Renal Tubular Acidosis

Lynn Rowbottom
Department of Clinical Biochemistry & Metabolic Medicine
Royal Liverpool & Broadgreen University Hospitals Trust

What is RTA?
Group of hyperchloraemic metabolic acidoses
Secondary to abnormality in urine acidification
Impaired acid excretion
Impaired bicarb reabsorption
GFR preserved

HCO3
Cl
N Anion Gap

Does this
pattern look
familiar?

Classification
Type 1 : Distal RTA
:Inadequate H+ secretion
Type 2 : Proximal RTA :Inadequate HCO3 reabsorption
Type 4 : Distal RTA with K. Mineralocorticoid deficiency
Type 3 : Rare (mixture of type 1 & 2)

Type 1 aka Classical Distal RTA - if H+ secretion is sole defect

Type 4 aka Generalised Distal RTA - if hyperkalaemia + acidosis

Acidosis recap
2500-3000 mmol/24h H+ produced per day
Acid

Production

Disposal

mmol/24h

CO2

Tissue
respiration

Lungs

20000

Lactate

Glycolysis

Gluconeogenesis
Oxidation

1300

Free fatty
acids

Lipolysis

Resterification
Oxidation

Ketoacids

Ketogenesis

Oxidation

400

H+ from urea
synthesis

Ureagenesis

Oxidation of amino acids

Renal excretion

1100
40

Role of kidney in H+ homeostasis

PROXIMAL TUBULE
Reabsorption of HCO3 (80%)
Reabsorption of glucose,
amino acids, organic anions,
phosphate

DISTAL TUBULE
Regeneration of remaining HCO3 (20%)
Secretion of H+
NH4+ generation from glutamine

Role of kidney in H+ homeostasis

PROXIMAL TUBULE
Reabsorption of HCO3 (80%)
Reabsorption of glucose,
amino acids, organic anions,
phosphate
Proximal tubular cell
CO2 + H2O CA
H2CO3
HCO3 +
-

H+
Na+

DISTAL TUBULE
Regeneration of remaining HCO3 (20%)
Secretion of H+
NH4+ generation from glutamine

Lumen

Distal tubular cell

HCO3+
H+

H2CO3

CO2
+
H2O

Lumen

CO2 + H2O CA
H2CO3

HCO3 + H+
-

Na+

H+

HPO4-2

H2PO4-

Role of kidney in H+ homeostasis

PROXIMAL TUBULE
Reabsorption of HCO3 (80%)
Reabsorption of glucose,
amino acids, organic anions,
phosphate

DISTAL TUBULE
Regeneration of remaining HCO3 (20%)
Secretion of H+
NH4+ generation from glutamine
Distal tubular cell

Lumen

CO2 + H2O CA
H2CO3

HCO3 + H+
-

NH4+
Gln

H+ + NH3

H+

NH3

NH4+

Type 1 (Distal RTA)

Features
Failure to lower urine pH (<5.5)
Impaired NH4+ excretion
Intact HCO3 reabsorption
Nephrocalcinosis, urolithiasis

Type 2 (Proximal RTA)

Features
Impaired HCO3 reabsorption
Isolated/generalised defect e.g as
part of Fanconis Syndrome
Bicarbonaturia (low threshold for
bicarb reabsorption)
Intact H+ secretion in distal cells

HCO3-

20
15
10

HCO3-

20
15
10

Type 3/mixed RTA

Initially used to describe transient & severe form
of distal RTA in infants
Currently used to describe a rare autosomal
recessive syndrome resulting from carbonic
anhydrase II deficiency
Features of both proximal and distal RTA
In addition to RTA, patients suffer osteoporosis,
cerebral calcification & mental retardation

Incomplete distal RTA

Features
Persistently high urine pH (even after an acute acid load)
Hypocitraturia
Normal HCO3 (no metabolic acidosis) as able to maintain
net H+ excretion
Hypercalciuria + hypocitraturia = nephrolithiasis

Type 4 RTA
(Hypoaldosteronism)
Aldosterone deficiency or
tubular resistance to action of
aldosterone
Features
Hyperkalaemia (impaired K
secretion)
Mild acidosis (impaired H+
secretion)
Impaired secretion of NH4+
Appropriately low urine pH
(5.3 in presence of acidosis)

Diagnosis of RTA
Hyperchloraemic metabolic acidosis not explained by
bicarbonate losses from the intestinal tract should
raise the suspicion of RTA
Plasma potassium (low in RTA 1 & 2, high in RTA 4)
Presence of other features of Fanconi syndrome
suggest type 2 RTA.
Amount of bicarb required to correct acidosis can help
distinguish between type 1 and type 2 RTA (type 2
requires much more bicarb)

Dynamic Function Tests

Early morning/first pass urine after overnight fast pH <5.5
Urinary acidification test NH4Cl 100mg/kg body weight.
Measure urine pH every hour for 8h
Normal - urine pH will fall below 5.5 at least once
Distal RTA (type1) - urine pH fails to fall below 5.5 &
often stays above 6.5
NH4Cl can be unpleasant & is not used in patients with
liver disease - Calcium chloride 1mmol/kg body weight

Management
Type 1 : Administer bicarb 1-2mmol/kg/day
Type 2 : Bicarb 5-15 mmol/kg/day (+K)
Type 4 : Fludrocortisone 0.1-0.2 mg/bds for
mineralocorticoid deficiency OR diuretic therapy
+ low K diet if mineralocorticoid resistant

Case 1
76 yo male presented with fall, c/o tiredness & SOB. No D/V.
PMH: Hypertension, COPD, OA, IDA.
No history of high alcohol intake.
Medication:
Domperidone
Clopidogrel
Sodium bicarbonate
Ferrous sulphate
Ascorbic acid
Lansoprazole and
Amlodipine
Inhalers
All observations unremarkable

Biochemistry Results
Na
K
Cl
HCO3
Urea
Creat
AGap
eGFR

141 mmol/L (132-144)

3.0 mmol/L (3.2-4.8)
116 mmol/L (98-108)
8 mmol/L (23-33)
6.6 mmol/L (3.0-8.0)
130 umol/L (60-120)
20 (10-20)
47 ml/min (>90)

Hb
HCT
MCV
PLT
WBC

10.2 g/dL (13.3 - 16.7)

31.1% (39.0 - 50.0)
87.7 fl (80-100)
244 109/L (150-400)
7.5 109/L (3.5-11.0)

Urine pH

5.0

pH
H+
pCO2
pO2
Std Bicarb
Base excess

7.27 (7.35-7.45)
54 nmol/L (35-45)
2.1 kPa (4.7-6.0)
12.4 kPa (11.3-14.0)
11 mmol/L (22-26)
-17.6 (-2.3 - +2.3)

ACa
PO4
Alb
TP

2.21 mmol/L (2.20-2.60)

0.76 mmol/L (0.80-1.50)
32 g/L (35-50)
55 g/L (60-80)

Provisional diagnosis - RTA

Discharged with sodium bicarbonate & potassium
citrate
Which type is this?

Case 2
40 yo female
Unexplained hyperchloraemic normal
anion gap metabolic acidosis
Medullary Sponge Kidney
Recurrent stone former
Hearing impairment
Osteopenia of hip (T-1.5) & spine (T-1.3)

Biochemistry results
Na
K
Cl
HCO3
Urea
Creat
AGap
eGFR

143 mmol/L (132-144)

4.1 mmol/L (3.2-4.8)
115 mmol/L (98-108)
18 mmol/L (23-33)
8.7 mmol/L (3.0-8.0)
84 umol/L (60-120)
14 (10-20)
66 ml/min (>90)

Urine pH

6.49

pH
H+
pCO2
pO2
Std Bicarb
Base excess

7.27 (7.35-7.45)
54 nmol/L (35-45)
6.8 kPa (4.7-6.0)
3.7 kPa (11.3-14.0)
19 mmol/L (22-26)
-4.6 (-2.3 - +2.3)

Glucose
ACa
PO4
TP
Alb

4.6 mmol/L (3.5-6.0)

2.31 mmol/L (2.20-2.60)
1.03 mmol/L (0.80-1.50)
60 g/L (60-80)
41 g/L (35-50)

Suggests distal (type 1) RTA

Urine citrate
Volume
Citrate
Cit/24h

Urine
1.65L
0.05 mmol/L
0.08 mmol/24h (1.3-6.0)

Also suggests dRTA (& explains stone formation)

Exclude bacterial contamination (UTI) or
malabsorptive disorders
Treatment:
Sodium bicarbonate (1g tds)
Potassium citrate (10ml nocte)
GP to monitor K

Case 3
76 year old female
Type 2 diabetes
Na
K
Cl
HCO3
Urea
Creat
AGap
eGFR

132 mmol/L (132-144)

6.0 mmol/L (3.2-4.8)
110 mmol/L (98-108)
17 mmol/L (23-33)
9.2 mmol/L (3.0-8.0)
128 umol/L (60-120)
11 (10-20)
66 ml/min (>90)

TTKG calculation
Urine K x Serum osmo
Serum K x Urine osmo
Indicates level of aldosterone
Normal TTKG ~ 8-9
In hyperkalaemia TTKG should be >10
If hyperkalaemic & TTKG <7 = possible
mineralocorticoid deficiency
If hypokalaemic TTKG should be <3

Calculation

Posmo = 280
Uosmo = 320
[K+]plasma = 6.0
[K+]urine = 10

10 x 280
6 x 320

= 1.5 reflects low aldo activity at

renal tubules

Consistent with Type 4 RTA - Measure renin &

aldosterone & consider fludrocortisone therapy

Thank you for your attention

lynn.rowbottom@rlbuht.nhs.uk