Medication and Acute Kidney Injury By: Dr. Wael Thanoon Younis C.A.B.M.,Mosul college of medicine.

Why do we need to consider medication in AKI Prescribing medication is a common intervention Complacent - medicines are dangerous Between 5 and 20 % of all AKI cases occur as a direct result of medication We need to consider medication because: Wide range of drugs which can cause/contribute to AKI Kidneys are responsible for the metabolism of two drugs:- vitamin D and insulin Kidneys are responsible for the excretion of many water soluble drugs and their metabolites

Why do we need to consider medication in AKI? On admission, a thorough review of medication is required to: Identify drugs which have potentially caused/contributed to AKI Avoid inappropriate combinations of medications which may exacerbate AKI Ensure all doses of medications prescribed continue to be correct and clinically appropriate

Common medications which can contribute to, or are affected by, AKI: Several options when reviewing medication in AKI: Stop Withhold Amend Continue First we need to know which medications to pay attention to

Common medications which can contribute to, or are affected by, AKI Consider Acute Nephrotoxic Drug Action Contrast media ACE Inhibitors NSAID’S Diuretics ARB’s

Contrast media Contrast induced nephropathy Can occur in any patient with intra venous or intra- arterial contrast Known renal dysfunction or CrCl = <60mls/min, consider non-contrast imaging Oral N-acetylcysteine – antioxidant. Neutralises free radicals IV sodium bicarbonate can also be used

ACE Inhibitors Used to treat hypertension, heart failure, nephropathy Work on the RAAS system Inhibit conversion of angiotensin I to angiotensin II Dilate efferent arterioles Reduced renal perfusion and GFR Hyperkalaemia – potassium retention due to reduction of aldosterone

NSAIDS Analgesic, antipyretic and anti-inflammatory Non-selective COX inhibitors Acetic acids – diclofenac, indomethacin Proprionic acids – ibuprofen, naproxen Salicylates - aspirin Enolic acid derivatives – meloxicam Anthranilic acid derivatives – mefenamic acid Two other groups which we never see Selective COX II inhibitors - celecoxib

Inhibit cyclooxygenase Impair prostaglandin synthesis Prostaglandins usually mediate renal blood flow Reduced prostaglandin synthesis = Reduced renal perfusion Tend to promote sodium retention and subsequent fluid retention therefore increasing blood pressure.

NSAID’s cause constriction HERE.

Diuretics Three main classes of diuretic Loop diuretics Act on the ascending links of the loop of Henle Inhibit reuptake of sodium Less water uptake therefore increased urine production Reduced circulating volume Reduced renal perfusion

Potassium sparing diuretics Act on the distal convoluted tubule Competitive antagonists which inhibit sodium/potassium exchange Inhibits reuptake of sodium therefore increasing water excretion. Reduces excretion of potassium - Hyperkalaemia Thiazide diuretics Act on distal convoluted tubule Inhibit reuptake of sodium therefore increasing water excretion Causes volume depletion and hypoperfusion

Angiotensin Receptor Blockers: Antagonise the action of angiotensin II by blocking the angiotensin II AT1-receptor. Reduces production and secretion of aldosterone Hyperkalaemia – potassium retention due to reduction of aldosterone

Other ‘problem’ drugs: Analgesics Opiates –. Reduce dose of standard release preps. Risk of accumulation. Fentanyl – minimal renal excretion Antibiotics Aminoglycosides – gentamicin – AVOID Glycopeptides – vancomycin - AVOID Antiepileptics Consider reducing dose and/or monitoring levels

Anticholinergics Digoxin Lipid lowering agents Lithium Can cause urinary retention Antihistamines Antipsychotics Antispasmodic Reduce dose Digoxin Accumulates – monitor level and consider reducing dose Lipid lowering agents Statins Fibrates increased risk of rhabdomyolysis Lithium Accumulation Can cause chronic interstitial nephropathy Proton pump inhibitors PPIs.

‘Sick Day Rules’ Many health care professionals provide advice to such patients that certain drugs should be temporarily discontinued during acute intercurrent illnesses, particularly where there is disturbed fluid balance. This advice is commonly described as ‘sick day rules’ or to take a ‘drug holiday’..

There are three main reasons for providing such advice: 1. Non-steroidal anti-inflammatory drugs impair renal autoregulation by inhibiting prostaglandin-mediated vasodilatation of the afferent arteriole and may increase the risk of AKI. 2. Drugs that lower blood pressure, or cause volume contraction, might increase the risk of AKI by reducing glomerular perfusion. 3. Drugs might accumulate as a result of reduced kidney function in AKI, increasing the risks of adverse effects.