders in which, despite a relatively well-preserved
glomerular filtration rate, metabolic acidosis develops
because of defects in the ability of the renal tubules to
perform the normal functions required to maintain acid-
base balance.

17. • The term is applied to a group of transport defects in the
reabsorption of bicarbonate (HCO3
-), the excretion of
hydrogen ion (H+), or both.
• The RTA syndromes are characterized by a relatively
normal GFR and a metabolic acidosis accompanied by
hyperchloremia and a normal plasma anion gap.

19. Normal Renal Function
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

20. Physiology of Renal Acidification
• Kidneys excrete 50-100 meq/day of acid generated daily.
• This is achieved by H+ secretion at different levels in the
nephron.
• The daily acid load cannot be excreted as free H+ ions.
• Secreted H+ ions are excreted by binding to either buffers,
such as HPO42- and creatinine, or to NH3 to form NH4
+.
• The extracellular pH is the primary physiologic regulator of
net acid excretion.

21. Renal acid-base homeostasis may be broadly divided
into 2 processes
1. Proximal tubular absorption of HCO3
- (Proximal
acidification)
2. Distal Urinary acidification
 Reabsorption of remaining HCO3
- that escapes proximal
absorption
 Excretion of fixed acids through buffering & Ammonia
recycling and excretion of NH4
+

22. Proximal tubule physiology
• Proximal tubule contributes to renal acidification by H+
secretion into the tubular lumen through NHE3 transporter
and by HCO3
- reabsorption.
• Approx. 85% of filtered HCO3
- is absorbed by the
proximal tubule.
• The remaining 15 % of the filtered HCO3
- is reabsorbed in
the thick ascending limb and in the outer medullary
collecting tubule.

23. Proximal tubule physiology
Multiple factors are of primary importance in normal
bicarbonate reabsorption
 The sodium-hydrogen exchanger in the luminal
membrane(NHE3).
 The Na-K-ATPase pump
 The enzyme carbonic anhydrase II & IV
 The electrogenic sodium-bicarbonate
cotransporter(NBC-1).

24. Distal Urinary Acidification
• The thick ascending limb of Henle’s loop reabsorbs about
15% of the filtered HCO3
- load by a mechanism similar to
that present in the proximal tubule, i.e., through Na+-H+
apical exchange(NHE3).

25. H+ secretion
• The collecting tubule (CT) is the major site of H+ secretion
and is made up of the medullary collecting duct (MCT)
and the cortical collecting duct (CCT).
• Alpha and Beta-intercalated cells make up 40% of the
lining while Principal cells and collecting tubule cells make
up the remaining.

26. Aldosterone and Renal acidification
• Favors H+ and K+ secretion through enhanced sodium
transport.
• Recruits more amiloride sensitive sodium channels in the
luminal membrane of the collecting tubule.
• Enhances H+-ATPase activity in cortical and medullary
collecting tubules.
• Aldosterone also has an effect on NH4+ excretion by
increasing NH3 synthesis

27. Summary of renal physiology
• H+ secretion, bicarbonate reabsorption and NH4
+
production occur at the proximal tubule.
• NH4+ reabsorption occurs at TAL of loop of Henle and
helps in ammonia recycling that facilitates NH4+ excretion
at MCT.

28. OBJECTIVES
• Physiology of Renal Acidification.
• Types of RTA and characteristics
• Lab diagnosis of RTA
• Approach to a patient with RTA
• Treatment

29. TYPES OF RTA
Proximal RTA (type 2)
• Isolated bicarbonate defect
• Fanconi syndrome
Distal RTA (type 1)
• Classic type
• Hyperkalemic distal RTA
• Hyperkalemic RTA (Type 4)

30. Renal Tubular Acidosis
Type 2 RTA Type 1 RTA
LOW serum K+
Type 4 RTA
HIGH serum K+

31. PROXIMAL RTA
• Proximal RTA (pRTA) is a disorder leading to HCMA
secondary to impaired proximal reabsorption of filtered
bicarbonate.
• Since the proximal tubule is responsible for the
reabsorption of 85-90% of filtered HCO3
- a defect at this
site leads to delivery of large amounts of bicarbonate to
the distal tubule.

32. • This leads to bicarbonaturia, kaliuresis and sodium
losses.
• Thus patients will generally present with hypokalemia and
a HCMA (hyperchloremic metabolic acidosis).

33. • Isolated defects in PCT function are rarely found. Most
patients with a pRTA will have multiple defects in PCT
function with subsequent Fanconi Syndrome.
• The most common causes of Fanconi syndrome in adults
are multiple myeloma and use of acetazolamide.
• In children, cystinosis is the most common.

34. • pRTA is a self limiting disorder and fall of serum HCO3
-
below 12 meq/l is unusual, as the distal acidification
mechanisms are intact.
• Urine pH remains acidic(<5.5) mostly but becomes
alkaline when bicarbonate losses are corrected.

35. Cause of hypokalemia in Type 2 RTA
Metabolic acidosis in and of itself decreases pRT Na+
reabsorption leading to increased distal tubule delivery of
Na+ which promotes K+ secretion.
The pRTA defect almost inevitably leads to salt wasting,
volume depletion and secondary hyperaldosteronism.
The rate of kaliuresis is proportional to distal bicarbonate
delivery. Because of this, alkali therapy tends to
exaggerate the hypokalemia.

36. • Patients with pRTA rarely develop nephrosclerosis or
nephrolithiasis. This is thought to be secondary to high
citrate excretion.
• In children, the hypocalcemia as well as the HCMA will
lead to growth retardation, rickets, osteomalacia and an
abnormal vitamin D metabolism. In adults, osteopenia is
generally seen.

37. To summarise Type 2 RTA
• Proximal defect
• Decreased reabsorption of HCO3
-
• HCO3
- wasting, net H+ excess
• Urine pH < 5.5
• K+: low to normal

38. Type 2 RTA
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

39. DISTAL RTA
• Distal RTA (dRTA) is a disorder leading to HCMA
secondary to impaired distal H+ secretion.
• It is characterized by inability to lower urine pH
maximally(<5.5) under the stimulus of systemic
acidemia. The serum HCO3
- levels are very low
<12 meq/l.
• It is often associated with hypercalciuria,
hypocitraturia, nephrocalcinosis, and
osteomalacia.

40. • The most common causes in adults are autoimmune
disorders, such as Sjögren's syndrome.
• In children, type 1 RTA is most often a primary, hereditary
condition.

41. • A high urinary pH (>5.5) is found in the majority of patients
with a secretory dRTA.
• Urine PCO2 does not increase normally after a
bicarbonate load reflecting decreased distal hydrogen ion
secretion.
• Serum potassium is reduced in 50% of patients. This is
thought to be from increased kaliuresis to offset
decreased H+ and H-K-ATPase activity.

42. What Charles Dicken’s character is theorized to
have suffered from RTA?
Tiny Tim
• Growth retardation
• Bone disease
• Intermittent muscle weakness
(hypokalemia)
• Kidney stones
• Progressive renal failure
• Death
Lewis DW, Am J Dis Child. 1992 Dec; 146(12): 1403-7.

43. To summarise Type 1 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

44. Type 1 RTA
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

46. Serrano A and Batlle D. N Engl J Med 2008;359:e1
A 16-year-old boy was referred for evaluation of distal renal tubular acidosis

47. Type 4 RTA (Hyperkalemic RTA)
• This disorder is characterized by modest HCMA with
normal AG and association with hyperkalemia.
• This condition occurs primarily due to decreased urinary
ammonium excretion.
• Hypoaldosteronism is considered to be the most
common etiology. Other causes include NSAIDS, ACE
inhibitors, adrenal insufficiency etc.

48. • In contrast to hyperkalemic distal RTA, the ability to lower
urine pH in response to systemic acidosis is maintained.
• Nephrocalcinosis is absent in this disorder.

49. To summarise Type 4 RTA
• Aldosterone deficiency or distal tubule resistance to
Aldosterone  Impaired function of Na+/K+-H+ (cation)
exchange mechanism
• Decreased H+ and K+ secretion plasma buildup of H+
and K+ (hyperkalemia)
• Urine pH < 5.5

50. Type 4 RTA
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

51. What happened to Type 3 RTA?
• 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

52. OBJECTIVES
• Physiology of Renal Acidification.
• Types of RTA and characteristics
• Lab diagnosis of RTA
• Approach to a patient with RTA
• Treatment

53. Lab diagnosis of RTA
• RTA should be suspected when metabolic acidosis is
accompanied by hyperchloremia and a normal plasma
anion gap (Na+ - [Cl- + HCO3
-] = 8 to 16 mmol/L) in a
patient without evidence of gastrointestinal HCO3
- losses
and who is not taking acetazolamide or ingesting
exogenous acid.

54. Functional evaluation of proximal bicarbonate absorption
Fractional excretion of bicarbonate
• Urine pH monitoring during IV administration of sodium
bicarbonate.
• FEHCO3 is increased in proximal RTA >15% and is low in
other forms of RTA
(FEHCO3 = fractional excretion of HCO3)

55. Functional Evaluation of Distal Urinary
Acidification and Potassium Secretion
• Urine pH
• Urine anion gap
• Urine osmolal gap
• Urine pCO2
• Urinary citrate

56. Urine pH
• In humans, the minimum urine pH that can be achieved is
4.5 to 5.0.
• Ideally urine pH should be measured in a fresh morning
urine sample.
• A low urine pH does not ensure normal distal acidification
and vice versa.
• The urine pH must always be evaluated in conjunction
with the urinary NH4
+ content to assess the distal
acidification process adequately.
• Urine sodium should be known and urine should not be
infected.

57. Urine Anion Gap
• Urine AG = Urine (Na + K - Cl).
• The urine AG has a negative value in most patients with a
normal AG metabolic acidosis.
• Patients with renal failure, type 1 (distal) renal tubular
acidosis (RTA), or hypoaldosteronism (type 4 RTA) are
unable to excrete ammonium normally. As a result, the
urine AG will have a positive value.

58. • There are, however, two settings in which the urine AG
cannot be used.
• When the patient is volume depleted with a urine sodium
concentration below 25 meq/L.
• When there is increased excretion of unmeasured anions

59. Urine Citrate
• The proximal tubule reabsorbs most (70-90%) of the
filtered citrate.
• Acid-base status plays the most significant role in citrate
excretion.
• Alkalosis enhances citrate excretion, while acidosis
decreases it.
• Citrate excretion is impaired by acidosis, hypokalemia and
UTI.

60. OBJECTIVES
• Physiology of Renal acidification.
• Types of RTA and characteristics
• Lab diagnosis of RTA
• Approach to a patient with RTA
• Treatment

63. OBJECTIVES
• Physiology of Renal acidification.
• Types of RTA and characteristics
• Lab diagnosis of RTA
• Approach to a patient with RTA
• Treatment

64. Treatment
Proximal RTA
• A mixture of Na+ and K+ salts, preferably citrate, is
preferable.
• 10 to 15 meq of alkali/kg may be required per day to stay
ahead of urinary losses.
• Thiazide diuretic may be beneficial if large doses of alkali
are ineffective or not well tolerated.
• Vit D

65. Treatment
Distal RTA
• Bicarbonate wasting is negligible in adults who can
generally be treated with 1 to 2 meq/kg of sodium citrate or
bicarbonate. Sodium citrate tolerated better than sodium
bicarb
• Potassium citrate, alone or with sodium citrate, is indicated
for persistent hypokalemia or for calcium stone disease.
• For patients with hyperkalemic distal RTA, high-sodium,
low-potassium diet plus a thiazide or loop diuretic if
necessary.

66. Hyperkalemic RTA
• Treatment and prognosis depends on the underlying
cause.
• Potassium-retaining drugs should always be withdrawn.
• Fludrocortisone therapy may also be useful in
hyporeninemic hypoaldosteronism, preferably in
combination with a loop diuretic such as furosemide to
reduce the risk of extracellular fluid volume expansion
• Dietary restriction of sodium

67. Take Home Points
• Distinguish RTA Types 1, 2 and 4
Some clues:
– Type 1: renal stones, hypercalciuria, high urine pH despite
metabolic acidosis
– Type 2: think acetazolamide and bicarbonate wasting;
Fanconi syndrome
– Type 4: aldosterone deficiency and hyperkalemia
• Mainstay of treatment of RTA
– Bicarbonate therapy

68. THANK YOU !