DRUGS AND THE KIDNEYالدكتور خلدون ذنون- كلية طب نينوى- المرحلة الرابعة
ObjectivesIt is recommended that the following materials be focused on by the student:
1. Safe, relatively safe, and unsafe drugs in renal impairment.
3. Certain drugs can inflict kidney injury by different mechanisms.
4. Certain drugs can cause acute and chronic renal failure.
5. Nephrotoxic drugs are not necessarily stopped but can be given in
modified dosage when renal impairment is present.
6. NSAIDs are widely used drugs and can be harmful to renal function
through various mechanisms.
Introduction and principles of drug use in relation to kidney functionMany drugs and drug metabolites are excreted by the kidney especially water soluble drugs. Such drugs may damage kidney.
Different mechanisms of drug nephrotoxicity.
Renal impairment alters the dose and frequency of administered drugs.
Creatinine clearance and GFR can guide drug dosage. s.cr is less reliable as it rises when kidney function is impaired by 50%.
Some drugs must be eliminated entirely in renal insufficiency.
ACEI may cause K+ retention and worsen renal impairment.
Diuretics are relatively ineffective in severe renal insufficiency. Thiazides should not be used . High doses of loop diuretics are used . Avoid k+ sparing diuretics e.g amiloride, spironolactone, triamitrine .
Dose modification of drugs in renal insufficiency
A- Mild renal insufficiency cr.cl 20-50ml/ min. S.cr 150-300( mol/ L ACEI, aminoglycosides, chlorpropamide, digoxin , lithium, fibrates, zidovudine.
B- Moderate renal insuff. cr.cl 10-20 ml/ min. S.cr 300-700 ( mol /L B-blockers (atenolol, sotalol) , opioids analgesics.
C- Severe renal insufficiency cr.cl < 10 s.cr > 700 ( mol /L Sulphonylureas (gliclazide), cephalosporin, penicillins, INH, azathioprine, cimetidine.
Avoidable drugs in renal insufficiencyA. Any degree of renal insufficiency
Mesalazine, metformin, NSAIDS, tetracycline (except doxycycline and minocycline).
B. Moderate or severe renal insufficiencyLithium and methotrexate.
C. Severe renal insufficiencyChlorpropamide and glibenclamide, chloramphenicol, chloroquine, fibrates.
Mechanisms of drug induced renal disease1. Haemodynamic
NSAIDS : inhibit prostaglandin synthesis .
ACEI : (efferent glomerular arteriolar tone . Toxic in renal artery stenosis and renal hypoperfusion.
Radiographic contrast media: intense vasoconstriction .
2. Acute tubular necrosisAminoglycosides, amphotericin : direct tubular toxicity.
paracetamol: with or without hepatotoxicity.
Radiographic contrast media: precipitate in tubules.
3. Loss of tubule and collecting duct functionLithium, cisplatin, aminoglycosides, amphotericin.
4. Immune mechanismsA. Glomerular
penicillamine and gold : membranous nephropathy .
penicillamine : crescentic or focal necrotizing GN associated with ANCA and small vessel vasculitis
NSAIDS : minimal change nephropathy.
B. Acute interstitial nephritisNSAIDS, penicillins, PPI.
C. Chronic interstitial nephritisLithium, ciclosporin, tacrolimus.
CIN with papillary necrosis : various analgesics.
5. Tubular obstruction (crystal formation)Acyclovir crystals.
Chemotherapy : uric acid crystals due to tumor lysis .
6. NephrocalcinosisOral sodium phosphate used for bowel cleansing.
7. Retroperitoneal fibrosisCabergoline. Methysergide & practolol , both removed from market.
May precipitate ATN in : heart failure, cirrhosis, sepsis, renal impairment, affect prostaglandin & vasodilatation causing acute renal failure.
Idiosyncratic immune reaction: minimal change nephropathy, acute & chronic interstitial nephritis.
Papillary necrosis, analgesic nephropathy, chronic renal failure.
Angiotensin converting enzyme inhibitorsAbolish the compensatory angiotensin II mediated vasoconstriction of the glomerular efferent arteriole which maintains glomerular perfusion pressure distal to RAS.
Rapid deterioration of renal function occurs in bilateral RAS or RAS of single functioning kidney.
Monitoring renal function of such patients before and after the start of ACEI is essential.