donors. 2 Pre-emptive transplantation should be the goal, if possible. \200 Formation of dialysis access (surgical review at least 6 months prior to start of dialysis is desirable). Access to palliative services for those who elect not to undertake dialysis treatment or to help manage symptom burden. \200 Timing initiation of dialysis \200\224 avoid symptomatic uraemia. Composition of an advanced CKD clinic \200 Nephrologist. \200 Specialist nurses (e.g. p re-dialysis counseling, anemia management, pre-transplant assessment, dialysis access preparation, palliative care). Renal dietitian. \200 Vascular access and transplant surgeon. \200 Pharmacist. \200 S ocial worker. \200 Counselor. Education \200 De \201 ned education program, involving specialist nurses and expert patients (peer support). Start when eGFR \211 20mL/min (ideally 12 months prior to RRT). \200 Use a variety of t echniques to impart information \200\224 1:1 sessions, group education, culturally appropr iate written material, visual aids (DVDs, image library), practical demonstrations, web-bas ed material. Include information on: Functions of the kidney. \200 Implications of impaired kidney function. \200 Cardiovasc ular risk and lifestyle modi \201 cation. \200 Symptoms to expect as function declines. \200 Concept of integrated care \200\224 they may need to move between different treatment modalities over time. Detailed discussion on different dialysis options, with practical demonstrations and visits to PD and HD departments. Transplant options. De \201 ne treatment plan when eGFR approaches 15mL/min \200\224 allows for timely access preparation and assessment for a home-based therapy, if required. ADVANCED CKD CARE 267 When to start dialysis \200 The IDEAL study compared \200\230 early \200\231 (eGFR 10 \200\223 15mL/min) vs \200\230 late \200\231 (5 \200\223 7mL/min) commencement of dialys is and showed no survival bene \201 t. However, quality of life is just as important a con sideration. \200 Guidelines recommend considering the commencement of dialysis when GFR < 15mL/min. However, this requires careful discussion with the patient and consideration of t he risks and bene \201 ts associated with RRT. Symptoms and signs of advanced CKD (e.g. pe rsistent nausea and vomiting, anorexia, malnutrition, volume overload, restless eggs), como rbidity, functional status, and physical and the psychological and social consequences of s tarting dialysis all need to be taken into account. GFR \211 5 \200\223 7mL/min, whether symptomatic or not. \200 Refractory hyperkalaemia , acidosis, pulmonary oedema, pericarditis, encephalopathy, and neuropathy are all (urgent) indications for dialysis (the aim should be to start dialysis before these are present). 2 Pre-emptive transplantation is the treatment of choice of ESRD. Consider when GFR <20mL/m in. If not possible, discuss whether a home-based therapy (HD or PD) is suitable. Early pla nning leads to improved choice. Fig. 3.8 A pathway of care for advanced CKD. \200\230 Crash landers \200\231 (or unplanne d starters): these individuals are unknown to renal services and present as emergencies wit hin 90 days of needing RRT ( 7 25 \200\223 30% of patients entering ESRD programs annually ). They miss out on pre-emptive education, usually start on HD with temporary vascular acce ss, and have worse outcomes in general. Reproduced from Focus on Preparing for End Stage Re nal Disease with kind permission of the NHS Institute for Innovation and Improvement. CHAPTER 3 Chronic kidney disease (CKD) 268 Conservative treatment of CKD: symptomatic management of ESRD As CKD advances, so does the symptom burden. Over half of patients who follow a conservative (i.e. non-dialytic) managem ent pathway report poor mobility, weakness, pain, and pruritus, and over one-third report p oor appetite, dif \201 culty sleeping, drowsiness, dyspnoea, and constipation. With proact ive identi \201 cation and management, the distress and disability caused by these symptom s can be considerably eased (see Table 3.17). Many units now run a service speci \201 call y for such patients, concentrating resources and care to provide physical and social suppor t. Patients may become increasingly reliant on family members and other carers. District nu rses, social workers, home care teams, physiotherapists, occupational therapists, and hospi ce services should be involved, as required. Table 3.17 Symptom control in advanced CKD Symptoms Causes Treatments Comment Relax dietary restrictions Anorexia Constipation, oesophagitis, nausea, dry mouth, gastroparesis, oral candidiasis, dysphagia, anxiety Arti \201 cial saliva, ice to moisten mouth Dexamethasone 2 \200\223 4mg od for up to 4 weeks Medroxyprogesterone 100 \200\223 200mg daily Mode of action unknown. Avoid if thromboembolic risk Thalidomide 100mg od SE: neuropathy Fluconazole 50 \200\223 100mg od If oral candidiasis Taste disturbance Consider trial of a zinc salt, e.g. zinc sulfate Dyspepsia Lansoprazole 30mg od or other PPI Ranitidine 150mg bd Lactulose 10 \200\223 20mL bd Osmotic Constipation Multifactorial Adequate \202 uid intake and dietary advice are important Senna 2 \200\223 4 tablets bd Stimulant Bisacodyl 5 \200\223 10mg od/bd Stimulant Docusate sodium 100 \200\223 200mg bd Stimulant and softener; good choice with opiates Macrogols 1 \200\223 3 sachets daily Osmotic CONSERVATIVE MANAGEMENT OF CKD 269 Symptoms Dyspnoea Causes Treat anemia, \202 uid overload, acidosis, anxiety Treatments IV iron and ESAs, diuretics, bronchodilators, O 2 advice on sleeping position Comment Lorazepam 0.5mg sublingual 4 \200\223 6h Midazolam 2.5mg SC 4 \200\223 6h Benzodiazepines can be a useful adjunct in dyspnoea, especially if anxiety a factor Nausea and vomiting Multifactorial Haloperidol 0.5 \200\223 2mg PO od Metoclopramide 5 \200\223 10mg tds PO Domperidone 10 \200\223 20mg tds PO Ondansetron 4 \200\223 8mg bd PO Constipating Dry skin and pruritus Control PO 4 and i PTH Emollients (e.g. aqueous cream, E45 , Diprobase ), Oilatum in bath water Antihistamines, e.g. cetirizine 5 \200\223 10mg od, chlorphenamine 4mg qds Capsaicin 0.025% cream if localized SE: burning sensation Thalidomide 100mg nocte if intractable SE: neuropathy Anxiety and depression Expert counseling and psychological support Anxiety Lorazepam 0.5 \200\223 1mg PO prn SSRIs (e.g. citalopram 20mg od) Low mood Metabolic (e.g. d Na + , i Ca 2+ ) 2 Check for reversible causes Confusion Constipation Drug toxicity Has an incorrect dose been prescribed for level of renal function? Restless legs Correct anemia, iron de \201 ciency and i PO 4 Clonazepam 250 \200\223 500 micrograms nocte Co-careldopa 12.5/50 nocte May give short-term relief, then exacerbate Pergolide 25 micrograms nocte SE: nausea CHAPTER 3 Chronic kidney disease (CKD) 270 Conservative treatment of CKD: general The decision not to have dialysis \200 Patients wh o start dialysis with signi \201 cant comorbidity and functional dependence typically have a short survival time, which may be \201 lled with hospital admissions, painful illnesse s, and unpleasant procedures. For such patients, continuing supportive care without commencing dialysis may allow a better quality of life, with little or no reduction in life expectancy . The decision whether to commence dialysis at ESRD is ultimately made by the patient (assumi ng the patient has capacity). The renal team has a duty to ensure that this decision is as informed as possible by explaining the implications of withholding dialysis and the pros an d cons of commencing it. Family members should also be involved. \200 The process cannot be rushed. A decision not to accept dialysis should be made over time and be consistently held. Patients may (and often do) change their minds (in either direction). \200 If severely ur aemic, a patient may be unable to be involved in the decision-making process. It can be dif \201 cult to determine whether debility is uraemic in origin (and 6 potentia lly reversible) or s to pre-existing comorbidity. \200 Patients referred late have no tim e to go through the pre-dialysis counseling process and may be denied the opportunity to ma ke informed decisions about their care. Withdrawal of dialysis \200 As with the decision of not to start dialysis, the decision t o withdraw should be made by the patient with the help and support of the multidisciplinary team. Withdrawal means that death will probably occur within a few days if the patient has no sig ni \201 cant residual renal function. The decision to withdraw may be prompted by a catast rophic medical event (e.g. a CVA, loss of vascular access). Less often, it is the culminati on of a number of smaller events, which have, in the view of the patient, had unacceptable consequences for their quality of life. Depression should be looked for and treated. \200 The decision to withdraw should be made over a period of time and be held consistently. Care of the dying patient \200 The patient should be able to die peacefully and with dign ity, in a place of his or her choosing, surrounded by loved ones. This requires planning so that care at home, in a hospice, or in hospital can be arranged at short notice. Agreed care pathways may facilitate the management of the last few days of life. Family support: before death, family members may be involved in the physical care of the pa tient and need support and help. At the time of death and afterwards, help should be availa ble to cope with the grieving process (this will need to be culturally appropriate). CONSERVATIVE TREATMENT OF CKD: GENERAL 271 Analgesia in advanced CKD \200 Pain is under-recognized and undertreated in patients with kidney disease. The fact that it is more dif \201 cult to treat is no excuse for inadequa te management. Opiate analgesia is very effective but must be used with caution. Accumulation l signi \201 cant side effects: constipation, drowsiness, confusion, respiratory depression, twitch ing, and seizures. If uncertain, seek expert pain advice. \200 Use the World Health Organization (WHO) analg esic ladder. Step 1 \200 Paracetamol: safe and effective in CKD. Requires no dose adjustment. \200 N SAIDs: Usually contraindicated (pre-dialysis l deterioration in GFR; dialysis l d residual renal function). Can be an effective short-term measure, esp. musculoskeletal pain. \200 Co-prescribe a PP I, as gastritis common. Step 2 \200 Tramadol: 90% renally excreted, so d dose and i interval (start 50mg 12h). Avoid codeine and dihydrocodeine if eGFR <15mL/min. (cid:2) Hepatic metabolites accumulate in CKD. If used, reduce dose by 50%. Step 3 Drug choice will depend on acuteness and severity of pain, desirable route of admini stration, and local availability. SC can be used for rapid relief, with subsequent conversi on to oral or transdermal. \200 Morphine or diamorphine: (cid:2) Avoid, if possible, as breakdown products accumulate. \200 If used short-term \200\224 morphine: initially 2.5mg SC 4 \200\223 12h prn. Diamorphine: initially 1.25mg SC 4 \200\223 12h prn. \200 Buprenorphine: Effective. Nausea a prominent side effect. \200 200 \200\223 400 micrograms sublingual o r transdermal patches. Alfentanil: First-line SC opioid in renal failure. \200 SC 250 micrograms 2 \200\2234h. \200 Can be given as a continuous infusion. \200 Use fentanyl for breakthrough, as alfentanil has sh ort half-life. Fentanyl: <10% renally excreted. \200 SC 25 micrograms 3 \200\223 6h. Lozenges for breakthrough pa in. Transdermal patch very effective once pain controlled by other means. Hydromorphone: initially 1.3mg orally 6 \200\223 8-hourly + 1.3mg prn for more severe pain. Oxycodone: start with OxyNorm (initially 2.5mg 8 \200\223 12h) for rapid pain control, and convert to OxyContin for less frequent administration. \200 Methadone: hepatic met abolites excreted in feces. However, large interpatient pharmacokinetic variability means i t should probably be reserved for use by physicians familiar with its eccentricities. 273 Chapter 4 Dialysis RRT: a brief history 274 Dialysis: an introduction 276 Haemodialysis (HD) 278 Haemodialysis apparatus 280 Dialysate 282 Dialysers and membranes 284 Dialysis prescription and adequacy 286 Anticoagulation 290 Dialysis access: AVF/PTFE 292 Haemodialysis access: lines 296 Flui d balance on dialysis 300 Intradialytic hypotension 302 Extended hours HD treatments 304 Ot her HD complications 308 Peritoneal dialysis (PD) 312 Types of PD 314 PD \202 uids 316 Pr escribing PD 318 Peritonitis 320 Peritonitis: management 322 Other PD complications 324 PD adequacy 328 Ultra \201 ltration (UF) failure 332 The well PD patient 334 CHAPTER 4 Dialysis 274 RRT: a brief history It is only in the last 50 years that it has become possible to keep ESRD patients alive. Th e challenge now is to allow them a quality of life that approaches, or matches, that of the general population. 1861 Term \200\230 dialysis \200\231 \201 rst coined 1913 First \200\230 arti \201 cial kidney \200\231 built and used in animals 1923 First human PD 1924 First human HD 1933 First (unsuccessful) cadaveric kidney transplant 1946 First dialysis in the UK 1946 PD used to treat ARF 1947 First cadaveric kidney transplant. Patient had pregnancy-related ARF. Graft placed external ly (on arm) and lasted 6 days (and ARF had resolved) 1948 Kolff \200\223 Brigham dialyser developed \200\224 a major technological advance 1948 HD used to treat ARF in the Korean war Early 1950s Cadaveric transplants for CRF (into thigh with ureterostomy); no immunosuppression \200 \224 all rejected within 6 months 1954 First successful monozygotic twin transplant * 1959 Non-monozygotic twin transplant (with whole body irradiation as immunosuppression) 1959 Intermittent PD, with repeated abdominal puncture, described 1960 Peter Medawar and Franc Burnet received Nobel Prize for describing principles of immunologi c rejection 1960 Scribner shunt \200\224 the \201 rst access device enabling repetitive use 1960 First long-term HD patients (Seattle, USA) 1962 6-mercaptopurine used successfully for immunosuppression 1963 Steroids and azathioprine used with greater success 1964 First home HD patients 1966 Cross-matching introduced 1966 Forearm AVF developed 1967 First successful liver and heart transplants 1968 Tenckhoff PD catheter introduced 1975 Haemo \201 ltration introduced 1976 Introduction of ciclosporin \200\224 1-year graft survival dramatically improves 1977 Continuous AV haemo \201 ltration described 1976 Continuous ambulatory peritoneal dialysis (CAPD) introduced 1982 First kidney pancreas transplant 1990 Joseph Murray awarded Nobel Prize for his pioneering transplant work 2013 First successful rodent transplantation of a bioengineered kidney RRT: A BRIEF HISTORY 275 CHAPTER 4 Dialysis 276 Dialysis: an introduction Normal functioning kidneys: \200 Remove excess salt, water, and acid. \200 Remove or regulate other electrolytes (e.g. K + , Ca 2+ , Mg 2+ , PO 4 ). \200 Remove waste products of metabolism (Ur and Cr are measured routinely, but there are many others). Make erythropoietin. \200 1 A -hydroxylate (and 6 activate) vitamin D. Dialysis acts as s urrogate for all but the last two of these (which can be achieved pharmacologically). Even at best, it is only partially effective. Transplantation more completely (but still partial ly) replaces normal kid- ney function and should be regarded as the optimum treatment of ES RD. Transplanted patients survive longer and have a better quality of life. However, not ev eryone is \201 t for transplantation \200\224 ESRD patients are often frail, with apprec iable comorbidity, especially vascular disease. Registry data and international comparisons In the UK there are now 23,500 prevalent HD pat ients (365 PMP) and 74000 PD patients (61 PMP). Annual dialysis growth has been declining i n recent years and now stands at 72% for HD (with a decrease of 72% for PD). The median age of prevalent patients is 58 years. Incidence rates have been stable since 2006, but with a n increase in patients > age 65 (Fig. 4.1). Resources Dialysis (and transplantation) are expensive. The cost of RRT is estimated to acc ount for 1 \200\2232% of the total NHS budget, even though it affects just 400 0 \200\22344 45 \200\22364 65+ Total 350 300 n o i t a l u p o p 250 n o 200 i l l i m r e p 150 e t a R 100 50 0 0 8 9 1 2 8 9 1 4 8 9 1 6 8 9 1 8 8 9 1 0 9 9 1 2 9 9 1 4 9 9 1 6 9 9 1 8 9 9 1 0 0 0 2 2 0 0 2 4 0 0 2 6 0 0 2 8 0 0 2 0 1 0 2 Year Fig. 4.1 UK incident RRT rates between 1980 and 2010. Reproduced from UK Renal Registry 15t h Annual Report: UK Renal Registry (2012), with permission. DIALYSIS: AN INTRODUCTION 277 0.05% of the population. The tariff for hospital or satellite based HD in the UK is current ly 7 23,000 per annum, depending on locality (with a \200\230best- practice \200\231 supp lement for those dialysing through an AV \201 stula). Although all modalities are expensi ve, transplantation is the most cost effective (but only after the \201 rst year). In the US (2011), Medicare expenditure on RRT rose to 7$30 billion (7$25 billion HD, $1.5 billion PD, 7$3 billion transplan- tation). Per patient per year the costs were: HD 7$88,000, PD 7 $72,000, transplant 7$33,000. International data \200 Prevalence rates of RRT vary across Europe and are often higher t han in the UK. In the USA there were 7430,000 prevalent dialysis patients in 2011 (HD 7395,000, PD 731,500). However, the annual growth rate (3.4%) was the lowest for 30 yea rs. Total ESRD prevalence was 1,901 PMP. \200 7101,000 patients started HD therapy in the US (80% of whom started on a dialysis catheter, rather than with an AVF. An astonishing 40 % had not seen a nephrologist prior to reaching ESRD), 77,500 started PD and 72,500 receive d a pre-emptive transplant. 16% started RRT with an eGFR of 15mL/min or over. The overall adjusted incidence of ESRD in the US was 357 PMP (Caucasian 280 PMP, Black 940 PMP, Native American 453 PMP, Asian 399 PMP, Hispanic 518 PMP). Diabetes mellitus was the most common cause of ESRD, followed by hypertension (source: USRDS Annual Data Report 2013). Survival RRT patients age 30 \200\22334 have a mortality rate 25x higher than the age match ed general population (for patients age >85 it is still 73x higher). Median survival for pa tients starting RRT in the age group 45 \200\22354 is cur- rently 10.5 years, for age 55 \200\22364 it is 5.6 years and for age 65 \200\22374, 3 years. The relative risk of death f or prevalent RRT patients (UK 2010) was 6.6. Diabetic patients have worse survival than non -diabetic patients. The sur- vival in older age groups is only slightly better than in pati ents with lung cancer. (See Fig. 4.2 for Kaplan \200\223 Meir curve.) 100 90 80 l a v v r u s 70 i 60 50 e g a t n e c r e P 18 \200\22334 35 \200\22344 45 \200\22354 55 \200\22364 65 \200\22374 75+ 40 30 20 10 0 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 9.5 10.0 Years Fig. 4.2 Kaplan \200\223 Meir Curve. Survival of incident patients (unadjusted) 1997 \200 \223 2010 cohort (from day 90), without censoring at transplantation. Reproduced from UK Re nal Registry 15th Annual Report: UK Renal Registry (2012), with permission. CHAPTER 4 Dialysis 278 Haemodialysis (HD) Overview \200 During dialysis, blood is exposed to dialysate (with phy siological concentrations of electrolytes) across a semi-permeable membrane. Small molecules such as Ur (MW 60Da), Cr (MW113Da) and electrolytes pass through pores in the membrane. Large molecules such as albumin (MW 60,000 Da), IgG (MW 140,000Da) and blood cells do not. Concentration differences across the membrane allow molecules to diffuse down a gradient. T his allows waste products to be removed and desirable molecules or ions (e.g. HCO 3 \200 \223 ) to be replaced. \200 Water can be driven through the membrane by hydrostatic force (ultra \201 ltration, UF). \200 By varying the pressure gradient across the membrane (transmembrane pressure, TMP), water removal can be controlled. In addition to a means to remove water ( 7 1 \200\223 4L) that has accumulated between dialysis sessions (ingestion of \202 uid, foods, and by-product of me tabolism), UF can also be used as a means of solute clearance by convection. What is required for haemodialysis? \200 Dialysis membrane ( b p. 284): a biocompatible m embrane with adequate surface area/permeability for solute clearance and ultra \201 ltrati on. Dialysate ( b p. 282): of suf \201 cient purity and containing the required concentration of electrolytes. Effective control and safety mechanisms ( b p. 280): pumps for blood and dialysate \202 o w, TMP, temperature, detection of blood leaks or air. \200 Vascular access: large volumes of blood are removed from a patient, exposed to a dialysis membrane, and then returned. Op tions are: \200 AVF \201 stula: optimal form of vascular access ( b p. 292). \200 PTF E graft: second best ( b p. 292). \200 Tunneled, cuffed central venous catheter: ideally not long term ( b p. 296). Temporary central venous catheter: for immediate use; e.g. in AKI. ( b p. 180). Anticoagulation ( b p. 290): prevents blood clotting in the extracorporeal circuit. Haemodialysis and haemo \201 ltration Haemodialysis \200 Solute clearance by diffusion ( mainly). \200 Dialysate is required. \200 Diffusion is maximized by maintaining high- \202 ow rates of blood and dialysate and by pumping the two through the dialyser in counter current directions. Larger MW (>20kDa) molecules are generally poorly removed. \200 Usually administered inte rmittently (e.g. 4h, 3x/week). HAEMODIALYSIS (HD) 279 Haemo \201 ltration \200 Solute clearance by convection (mainly). \200 Achieved by gen erating a TMP across the membrane. \200 No dialysate required. \200 Large volumes need to be \201 ltered to achieve adequate solute clearance. This would cause hypovolaemia unless replacement \202 uid administered (usuall y pre-prepared 5 \200\223 10L bags). Removes larger MW (30 \200\223 50kDa) molecules (e.g. vitamin B12 and B2 microglobulin) more ef \201 ciently than dialysis. Continuous (24h) HF is associated with greater haemodynamic stability and often favored for RRT in a critical care setting ( b p. 174). Haemodia \201 ltration - Enhances clearance of middle molecules by combining diffusion (HD ) and convection (HF) to obtain the best from both modalities. See \201 gure 4.x. Both dialysate and replacement \202 uid are required. Online HDF (OL-HDF) uses ultrapure dialysate produced by the dialysis machine as replacement \202 ui d. This i convective volume and d cost. Bene \201 ts potentially include superior removal of higher MW uraemic toxins, greater hae modynamic stability and d ESA requirements. HDF may also be associated with d mortality (DOPPS 2006), although two RCTs (CONTRAST and t he Turkish OL-HDF study) failed to prove this convincingly (although post hoc analysis of C ONTRAST did show a 39% mortality risk reduction in patients receiving higher convection vol umes (>22L/session)). A recent large (>900 patients) RCT with 3-year follow-up (ESHOL) reported that post-dilutio n (see \201 gure 2.16) OL-HDF improves all- cause mortality (30% risk reduction \200\224p rincipally stroke and infection), in comparison to standard high- \202 ux HD. - Post hoc a nalysis showed a 40% and 45% mortality reduction in those receiving convection volumes of 23 \200\22325 L/session and 25 L/ session, respective ly (possibly confounded by better dialysis access and longer hours in this group \200\224bo th confer a survival bene \201 t). - Whether the apparent bene \201 t seen is the result of improved middle 2 microglobulin), greater haemodynamic stability, MW toxins (e.g. less intradialytic d BP, or other factor is uncertain. Regardless, OL-HD F is likely to become increasingly popular, particularly in the subgroup of patients with n o residual renal function and greater propensity for haemodynamic instability. Potential indications - Patients with no imminent transplant options; e.g. highly sensitize d patients on the deceased donor waiting list. Large patients already on 4.5-5h high- \202 ux dialysis with sub-optimal clearance. Long-term dialysis patients. - Patients with symptomatic hypotensive episodes on dialysis. - Patients with post-dialysis symptoms and long recovery time. - Patients generally not thr iving on dialysis (after other causes excluded). - ? Dialysis amyloid (b page 632). CHAPTER 4 Dialysis 280 Haemodialysis apparatus Principle Blood is removed from the patient, anticoagulated, pumped through a dia- lyser, and then returned to the patient (see Fig. 4.3). Within the dialyser , blood and dialysate ( \202 owing in opposite directions) are separated by a semi-permeab le dialysis membrane. Venous pressure monitor Air trap and air detector Clean blood Saline solution Fresh dialysate Dialyser Patient Used dialysate Inflow pressure monitor Blood pump Heparin pump (to prevent clotting) Arterial pressure monitor Removed blood for cleaning Fig. 4.3 The HD circuit. Schematic of haemodialysis machine. Reproduced with license under the Creative Commons Attribution 3.0 Unported license. Source: Yassine Mrabet. Apparatus \200 Blood pump: usually a roller \200\230 peristaltic \200\231 pump. \200 Bubble trap: traps air l d risk of air embolism. \200 Blood \202 ow rate: usually 200 \200\223 500mL/min. \200 Dialysate \202 ow rate: up to 600mL/min. \200 Heaters: dialy sate and blood are kept at 37 * C. \200 Dialyser: a rigid polyurethrane shell ( 7 30cm lo ng), containing hollow \201 bres (capillaries) of dialysate membrane. This arrangement maximizes the available s urface area for dialysis (0.5 \200\223 2.1m 2 ). Two ports each allow blood and dialysate to enter and exit. Priming volume (saline) 7 50 \200\223 100mL. Dialyser ef \201 ciency: depends on membrane thickness, pore size, and dialyser structure. Ef \201 ciency of solute clearance is measured as KoA (mass transfer urea coef \201 cien t), provided for each dialyser by the manufacturer. KoA varies from 300 to 1,100 (>600 = hi gh ef \201 ciency dialyser, requiring higher blood and dialysate \202 ows). HAEMODIALYSIS APPARATUS 281 Alarms and monitors These will stop the blood pump and clamp lines if the situation demands , effectively creating what is known as a \200\230closed circuit \200\231. \200 Air dete ctors: located distally in the venous circuit, prevent air emboli. \200 Pressure monitors : Arterial l detect d pressure s to poor access \202 ow and line disconnections. Venous l detect i pressure s to resistance to venous return (usually represents an access problem). Dialysate out \202 ow pressure l monitor TMP (to vary UF rate). Dialyser integrity. \200 Temperature. \200 Conductivity: Electrical conductivity is used to monitor proportioning of dialysate to water. Many machines use conductivity to enable changes to Na + concentration. Newer machines \200 Blood volume monitoring: haematocrit (Hct) in the arterial line is us ed as a surrogate for blood volume ( d plasma H 2 O l i Hct). Used to \201 ne-tune UF and BP control. Access recirculation measurements: ensures the same small volume of blood is not dialysed repetitively. Delivered Kt/V: Ur concentration in the dialysate out \202 ow line or dialysate conductivi ty used to calculate delivered dialysis dose. Vascular access monitoring: quickly alerts to the possibility that dialysis cannulae or the vascular access device have become dislodged from their normal working position. CHAPTER 4 Dialysis 282 Dialysate Box 4.1 Summary \200 A solution of ultrapure water, Na + (132 \200\223 150mmol/L), K + ( usually 1.0 \200\223 3.0mmol/L), Ca 2+ (1.0 \200\223 1.25mmol/L), Mg 2+ , Cl \200\223 , dextrose, and buffer. Ultrapure water is generated in a treatment plant (involves micro \201 lters, activated carbon, deionization, and reverse osmosis) to exclude particul ate matter, ions, and minerals potentially harmful to humans (see Fig. 4.4). UK Renal Association standards for water purity are <0.25IU/mL endotoxin, <100cfu/mL microbial count. H + ions have a low plasma concentration and are not removed by dialysis. Buffer (alkali eq uivalent) is added to dialysate instead. Bicarbonate is now preferred to acetate as a buffer. \200 HD machines either mix dialysat e concentrate, buffer, and water for the individual patient or this is done centrally before distribution around several mac hines. Ultrapure water An average patient is exposed to 560L of water during three HD sessions, so it must be of suf \201 cient purity to enter the bloodstream. City Water Water Softener Activated Carbon RO RO Filtration Filtration C D I 1 2 Drain Pump Filtration Loop HD Machine HD Machine Fig. 4.4 Ultrapure water treatment system for haemodialysis. Reproduced from Nephrol. Dial. Transplant. (2002) 17(suppl 7): 54 \200\223 61, with permission. RO = reverse osmosis. CD I = continuous deioniser. Carbon \201 lters removes chlorine/chloramines to <0.1mg/L (chloramines can lead to haemo lysis). Softeners remove Ca2 + and Mg2 + by ionic exchange, as \200\230 hard \200\231 wat er can damage machines and cause muscle weakness. Micron \201 lters remove suspended part icles. Reverse osmosis (RO) removes bacteria, endotoxins, pyrogens, viruses, and solutes (c an lead to hypotension, nau- sea, vomiting.) Regular testing must ensure purity standards ( see Box 4.1). DIALYSATE 283 Dialysate concentrates Dialysate contains pure water as well as several different concen- t rates: sodium, potassium, calcium, bicarbonate, magnesium, and glucose. In an ideal world, the proportions of each of these concentrates should be individualized for every HD patient . Potassium (K + ) Around 80 \200\223 140mmol is removed per HD session. The gradient of K + between serum and dialysate is important, and most K + is removed in the \201 rst hour. Dialysate K + varies from 1 to 3mmol/L. The higher the gradi- ent, the more the K + removal which is associated with a greater risk of haemodynamic instability. Sodium (Na + ) Dialysate Na + concentration controls salt and water removal from the plasma (see b p. 301). Bicarbonate (HCO 3 \200\223 ) HD aims to ameliorate a pre-dialysis acidos is without causing a post-dialysis alkalosis. Dialysate concentrations vary from 36 to 40mm ol/L. Calcium (Ca 2+ ) 40% of plasma calcium is bound to protein, the remainder is ionized (1.1 \200\223 1.5mmol/L) and therefore dialysable. Guidelines recommend lower- ing dialysate Ca 2+ to maintain neutral or negative Ca 2+ balance to prevent vascular calci \201 cation. Ho wever, higher patient:dialysate gradients are asso- ciated with sudden cardiac death. Most units utilize a dialysate Ca 2+ of 1.25mmol/L. CHAPTER 4 Dialysis 284 Dialysers and membranes Biocompatibility \200 Dialysis membranes are not inert. They can activate complement and in \202 ammatory cascades ( l short- and long-term complications). A biocompatible membrane is one that elicits the minimum in \202 ammatory response in patients exposed to it. Improved biocompatibility may l : \200 d hypersensitivity reactions. \200 Less intradia lytic d BP. \200 Slower loss of residual renal function. \200 Improved nutrition. \200 d amyloid deposition. \200 d morbidity and mortality ( X ). Cellulose membranes (e.g. C uprophan ) \200 The original membrane and least biocompatible. \200 Largely supersed ed by synthetic membranes. Modi \201 ed cellulose (e.g. Hemophan ) More biocompatible. Synthetic membranes (e.g. Polysulfone , polyamide, polyacrylnitrile) \200 More recentl y developed. \200 Most biocompatible. \200 More permeable than cellulose membranes: Solute clearance similar to cellulose membranes. \200 i B 2 microglobulin clearance. High vs low \202 ux High- \202 ux membranes are usually synthetic membranes with a large pore size l enhanced clearance of middle and large molecules. X May lead to better outcome s. Surface area i dialyser surface area (usually 0.5 \200\223 2.1m 2 ) l i delivered dialysis . See Fig. 4.5. DIALYSERS AND MEMBRANES 285 Mixed, heated, and deaerated dialysate To waste Balancing chamber From patient Ultra filter Arterial Venous To patient Dialyser Ultra filter Fig. 4.5 Haemodia \201 ltration circuit using online ultra \201 ltration for production o fultra-pure dialysate and replacement \202 uids. CHAPTER 4 Dialysis 286 Dialysis prescription and adequacy Introduction Intermittent HD places exacting demands on a patient. As it only partially replaces renal function, \202 uid and dietary restriction s remain signi \201 cant and burdensome. Dialysis can be considered adequate if it provides relief of uraemic symptoms and controls acidosis, \202 uid balance, and serum K + . It should also allow a feeling of physical an d psychological well-being. Aspects of dialysis adequacy \200 Solute clearance . Small molecule clearance is relative ly easy to measure ( b p. 287). Aim to achieve a target Kt/V of >1.2 or URR >65% (see box b elow). Blood pressure and \202 uid balance . As a general rule, i BP in a dialysis patient shoul d be treated by d \200\230 dry weight \200\231 (i.e. post-dialysis weight). This should b e the weight at which salt and water balance is optimal. Oligo-anuric patients (majority of long-term HD patients) need to restrict their interdialytic salt and \202 uid intake in order to achieve this, aiming for weight gains of 1 \200\223 2.5kg (maximum) between sessi ons. It is dif \201 cult to be achieve prescriptive BP targets in the HD population (lack of evidence and a heterogeneous population). However, pre- and post- dialysis BP <140/90mmH g is desirable. This would preferably be achieved without anti-hypertensive medication. Int er- or intra-dialytic hypotension should be avoided. Nutrition. Blood Ur levels depend on rate of production as well as rate of excretion. (cid:2) A low pre-dialysis Ur may re \202 ect poor nutrition, rather th an good dialysis. Targets: \200 Serum albumin >35g/L. \200 Normalized protein catabolic rate (nPCR) >1.0g/kg/day ( b p. 287). \200 Acceptable anthropometric measures. Clearance of other molecules: \200\230 Middle \200\231 molecule clearance thought to be important to prevent the long-t erm complications of dialysis. B 2 microglobulin is the most used marker. Phosphate clearance is also important and appears to correlate more with hours of dialysis than rate of small molecule clearance. \200 Quality of life a nd life expectancy . There is a potential trade-off to be made between the number of hours spent on the machine ( i dialysis dose) and quality of lif e. For patients with a limited life expectancy, the latter may be a more important consider ation (although reducing hours below 4h 3x week is only rarely indicated). DIALYSIS PRESCRIPTION AND ADEQUACY 287 Measuring dialysis adequacy In the 1980s, the National Cooperative Dialysis Study (NCDS) es tab- lished timed average Ur concentration as a determinant of morbidity and mortality on H D. Subsequent mathematical analysis of these data has led to the development of urea kineti c modeling (UKM) as the accepted method of measuring small solute clearance. Kt/V is a measure of Ur clearance where: K = dialyser urea clearance. \200 t = time on dialysis. \200 V = volume of distribution of Ur (estimated from patient size). The single pool Kt/V assumes that, at the end of dialysis, the concentra- tions of intracel lular and extracellular Ur are equal: = \210\222 \210\222 + \210\222 4 3 5 . spKt V/ ln[ Upost/Upre 0 008 . t ] [ Upost/Upre ] \227 UFvol/wtp oost (Upre, urea pre-dialysis; Upost, urea post-dialysis; UFvol, volume removed on dialysis) The two compartment model acknowledges that, in reality, it takes time for Ur to be redistr ibuted post-dialysis and that the extracellular Ur concentration is lower than intracellula r. An equilibrated Kt/V or eKt/V can be calculated from the spKt/V. A simpler measurement of Ur clearance is the urea reduction ratio (URR), which does not tak e account of the amount of \202 uid removed by ultra \201 ltration. It is thus less accu rate but has been shown to correlate with outcome: \210\222 \227 URR =(1 Upre/Upost) 100 Normalized protein catabolic rate (nPCR) A measure of Ur generation, which re \202 ects nu tritional status. It can only be reliably used in patients who are \200\230 stable \200 \231 so Ur generation will broadly re \202 ect protein intake. It is felt that patients re quire an nPCR >1.0g/kg/ day. nPCR of <0.8g/kg/day is associated with higher mortality. Residual function When HD is \201 rst commenced, residual renal function may contribute g reatly to the total amount of solute clearance (Kru). This is usually calculated with a 24h urine collection. Residual function tends to dimin- ish quickly on HD (secondary to repeti tive d BP 9 bio-incompatibility) ( b p. 284). CHAPTER 4 Dialysis 288 Ensuring adequacy Kt/V UK and US guidelines suggest a single pool Kt/V >1.2 for patients di a- lysed x 3/week, equating to a URR of 7 65%. The landmark HEMO study compared two target Kt/V levels. Patients with a target Kt/V of 1.2 had no difference in mortality or cardiac e vents, compared to those with a Kt/V of 1.6. 2 Residual renal function should always be taken into account. Prescribed vs delivered Kt/V \200\224variables in the dialysis prescription Most guidelines suggest monthly measurement of Kt/V. Online meth- ods of measuring Kt/V are provided on mo dern dialysis machines (often using Na + clearance to estimate urea clearance). If Kt/V fai ls to meet target, options are to: Improve vascular access \200\224 if \202 ows are poor or if there is access recirculation, it will be hard to improve clearances. Increase blood \202 ow/larger needles \200\224 bene \201 cial if access reasonable. \200 Increase dialyser size \200\224 modest impact. \200 Increase dialysate \202 ow. \200 Increase dialysis time/frequency \200\224 major bene \201 t. \200 Consider HDF. Computer modeling software can help decide which elements of the prescription require modi \201 cation to improve Kt/V. (cid:2) HD adequacy is multifaceted. Achieving a desired Kt/V does not nec- essarily equate to optimal dialysis. DIALYSIS PRESCRIPTION AND ADEQUACY 289 Management of dialysis patients on non-renal wards - For elective procedures, inform your r enal team at the pre- assessment stage. On the day of admission contact them again (arrangements for routine dial ysis will need to be made). 1 Many dialysis patients are oligo-anuric, so DO NOT routinely administer IV \202 uids (u nless the patient is haemodynamically compromised \200\224if so, use small boluses, assess volume status regularly and call for expert help). 1 DO NOT give K+ supplementation. Discuss with renal team if being considered. DO NOT place a urinary catheter unless there is a clear urological indication. Oligo-anuria is virtually universal in this patient group! If the patient is clinically overloaded inform the renal team immediately, as the patient m ay require urgent dialysis.