What is renal glycosuria
-Disorder of the proximal tubule where glucose is not reabsorbed
Give the defect, mechanism, clinical features and treatment of renal glycosuria
- defect= sodium glucose transporter 2 (SGLT2)
- mechanism = failure of glucose reabsorption in proximal tubule
- clinical features = incidental finding on testing, benign
- treatment = SGLT2 inhibitors (e.g empagliflozin) now established as treatments for type 2 diabetes
What is aminoaciduria (e.g cystinuria)
Disorder in the proximal tubule where amino acids like cystine are not reabsorbed
Give the defect, mechanism and clinical features of cystinuria
- defect = renal basic amino acid transporter (rBAT)
- mechanism = failure of cystine reabsorption, increased urinary cystine concentration which can lead to stone formation
- clinical features = renal colic, recurrent stone formation
- treatment =
Give the treatment of cystinuria
- high fluid intake = causes high urine flow and lower concentration of cystine
- alkalinise urine = increases solubility of cystine
- chelation = through penicillamine, captopril
- management of individual stones = percutaneous treatment, surgery
What is hypophosphataemic rickets
Disorder of the proximal tubule where phosphate is not reabsorbed
The commonest form is the x linked hypophosphataemic rickets (XLH)
Give the defect, mechanism, clinical features and treatment of hypophosphataemic rickets (XLH)
- defect = PHEX gene - zinc dependent metalloprotease
- mechanism = PHEX mutation causes increased FGF-23 levels which leads to decreased expression and activity of the NaPi-2 in the proximal tubules
- clinical manifestation = bow legged deformity, impaired growth
- treatment = phosphate replacement
What is type 2 renal tubular acidosis
Disorder in the proximal tubule where bicarbonate is not reabsorbed
Give the defect, mechanism, clinical features and treatments of type 2 renal tubular acidosis
- defect = sodium/hydrogen antiporter
- mechanism = failure to bicarbonate reabsorption
- clinical features = acidosis, impaired growth
- treatment = bicarbonate supplementation
What can defects in carbonic anhydrase produce
-mixed proximal/distal renal tubular acidosis
What drug can be used to inhibit carbonic anhydrase and when might this be useful
acetazolamide
- causes mild diuretic effect and induces a metabolic acidosis
- used to treat altitude sickness because it allows rapid compensation of respiratory alkalosis
What is fanconi syndrome
Multiple disorders of reabsorption in the proximal tubule
Give the cause, mechanism and clinical features of fanconi syndrome
- cause = genetic (e.g cystinosis, Wilson’s disease), myeloma, lead poisoning, cisplatin
- mechanism = generalised proximal tubular dysfunction possibly due to failure to generate sodium gradient by Na/K ATPase
- clinical features = glycosuria, aminoaciduria, phosphaturic rickets, renal tubular acidosis
What is Barrter’s syndrome
Disorder in the thick ascending limb of the loop of Henle
Give a defect and mechanism of Barrter’s syndrome
- defect = NaKCC2, ROMK, ClCKa/b, Barrtin
- mechanism = failure of sodium, potassium and chloride cotransport in thick ascending limb, salt wasting, hypokalaemic alkalosis due to volume contraction, failure of voltage dependent calcium and magnesium absorption
Give clinical feature of Barrter’s syndrome
Antenatal - polyhydramnios, prematurity, delayed growth, nephrocalcinosis
Classical - delayed growth, polyuria, polydipsia
Similar effects to loop diuretics (e.g furosemide, bumetanide)
What is Gitelman’s syndrome
Disorder of the NCCT (thiazide sensitive chloride channel) in the distal tubule
Give the defect, mechanism and clinical features of Gitelman’s syndrome
- defect = NCCT (thiazide sensitive chloride channel)
- mechanism = failure of sodium/chloride cotransport in distal tubule, hypokalaemic alkalosis due to volume contraction, impaired magnesium absorption, increased calcium
- clinical features = polyuria, polydipsia, tetany
Give the defect, mechanism and causes of type 1 (distal) renal tubular acidosis
- defect = luminal H+ ATPase or H+/K+ ATPase
- mechanism = failure of H+ excretion and urinary acidification
- causes = genetic (e.g Sjogren’s syndrome) and acquired (e.g chronic pyelonephritis, drugs - amphotericin)
Give the effects of excessive aldosterone activity
- sodium retention
- hypertension
- hypokalaemic alkalosis
Give a primary and secondary of excessive aldosterone production
Conn’s syndrome (primary)
Renal artery stenosis (secondary)
Give the defect, mechanism, clinical feature and treatment of glucocorticoid remediable aldosteronism
- defect = chimeric gene - 11beta hydroxylase and aldosterone synthetase
- mechanism = aldosterone is produced in the adrenal in response to ACTH so levels inappropriately high
- clinical feature = sodium retention,hypertension, hypokalaemic alkalosis
- treatment = suppress ACTH using glucocorticoids
Give the defect, mechanism, clinical features and treatment of liddle’s syndrome
- defect = activating mutation of ENaC
- mechanism = sodium channel always open so constant aldosterone like effect
- clinical features = sodium retention, hypertension, hypokalaemia alkalosis
- treatment = amiloride (blocks ENaC)
Give the defect, mechanism, clinical features and treatment of syndrome of apparent mineralocorticoid excess (AME)
- defect = 11-beta hydroxysteroid dehydrogenase
- mechanism = cortisol not broken down in the renal tubules, therefore activates mineralocorticoid receptor
- clinical features = sodium retention, hypertension, hypokalaemic alkalosis
- treatment = spironolactone (mineralocorticoid receptor antagonist)
