 \200 \200 CHAPTER 12.3 Chronic kidney disease in diabetic patients 473 Table 12.3.1 Modi \201 cations of antidiabetic drugs in patients with type 2 diabetes (ada pted from the K/DOQI guidelines) Class Drug Dosing recommendation CKD stages 3, 4, or kidney transplant Dosing recommendation dialysis First-generation sulfonylureas Acetohexamide, tolazamide, tolbutamide Avoid Avoid Avoid when GFR <50 mL/min/1.73 m2 Chlorpropamide Avoid Second-generation sulfonylureas Glipizide, gliclazide Preferred sulfonylurea. No dose adjustment necessary. Preferred sulfonylurea. No dose adjustment necessary. Glyburide Avoid Avoid Glimepiride Initiate at low dose, 1 mg daily Avoid A-Glucosidase inhibitors Acarbose, miglitol Avoid Not recommended if SCr >180 mol/l Biguanides Metformin See text Avoid Meglitinides Repaglinide No dose adjustment necessary No dose adjustment necessary Nateglinide Initiate at low dose, 60 mg before each meal Avoid Thiazolidinediones Pioglitazone, rosiglitazone No dose adjustment necessary No dose adjustment necessary Incretin mimetic Exenatide No dose adjustment necessary No dose adjustment necessary Amylin analog Pramlintide No dose adjustment necessary for GFR 20 \200\22350 mL/min/1.73 m2 No data available Reduce dose by 75% (25 mg/day) DPP-4 inhibitor Sitagliptin Reduce dose by 50% (50 mg/day) when GFR <50 and \211 30 mL/min/1.73 m2 and by 75% (25 mg/d ay) when GFR <30 mL/min/ 1.73 m2 DPP-4, dipeptidyl peptidase-4. Consequences of decreased kidney function Patients with diabetes and CKD should be referred early to a nephrologist for management of the complications of progressive CKD. Referral c riteria vary, but all diabetic patients should be reviewed when they reach CKD 3. Metformin This should be used with caution in patients with CKD. The use of metformin in CK D carries a risk of severe lactic acidosis; the risk increases with decreasing GFR. Various thresholds have been proposed to withdraw met- formin based on serum creatinine: \200 \200 140 mol/L in men; 130 mol/L in women; Anemia Anemia increases the risk of cardiovascular events in dia- betics with CKD. Anemia s hould be treated by erythropoetin-stimulating agents (ESAs) when Hb <11 g/dL, and after exc luding: \200 or GFR: \200 40 \200\22350 mL/min/1.73 m2. The use of metformin should be reviewed when the patient reaches CKD 3 and is contraindicat ed in CKD 4 and 5. iron de \201 ciency (transferrin saturation >20% and ferritin >100 g/L); chronic or acut e inflammation (C-reactive protein <5 mg/L); folate or vitamin B12 de \201 ciency. Sulfonylureas First-generation sulfonylureas should be avoided. Second-generation sulfonylu reas may be used in patients who have learned to prevent hypoglycemic episodes, as long as diabetes is controlled and nutritional status is satisfac- tory. The target Hb is between 11 and 12 g/dL, with a rate of increase of \211 1 g/dL over 2 wee ks. ESAs should not be used in the presence of uncontrolled hypertension. Thiazolidinediones These may be used in patients without heart failure. Caution is advised in patients with ischemic heart disease. Higher rates of fractures have been reported in pa tients treated by thiazolidinediones. Mineral metabolism Disturbances in mineral metabolism increase cardiovascu- lar risk, and a re associated with renal osteodystrophy in diabetics with CKD. Targets for calcium, phospha te and PTH are identical to those defined for patients with CKD from other causes. Insulin When insulin therapy is used care should be taken to avoid hypoglycemic episodes as the renal clearance of insulin falls with advancing renal impairment. C. COMBE AND V. RIGALLEAU 474 In patients treated with the starch-containing solution ico- dextrin, a glucose-speci \201 c monitor and test strips should be used, as metabolites of icodextrin interfere with many glucometers. Electrolyte disturbances Metabolic acidosis should be corrected by bicarbonate supplementat ion. Hyperkalemia may result from diet, adverse effects of renin \200\223angiotensin inhibi tors, or acidosis at CKD stages 3 and higher. Hemodialysis Hemodialysis may be performed in patients with type 1 or type 2 diabetes. If t he patient chooses hemodialysis, vascular access should be planned and undertaken early (ty pically when the patient reaches CKD 4). The best form of vascular access is a native AVF. Prosthetic grafts should only be used when it is not possi- ble to form a native AVF. Vascu lar catheters should only be used in emergency cir- cumstances or if no other type of vascu lar access can be made. Catheter use is associated with more frequent infective complicatio ns and increased mortality. Fluid retention Fluid retention is frequent in diabetic CKD. Salt restriction and diuretic therapy are the basis of \202 uid control in these patients. Malnutrition Malnutrition is common in diabetics with CKD. Inappropriate dietary counseling may lead to malnutrition through excessive dietary restriction. End-stage renal disease Therapeutic strategies All techniques of renal replacement therapy (RRT) may be used in patients with diabetes. A decision should be made early (when the GFR falls to <30 mL/min/1.73 m2) with the patient on the type of RRT to be used. Vaccination ag ainst hepatitis B should be performed early in all patients with progressive CKD (stage 3). It is important to avoid venous punctures in the nondomi- nant arm to preserve the veins f or creation of an arteriov- enous \201 stula (AVF) for hemodialysis. Other complications of diabetes Cardiovascular disease Coronary artery disease Asymptomatic patients should be screened every 2 years using a noninvasive method (exercise test, echoc ardiogra- phy with dobutamine). Coronary angiography is frequently needed as part of the pr etransplant evaluation. Diabetic patients with CKD and coronary artery disease should be tr eated aggressively with -blockers, statins, and aspirin or clopidogrel. Kidney transplantation RRT by renal transplantation is associated with a lower morbidity an d mortality, and should be encouraged wher- ever possible. Cardiovascular morbidity is the main limitation for trans- plantation in diabetic patients. Kidney transplantation may be p erformed in patients with type 1 or type 2 diabetes. The threshold for kidney transplantati on will vary between centers but is usually <20 \200\22310 mL/min/1.73 m2. Kidney transplan tation may be performed either from a liv- ing or a cadaveric donor. Peripheral vascular disease Peripheral vascular disease is a frequent complication in patie nts with diabetes and CKD. Patients should be regularly assessed by clinical examina- tion with appropriate investigations as needed. Erectile dysfunction This is a frequent complication often resulting from a com- bination o f vasculopathy and the side-effects of drugs used to treat hypertension and ischemic heart disease. Phosphodiesterase type 5 inhibitors (sildena \201 l, tadala \201 l, vardena \201 l) may be used unless the patient has uncontrolled ischemic heart disease or uses nitr ates. Combined kidney and pancreas transplantation Combined kidney and pancreas transplantation s hould be considered in patients with type 1 diabetes. It is inappropriate in patients with type 2 diabetes. The criteria for acceptance onto the combined list and the threshold for k idney and pancreas transplantation will vary between centers (combined transplantation usua lly con- sidered below 20 mL/min/1.73 m2). Various techniques may be used for pancreas tran splanta- tion, including islets transplantation. In some centers peritoneal dialysis is con traindicated in patients in whom pancreas transplantation is planned. Diabetic retinopathy Annual screening for diabetic retinopathy should be under- taken. Diabetic foot Diabetic patients with CKD have a high risk of diabetic foot lesions. High ri sk patients (previous ulcer or peripheral neuropa- thy) require speci \201 c advice about the use of appropriate footware and recognizing the early signs of infection. Close liaison with local podiatry services is important. Feet should be examined periodically and should form part of the regular assessment of the diabetic patient in both nephrology and dialysi s clinics. Peritoneal dialysis Peritoneal dialysis may be performed in patients with type 1 or type 2 diabetes. The technique is well-suited to patients who are waiting for a cadaveric transpla nt. The glucose load associated with peritoneal dialysis might be as high as 100 \200\22320 0 g/day (i.e. 400 \200\223800 kcal/day). Pregnancy Women with diabetes and CKD are at increased risk of pre- term birth, pre-eclamps ia, and worsening of renal function. CHAPTER 12.3 Chronic kidney disease in diabetic patients 475 Preconception counseling should be offered to all women wishing to start a family so that m edical care can be opti- mized and the risks of pregnancy discussed. Insulin should be used to control blood sugars during preg- nancy. ACEIs and ARBs should be discontinued as soon as preg- nancy is con \201 rmed if they have not been stopped precon- ception, because of the risk of teratogenicity. Lewis EJ, Hunsicker LG, et al. The effect of angiotensin-converting- enzyme inhibition on d iabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993; 329: 1456 \200\22314 62. Nathan DM, Cleary PA, et al. Intensive diabetes treatment and car- diovascular disease in p atients with type 1 diabetes. N Engl J Med 2005; 353: 2643 \200\2232653. Internet resources National Diabetes Support Team, UK guidelines: http://www.diabetes.nhs.uk/downloads/NICE_and_ Diabetes.pdf UK Renal Association guidelines for diabetic patients with CKD: Patients \200\231 involvement in their own care Patients should be educated to be proactive in their own treatment, particularly with regard to: \200 \200 \200 \200 glycemic control; blood pressure; nutrition; exercise. http://www.renal.org/CKDguide/full/ CKDprintedfullguide.pdf US National Kidney Foundation K DOQI guidelines: http://www.kidney.org/professionals/kdoqi/guide line_diabetes/ Further reading Genuth S, Eastman R, et al. Implications of the United kingdom prospective diabetes study. Diabetes Care 2003; 26(Suppl 1): S28 \200\22332. See also Diabetes mellitus, p. 144 CKD in pregnancy, p. 476 Selection and preparation of recipients, p. 544 K/DOQI Clinical Practice Guidelines and Clinical Practice Recommendations for Diabetes and Chronic Kidney Disease. Am J Kidney Dis 2007; 49: S1 \200\223S179. N. BRUNSKILL 476 Chronic kidney disease in pregnancy Introduction Chronic kidney disease in pregnancy provides a clinical challenge for nephrolo gists and obstetricians tasked with managing the reciprocal effects of pregnancy on renal d is- ease, and of underlying pre-existing renal disease on preg- nancy outcomes. In order to assess these women it is necessary to appreci- ate the changes in renal physiology and fun ction that occur in normal pregnancy: Pregnant women in the mild category have a rate of live outcomes similar to that of the pre gnant population as a whole, despite an increase in prematurity. Results are less certain i n the moderate and severe categories. Premature delivery is very common, and reports of fet al loss cluster in those women with worse renal function. Nonetheless with modern neonatal surveillance and inten- sive care most women can anticipate a successful obstetric outcome. The underlying renal disease seems to be of little impor- tance as a determinant of outcom e, although pregnancies in women with renal involvement in some systemic dis- eases such as vasculitis and lupus nephritis may be associ- ated with a poorer prognosis. Changes in renal physiology and function in normal pregnancy Kidney length and volume incre ase, and the collecting sys- tem dilates \200\223 more markedly on the right side. Renal p lasma \202 ow increases by 80%. Gestational vasodilatation results in decreased maternal blood pressure in the \201 rst and second trimesters. Glomerular \201 ltration rate (GF R) increases by 50% in the \201 rst trimester. Serum creatinine concentration falls by 10 % in the \201 rst tri- mester and 30% by the last trimester. In the third trimester mater nal plasma volume is increased by 40% over prepregnancy values. There is a concurrent fall in serum albumin concentration to 30 \200\22335 g/L. Many of these functional changes are a ttenuated or absent when renal disease is present. Therefore blood tests and other clinical investigations must be interpreted in the light of these functional changes. For example i n pregnant women: \200 Effect of pregnancy on underlying renal disease As with obstetric outcomes the probability that pregnancy will adversely affect maternal renal function is largely dependent on remain ing renal function and blood pressure control. The identity of the underlying renal disease per se appears to have little in \202 uence. Women with mild renal impairment demonstrate a gesta- tional increase in GFR, and renal function is usually main- tained. However, thos e with severe renal impairment may suffer signi \201 cant loss of renal function in pregna ncy, with a steeper trajectory of decline compared to that observed before conception. In s ome this may recover after delivery but in others func- tional deterioration accelerates af ter delivery. Those with a serum creatinine >180 mol/L have a 33% chance of ESRD by 12 mo nths postpartum. The presence of >1 g proteinuria/24 h is an aggravating factor. Prepregnan cy risk strati \201 cation for women with renal dis- ease based on renal function may chan ge with the advent of new CKD classi \201 cations and eGFR reporting. More women with iden ti \201 ed pre-existing renal impairment identi \201 ed by eGFR may be encountered by ren al/obstetric services in the future. \200\230normal \200\231 serum creatinine may represent signi \201 cantly impaired renal f unction; formulaic estimations of glomerular filtration rate (eGFR) are not valid in pregna ncy; a dilated collecting system does not generally re \202 ect underlying obstruction to urinary \202 ow; a depressed serum albumin concentration in a proteinuric patient does no t necessarily indicate nephrotic syndrome. Effect of renal disease on obstetric outcomes In general, pregnancies of women with renal d isease are associated with increased risks of adverse obstetric out- comes, including an in creased incidence of: \200 \200 \200 \200 Preconception counseling and preparation of women with CKD for pregnancy Ideally all women with CKD should be offered preconcep- tion counseling to discuss the risks of pregnancy to the mother and fetus, and the potential impact on maternal renal function. In addition it i s often necessary to discontinue unsafe med- ications in pregnancy with the substitution of more \200\230preg- nancy-friendly \200\231 agents. The following antihypertensives are sa fe and commonly used in pregnancy: \200 methyldopa; \200 labetalol; \200 hydralazine; \200 nifedipine. pre-eclampsia; babies born prematurely; babies born small for gestational age; reduced feta l survival. The key determinants of adverse obstetric outcomes are: \200 \200 the presence of hypertension; the degree of underlying renal impairment. Poorly controlled blood pressure (MAP >105 mmHg) is associated with an 10-fold increase in the risk of fetal death. With respect to degree of renal impairment, it is conven- tional to stratify women as follows: 1. Mild: serum creatinine \211 124 mol/L. 2. Moderate: ser um creatinine 124 \200\223220 mol/L. 3. Severe: serum creatinine >220 mol/L. CHAPTER 12.4 Chronic kidney disease in pregnancy 477 Maternal BP control may be problematic and should be rigorously managed, but deaths are rar e. Increasing dialysis dose improves fetal outcomes. Other antihypertensives should be avoided. If a woman with treated hypertension is planning a preg- nancy, suf \201 cient time must be allocated to ensure adequacy of blood pressure control following transition from usual medication onto \200\230pregnancy-friendly \200 \231 antihypertensives. The following commonly prescribed drugs in CKD should be discontinu ed, preferably before pregnancy: \200 \200 \200 \200 \200 Prescribing hemodialysis to pregnant patients More frequent/daily dialysis. 16 \200\22324 h dialysis per week. Aim for predialysis urea <20 mmol/L. Establishing target weights may be dif \201 cult. Aim for lowest ultra \201 ltration possible per treatment. Adjustment of dialyzate composition may be required to avoid alkalosis, hypocalcemia and hypokalemia. Min imize heparin. ACEIs; ARBs; statins; bisphosphonates; cytotoxic agents. Renal biopsy in pregnancy Experience suggests that renal biopsy in pregnancy is no more haz ardous than in the nonpregnant situation. Some caution is required because the published ex peri- ence of renal biopsy in pregnancy amounts to only a few hundred cases compared to sev eral thousand in nonpreg- nant subjects. The standard cautions and contraindications used t o guide the performance of renal biopsy in nonpregnant patients apply equally in pregnancy. After 24 weeks gestation it may be dif \201 cult or uncomfort- able for women to assume t he prone position for biopsy. In this case potential operators should avoid the perform- an ce of renal biopsy in an unfamiliar manner or with the patient in an unusual position as th is may increase the risk of complications. Renal biopsy in pregnancy may be indicated to as sist in the management of: \200 \200 \200 Prescribing peritoneal dialysis to pregnant patients Increasing abdominal girth in pregnanc y may necessitate lower dialyzate dwell volumes. Frequency of exchanges should be increased . Dif \201 culty may be encountered in achieving adequate dialysis. Other considerations in dialysis management Erythropoetin is safe and a 50% increase in dos e may be required. IV iron sucrose preparations can be used in pregnancy. Modify dietary ad vice to ensure adequate nutrition. Vitamin D dosages may require adjustment. Pregnancy in the renal transplant patient Successful renal transplantation often restores f ertility in women with ESRD. More than 14 000 pregnancies have been documented in renal all ograft recipients and registry data indicate a live birth rate of 80%. Nonetheless these a re high risk pregnancies requiring fre- quent monitoring due to obstetric problems: \200 30% worsening hypertension/pre-eclampsia; \200 50% preterm delivery; \200 20% intraute rine growth retardation. acute kidney injury; nephrotic syndrome; altered activity of a pre-existing systemic diseas e such as lupus nephritis. However, renal biopsy in pregnancy is not recommended for the investigation of: \200 \200 \200 stable CKD; non-nephrotic proteinuria; pre-eclampsia. As in pregnant women with native kidney CKD, the risk of adverse obstetric outcomes is depe ndent largely on: \200 \200 If a maternal indication for renal biopsy develops at a stage of pregnancy when fetal survi val is likely to be good (cer- tainly after 32 weeks, and possibly after 28 weeks gesta- ti on) the pregnancy should be brought to an end and biopsy performed thereafter. the degree of graft (dys)function; adequacy of BP control. The pelvic location of the transplanted kidney does not hinder vaginal delivery and cesarea n section is reserved for obstetric reasons only. Pregnancy in the dialysis patient Fertility is severely curtailed in women receiving dialys is. Nonetheless studies show that pregnancy occurs in 1 \200\2237% of women of childbearing age on dialysis. Regular menstrual periods are now more common in pre- menopausal dialysed women, and improved dialytic tech- niques and anemia management may have increased fertili ty and the incidence of conception on dialysis. The incidence of pregnancy is better in tho se with residual renal function and is 2 \200\2233 \227 greater in hemodialysis patients co mpared to those treated by peritoneal dialysis. Appropriate contraceptive advice should the refore be provided to female dialysis patients who may conceive. Fetal survival is of the o rder of 30 \200\22350% with an average gestation of 32 weeks. Guidelines for considering pregnancy in renal transplant recipients Stable graft function w ith serum creatinine <180 mol/L. No ongoing or recent acute rejection. Normal or well-con trolled BP. Minimal or absent proteinuria. Low risk of opportunistic infection. If these cr iteria are met then pregnancy can be considered from 1 year after transplantation. Effect of pregnancy on renal graft survival Pregnancy exerts minimal effects on both short- and long- term survival of stable, well-functioning grafts. A harmful effect on renal func tion is more likely if the pre- pregnancy serum creatinine is >180 mol/L. N. BRUNSKILL 478 Internet resources SafeFetus.com, useful site to assess safety of prescribing in pregnancy: Transplant immunosuppresive drugs in pregnancy Prednisolone <15 mg/day. Azathioprine is safe and should continue at prepregnancy levels. C iclosporin and tacrolimus can be continued according to levels; dosage may need to be incre ased. Mycophenolate mofetil and rapamycin are contraindicated in pregnancy. These agents sh ould be discontinued at least 6 weeks before conception. Methylprednisolone is the drug of choice for the treatment of acute rejection in pregnancy. http://www.safefetus.com/ Pregnancy as a test of renal function: a streamed lecture held on the RCP Edinburgh website: http://rcpe.ac.uk/education/education/streamed_ lectures/renal-med.php Lupus UK, patient fr iendly information on planning preg- nancy in patients with SLE: http://www.lupusuk.com British Transplantation Society: Further reading Davison JM. Renal disorders in pregnancy. Curr Opin Obstet Gynecol http://www.bts.org American Society of Transplantation: 2001; 13: 109 \200\223114. Holley JL, Reddy SS. Pregnancy in dialysis patients: a review of out- comes, complications, and management. Semin Dial 2003; 16: 384- 387. http://www.a-s-t.org/ See also Renal biopsy, p. 32 Acute kidney injury in pregnancy, p. 378 Hypertensive disorder s in pregnancy, p. 310 Jones DC, Hayslett JP. Outcome of pregnancy in women with mod- erate or severe renal insuf \201 ciency. N Engl J Med 1996; 335: 226 \200\223 232. Krane NK, Hamrahian M. Pregnancy: Kidney diseases and hyperten- sion. Am J Kidney Dis 2007; 49: 336 \200\223345. McKay DB, Josephson MA. Reproduction and transplantation: re- port on the AST consensus con ference on reproductive issues and transplantation. Am J Transplant 2005; 5: 1592 \200\2231 599. Sibanda N, Briggs JD, Davison JM, Johnson RJ, Rudge CJ. Pregnancy after organ transplantati on: a report from the UK transplant pregnancy registry. Transplantation 2007; 83: 1301 \200 \2231307. 479 Chapter 13 Dialysis Chapter contents Dialysis strategies 480 Vascular access 488 Hemodialysis, hemo \201 ltrat ion and hemodia \201 ltration 494 Peritoneal dialysis 506 Adequacy of dialysis 518 Medical management of the dialysis patient 528 Psychological aspects of treatment for renal failur e 538 G. WARWICK 480 Dialysis strategies Introduction Many kidney diseases cause a slowly progressive decline in renal function over 10 \200\22320 years. There are few curative treatments and, even where the primary disease is inactive (e.g. vasculitis), renal function often continues to decline once a critical n ephron mass has been lost. Intensive treat- ments aimed at tight BP control, blockage of th e renin \200\223 angiotensin system and control of other cardiovascular risk factors may re duce the rate of renal function loss. However, this may only delay the time before replacem ent of renal function is required. Ideally patients with progressive kidney disease should be referred for nephrology assessme nt well before this point. This will allow: \200 identification and treatment of reversible causes of CKD; slowing of progression of renal d isease; management of complications of CKD (e.g. bone dis- ease, anemia, salt and water imb alance, acidosis, increased cardiovascular risk); preparation of patients for renal replace ment therapy. \200 Epidemiology of end-stage renal disease The incidence of CKD requiring replacement of renal func- tion is expressed as new patients per million of the popula- tion (pmp) per year sta rting renal replacement therapy (the \200\230take-on \200\231 rate). There is considerable variation in this rate between coun- tries (Fig. 13.1.1). Lack of resources and the cost o f dialysis therapy account for the low rate in many underdeveloped countries. In these coun tries, the dialysis \200\230take-on \200\231 rate underestimates the incidence of CKD requ iring renal replacement. However, even among developed countries there is con- siderable va riation. For instance, the rates of >300 per mil- lion of the population per year in Taiwan and the USA are three times the rates in the UK, The Netherlands, Australia, New Zealand a nd Nordic countries. Some of these differences may be due to real differences in the incide nce of advanced CKD which increases dramati- cally with: \200 \200 Preparing patients for renal replacement therapy When it is clear that renal function is pr ogressively declin- ing and that eGFR will fall to <10 \200\22315 mL/min/1.73 m2, preparati ons should be made to inform patients about treatment choices so that renal replacement the rapy (RRT) may start in a planned and programmed manner. The options to consider are: \200 RRT by dialysis: hemodialysis (HD); peritoneal dialysis (PD). RRT by renal transplantation; Supportive treat ment without dialysis. \200 A particular advantage of this approach is that vascular or peritoneal access can be establ ished well in advance of the time when treatment will be required. The optimal time to star t preparation is unknown but may be as long as a year before dialysis is required. Potentia l problems are: \200 increasing age; ethnicity (particularly South East Asian, Polynesian, Native American); soc ial deprivation. estimating accurately when dialysis will be required (see optimal time to start dialysis); the rate of decline of renal function is not always pre- dictable; the level of function at which patients develop symp- toms or signs attributable to uremia is also variable. However, this variation probably also re \202 ects attitudes of nephrologists and other he althcare workers as to which patients will bene \201 t from dialysis and variation in the level of renal function at start of dialysis. The prevalence of CKD is also highly variable between countries (Fig. 13.1.2). In the UK in 2005, there were 706 patients pmp receiving treatment by dialysis or transplantation. The prevalence rate in Japan, Taiwan and USA is m ore than twice that in the UK. The pool of patients continues to expand with an increase in the UK of 5% per year since 2000. Modeling suggests that the pool of patients will continu e to grow for at least another 20 years. The low clearance/predialysis clinic There is good evidence that patients with progressive CKD are best managed in dedicated clinics often termed low clearance or predialysis clinics . These clinics are run with a multidisciplinary team which may include: \200 \200 \200 \200 \200 \200 \200 experienced renal nurses; specialist renal dieticians; social workers; clinical psychologis ts; renal pharmacists; trained counselors; nephrologists. Clinical features of progressive CKD An important objective of these clinics is to educate and inform the patients and family/ca rers about the progressive nature of the renal failure and the importance of making a plan for treatment. Clinic visits are often supplemented by other support which may include: \200 home visits; \200 support group meetings; In most patients: \200 symptoms of CKD will only develop once GFR <30 mL/ min/1.73 m2 (CKD stage 4); severe sympto ms will generally only appear when GFR <15 mL/min/1.73 m2 (CKD stage 5). As the GFR falls to <15 mL/min/1.73 m2 the typical symp- toms of uremia occur and virtually any organ system may be affected (Table 13.1.1). CHAPTER 13.1 Dialysis strategies 481 400 350 300 250 p m p 200 e t a R 150 100 50 0 d n a l e r I ) 0 9 a i s y a l a M y r a g n u H d n a l g n E s d n a l r e h t e N ) 0 d n a l o P d n a l a e Z w e N d n a l i a h T s e l a l a t a C / n a p S y a w r o N k r a m n e D a c u l a d n A / n a p S e u q s a B / n a p S d n a l t o c S n o e L Y y e k r u T n e d e w S h s e d a l g n a B n a p a J y a u g u r U a i l a l n e l a V / n a p S y l a t I a d a n a C d n a l e c I n a t s i k a P a i t a o r C ) x e M s e n p p y r a n a C / n a p S d n a l n F a e r o K s e t a t S n a w a T e a g r u o b m e x u L y n a m r e G a i s s u R e c e e r G p s p s p e R h c e z C e a r s I i i r t s u A l i h C y a d ( K U h c t u D h c n e r F i r t s u A W i y a d ( K U ( o c s i l a J i i i l i f d e t i n U i n r e h t r o N o p e R . s a C / n a p S i h P i i , m u g l e B , m u g l e B i i i i Country Fig. 13.1.1 Incidence of CKD 5 requiring renal replacement therapy in different countries. pmp, per million population. 2000 1800 1600 1400 ) p m p ( 1200 v e r p T R R 1000 800 600 400 200 0 a i s y a l a M y r a g n u H a i l a r t s u A y a u g u r U n a p a J l d n a l g n E d n a l a e Z w e N d n a l e r I n e l a V / n a p S s e l a s d n a l r e h t e N a d a n a C K U y l a t I k r a m n e D y a w r o N a i t a o r C d n a l n F l a t a C / n a p S y r a n a C / n a p S e a c u l a d n A / n a p S d n a l t o c S a g r u o b m e x u L a e r o K n a w a T s e t a t S e u q s a B / n a p S y n a m r e G e c e e r G n o e L Y p s n e d e w S p s p e R h c e z C h s e d a l g n a B d n a l i a h T d n a l o P n a t s i k a P s e n p p ) x e M d n a l e c I a i s s u R y e k r u T e a r s I i r t s u A i l i h C h c t u D h c n e r F W i i i ( o c s i l a J f d e t i n U i l i i o p e R i n r e h t o N . s a C / n a p S h P i i , m u g l e B , m u g l e B i i i i Fig. 13.1.2 Prevalence of renal replacement therapy (RRT) in different countries. pmp, per million population. \200 \200 \200 patient information days; visits to HD units; visits to PD training centers; meetings with established patients. Issues regarding choice of RRT modality It is important to emphasize that many patients wit h estab- lished kidney failure often require more than one modality of treatment. The optio ns of HD, PD, renal transplantation and support- ive care should be viewed as an integrated package of care for patients with established kidney disease. Over time, patients may move between different forms of dialysis at different sites (home versus hospital), to renal tr ansplantation and back to dialysis. Written and visual material is used to supplement these visits and demonstrations. This all ows patients to select the modality of RRT which is most suitable taking into account medic al problems, social issues, lifestyle and other factors. It requires time, patience and per sistence. G. WARWICK 482 Table 13.1.2 Guidelines for initiating renal replacement therapy Table 13.1.1 Symptoms and signs of uremia System Symptoms Signs Other criteria/ descriptors Source Year Indicative eGFR (mL/ min/1.73 m2) Weight loss Anorexia Nausea/vomiting Diarrhea Gastrointestinal 2006 <15 If evidence of characteristic complications of uremia. US NKF K/DOQI Breathlessness Edema Signs of volume overload Cardiorespiratory 2002 8 \200\22310 Dialysis may be started at any time if GFR <15 and symptoms or signs attributable to uremia ; in all patients dialysis should be started before GFR <6 irrespective of symptoms. European Best Practice Paresthesia Restless legs Insomnia Seizures Coma Peripheral neuropathy Neurological 2005 6 \200\22310 Commence dialysis if GFR <10 or if there is evidence of uremia or its complications such as malnutrition; if there is no evidence of uremia or its complications, commence dialysis wh en GFR falls to <6. CARI Impotence Menstrual irregularity Endocrine Tiredness, lethargy Bruising Increased bleeding Pallor Hematological Pruritus Dry skin Excoriation Dermatological 2002 <14 Where there is evidence of malnutrition; symptoms interfere with quality of life; or there is predictable decline in GFR. UK Renal Association Different treatments may be appropriate at different times in an individual \200\231s treat ment \200\230career \200\231. Equally it is important to give a realistic picture of life on RRT. Even those who do well are likely to have temporary peri- ods where they experience intercurrent illness or prob- lems related to dialysis treatment. K/DOQI, Kidney Disease Outcomes Quality Initiative; CARI, Caring for Australians with Renal Impairment. Choosing the time to start dialysis treatment There is no universal agreement on the optima l time for starting dialysis. Dialysis imposes considerable physical, social and eco- nomic costs for patients. These have to be balanced against the bene \201 ts of control of urem ia and salt and water bal- ance in terms of symptom improvement, quality of life and prolon gation of survival. Psychosocial aspects of predialysis care Many patients may feel well with no symptoms despi te sig- ni \201 cant reductions in GFR. In some societies and cultures, there may be dif \201 culties in accepting advice about preparation for a future illness. There may be compl ex psychological and social issues regarding acceptance/denial of the diagnosis and prognos is; adherence to treatment regimens; participation in predial- ysis counseling/ education. There are several other aspects which should be consid- ered in predialysis clinics: Absolute indications for starting dialysis These are all the consequences of advanced renal failure and are usually accompanied by a severe biochemical dis- turbance: \200 uncontrolled uremic symptoms (e.g. nausea, vomiting, itching, insomnia, neuropathy); salt a nd water overload; persistent hyperkalemia; progressive malnutrition; pericarditis; severe acidosis. Employment An important part of planning for RRT should be to mini- mize disruption for pat ients who are in employment. \200 \200 \200 \200 Social interactions Involvement of family, carers and often professional social workers is helpful to maintain normal social function and to assist with access to support at home and other bene \201 ts. Guidelines for commencement of dialysis Exactly when dialysis should be started for individ ual patients is not clear. Patients known to a nephrologist should be started on dialysis b efore the onset of life-threatening complica- tions. The inability to reliably predict when an individual patient will become symptomatic has led many experts and guide- lines to rec ommend starting dialysis electively based on measurements of GFR. Sexual health Advice is often sought about sexual activity. There is a high prevalence of e rectile dysfunction and low libido. Although pregnancy is rare in patients with advanced CK D, patients of childbearing age should be advised about contraception. Hepatitis B vaccination This should be performed using a high dose regimen as soon as it is clear that patients will progress to RRT; earlier vaccination leads to a greater rate of s eroconversion. CHAPTER 13.1 Dialysis strategies 483 Guidelines from different authorities regarding the level of renal function to start dialys is are shown in Table 13.1.2. However, all of these still leave room for clinical judgment. Hemodialysis Hemodialysis (HD) therapy is often the default for many patients, especially t hose presenting late as uremic emer- gencies without established vascular or peritoneal acc ess or after PD has failed. GFR at commencement of dialysis Over the last 20 years the level of renal function (as esti - mated by derived GFR) at which dialysis has started has tended to increase. Data from the United States Renal Data System (USRDS) show that the mean eGFR at start of dialysis has i ncreased progressively since 1995 and was 9.8 mL/min/1.73 m2 in 2004. In the UK the mean eG FR of patients starting RRT was: \200 \200 Home HD Home HD is a successful treatment with excellent out- comes in terms of survival an d quality of life. This form of treatment was pioneered in the late 1960s when chronic dial ysis started and is still the treatment of choice in some centers around the world. Home HD was endorsed by the UK National Institute for Clinical Excellence in 2002 although this wa s not a surprise to experienced nephrologists. Over the years, both the percentage and abso lute numbers of patients carrying out HD at home has declined. This re \202 ects the aging dialysis population and the increased availability of center or satellite unit based dialy sis nearer patients \200\231 homes. Nevertheless, it is important to identify suitable cand idates for home HD in the predialysis phase based on local facili- ties/resources, patient preference and the availability of a suitable helper and home premises. These patients can then be fast-tracked to an independent treatment at home. 6.0 mL/min/1.73 m2 in 1997; 7.9 mL/min/1.73 m2 in 2005. The starting eGFR seems to be stable over more recent years. Predicting rate of decline in GFR Even with the use of eGFR-vs-time plots to extrapolate wh en a certain eGFR value (e.g. 10 mL/min/1.73 m2) will be reached, many patients develop sym ptoms earlier than anticipated or conversely kidney function may stabilize for many years. Commencing dialysis with a higher GFR: \200\230early start \200\231 Some experts have sugg ested that starting dialysis earlier will lead to improved survival. However, there are no con- trolled studies proving this and there are con \202 icting data from observational an d cohort studies. An important confounding factor is adjustment for lead time bias. Surviva l must be counted from the point where dialysis may have been started and therefore will in clude a period of nondialysis treatment for patients starting later. A randomized study to investigate this is dif \201 cult due to issues with funding earlier dialysis treatment an d patient consent/recruitment. Despite these problems, one such trial is underway in Austra lia and New Zealand (The IDEAL study: Initiation of Dialysis Early and Late) in which patie nts are being randomized to start RRT at esti- mated GFRs of 5 \200\2237 versus 10 \200\223 14 mL/min/1.73 m2 (Cockcroft \200\223Gault formula). The study is due to report in 2010 and potentially will give important information on this dif \201 cult question. Unit-based HD Many patients choose HD at a main center or satellite unit when offered choic e. In the UK, the percentage of patients starting HD (versus PD or pre-emptive transplantat ion) as initial therapy has increased from 58% in 1998 to 76% in 2005. Some of this re \202 ects the previous overreliance on PD due to a lack of HD facilities.