What are the regulatory functions of the kidney?
Fluid balance Acid-base balance Electrolyte balance
What are the excretory functions of the kidneys?
Waste products Drug elimination
What are the endocrine functions of the kidneys?
RAAS Erythropoietin Prostaglandins
What are the metabolic functions of the kidney?
Vitamin D Polypeptides - insulin and PTH
What do carbonic anhydrase inhibitors do?
Prevent action of carbonic anhydrase in the PCT, which affects reabsorption rate of Na due to Na-H antiport
General functions of kidneys?
REEM Regulatory Excretory Endocrine Metabolic
Why are carbonic anhydrase inhibitors rarely used as a diuretic?
Risk of metabolic acidosis and hypokalaemia
What are carbonic anhydrase inhibitors used for?
Glaucoma
Name an osmotic diuretic
Mannitol
How do osmotic diuretics work?
Increase the osmotic gradient systemically and in the renal tubules.
When are osmotic diuretics used?
Severe cerebral or pulmonary oedema
Why are osmotic diuretics not commonly used?
Can cause excessive water loss and hypernatraemia
Name some ADH antagonists
Lithium
Demeclocycline
How do ADH antagonists work?
Reduce the concentrating ability of collecting ducts by decreasing expression of aquaporin
Which transporters do loop diuretics work on and where? Effect of this?
Na-K-2Cl in the thick ascending limb of the loop of Henle
Prevent reabsorption of Na and Cl and prevent concurrent excretion of Ca and Mg due to a more positive lumen potential from K
Name a loop diuretic
Furosemide
Adverse effects of loop diuretics?
Hypokalaemia due to no reabsorption by Na-K-2Cl
Bumetanide can cause myalgia
Furosemide can cause reversible ototoxicity
Indications for loop diuretics?
Heart failure - also have a slight venodilatory effect
Liver failure causing fluid overload
DDIs of loop diuretics
Cannot be used with aminoglycosides due to risk of ototoxicity and nephrotoxicity
Rarely with digoxin or steroids due to risk of hypokalaemia
Which transporters do thiazide diuretics affect and where? Effect of this?
The Na-Cl symporter in the DCT
Have a diuretic affect whilst promoting Ca reabsorption
ADRs of thiazide diuretics?
Hypokalaemia
Hypercalcaemia
Hyperuricaemia (leading to gout)
Erectile dysfunction
Indications for thiazide diuretics?
Heart failure
Hypertension
Kidney stones due to calcium reabsorption
DDIs of thiazide diuretics?
Digoxin or steroids due to risk of hypokalaemia
Beta-blockers due to risk of hyperglycaemia, hyperlipidaemia and hyperuricaemia
Carbamazepine due to risk of hyponatraemia
Name some potassium sparing diuretics
Amiloride
Spironolactone
How do potassium-sparing diuretics work?
Act on ENaC channels in the late DCT and CD - so have no effect on potassium reaborption
DDIs of potassium-sparing diuretics?
ACE-inhibitors - risk of hyperkalemia
Amiloride often given alongside furosemide to balance potassium
Why can any diuretic that decreases sodium absorption before the DCT cause hypokalaemia?
Less sodium is reabsorbed, so there is a decrease in circulating volume and activation of RAAS
Causes aldosterone to be expressed, increasing expression of Na-K-ATPase in basolateral membrane of principal cells, and increasing K+ channels for excretion
Name some aldosterone antagonists
Spironolactone
Eplerenone
How do aldosterone-antagonists work?
Inhibit action of aldosterone on mineralocorticoid recepors
Less Na-K-ATPase and ENaC synthesis
Half-life of spironolactone?
Metabolised to canrenone, which has a half-life of 18-24 hours, allowing longer-term use.
ADRs of spironolactone?
Hyperkalemia
Some androgenic cross-reactivity causing gynaecomastia
Indications for spironolactone?
Heart failure
Hypertension
Liver failure
Hyperaldosteronism e.g. Conn’s syndrome
How does digoxin have a diuretic effect?
Inhibits tubular Na-K-ATPase
What are general ADRs of any diuretic?
Anaphylaxis or rash
Hypovolaemia
Hypotension (which can cause acute renal failure)
Electrolyte disturbances
Metabolic abnormalities
What is digoxin used for?
AF
What must be monitored with diuretics?
U&Es
Which diuretics would you prescribe in HF? Alongside what?
Loop or thiazide diuretics
Alongside ACEi or beta-blockers
What diuretics are used for hypertension?
Thiazide diuretics or aldosterone antagonists
What diuretics are used for liver failure?
Aldosterone antagonists and loop diuretics
What are the two main issues with prescribing drugs in renal disease?
Drugs may reduce kidney function by direct or indirect toxicity
Drugs at normal doses may accumulate to toxic levels of they are excreted via kidneys and renal function is impaired
Name some potentially nephrotoxic drugs
ACE inhibitors
Aminoglycosides
Penicillins
Cyclosporin A
Metformin
NSAIDs
Why is renal function in the elderly over-estimated?
Creatinine is dependent on body mass
Therefore start with a low dose and titrate cautiously
What can cause diuretic resistance?
Incomplete treatment of primary disorder
Continuation of high Na intake
Patient non-compliance
Poor absorption
Volume depletion decreasing filtration of diuretics
Volume depletion increasing aldosterone
NSAIDs reducing renal bloodflow
What are the effects of angiotensin and prostaglandins on renal blood flow?
Angiotensin constricts the efferent, increasing filtration pressure and GFR
Prostaglandin dilates the afferent, increasing GFR
ECG changes in hyperkalaemia?
No P-waves
Prolonged QRS complex
Tented T waves
Treatment of hyperkalaemia?
Calcium gluconate
Insulin/dextrose
Calcium resonium
Sodium bicarbonate
(Salbutamol)