|
| | Renal
tubular acidosis
- Ammonium excretion low in renal tubular acidosis
- Ammonium in urine = (urine osmolal gap)/2
- Urine osmolal gap= Measured osmolality-calculated osmolality
- Calculated osmolality= 2(Na + K) + urea + glucose
Distal RTA
RTA-2
RTA-4
Distal RTA ("classical",
"gradient", type I)
Characterized by an inability to generate a normal minimum urinary pH even in
the presence of severe systemic acidosis
Aetiology
Primary: hereditary (autosomal dominant)/sporadic
Secondary:
- associated with auto-immune disease, especially Sjogren’s. Also other
conditions associated with dysglobulinaemia or hypergammaglobulinaemia, primary
biliary cirrhosis
- drugs: ampthotericin, analgesic nephropathy
- nephrocalcinosis (eg due to hyperparathyroidismh, chronic vitamin D poisoning)
- direct damage to renal medulla: pyelonephritis, papillary necrosis, chronic
obstructive uropathy, medullary sponge kidney, sickle cell
- fibrosing alveolitis (rare)
Pathophysiology
- due to a failure of distal nephron and collecting duct to generate the
800-900:1 H+ gradient found in normals. Results in failure to
reabsorb filtered bicarbonate that was not reabsorbed in proximal tubule. Also
results in failure of titration of phosphate buffer and decreased excretion of
NH4+ (decreased by alkaline urine). Failure of excretion
of NH4+ encourages urea synthesis (as an alternative
route of excretion of nitrogen) and hence H+ synthesis
- precise nature of defect is not known. Could be a failure of active hydrogen
ion secretion in the distal nephron or it could be abnormal permeability to H+
allowing leak-back after secretion into tubule. Latter mechanisms occurs in
RTA-1 associated with amphotericin: this inserts itself into the luminal cell
membrane and provides a channel for back leakage of H+ into the
cell or of bicarbonate out of the cell into the lumen
- except in rare patients with mixed syndromes proximal tubular function is
normal in terms of H+ excretion and bicarb reabsorption
- hypokalaemia that is frequently present is due to lack of H+ flux
out of the tubular cell into the lumen which encourages K+ exchange
instead and to secondary hyperaldosteronism due to impaired Na reabsorption
due to decreased Na/H exchange. Correction of acidosis allows more H+
secretion and hence ameliorates Na and K loss
- renal stones generally due to hypercalciuria and hypercitraturia
Clinical features
- presents in infancy, childhood or adult life
- usually presents with acute acidosis and hyperventilation, often accompanied
by muscular weakness due to hypokalaemia
- in most patients attacks of acute acidosis represent a worsening of mild
chronic hyperchloraemic metabolic acidosis which may have been fully
compensated until presentation
- 70% have either nephrocalcinosis (very rarely a feature of other types) or
calcium containing renal calculi
- rickets and growth stunting are frequent features in childhood cases. ±
osteomalacia in adults
Investigations
- in acute state diagnosis is usually simple: urinary pH>5.5 (and usually
6) in the presence of a normal anion-gap metabolic acidosis, hyperchloraemia,
and normal or near normal urea and creatinine
- severe hypokalaemia
- hypercalciuria
- ± evidence of renal calcification
- failure to acidify urine maximally in presence of severe acidosis (bicarb
<12) helps to distinguish condition from RTA 2 and 4
- diagnosis during the chronic non-acute state requires a short acid load
test. This should not be performed if bicarbonate <19 mmol/l
Treatment
- correct hypokalaemia before acidosis
- isotonic sodium bicarbonate IV. Aim to restore abnormality over a few hours
- oral sodium bicarbonate is required in chronic condition
RTA-2 (bicarbonate wasting)
- Superficially clinically similar to RTA-1
- Rare as an isolated defect and in the great majority of patients is
associated with multiple abnormalities of proximal tubular function with
reabsorption defects for glucose, amino acids and phosphate (Fanconi syndrome)
Aetiology
- Nearly always some factor which damages proximal tubular function can be
identified. Causes of an isolated defect include a familial autosomal dominant
form, treatment with acetazolamide and carbonic anhydrase II deficiency
- Causes of Fanconi syndrome include:
Genetic causes: cystinosis, Wilson’s disease, hereditary fructose
intolerance
Acquired: - vitamin D deficiency
- lead poisoning
- multiple myeloma
- outdated tetracycline therapy
- hyperPTH
- nephrotic syndrome
Pathophysiology
- depression of capacity of proximal tubule to secrete H+ and thus
reabsorb bicarbonate. Usually bicarbonate does not appear in urine until
plasma bicarb >25-28 mmol/l. In RTA-2 this threshold is lowered so that
distal nephron is flooded with bicarbonate. This exceeds the capacity of the
distal nephron to secrete sufficient H+ to reabsorb the bicarb,
which therefore spills over into the urine
- loss of bicarb results in a fall of plasma bicarb. and thus a fall in
filtered bicarbonate. Eventually this reaches a level at which the proximal
nephron can cope and then the distal nephron is fully capable of producing a
normally minimal urinary pH of 4.5-5.3
- acidosis is predominantly due to the bicarbonate leak but is in part due to
failure of titration of phosphate and failure of appropriate NH4+
excretion due to inappropriately high urine pH (at least while plasma bicarbonate
remains above renal threshold)
- high distal load of sodium bicarbonate responsible for Na wastage. This
leads to secondary hyperaldosteronism and hypokalaemia due to K wastage
- polyuria due to distal sodium bicarbonate load and effects of K deficiency
on renal concentrating mechanism
Clinical features
- provided patient is sufficiently acidotic urine pH falls to normal minimum
- nephrocalcinosis and renal calcul are virtually never present
- ± marked polyuria and polydipsia, especially in
those patients in whom the acidosis has been fully controlled by bicarbonate
therapy
- proximal myopathy, osteomalacia or rickets are common associations. Probably
because of frequent aetiological involvement of disorders of vitamin D supply
or metabolism
- presents with chronic ( or acute exacerbation) of normal anion gap acidosis
with a marked tendency to K deficiency
Treatment
- large amounts of bicarbonate may be required
- correction of acidosis does not help and may worsen K deficiency and
polyuria by increasing sodium bicarbonate load to distal nephron. Give K
supplements as potassium bicarbonate
- if amount of oral bicarbonate is intolerable hydrochlorothiazide may help by
decreasing the filtered load of bicarbonate. However it may increase the need
for potassium supplements
RTA-4 (hyperkalaemic)
Often associated with slight/moderate glomerular impairment but hyperkalaemia
is quite out of proportion to this
Pathophysiology
- basic abnormality in most cases is hypoaldosteronism or failure of
aldosterone action
- this diminishes the capacity of the H+ secreting mechanism in the
distal nephron but not its power to sustain a pH gradient if bicarbonate
delivery from the proximal tubule is small
- hyperkalaemia (due to aldosterone deficiency) suppresses renal production of
NH4+ with resultant increased production of urea and H+.
This is largely responsible for the acidosis
- amiloride may lead to RTA-4 by blocking reabsorption of Na in the cortical
collecting ducts. This reduces the negative luminal potential required for K
and H secretion
Aetiology
Primary adrenal disease (eg Addison’s) and some in-born errors of steroid
synthesis
Renin deficiency:
- chronic renal disease, especially diabetic and chronic tubulointerstitial
disease (including pyelonephritis)
- NSAIDs (renin production is to some extent dependent on PGs)
- ACE inhibitors
- b blockers
- potassium sparing diuretics and aldosterone antagonists
Clinical features
Presents with metabolic acidosis with normal or near-normal anion gap and
hyperkalaemia. If the plasma bicarbonate fall sufficiently the distal tubule is
able to mount a normal blood/urine pH gradient
Treatment
Mineralocorticoid (typically 0.05-0.15 mg/day of fludrocortisone) for those
with significant acidosis or potentially dangerous hyperkalaemia
Further reading
Cohen RD. The renal tubular acidoses. Oxford Textbook of Medicine, 3rd
ed, 1996
© Charles Gomersall December 1999 |
