West Midlands Guidelines for managing CKD Mineral and Bone Disorders in Haemodialysis Patients

Background West Midlands Audit Oct 2006 Presented West Midlands Audit Meeting 2007 Highlighted significant variation in practice and achievement of targets across the region

Audit: key conclusions Discrepancies between dietitians and clinicians within units: – Target ranges – Upper levels of intervention – 1 st line intervention – Frequency in changes to medication – Standard Dialysate used Variation found across units in the ranges and standards used but majority of units following: – PO4 <1.8mmol/l (RAS) – CrCa mmol/l (RAS) – PTH 4XULN(RAS) – CaxPO4 <4.7

Wide range in PO4 control across the units (range between 42-76%)

SATELITTE AND BASE UNITS COMBINED PERCENTAGE OF PATIENTS PTH < 150 PTH > 300 PTH % OF PATIENTS ACHIEVING PTH LEVEL OF ng/L ( KDOQI)

WM Renal Network identified need to develop regional guidelines to standardise practice across the region.

Steering Group TrustSteering Group DietitianSteering Group Nephrologist HEFT (co-chairs)Jo MartinDr Indranil Dasgupta UHBEmma TaylorDr Fouad Al-Baaj Coventry & WarwickshireBeverley Beynon-Cobb / Caroline Bird Dr Daniel Zehnder Dudley Group of HospitalsChristine MorganNo Nephrologist North StaffordshireNo DietitianDr Dominic De-Takats Royal Shrewsbury HospitalsSylvia GraceNo Nephrologist ( Dr Kevin Eardley aware of process) Royal Wolverhampton HospitalsNo DietitianDr Johann Nicholas Dudley PCT Pharmacuetical AdvisorClair Huckerby West Midlands Renal NetworkNanette Grant

The process 1 st meeting Nov 2008 Subsequent meetings on Jan 09, May 09, July 09, Sept 09, March 10, Oct 10 Conducted a West Midlands Renal Dietetic Staffing Survey Evidence review (Before KDIGO) on: – Calcium Content of Dialysis Fluid – Elemental Calcium content of binders – PTH levels and starting dose of vitamin D – PTH Assay – Vascular Calcification in Diabetics – Vitamin D monitoring and supplementation Review of RAS and KDIGO Guidelines / Renal Registry Data Invited Expert: Dr Alan Jones, Biochemist re: PTH Assay, Vitamin D monitoring and Bone Alkaline Phosphatase

Good Practice Recommendations 1.Dietetic referrals 2.Dialysis adequacy 3.Phosphate target and dietetic input 4.Corrected calcium target 5.PTH assays, target, unit 6.Dialysis fluid Ca concentration 7.Phosphate binders 8.Indications for using Ca and non-Ca binders 9.Pharmacological treatment with active vitamin D compounds 10.Treatment of severe uncontrolled SHPT

Guideline 3: Phosphate Good practice recommendation: Patients with a serum phosphate level > 1.4mmol/l should be referred to a Renal Dietitian All patients should have their serum phosphate levels maintained <1.6mmol/l with adequate dialysis, dietary modification and/or use of phosphate binders. Treatment changes should be made taking into account trends in levels rather than individual measurements

Guideline 5: Parathyroid Hormone (PTH) Good practice recommendation: PTH should be monitored at least 3monthly and treatment changes should be based on trends of serum PTH rather than a single measurement. Changes in serum phosphate, corrected calcium and alkaline phosphatase levels should be taken into consideration when making treatment changes. Raised alkaline phosphatase levels in the absence of evidence of liver disease would suggest high bone turnover. PTH levels should be maintained within 2-9 times of upper limit of laboratory reference range. The group acknowledge that it is not logistically feasible to standardise PTH assay across the region. Laboratories should express PTH values in pmol/L to enable comparison between units for audit purposes. However, we need to recognise that there remains variability between assays. Patients on Paricalcitol and Cinacalcet need more frequent monitoring of PTH levels particularly following initiation or changes to treatment.

Guideline 6: Dialysis fluid Calcium Concentration Good Practice Recommendation: To use standard dialysis fluid calcium concentration of 1.5mmol To use dialysis fluid calcium concentration of 1.25mmol for patients with adynamic bone disease (ADBD), evidence of vascular calcification or hypercalcaemia To use dialysis fluid calcium concentration of 1.75mmol for patients with hypocalcaemia.

Implementation Endorsed by WM Renal Network in September 2010 Circulated to all Clinical Directors across West Midlands in November 2010 Steering Group Unit representative to lead implementation within unit To re-audit in 2012

Proposed key changes (take home message) Phosphate target: < 1.6mmol/l PTH: – 2-9 times ULN – change expression to pmol/l – which will equate to target range of 15-68pmol/l – Change to 3 monthly monitoring Change standard calcium dialysate to 1.5mmol/l

West Midlands Guidelines for managing CKD Mineral and Bone Disorders in Haemodialysis Patients

Proposed local changes Phosphate target: < 1.6mmol/l PTH: – 2-9 times ULN – change expression to pmol/l – which will equate to target range of 15-68pmol/l – Change to 3 monthly monitoring Change standard calcium dialysate to 1.5mmol/l (Lateral abdominal x-ray on new HD patients to assess for vascular calcification) (Monitor 25- hydroxyvitamin D (25(OH)D) levels)

Guideline 1: Dietetic Referral Good Practice Recommendation: All patients with CKD Stage 4 and with a serum phosphate level > 1.4mmol/l should be referred to a Renal Dietitian for a full dietary assessment Good Practice Recommendation: Renal Dietetic staffing levels should be based on the BRS Renal Workforce Planning Recommendations 2002 which state: o 1WTE per 135 haemodialysis patients o 1WTE per 180 low clearance patients o 1 WTE per 270 peritoneal patients o 2 WTE per 28 bedded ward

Guideline 2: Dialysis Adequacy Good Practice Recommendation: Minimum haemodialysis hours should be based on 4hours x 3times per week In relation to phosphate control, urea reduction ratio (URR) should be maintained > 65% and/ or equilibrated Kt/V should be maintained >1.2

Guideline 4: Corrected Calcium Good practice recommendation: Pre-dialysis serum calcium, adjusted for serum albumin, should be within the normal laboratory reference range Treatment changes should be made taking into account trends in levels rather than individual measurements

Guideline 7: Phosphate Binders Good Practice Recommendation: Phosphate Binder should be started when phosphate levels ≥ 1.6mmol/l despite adequate dialysis and dietary modification

Guideline 8a: Calcium Containing Phosphate Binder Good Practice Recommendation: The choice of phosphate binder should be individualised, depending on clinical circumstances. In comparison to calcium carbonate, calcium acetate has a higher binder capacity per mg elemental calcium and it’s action is less pH dependant (Sheikh et al 1989) Calcium carbonate may be less effective with used with inhibitors of gastric acidity e.g. proton pump inhibitors.

Guideline 8c: Non-Calcium Containing Phosphate Binder There is insufficient evidence to recommend any one non- calcium binder over another Good Practice Recommendation: Starting any binder should be at the clinician’s discretion and should take into account all relevant patient factors.

Guideline 8d: Aluminium Hydroxide Good Practice Recommendation: Aluminium hydroxide should be used as last resort and for a limited period of 3 months; further use will be at the clinician’s discretion.

Guideline 8b: Elemental calcium content of Phosphate Binders There is insufficient evidence to make a recommendation limiting the oral calcium from diet or binders. Good Practice Recommendation: An individualised strategy to limit the total calcium intake should be in place for patients: o on higher dialysis fluid calcium concentration (>1.5mmol/l) o with pre-existing vascular calcification or at risk of vascular calcification (e.g. diabetics). A lateral abdominal x-ray can be used to assess vascular calcification. o with elevated serum calcium levels o with low serum PTH levels

Guideline 9: Pharmacological treatment with active vitamin D compounds There is insufficient evidence to recommend either calcitriol or alfacalcidol as the first line vitamin D therapy. The group felt that as alfacalcidol is a prodrug, calcitriol should be used in preference. There is insufficient evidence to make a recommendation on the starting dose of calcitriol or alfacalcidol based on PTH levels. Good Practice Recommendation: Commence calcitriol or alfacalcidol at the lowest dose and titrate according to serum calcium and subsequent PTH values. Aim to maintain corrected calcium within the normal laboratory reference range and phosphate levels ≤ 1.6mmol/l. Paricalcitol should be considered on patients with high serum PTH levels and a serum calcium level at the upper level of the normal reference range despite maximum oral or intravenous active vitamin D therapy. Good Practice Recommendation: Monitoring and supplementing 25- hydroxyvitamin D (25(OH)D) to counteract vitamin D insufficiency. It is reasonable to identify vitamin D deficiency among dialysis patients and if levels ≤ 75nmol/l to give supplementation with the view of achieving levels ≥ 75nmol/l. It is reasonable to identify vitamin D deficiency among dialysis patients and give supplementation with vitamin D 3 (cholecalciferol) or vitamin D 2 (ergocalciferol) as a single substance not combined with calcium or other vitamins. Vitamin D supplementation should not be confused with calcitriol or alfacalcidol treatment.

Guideline 10: Treatment of uncontrolled severe secondary hyperparathyroidism. Good Practice Recommendation: For patients who are fit for surgery, total parathyroidectomy without re- implantation should be considered as treatment for persistent severe secondary hyperparathyroidism (PTH levels > 9 times upper limit of normal reference range) despite maximum medical therapy and clinical evidence of morbidity in association with this. In the presence of calciphylaxis parathyroidectomy should be considered in patients with lower PTH levels. Cinacalcet should be considered in patients with persistent severe secondary hyperparathyroidism who are high surgical risk for parathyroidectomy in accordance with the NICE guidelines. Cinacalcet should also be considered in such patients who are fit for surgery but for whom surgery is not immediately available for whatever reason.