CHRONIC KIDNEY DISEASE Contents Stages of Chronic Kidney Disease Dosing adjustments Hyperphosphataemia management Secondary hyperparathyroidism Anaemias Hyperkalaemia Acidosis Hypertension STAGES OF CHRONIC KIDNEY DISEASE (CKD) Stage GFR/ Creatinine Clearance ml/min Description 1 >90 Kidney damage with normal or increased GFR 2 60-80 Kidney damage with mild reduction in GFR 3 30-59 Moderate damage with reduced GFR 4 15-29 Severe reduction in GFR 5 <15 Renal Replacement / conservative management Review by: June 2017
DOSING ADJUSTMENTS IN CKD The level of renal function below which the dose of a drug must be reduced depends on the proportion of the drug eliminated by renal excretion and its toxicity Glomerular filtration rate (GRF) is a measure of the efficiency with which the kidneys can remove waste products such as creatinine and drugs from the bloodstream. egfr (reported on Meditech) is a useful indication in detecting CKD and allows timely and appropriate referral to renal specialists. If a patient s renal function is not changing rapidly, a population-based estimate of creatinine clearance can be derived from measurement of serum creatinine using the Cockcroft and Gault equation; Creatinine Clearance (ml/min) = F x (140-age)(weight in kg) Serum creatinine (micromol/l) where F = 1.23 (male) 1.04 (female) If the patient is overweight use the ideal body weight (IBW) in place of the actual body weight. Ideal body weight can be calculated as (kg): Males 50 + (2.3 x every inch over 5 ft) Females 45.5 + (2.3 x every inch over 5 ft) egfr estimates (ml/min/1.73m 2 ) are not the same as Cockcroft and Gault estimates of creatinine clearance (CrCl) (ml/min). egfr should not be used to adjust drug dosing. Most doses quoted in standard reference sources are based on Cockcroft and Gault equation and therefore this should remain the gold standard to estimate GFR when adjusting drug doses to an individual s renal function. Further help on drug dosing in CKD can be sought from ward pharmacist or the renal team.
MANAGEMENT OF HYPERPHOSPHATAEMIA Phosphate binders Phosphate binders are initiated in patients with serum phosphate > 1.4 mmol/l, despite dietary restriction. Compliance with low phosphate diet and phosphate binder therapy should be checked before increasing phosphate binder therapy. For patients who are hypocalcaemic or normocalcaemic (at lower end of scale) Calcium carbonate (Calcichew) 1.25g tablet (equivalent to 500mg elemental calcium per tablet) One tablet three times daily with meals. Increase to 2 tablets three times a day after 1 month if phosphate 1.4mmol/L (ensure patient remains normocalcaemic) Calcium acetate (Phosex) 1g tablet (equivalent to 250mg elemental calcium per tablet) One tablet three times daily with meals. Increase to 2 tablets three times a day after 1 month if phosphate 1.4mmol/L (ensure patient remains normocalcaemic) If calcium remains < 2.13 refer to Nephrology If phosphate remains 1.4mmol/L or if hypercalcaemic Sevelamer carbonate 800mg tablet One tablet three times daily with meals. Increase by 800mg three times a day after 1 month until phosphate 1.4mmol/L. Maximum 2400mg tds If phosphate remains 1.4mmol/L refer to Nephrologist of the week Aluminium hydroxide (Alucaps) 475mg capsules For initiation by Renal Team only 475mg three times daily with meals. Increase by 475mg tds until phosphate 1.4mmol/L. Maximum 1425mg tds
Lanthanum (Fosrenol) 500mg, 750mg, 1000mg chewable tablets For initiation by Renal Team only 750mg tablet three times daily with meals. Dosage should be titrated until phosphate 1.4mmol/L Precautions and adverse effects Serum corrected calcium and phosphate should be checked monthly and parathyroid hormone (PTH) every three months. For patients taking aluminium hydroxide, aluminium levels should be checked every three months. If hypercalcaemia develops, calcium based binders should be stopped and replaced where indicated by non-calcium containing binders (sevelamer). Review of vitamin D dosage may also be necessary. Phosphate binders must not be taken within 2 hours of oral iron supplements. Oral calcium may interfere with the absorption of bisphosphonates, ciprofloxacin, levothyroxine and tetracycline. These agents should be taken at least two hours before or four to six hours after calcium. Aluminium hydroxide may reduce the absorption of antibiotics (e.g.; cefaclor, quinolones, tetracyclines). Aluminium hydroxide is contra-indicated in patients with hypophosphataemia or porphyria. Accumulation in renal failure has been linked with neurotoxicity, osteomalacia and a reduced response to erythropoietin.
MANAGEMENT OF SECONDARY HYPERPARATHYROIDISM Vitamin D sterols and calcimimetric agents Alfacalcidol 250nanogram, 500nanogram, 1microgram capsules Initially 250nanograms daily. Adjust in increments of 250nanograms per day, initially at weekly intervals according to PTH and calcium levels. Once dose is stabilised review monthly. Calcitriol 250nanogram, 500nanogram capsules 1microgram/mL, 2microgram/mL injection For initiation by Renal Team only Initially 250nanograms daily. Adjust in increments of 250nanograms per day, initially at weekly intervals according to PTH and calcium levels. Once dose is stabilised review monthly. Cinacalcet For initiation by Renal Team only in line with NICE Guidance TA117 Initially 30mg daily. Titrate dose in 30mg increments at monthly intervals until PTH controlled. Check corrected calcium one week after each dose change as a reduction in PTH levels is associated with concomitant decrease in serum calcium levels. PTH levels should be checked at least 12 hours after dosing. Precautions and adverse effects PTH should only be measured routinely in patients with progressive CKD 3 and in stages 4 and 5. Only measure PTH in CKD stages 1 and 2 or non-progressive stage 3 if there is a clinical indication to do so (e.g., hypercalcaemia). PTH levels should be maintained between normal and twice the upper limit for CKD stage 4 and between two to four times the upper limit of normal for CKD stage 5. Treatment with vitamin D sterols should be initiated only in patients with serum levels of corrected calcium < 2.37mmol/L and serum phosphate <1.49mmol/L. During treatment with vitamin D sterols and cinacalcet, serum levels of calcium and phosphaste should be monitored monthly. Hypercalcaemia during treatment with vitamin D sterols can be corrected by stopping treatment until plasma calcium levels normalise (about 1 week). Plasma PTH levels should be monitored every 3 months for patients on Vitamin D sterols and monthly for patients on cinacalcet. Note 250 nanograms = 0.25 micrograms. Prescriptions for alfacalcidol should be written in terms of milligrams in line with the trusts medicines policy.
MANAGEMENT OF ANAEMIA Management of anaemia should be considered in people with anaemia of chronic kidney disease when their haemoglobin (Hb) level is less than or equal to 11g/dl.Treatment should maintain stable Hb between 11.5g/dl and 13g/dl. IRON-DEFICIENCY ANAEMIAS Oral Iron Use of modified release iron preparations is not recommended since these preparations release iron beyond the duodenum, an area where iron absorption is low. Ferrous sulphate 200mg tablets three times daily (equivalent to 65mg elemental iron per tablet) Precautions and adverse effects Absorption of oral iron may be reduced by calcium salts (commonly used as phosphate binding agents) and tetracyclines. Oral iron should not be administered concomitantly with parenteral iron. Oral iron reduces absorption of bisphosphonates, entacapone, levodopa, quinolones, tetracyclines, levothyroxine (give at least 2 hours apart) Adverse effects include gastro-intestinal irritation (nausea, constipation, diarrhoea) and stools may be discoloured (black). The incidence of side effects due to ferrous sulphate is no greater than with other iron salts when compared on the basis of equivalent amounts of elemental iron. Parenteral Iron Commence on advice of renal team in patients with ferritin < 100 micrograms/l after three months oral iron or <200 micrograms/l if GI intolerant to oral iron Iron Sucrose (Venofer) 100mg/5ml injection Please contact the renal team for further advice on dosing. Maximum dose 200mg. Risk of anaphylactic reaction. Infuse the first 25mg over 15 minutes. If no reaction increase rate to a maximum of 200mg/ hour Venofer may be available from pharmacy sterile production unit on request. Please contact the unit on Ext 5679
Precautions and adverse effects See above regarding risk of anaphylaxis and test dose. Facilities for cardiopulmonary resuscitation must be available whilst parenteral iron is administered. Target ferritin in renal patients is 200-500 micrograms/l. Note ferritin is an acute phase reactant protein and may be elevated in the presence of infection and inflammation. Contra-indicated in patients with a history of asthma or other atopic allergy and in severe hepatic disease. ERYTHROPOETINS Darbepoetin For initiation by Renal Team only Epoetin alfa (Eprex) Starting dose of 0.45 microgram/kg (rounded to nearest syringe strength) once weekly by subcutaneous route. Monitor Hb monthly initially to maintain Hb 11.5-13 g/dl. Once dose stable, follow up interval extended to 8-16 weeks By intravenous injection over 1 to 5 minutes (given during or at end of dialysis). Further dosing advice available from renal unit For initiation by Renal Team only for patients on haemodialysis unit By intravenous injection over 1 to 5 minutes (given during or at end of dialysis). Further dosing advice available from renal unit Darbepoetin is a hyperglycosylated derivative of epoetin. It has a longer half life and can be administered less frequently than epoetin. Other factors which contribute to the anaemia of chronic kidney failure such as iron or folate deficiency should be corrected before treatment and monitored during therapy. Serum ferritin should be >200mcg/L before commencing erythropoietin. Supplemental iron may improve the response in resistant patients. Aluminium toxicity, concurrent infection or other inflammatory disease can impair the response to erythropoietin. Precautions and adverse effects CSM advice; There have been rare reports of pure red cell aplasia in patients treated with epoetin alfa. The CSM has advised that in patients that fail to respond to epoetin alfa therapy, with a diagnosis of pure red cell aplasia, treatment with epoetin alfa must be discontinued and testing for erythropoietin antibodies considered. Patients who develop pure red cell aplasia should not be switched to another form of erythropoietin. Contraindicated in uncontrolled hypertension or patients unable to receive thromboprophylaxis.
Monitor haemoglobin, blood pressure and potassium (risk of hyperkalaemia). If diastolic blood pressure >100mmHg or systolic blood pressure >200mmHg after 3 consecutive readings in a week, discontinue erythropoietin therapy. Patients receiving ciclosporin or tacrolimus should have their levels monitored. Adverse effects include hypertensive crisis with encephalopathy-like symptoms and seizures, allergic reactions and thrombotic events.
MANAGEMENT OF HYPERKALAEMIA IN PATIENTS WITH CKD Guidelines for the treatment of hyperkalaemia (See also section in nutrition & blood) Checklist; Is the potassium result a true value? Could the blood have haemolysed? If patient is a dialysis patient, is this a pre or immediately post dialysis reading? Pre-dialysis readings are usually high & immediate post dialysis samples are low until the patient re-equilibrates (up to 4 hours post dialysis) Is the patient due to have imminent dialysis? If the potassium level is not life threatening and haemodialysis is planned within 12 hours no action may be required please contact the renal department for further advice Is hyperkalaemia acute or chronic? Does the patient often have high or low potassium? Is there a drug cause e.g.; ACE inhibitor, ARB, NSAIDs, amiloride, spironolactone? Can the drug be stopped safely? Immediate treatments Treatment should be given immediately if potassium is greater than 6.5mmol/L especially if there are ECG changes or neuromuscular symptoms. 1. Intravenous calcium Give 10mL intravenous calcium gluconate 10% (2.25mmol Ca 2+ in 10mL) over 5 minutes when the ECG changes include widening of the QRS complexes with slurring of the ST segments. Although this is the standard dose of calcium gluconate, more should be given without hesitation in resistant cases until the ECG returns to normal. A dose of 30mL is commonly required, although up to 90mL can be given in rare cases. Calcium chloride (10mmol in 10mL) can be given instead of calcium gluconate, however care is required with repeated dosing due to the greater concentration of calcium in the chloride preparation. 2. Insulin and glucose Give 10 to 15 units of Actrapid insulin and 50mL glucose 50% over 20 minutes into a large vein. Insulin will promote the transport of extracellular potassium into the cells. Glucose covers the insulin-induced hypoglycaemia. Blood glucose should be checked 30 minutes after treatment and then hourly for up to 6 hours to avoid hypoglycaemia. Plasma potassium will decrease by about 1mmol/L within 30 minutes and the effect should last for 1 or 2 hours.
3. Nebulised salbutamol Nebulising 2.5 to 10mg salbutamol will reduce serum potassium by 0.5 to 1.5mmol/L. Use lower doses in patients with ischaemic heart disease. Caution as sympathetic activity will be increased causing tachycardia arrrhythmias and fine tremors 4. Sodium bicarbonate Raising the systemic ph results in hydrogen ion release from the cells and moves potassium into cells. There is also a direct effect independent of ph. Effects begin within 30-60 minutes and last for 6-8 hours. Give sodium bicarbonate 1000mg three times a day orally or 500mls 1.26% IV (via central or peripheral line) over 6 hours. Caution in fluid restricted patients as can cause salt and water overload Maintenance treatments 1. Calcium Resonium Ion exchange resin exchanges calcium for potassium in the gut. More useful in chronic rather than acute hyperkalaemia as effects begin in 2-12 hours and last for 24-48 hours after stopping. Give calcium resonium 15g orally in water three to four times a day. Caution; can cause severe constipation, therefore always prescribe laxatives concomitantly. If the patient remains hyperkalaemic and unresponsive to treatment, call for consultant help. SODIUM BICARBONATE If bicarbonate <25mmol, commence Sodium Bicarbonate capsule 500mg three times daily. Increase according to bicarbonate levels and tolerability.
MANAGEMENT OF HYPERTENSION IN CKD Blood pressure should be lowered to <130/80mmHg Treatment of hypertension affords the dual benefit of slowing the rate of progression of CKD and reducing cardiovascular risk in patients with CKD. Angiotensin converting enzyme (ACE) inhibitors should be considered as the agents of first choice in the management of hypertension in patients with progressive renal disease. ACE inhibitors or Angiotensin Receptor Blocker (ARB) treatment should form part of the antihypertensive therapy of patients with CKD and urinary protein excretion of >1g/day (urine protein:creatinine ratio of >100mg/mmol or >1mg/mg) unless there is a specific contraindication. Treatment with ACE inhibitors- commence if serum potassium within normal range Lisinopril Start at 2.5mg daily. Titrate to 20mg daily over 4 weeks. Dosage can be doubled weekly. At each dose change check U/Es to ensure renal stability and absence of hyperkalaemia. If no dose change, check U/Es at 1 week, 1 month, 3 months, 6 months and annually. Begin treatment with ARB if patient unable to tolerate ACE inhibitor due to ACE induced cough Losartan Start at 50mg daily (25mg daily in intravascular volume depletion or patients >75. Increase to 100mg daily if tolerated. Irbesartan Start at 150mg daily. Increase to 300mg daily if tolerated. In haemodialysis of elderly consider initial dose of 75mg daily. Treatment with ACE inhibitor or ARB should be continued if a GFR decline over 4 months is <30% from baseline and serum potassium is 5.5mmol/L Dual blockade with a combination of ACE inhibitor or ARB should usually only be initiated under specialist supervision. For patients unable to tolerate ACE inhibitors due to cough, dual blockade using an ARB plus the direct renin inhibitor aliskiren may be considered. This combination should be initiated by consultant nephrologists only.
If on maximum dose of ACE inhibitor or ARB and BP> 130/80mmHg, start; Furosemide Start at 20mg each morning and titrate upwards according to response. Monitor U/Es at one to two weekly intervals. Note; larger doses of diuretics may be indicated in CKD patients. Doses up to 500mg daily are sometimes used in management of oedema. or for patients with CKD 1-3 Bendrofluazide 2.5mg daily If BP still above 130/80mmHg add; Amlodipine Start at 5mg daily and increase to 10mg daily if still above target value two weeks after starting medication or if proteinuric & unable to tolerate ACE inhibitor or ARB due to hyperkalaemia start; Diltiazem MR Start at 200mg daily and increase to max 300mg daily if still above target value two weeks after starting medication. Heart rate should be monitored and if falls below 50bpm dose should not be increased. Note; Diltiazem is used in place of amlodipine, NOT in addition to. Diltiazem should not be given in combination with beta blockers due to increased risk of AV block and bradycardia. Different versions of modified release preparations may not have the same clinical effect. To avoid confusion between different formulations, prescribers should specify the brand to be dispensed. If BP still above 130/80mmHg add; Doxazosin (standard release) Start at 1mg daily, increase after 1-2 weeks to 2mg daily, and thereafter to 4mg daily, if necessary to a maximum 16mg daily if still above target value. If BP remains above 130/80mmHg despite use of the above agents, please consider referral to Nephrology