Renal Tubular Acidosis and Uraemic Acidosis

OVERVIEW

Metabolic acidosis can occur in both acute and chronic renal disorders

  • the anion gap may be elevated, due to uraemic acidosis
  • the anion gap may be normal, due to renal tubular acidosis (RTA)

URAEMIC ACIDOSIS

Uraemic acidosis results from the loss of functional nephrons

  • involves injury to glomeruli and tubules
  • decreased glomerular filtration rate (GFR) (e.g. <20 mL/min)
  • failure to excrete acid anions
  • accumulation of acidic anions such as phosphate and sulfate occurs
  • causes high anion gap metabolic acidosis (HAGMA)
  • low plasma HCO3
  • patients manifest as renal failure, often have prolonged survival and develop chronic complications such as bone demineralisation

RENAL TUBULAR ACIDOSIS (RTA)

Renal tubular acidosis (RTA) involves defects isolated to the renal tubules only

  • GFR may be normal or only minimally affected
  • primary problem is defective renal acid-base regulation due to impaired ability to acidify the urine and excrete acid
  • results in net acid retention and hyperchloremic normal anion gap metabolic acidosis (NAGMA)
  • may be incomplete and only develop in the presence of an acid load
  • occurs despite a normal or only mildly reduced glomerular filtration rate (GFR)
  • causes are numerous
  • poorly understood by many physicians
  • RTA is often detected incidentally through an abnormal blood workup, but some patients present with clinical features such as poor growth, dehydration, or altered mental state

COMPARISON OF TYPES OF RENAL TUBULAR ACIDOSIS (RTA)

Type 1 distalType 2 proximalType 4
Defectreduced H+ excretion in distal tubuleimpaired HCO3 reabsorption in proximal tubuleimpaired cation exchange in distal tubule
Hyperchloremic NAGMAyesyesyes
Minimum urine pH>5.5<5.5 (but usually >5.5 before acidosis becomes established)<5.5
plasma HCO3<15usually >15usually >15
Plasma Klow-normallow-normalhigh
Renal stonesyesnono

TYPE 1 RTA

‘Classic’ or distal RTA

  • reduced secretion of H+ in distal tubule results inability to maximally acidify the urine

Causes

  • hereditary (most common, diagnosed in infants and children)
  • autoimmune (e.g. Sjogrens, SLE, thyroiditis)
  • nephrocalcinosis (e.g. primary hyperparathyroidism, vitamin D intoxification)
  • nephrotoxins (e.g. amphotericin B, toluene inhalation)
  • obstructive nephropathy

Investigation

  • urine pH remains >5.5 despite severe acidaemia (HCO3 < 15mmol/L)
  • HCO3 loading test leads to increased urinary HCO3
  • may require an acid load test to see whether urinary pH remains > 5.5
  • hyperchloraemic acidosis, alkaline urine, and renal stone formation
  • secondary hyperaldosteronism results in increased K+ loss in urine

Treatment

  • NaHCO3 (corrects Na+ deficit, ECF volume and corrects hypokalaemia)
  • sodium and potassium citrate solutions can be useful if hypokalaemia persistent
  • citrate also binds Ca2+ in the urine and can help to prevent renal stones

TYPE II RTA

‘Proximal’ RTA

  • termed proximal because the main problem is impaired reabsorption of bicarbonate in the proximal tubule
  • at normal plasma HCO3, 15% of filtered HCO3 is excreted in the urine -> in acidosis when HCO3 levels are low the urine can become HCO3 free
  • symptoms take place when there is an increase in plasma HCO3 -> proximal tubule cannot reabsorb the increased filtered load -> delivered to distal tubule and is unable to be reabsorbed -> urinary loss of HCO3
  • results in metabolic acidosis with an inappropriately high urinary pH and hyperchloraemia (Cl- replaces HCO3 in circulation)
  • with increased distal tubular Na+ delivery, hyperaldosteronism results, leading to K wasting

Causes

  • hereditary (most common, diagnosed in infants and children)
  • part of Fanconi syndrome (proximal tubular defects with impaired reabsorption of glucose, phosphate and amino acids as well as HCO3)
  • vitamin D deficiency
  • cystinosis
  • lead nephropathy
  • amyloidosis
  • medullary cystic disease

Investigations

  • metabolic acidosis (usually not as severe as distal RTA)
  • plasma HCO3 usually > 15mmol/L
  • high urinary HCO3 (inappropriate)
  • hypokalaemia
  • during the NH4Cl loading test urinary pH drops < 5.5

Treatment

  • treat underlying disorder
  • NaHCO3 and K+ supplementation not always necessary (if required will require large doses)
  • thiazide diuretics (some patients respond to this which results in increased proximal HCO3 reabsorption)

TYPE III RTA

  • This term is no longer used
  • considered a subtype of Type 1 where there is a proximal bicarbonate leak in addition to a distal acidification defect (mixed proximal and distal RTA)

TYPE IV RTA

Tubular hyperkalaemia

  • associated with renal failure caused by disorders affecting the renal interstitium and tubules
  • GFR >20mL/min (unlike uraemic acidosis)
  • always associated with hyperkalaemia (unlike others)
  • defect in cation-exchange in the distal tubule with reduced secretion of both H+ and K+
  • physiological reduction in proximal tubular ammonium excretion (impaired ammoniagenesis) due to to hypoaldosteronism, results in a decrease in urine buffering capacity
  • associated with: Addison’s disease or post bilateral adrenalectomy
  • acidosis not common unless there is associated renal damage affect the distal tubule
  • the H+ pump in the tubule is not abnormal so that patients with this disorder are able to decrease their urinary pH to < 5.5 in response to the acidosis

Causes

  • Aldosterone deficiency (hypoaldosteronism)
    • Primary
    • Secondary / hyporeninemic (including diabetic nephropathy)
  • Aldosterone resistance
    • Drugs: NSAIDs, ACE inhibitors and ARBs, Eplerenone, Spironolactone, Trimethoprim, Pentamidine
    • Pseudohypoaldosteronism

Investigations

  • mild metabolic acidosis
  • plasma HCO3 usually > 15mmol/L
  • hyperkalaemia

References and Links

LITFL

Journal articles and textbooks

  • Bersten AD, Soni N. Oh’s Intensive Care Manual (6th edition), Butterworth-Heinemann 2009. [Google Books Preview]
  • Brunner R, Drolz A, Scherzer TM, et al. Renal tubular acidosis is highly prevalent in critically ill patients. Critical care. 2015; 19:148. [pubmed]
  • Haque SK, Ariceta G, Batlle D. Proximal renal tubular acidosis: a not so rare disorder of multiple etiologies. Nephrology, dialysis, transplantation. 2012; 27(12):4273-87. [pubmed]
  • Morris CG, Low J. Metabolic acidosis in the critically ill: part 2. Causes and treatment. Anaesthesia. 2008; 63(4):396-411. [pubmed]
  • Pereira PC, Miranda DM, Oliveira EA, Silva AC. Molecular pathophysiology of renal tubular acidosis. Current genomics. 2009; 10(1):51-9. [pubmed]
  • Ring T, Frische S, Nielsen S. Clinical review: Renal tubular acidosis–a physicochemical approach. Critical care. 2005; 9(6):573-80. [pubmed]
  • Warnock DG. Uremic acidosis. Kidney international. 1988; 34(2):278-87. [pubmed]
  • Yaxley J, Pirrone C. Review of the Diagnostic Evaluation of Renal Tubular Acidosis. The Ochsner journal. 2016; 16(4):525-530. [pubmed]

FOAM and web resources


CCC 700 6

Critical Care

Compendium

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

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