Last updated: Lesson of the Month - January 2019…
on 01 Jan 2019

August 2014

A New Diagnosis of Distal Renal Tubular Acidosis

Paren Chohan BSc. MBCHB, Foundation Year and Yogita Aggarwal  MRCP (SpR)


The Presentation:

History:  A 27 year old female was admitted with a one day history of intolerable dysphagia, odynophagia and upper abdominal pain which had been low-grade for 1 month.  She was unable to keep down fluids or any of her medication. She had lost 2Kg of weight in the last month.  No other symptoms were elicited on presentation.


Her past medical history included:

  1. Primary Sjogrens Syndrome with Sicca symptoms and Raynaud’s phenomenon – this had been diagnosed when she was 6 years old and she was under the care of a rheumatologist.  She was maintained on Prednisolone and had previously failed to tolerate hydroxycholorine therapy due to its associated side effects.
  2. Raynaud's Syndrome
  3. Renal Stones of unknown aetiology


Her medications were as follows:  Proton pump inhibitor, lubricant eye drops, Prednisolone 5mg od, multivitamins, Calcium and vitamin D supplements for bone protection.

She lived with her parents and was studying at university.  She denied recreational drug use and was compliant with medications and follow-ups with her rheumatologist.



On examination she had the following observations:

  • The patient appeared to be relatively well.
  • Afebrile                                                   
  • BM 5.4
  • 85/60**   usually 105/70                               
  • 90bpm
  • RR 21 – increased
  • BMI 18** usually 19.5                             
  • Normal height in keeping with parental parameters and normal pubertal development.
  • Evidence of moderate dehydration.
  • Normal cardio-respiratory, abdominal, neurological, and musculoskeletal examination.



  • Urine dip – trace protein only with a slight elevated specific gravity.
  • Venous Blood Gas (VBG) showed a severe hypokalaemic hyperchloraemic metabolic acidosis with a normal anion gap:

        pH: 7.14                Na: 144          

        BE: -11                  Cl: 111  (96-106mEq/l)             

        HCO3: 14              K: 1.9

        Ca: 1.188              Lactate 1.2

  • Anion gap: (Na + K) – (Cl +HCO3)= (144 + 1.9) - (111 + 14) = 20.9  (reference range 16 +/- 5 mEq/l)
  • Laboratory blood tests showed:

       Na 146                     K 2.2                  Urea 8 (baseline 3)                  Creatinine 90 (baseline 50)

       Albumin 43              Corrected Calcium 1.96mmol/l                           Magnesium 0.7

       FBC/Clotting  - normal

  • ECG - normal



The patient received fluid resuscitation with hartmanns solution and was started on IV potassium replacement in a cardiac monitored setting.  Her renal function improved to normal.

Based on these VBGs and the patient's past medical history a probable diagnosis of distal renal tubular acidosis was made, especially as there is a known strong association with autoimmune disease. The anion gap was higher than expected due to concurrent pre renal acute kidney injury (AKI).  The degree of hypokalaemia, hyperchloraemia and low bicarbonate level were disproportionate for the AKI and symptoms causing her presentation.  Further the AKI did not account for the hypocalcaemia or history of recurrent renal stones. She also had an OGD which showed mild oesophagitis thought to be related to vomiting.

The urine pH was 7.3 and failed to fall <5.3 with the urine acidification test.  Urine retinol binding proteins were requested – this test was positive.  Further urine tests showed: increased urinary potassium losses, low urine citrate excretion, low urine ammonium excretion and a low urine osmolality.

The patient was discharged with calcium, magnesium, potassium citrate, bicarbonate and vitamin supplementation.  She was advised to drink more than 3L of fluid a day in order to reduce the likelihood of stone formation.  A urine stones analysis was requested – the results are summarised above.


Discussion & Learning Points

Renal tubular acidosis (RTA) describes several tubular disorders which result as a failure of the kidneys to excrete hydrogen ions or reabsorb bicarbonate ions.

There are four types:

  • Type 1 - Also known as distal RTA.  It is called type 1 as it was discovered first.
  • Type 2 - Proximal RTA.  Caused by the failure of the proximal tubular cells to reabsorb bicarbonate from the urine leading to acidosis (lack of bicarbonate buffer).
  • Type 3 - Mixed.  A rare autosomal recessive form due to deficiency of the enzyme carbonic anhydrase 2 (CAII), which can lead to a mixture of types 1 and 2
  • Type 4 - Hyperkalaemia.  Distal nephron aldosterone resistance and presents with hyperkalaemia


Distal RTA

Caused by failure of the alpha intercalated cells, found in the distal tubule and collecting tubule, to excrete acid.  The diagnosis is suspected with a urine pH >5.5 in the context of systemic acidosis due to low serum bicarbonate, and a near normal GFR.  Urine infections have to be eliminated.  When the urine acidification test is applied the urine pH fails to fall to <5.3.

The causes can be divided into inherited or acquired.  Inherited aetiology is due to mutations in the transporter channels found on the basolateral (i.e. AEC1 mutations) and apical membranes (i.e. vH+-ATPase mutations) of the alpha-intercalated cells.

Acquired aetiology is more common and includes:

  1. Autoimmune disease
  2. Obstructive uropathy
  3. Nephrocalcinosis
  4. Renal transplantation
  5. Toxins and medications
  6. Sickle cell anaemia


Clinical features include:

  1. Being asymptomatic with a metabolic acidosis of normal anion gap,
  2. Renal calculi – usually calcium phosphate stones – due to hypocitraturia, hypercalciuria and alkaline urine
  3. Nephrocalcinosis
  4. Bone demineralisation
  5. Symptomatic hypokalaemia: weak muscles, tetany


To make a diagnosis, the following is usually observed:

  1. Metabolic acidosis with normal anion gap
  2. Serum - Hypokalaemia, hyperchloraemia
  3. Urine – relative high urine potassium losses, hypocitraturia, hypercalciuria, alkaline urine, infrequently low osmolality low ammonium excretion
  4. Sometimes concurrent nephrocalcinosis,  see picture 1
  5. Urine that fails to acidify with the urine acidification test
  6. Low grade proteinuria due to loss of tubular proteins
  7. A renal biopsy is not required unless other concurrent conditions are thought to exist where management will change


[Text Box: Picture 1.: Nephrocalcinosis Courtesy of ]


Treatment and management includes:

  1. Counselling the patient that there is no cure for RTA and treatment focuses on symptom control and minimising future complications such as renal stone formation and bone demineralisation
  2. High fluid intake esp. if the patient is a ‘stone former’ – ideally more than 3L a day
  3. Correction of acidosis with oral alkali. 1-2mmol/kg is given in order to achieve a serum bicarbonate of more than 20mmol/l
  4. Potassium replacement
  5. Citrate replacement – increasing urine citrate excretion can reduce stone formation
  6. Bone protection
  7. Renal function, blood pressure and urine protein excretion monitoring
  8. Treatment compliance



  1. Oxford Desk Reference: Nephrology (2009) by Jonathan Barratt, Kevin Harris, and Peter Topham
    1. Chapter 2 – Fluid and electrolyte disorders
    2. Chapter 5 – Tubular Disease
  2. Soriano JR. Renal Tubular Acidosis: The Clinical Entity. JASN August 1, 2002 vol. 13 no. 8 2160-2170
  3. Karet FE.  Inherited Distal Renal Tubular Acidosis.  JASN August 1, 2002 vol. 13 no. 8 2178-2184
  4. Walsh B Birgese F, Gabillat N et al.  Cation transport activity of anion exchanger 1 mutations found in inherited distal renal tubular acidosis. Am J Physiol Renal Physiol. 2008 Aug; 295(2):F343-50.

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