DRUGS AND THE KIDNEY
DR.ALI A.ALLAWIASSISTANT PROFESORCONSULTANT NEPHROLOGISTThe 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 thatcause: Hypovolaemia, e.g.(a) Potent loop diuretics such as furosemide, especially in elderly patients(b) Renal salt and water loss, such as fromhypercalcaemia induced by vitamin D therapy (sincehypercalcaemia adversely affects renal tubular saltand water conservation)Decrease in cardiac output, which impairs renalperfusion (e.g. beta-blockers)Decreased renal blood flow (e.g. ACE inhibitorsparticularly in the presence of renovasculardisease). Pre-renal
Several mechanisms of drug-induced renal damage exist and may co-exist. Acute tubular necrosis produced by directnephrotoxicity :Examples include prolonged orexcessive treatment with aminoglycosides (e.g.gentamicin, streptomycin), amphotericin B, heavymetals or carbon tetrachloride. The combination ofaminoglycosides with furosemide is particularlynephrotoxic.Acute tubulointerstitial nephritis with interstitial oedema and inflmmatory cell infitration. Thiscell-mediated hypersensitivity nephritis occurs withmany drugs, including penicillins, sulphonamides andNSAIDs .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, ergotderived 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 patientson NSAID, since prostaglandins play an importantrole in regulating renal blood flow. This is particularlylikely in patients with other disorders, such as heartfailure, cirrhosis, sepsis and preexisting renal impairment. In addition, idiosyncratic immune reactions may occur, causing minimal change nephrotic syndromeand acute interstitial nephritis . Analgesic nephropathy is now a rare complication oflongterm 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 identifidby 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 withrenal disease