DRUGS AND THE KIDNEY DR.ALI A.ALLAWI ASSISTANT PROFESOR CONSULTANT NEPHROLOGIST

 The kidney is susceptible to damage by drugs because it is the route of excretion of many water­soluble compounds, including drugs and their metabolites.  Some may reach high concentrations in the renal cortex as a result of proximal tubular transport mechanisms.  Others are concentrated in the medulla by the operation of the countercurrent system. The same applies to certain toxins. Drug-induced renal disease

 Very commonly, drugs contribute to the development of acute tubular necrosis as one of multiple insults. Numerically, reactions to NSAIDs and ACE inhibitors are the most important.  Haemodynamic renal impairment, acute tubular necrosis and allergic reactions are usually reversible if recognised early enough. Other types, however, especially those associated with extensive fibrosis, are less likely to be reversible.

 Impaired perfusion of the kidneys can result from drugs that cause:  Hypovolaemia, e.g. (a) Potent loop diuretics such as furosemide, especially in elderly patients (b) Renal salt and water loss, such as from hypercalcaemia induced by vitamin D therapy (since hypercalcaemia adversely affects renal tubular salt and water conservation)  Decrease in cardiac output, which impairs renal perfusion (e.g. beta-blockers)  Decreased renal blood flow (e.g. ACE inhibitors particularly in the presence of renovascular disease). Pre-renal

Several mechanisms of drug-induced renal damage exist and may co-exist.  Acute tubular necrosis produced by direct nephrotoxicity :Examples include prolonged or excessive treatment with aminoglycosides (e.g. gentamicin, streptomycin), amphotericin B, heavy metals or carbon tetrachloride. The combination of aminoglycosides with furosemide is particularly nephrotoxic.  Acute tubulointerstitial nephritis with interstitial oedema and inflmmatory cell infitration. This cell-mediated hypersensitivity nephritis occurs with many drugs, including penicillins, sulphonamides and NSAIDs.  Chronic tubulointerstitial nephritis due to drugs.  Membranous glomerulonephritis, e.g. penicillamine, gold, anti-TNF Renal

 Retroperitoneal fibrosis with urinary tract obstruction can result from the use of ddrugs (methysergide, lysergic acid, ergot derived dopamine receptor agonists (cabergoline, bromocriptine, pergolide), ergotamine, methyldopa, hydralazine, beta-blockers (proctolol).  Tubular obstruction (crystal formation) :Aciclovir,Crystals of the drug form in tubules. Aciclovir is now more common than the original example of sulphonamides. Post-renal

 Impairment of renal function may develop in patients on NSAID, since prostaglandins play an important role in regulating renal blood flow. This is particularly likely in patients with other disorders, such as heart failure, cirrhosis, sepsis and pre­existing renal impairment.  In addition, idiosyncratic immune reactions may occur, causing minimal change nephrotic syndrome and acute interstitial nephritis.  Analgesic nephropathy is now a rare complication of long­term use. NSAIDs

 These abolish the compensatory angiotensin II­mediated vasoconstriction of the glomerular efferent arteriole that takes place in order to maintain glomerular perfusion pressure distal to a renal artery stenosis and in renal hypoperfusion.  Monitoring of renal function before and after initiation of therapy is essential. ACE inhibitors

 Patients with renal impairment are readily identifid by having a low estimated glomerular fitration rate (eGFR < 60 mL/min) based on their serum creatinine,age, sex and ethnic group.  This group includes a large proportion of elderly patients.  If a drug (or its active metabolites) is eliminated predominantly by the kidneys, it will tend to accumulate and so the maintenance dose must be reduced. For some drugs, renal impairment makes patients more sensitive to their adverse pharmacodynamic effects. Prescribing drugs for patients with renal disease

Some drugs that require extra caution in patients with renal disease

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