Medicines and CKD Nikki Lawton Medicines Optimisation Pharmacist NMCCG

Outline QOF requirements for CKD Hypertension treatment Lipid lowering treatment Antiplatelets and anticoagulants Nephrotoxic drugs and risk factors Mechanisms of nephrotoxicity Common issues in renal impairment Summary

QOF requirements for CKD 2014/15 Register of patients over 18 with CKD stage 3-5 (6 points) % patients on register with BP 140/85 or less in last 12months (11 points) % patients on register with HTN and proteinurea on ACE/ARB (9 points) % patients on register with ACR (or PCR) in last 12 months (6 points) 2015/2016 – only the register remains!

Blood pressure targets in CKD NICE targets SBP<140 and DBP<90 SBP<130 and DBP<80 if diabetic QOF target 140/85 or less, irrespective of presence of diabetes (audit standard)

Hypertension treatment (NICE CG182) ACE/ARB and titrate to maximum tolerated dose Measure serum K and eGFR before starting and 1-2 weeks after starting and each dose increase. Do not use ACE plus ARB If BP target not reached treat as per NICE Hypertension guideline CG127

GMMMG Formulary ACEs Ramipril, Perindopril and Lisinopril ARBs Candesartan, Irbesartan, Losartan and Valsartan Check licensed indications

Lipid lowering treatment (NICE CG181) Treat as primary prevention for CVD, (unless already secondary prevention) Atorvastatin 20mg if 10% or more risk of CVD event in 10 years Increase dose if <40% reduction in non-HDL cholesterol achieved If eGFR<30, consult renal specialist before increasing dose

Antiplatelets and anticoagulants (NICE CG182) Offer antiplatelets for secondary prevention of CVD (be aware of ↑bleeding risk) Consider apixaban over warfarin in patients with eGFR and AF plus 1 or more risk factors Risk factors – prior stroke or TIA, 75 or older, HTN, DM or symptomatic HF

Nephrotoxic drugs Monitor GFR at least annually in people prescribed nephrotoxic drugs (NICE) Stop any nephrotoxic or potentially nephrotoxic medications (NMCCG CKD guidelines) Definition Examples?

Risk factors for nephrotoxicity Drug choice Increasing age (>60) Underlying renal insufficiency (GFR<60) Volume depletion (reduced fluids + salts) Diabetes Heart failure Multiple nephrotoxins

Mechanisms of nephrotoxicity Altered intraglomerular haemodynamics Tubular cell toxicity Inflammation Crystal nephropathy Rhabdomyolysis Thrombotic microangiopathy

Altered intraglomerular haemodynamics Altered blood flow and decreased GFR in kidney Examples – ACEs, ARBs, NSAIDs, ciclosporin, tacrolimus Correct volume depletion first Monitor renal function, especially in high risk patients

Tubular cell toxicity Increased concentration of toxin in tubules Examples – aminoglycosides (gentamicin), anti-retrovirals, contrast dyes Administer during active part of day Limit duration of therapy Monitor renal function and drug levels

Inflammation Can lead to fibrosis and renal scarring Examples – lithium, NSAIDs, penicillins, cephalosporins, quinolones, gold, aspirin, ciclosporin, diuretics, Avoid long term use Maintain drug level in therapeutic range Avoid volume depletion

Crystal nephropathy Drugs which produce crystals insoluble in urine, leading to blockage Examples – methotrexate, ciprofloxacin, oral aciclovir Ensure adequate hydration High urine flow

Rhabdomyolysis Myoglobin from myocytes causes toxicity, obstruction and reduced GFR Examples – statins, many drugs of abuse including cocaine, heroin, ketamine and methadone

Thrombotic microangiopathy Platelet thrombi cause immune reaction or direct toxicity Examples – clopidogrel, ticlodipine and quinine, ciclosporin

Common issues in renal impairment (1) Metformin contraindicated if CrCl<60mls/min (lactic acidosis) Alendronic acid not recommended if GFR<35mls/min Simvastatin avoid doses >10mg if CrCl< 30mls/min High sodium content e.g. antacids, soluble tablets (water retention)

Common issues in renal impairment (2) Digoxin - ↑ risk of toxicity as renal clearance ↓ Insulin – as renal failure progresses clearance ↓ so requirements may ↓ so dose ↓ OTC medication e.g. ibuprofen BMI – if BMI 30 drug doses may need to be adjusted

Summary Numerous common nephrotoxic drugs Various mechanisms Patient risk factors Monitoring renal function Renal impairment is often reversible if the offending drug is discontinued or