Hemodialysis Jugular venous catheters are the commonest form of vascu- lar access as there is usually only a short period of hemodi- alysis before transplantation. There are inherent dif \201 culties of creating arteriovenous \201 stulas in small children. Logistical pr oblems occur transporting patients from long distances to central specialized pediatric hem odialysis units. Dialysis and transplant options Transplantation For all children dialysis should be seen only as a temporary measure before transplantation . Restoration of good kidney function after transplantation offers the best opportunity for improved growth, school attendance and long-term psychosocial rehabilitation. A. WATSON 466 Further reading Batte S, Watson AR, Amess K. The effects of chronic renal failure on Hemodialysis is therefore chosen for mainly social reasons or when peritoneal dialysis acce ss is not possible, i.e. peri- tonitis or abdominal problems. Bicarbonate dialysis should b e standard and machines should be capable of ultra \201 ltration control. Hemodia \201 lt ration may have advantages over hemodialysis but requires ultrapure water. Hemodialysis reg imes are usually 4 h three times per week. Daily dialysis may result in better growth, impr oved bone disease and less anemia. Home hemodialysis is feasible but should only be attempt ed in those predicted to need long-term dialysis and who have good vascular access and a de dicated carer. siblings. Pediatr Nephrol 2006; 21: 246 \200\223250. Dixon P, Iurilli J, Watson AR, Neill E, Foy J, Martin M. Acceptability of a reformulated re nal-specific micronutrient supplement. Pediatr Nephrol 2004; 19: 1433 \200\2231443. Fischbach M, Edefonti A, Schroder C, Watson A, The European Pediatric Dialysis Working Grou p. Hemodialysis in children: gen- eral practical guidelines. Pediatr Nephrol 2005; 20: 1054 \200\2231066. Klaus G, Watson A, Edefonti A, et al. Prevention and treatment of renal oste odystrophy in children on chronic renal failure: European guidelines. Pediatr Nephrol 2006; 21: 151 \200\223159. Lewis M, et al. Demography and management of childhood estab- lished renal failure in the U K. In: Ansell D, Feest TG, Tomson C, Williams AJ, Warwick G (eds), UK Renal Registry Report . Bristol: UK Renal Registry; 2006. Chapter 13. Smith GC, Inward C. How and when to measure blood pressure. In: Webb N, Postlethwaite R (ed s), Clinical pediatric nephrology. Oxford: Oxford University Press; 2003. pp. 135 \200\2231 50. Psychosocial support This is an essential component of pediatric care. Every child should b e seen in the context of the family and stress upon the patient, parents and siblings recog nized. A social worker should assess each family at home to assess needs and any entitlemen t to state support, e.g. dis- ability allowance. A psychologist can help with the impact of illness upon the child, i.e. needle phobias, behavior disturbance, night- mares. Education al support is mandatory for children on hemodi- alysis but it is also important to liaise w ith schools if the child is on peritoneal dialysis and post transplantation. Most specialis t units have a holiday strategy which can include support for families, holidays for a pati ent group to build self-esteem and give families a break, and sport-ori- ented camps to inc rease participation and socialization. Youth workers can help support young people (aged 12 \200\22320 years) having major adjustment issues. Children and families should be discusse d at regular psy- chosocial team meetings in order to share knowledge and anticipate proble ms. Watson AR. Strategies to support the families of children with end stage renal failure. Pediatr Nephrol 1995; 9: 628 \200\223631. Watson AR. Meeting the information needs of children and their fami- lies . In: Postlethwai te R, Webb N (eds), Clinical pediatric nephrology, 3rd ed. Oxford University Press, Oxford; 2003. pp. 465 \200\223474. Watson AR. Hospital youth work and adolescent support. Arch Dis Child 2004; 89: 440 \200\223442. Watson AR. Problems and pitfalls of transition from pediatric to adult renal care. Pediatr Nephrol 2005; 20: 113 \200\223117. Internet resources British National Formulary for Children: http://www.bnfc.org NKF K/DOQI Guidelines. Clinical Practice Guidelines and Clinical Practi ce Recommendations. 2006 Updates. Peritoneal Dialysis Adequacy: http://www.kidney.org/professionals/kdoqi/ guideline_upHD_PD_VA/pd_wg.htm Child and carer i nformation on kidney disease: http://www.nuh.nhs.uk/ext/ckn/information.htm http://www.ich.ucl.ac.uk/factsheets/index.html NICE Clinical Guidance CG39. Anemia manageme nt in people with chronic kidney disease. Sept 2006: Follow-up The survival rate of children with CKD is good and the majority will transfer to adult care. In patients with CKD 1 \200\2233 this may be the primary care physician with in structions to refer back to adult services if increasing proteinuria or creatinine develop. Patients with CKD 4 or 5 need an organized transfer to adult units when they have followed a transition process with adequate information and preparation. Transition issues need to be addressed in both the pediatric and adult units and processes agreed so that follow-up a nd hopefully patient compliance is assured. http://guidance.nice.org.uk/CG39 See also Urinary tract infections in infancy and childhood, p. 252 Hypertensive children, p . 304 Acute kidney injury in infants and children, p. 372 Congenital abnormalities of the u rinary tract, p. 658 Vesicoureteric re \202 ux and re \202 ux nephropathy, p. 648 This page intentionally left blank K. BUCK 468 Chronic kidney disease in the elderly \200 Introduction Life expectancy in most developed countries has increased substantially in rec ent years. Around 20% of the total popu- lation are aged >65 years and 6% are >75 years; th ese \201 g- ures are likely to increase further. The greater life expectancy of females m eans that they increase as a pro- portion of the population in older cohorts and among thos e with CKD. The presence of ESRD requiring dialysis increases the risk of death three-fold at the age of 75 years compared to the healthy population. However, it should be noted that the increase in risk and years of life lost are substantially less than for the middle-age d dialysis patient. The incidence of newly diagnosed CKD increases signi \201 - cantly wit h age and the mean age for new referrals in developed countries is now 60 \200\22365 years. The median age of patients starting dialysis in the UK in 2006 was 65 years, which has cha nged little over the previous 6 years. Elderly patients with ESRD have been significantly d isadvantaged in terms of referral for RRT and tran- splantation. This has been because of a combination of reluctance to use scarce facilities for those with less to gain and a perce ption that the elderly will tolerate the process less well. Late referral of elderly patien ts has been a particular problem with its attendant increased mortality and morbidity, incr eased time of hospitalization, and dis- advantage with regard to choice of therapy and acce ss to transplantation. The introduction of reporting of eGFR in the UK in 2006 was primaril y to reduce late referral by highlighting that relatively low levels of creatinine in elder ly patients may represent advanced renal impairment. The marked aging of the dialysis popul ation in recent years can be attributed to: \200 \200 they are more vulnerable to complications; they have a greater mortality from infection and cardio- vascular disease; they survive for shorter periods; Treatment costs are higher for elderly patients compared to younger patients. There are ine vitable dif \201 culties in making selection deci- sions over life-prolonging treatment in elderly patients who develop ESRD. However, it is widely accepted that some frail elderly patients are unsuitable for dialysis. Some units will offer a \200\230trial of dialysis \200\231 in more marginal cases with the agreement of clinicians, family and patient that t he decision will be reviewed at an interval and the explicit possibility that it may subseq uently be appropriate to withdraw treatment. Causes of chronic kidney disease in the elderly The causes of renal failure among elderly p atients differ substantially when compared to younger cohorts (Table 12.2.1). The most comm on diseases leading to renal failure are: \200 \200 \200 vascular disease including hypertension; diabetes; obstructive uropathy; Although there is no identi \201 able cause in a signi \201 cant minority. Glomerulonephr itis accounts for a smaller proportion of cases than in younger groups. Cardiovascular dise ase is highly prevalent in the elderly in developed countries. Vascular disease of the main renal arteries should be sus- pected as a cause in patients with asymmetrical kidneys, car diac or peripheral vascular disease, and diabetes melli- tus. Renal artery stenosis is pres ent in 15 \200\22320% of many series of patients with ESRD and is more common with increas- ing age. The bene \201 t of renal artery angioplasty stenting remains under study, but is probably indicated in patients with dete- riorating function and \200\230 \202 ash pu lmonary edema \200\231. Prostatic obstruction is a potential cause that should always be co nsidered in elderly males. Relief of the obstruc- tion may lead to signi \201 cant recover y of renal function. Amyloidosis is also increasingly common with age, being a signi \201 cant cause of nephrotic syndrome in the elderly. Periorbital hemorrhage is a classic sign. The prognosis is often poor because cardiac amyloid may lead to terminal cardiac failure. an expansion in the number of places; increased referral rates (supported by concerns about agism); technical advances that have made dialysis more toler- able; improved survival on dialysis. Elderly patients with CKD have increasing numbers of comorbidities including dementia altho ugh these vary greatly. These factors have to be taken into account when discussing treatme nt options with patients and selecting appropriate candidates for dialysis. It is clear, ho wever, that chronological age alone is not a reason to exclude patients from RRT. Some phys icians evoke the concept of biological age although this is, in real- ity, a subjective jud gment. The presence of severe vascular disease and diabetes car- ries a particularly poor p rognosis. Social and psychological factors may also be crucial factors determining the succ ess or otherwise of dialysis. The elderly have greater challenges in adjusting to dialysis regimens: \200 \200 Renal replacement therapy in the elderly The main treatment options available for elderly p atients with ESRD are: \200 \200 \200 home-based peritoneal dialysis (CAPD or APD); hospital-based hemodialysis; renal transplant ation. The proportion receiving each will depend on the availabil- ity of hospital-supervised dial ysis spaces and of donor organs. they \201 nd learning techniques more dif \201 cult; they spend more time in hospital; CHAPTER 12.2 Chronic kidney disease in the elderly 469 Table 12.2.1 Causes of chronic kidney disease in the elderly The demands on the patient can be reduced by automa- tion but are still considerable for ma ny elderly patients. There are moves in the UK to assist patients with auto- mated PD (APD) by daily carers visiting to help with machine set-up and emptying waste bags (assisted APD ). This is likely to help elderly patients wishing to receive therapy at home and has incre asingly become standard practice in a number of countries over the past few years. There ar e a number of relative contraindications to PD that are relevant in older patients includin g: \200 \200 \200 \200 Cause Approximate frequency Atherosclerotic disease 17 \200\22338% Diabetes 10 \200\22328% Unknown cause 12 \200\22329% Glomerulonephritis 6 \200\22328% Infective/obstructive 1 \200\22317% previous abdominal surgery; severe chronic obstructive airways disease; diverticulitis; unt reatable hernias. Neoplastic 2 \200\2234% Hereditary 2 \200\2236% Toxic 1 \200\22318% Congenital <1% In contrast to hemodialysis, where technique-related drop- out occurs early, dropout from P D is continuous. Most renal registries suggest that the survival of elderly uremic patients is broadly equivalent whether PD or hemodialysis is used. Infection (peritonitis, exit sit e and tunnel infections) is no more common in the elderly than in younger patients. Some qu ality of life studies suggest that patients managing PD in their own home fair better than those undergoing hospital-based hemodialysis. Miscellaneous 1 \200\2232% Historically in the UK as many as 70% of patients aged >65 were allocated to peritoneal dia lysis. The choice between home- or center-based treatments should be made with consultation between the patient and renal team. An assessment by trained members of the multidisciplin ary dialysis team, performed in the patient \200\231s home, is invaluable in determining th e suitability of individuals for peritoneal dialysis. All patients should have an optimal h emoglobin concentra- tion. Those with poor cardiac function or myocardial ischemia (likely causes of mortality) should be assessed and treated. Transplantation should be considered i n \201 t patients up to the age of 70 years and is increasingly an option in selected pat ients over that age. Patients should be screened for car- diac (including coronary angiogra phy if appropriate), respi- ratory and urological disease. All diabetic patients should hav e full cardiovascular assessment including coronary angiography. Hemodialysis Given the complexity of managing PD, a greater propor- tion of elderly compared to younger patients are on unit- based hemodialysis. Establishing vascular access can pose signi \201 cant dif \201 culties because peripheral arterial disease and small, fragile veins make g ood \201 stula formation dif \201 cult. However, the increased risk of bacteremias with tunneled lines (internal jugular and subclavian) means that \201 stula formation should b e attempted if at all feasible and can be aided by Doppler and arteriographical imaging. Th e increased maturation times of \201 stulae in the elderly and increased surgical failure rates mean that access sur- gery should be planned early. Older patients are more vulnerab le to the recognized adverse effects of hemodialysis including: \200 \200 \200 \200 \200 Peritoneal dialysis Peritoneal dialysis has some important potential advan- tages for older patients, although only 15% of elderly patients in Europe and 8% in the USA are treated b y this method. Advantages include: \200 \200 \200 \200 hypotension; arrythmias; chronic malnutrition; increased incidence of infection; depression . independence from the dialysis unit; more physiological removal of \202 uid and electroly tes; reduced cardiovascular instability; preservation of native renal function. Outcomes of dialysis Both quality and quantity of life are important. However, both are dif \201 cult to measur e because of: \200 \200 \200 There are also some limitations particularly relevant to older patients. PD requires: \200 \200 \200 \200 \200 \200 \200 variable referral patterns; differing take-on rates; unequal access of elderly patients to transplantation. Various tools have been used to measure quality of life, e.g. Karnofsky sc ores and Short Form (SF)-36. As with survival, there is likely to be an effect of selection for acceptance for dialysis. Studies suggest that the patient \200\231s support and enviro n- ment, as well as selection for treatment, may determine the degree of rehabilitation. manual dexterity; personal hygiene; visual acuity; strength to lift bags of \202 uid; mot ivation; preserved cognitive function; the ability to learn new skills. K. BUCK 470 Erythropoetin has a clear role in improving quality of life in both dialysed and nondialyse d patients. Overall survival of the elderly on dialysis improved consid- erably during the 1980s; this continued but at a reduced rate into the 1990s. There is still a signi \201 ca nt actuarial shortfall in life expect- ancy, but the shortfall is much less than in younger popula- tions. Cause of death, as in younger populations, is led by cardio- vascular disea se and infection. The issue of withdrawal from dialysis is increasingly impor- tant as olde r and frailer patients embark on RRT. Decision-making may be complicated by the deteriorati on of mental capacity due to a variety of causes. Discontinuation of dialysis is the second most common cause of death after cardiovascular disease in many countries. Signi \201 can t factors associated with discontinuation are the emergence of dementia or malignancy. With drawal of RRT is likely to increase in the future if more \200\230marginal \200\231 cases are given a \200\230trial of dialysis \200\231. Mycophenolate mofetil has been associated with increased rates of serious infection when co mpared to azathioprine in patients aged >60 years. Survival of older transplant recipients (65 \200\22369 years) at 5 years seems relatively good at 70% although 10 year sur- vival i s 33%, which is less than half the rate in younger patients. In a single series examining the outcome in recipients aged >70 years, the patient and graft survival at 5 years were bo th just over 50%. Interestingly, if graft survival \201 gures are adjusted to take into a ccount death with a functioning graft (i.e. discounting grafts lost due to death of the rec ipient) then graft survival in most series equates to that in younger cohorts. This indicat es the impact of recipient death on graft survival. While rejection stands out as the major cause of graft loss in the younger recipient, \200\230death with a functioning graft \200 \231 is the major cause of loss in the elderly and accounts for 50% of graft losses. The m ajority of deaths are from cardiovascular disease fol- lowed by infection. It should also b e noted that malignancy is substantially increased as a cause of death compared with the ag e- matched general population, with skin cancers and lym- phoma standing out. Given the sca rcity of donor organs an important question is whether there are signi \201 cant bene \201 ts to transplantation compared to dialysis in older patients? Analysis is complicated by the bias towards selection of \201 tter patients for transplantation but comparisons c an be made between recipients and waiting list patients. The data suggest that graft recipi ents have about half the rate of death compared to those who remain on dialysis. The only c ause of death increased in recipients is malig- nancy. Studies of quality of life suggest s igni \201 cant improvements in those who are transplanted compared to those remaining on d ialysis. It has been suggested that, given the scarcity of donor organs, elderly patients s hould have \200\230age-matched \200\231 donor organs that might be considered \200\230mar ginal \200\231 for younger recipients. Few units have an overt policy in place but series s uggest that such matching probably occurs. While overall patient survival may not be compro mised, older more marginal kidneys are associated with: \200 \200 \200 Transplantation Transplantation in elderly patients remains an area of debate in spite of t he widespread acceptance that this is the optimal approach to the treatment of ESRD in most patients. A very small proportion of elderly patients receive a trans- plant (<1% in those aged >70 years). This restriction could be justi \201 ed in former years when allograft s urvival was poor amongst older patients. There is now an increasing number of grafts alloca ted to patients aged >65 years: in 1999, 8.4% of cadaver grafts in the USA were placed in p atients aged 65 \200\22375 years. The shortage of donor organs is now the main factor limit - ing transplantation in older patients. The principal cause of graft loss in the elderly i s death with a functioning graft. Selection of potential recipients who are likely to have the best survival is therefore important in maximizing the use of scarce cadaver kidneys. T his usually takes into account an assessment of cardiovas- cular health (looking for eviden ce of cardiac, cerebrovascu- lar and peripheral disease), the presence of prostate disease and other general factors such as physical incapac- ity and dementia. Healthy elderly subje cts are subject to some reduction in activity of both humoral and cellular immune responses to antigens. Uremia itself is associated with generalized immuno- suppression. Perhaps as a consequence, it is well-recognized that older graft recipients have fewer and milder epis odes of early acute rejection. However, they are also more vulnerable to bacterial and vira l infections and have a much higher death rate from infection. These factors have persuaded most clinicians of the need to reduce the doses of immunosuppressive drugs in the elderly, especially corticosteroids. Furthermore, the metabolism of both prednisolone and ciclospor in in the microsomal P450 system is less active. delayed graft function; reduced graft survival; worse renal function. Conservative management in the elderly There is increasing interest in conservative care of patients with ESRD, largely in those with extensive comorbidities. Many, but not all, are elderly patients. One study, comparing dialysis with conservative therapy, concluded that d ialysis did not confer a signi \201 cant survival bene \201 t (judged by the putative sta rt date for dialysis) in a cohort of patients recommended for palliative care by a multidis ciplinary team. These patients tended to be older, diabetic and were more functionally impa ired. Many units have developed links with palliative care serv- ices and/or have appointed specialist palliative care renal CHAPTER 12.2 Chronic kidney disease in the elderly 471 nurses to manage the increasing numbers of elderly, debili- tated patients being referred t o renal services. There is also a growing appreciation of the range of debili- tating sympt oms experienced, especially by the elderly receiving dialysis. These specialist palliative \200\223renal nurses may facilitate management of some of these symptoms such as pain, naus ea, tiredness and constipation. The increasing emphasis on palliative care is likely to imp rove communication about end-of-life issues between the multidisciplinary team, patients an d their carers. Bone disease The elderly are predisposed to bone disease even in the absence of renal disea se. Osteopenia and reduction in bone trabecular volume are found in \200\230normal \200 \231 elderly. A balanced diet, exercise and sunlight are all of importance. Conclusions Renal failure is predominantly a disease of the elderly; the underlying conditi ons vary from younger patients. Dialysis should not be withheld on the grounds of age alone . Signi \201 cant numbers of the very elderly may opt not to receive dialysis or be though t to be unsuitable for treat- ment because of extensive comorbidities. Ideally, patients sh ould make an informed choice as to their modality of renal replacement therapy; in reality there are often economical and logistical factors pressuring the decision. Transplantation is an excellent treatment for \201 t elderly patients but the scarcity of cadaver kidneys means some selection occurs. Speci \201 c problems in the elderly with renal disease Cardiovascular disease Cardiovascu lar disease is the major cause of morbidity and mortality in patients with ESRD and is even more marked in older patients. Hypertension is a major cardiovascular risk factor, devel- ops with progressive renal impairment and is associated with left ventricular hypertrophy, ischemic heart disease, arrhythmias and sudden death. Anemia is another very important prec ipitant of left ven- tricular hypertrophy, and treatment of hemoglobin to a concentration o f 10 \200\22312 g/dL with erythropoetin is consid- ered optimal. An important cause of dial ysis failure in the elderly is poor cardiac output often in association with a dilated isch emic cardiomyopathy. This possibility should be carefully assessed and may demand revascula rization procedures in selected cases. Peripheral vascular disease is frequent in elderly p atients with ESRD. Further reading Cameron JS, Mac as-N ez JF. Chronic renal failure in the elderly. Oxfor d textbook of clinical nephrology, 3rd edn. Chapter 14.2: pp. 2165 \200\2232191. Lamping DL, Constantinovici N, Roderick P, et al. Clinical outcomes, quality of life, and c osts in the North Thames Dialysis Study of elderly people on dialysis: a prospective cohort study. Lancet 2000; 356(9241): 1543 \200\2231550. Ouseph R, Hendricks P, Hollon JA, Bhimani BD, Lederer ED. Under- recognition of chronic kid ney disease in elderly outpatients. Clin Nephrol 2007; 68: 373 \200\223378. Malnutrition The healthy elderly have some reduction in the absorption of nutrients and ten d to have diets that are higher in carbo- hydrates. They may also be somewhat limited \201 nancially which may reduce the intake of foods rich in protein and essential nutrients . Older patients may also become depressed and stop eat- ing. Malnutrition may become evide nt as non \202 uid weight loss, low serum albumin and a reduction in creatinine due to los s of muscle mass. Patients should be encouraged to take \211 1 g/kg of protein per day and should also be given water-soluble vitamins that might be lost during dialysis (folate, py ridoxine) and alphacalcidol. Smith C, Da Silva-Gane M, Chandna S, Warwicker P, Greenwood R, Farrington K. Choosing not t o dialyse: evaluation of planned non- dialytic management in a cohort of patients with end- stage renal failure. Nephron Clin Pract 2003; 95: c40 \200\22346. Wong CF, McCarthy M, Howse ML, Williams PS. Factors affecting survival in advanced chronic kidney disease patients who choose not to receive dialysis. Ren Fail 2007; 29: 653 \200\223 659. Internet resources British Geriatrics Society: http://www.bgs.org.uk/ Chronic kidney disease and older people \200\224implications of the publication of the Part 2 of the National Service Framework for Renal Services: http://ageing.oxfordjournals.org/cgi/content/ full/34/6/546 Geriatrics and Ageing: CME Port al to Clinical Issues Speci \201 c to the Care of Ageing Adults: Neuropsychiatric issues Older dialysis patients are predisposed to developing neu- rologica l complications due to: \200 intradialytic hypotension; \200 reduced cerebral blood \202 ow; \200 carotid disease; \200 malnourishment. http://www.geriatricsandaging.ca/ See also Acute kidney injury in the elderly, p. 384 Dialysis strategies, p. 480 Medical management o f dialysis patients, p. 528 Selection and preparation of recipients, p. 544 Cerebral atrophy is known to be commoner among even younger dialysis patients. C. COMBE AND V. RIGALLEAU 472 Chronic kidney disease in diabetic patients Introduction The coexistence of diabetes and chronic kidney disease (CKD) is associated wit h a high burden of complications resulting from synergistic effects on cardiovascular and m etabolic-related morbidity and mortality. The complexity of treatments used in patients wit h diabetes and CKD requires a co-ordinated multi- disciplinary approach with particular emp hasis on involve- ment of patients themselves in their ongoing manage - ment. Cardiovascular risk Most patients with diabetes and CKD will not reach CKD 5, because they die earlier from cardiovascular causes. All measures aimed at preserving renal function als o reduce cardiovascular risk, particularly the reduction of blood pressure and proteinuria. Lifestyle and nutrition Patients should be advised to perform aerobic exercise on a regular basis (aim for \211 30 min each day). Smoking cessation should be encouraged. Weight loss to a target body mass index within the normal range (18.5 \200\22324.9 kg/m2) should be en couraged. Protein Protein intake restriction should be considered and dis- cussed with the patient. Protein restriction may slow progression of CKD but may also lead to protein-calor ie malnutrition. Protein restriction to 0.6 \200\2230.8 g/kg/day should therefore only be u ndertaken with appropriate education, detailed dietary assessment and supervision to ensure that malnu- trition is prevented. In patients with CKD 5 treated by dialysis, intake shoul d be \211 1.2 g/kg/day. Carbohydrates and fat (unsaturated fats and \211-3-enriched) Thes e should be increased to reach an appropriate caloric intake ( \211 35 kcal/kg/day in patie nts <60 years if no weight loss is needed). Preservation of renal function Preservation of renal function in diabetics is based on achi evement of therapeutic goals. It is important to realize that these goals are continually u nder review as more evidence emerges. Blood pressure Aim for a target blood pressure of \211 130/80 mmHg. Avoid systolic BP of < 110 mmHg. Where possible ACEIs and/or ARBs should be used as the antihypertensive drugs of choice in view of their antipro- teinuric effect. Proteinuria Aim for the greatest decrease in microalbuminuria possible with ACEI and/or ARB . Aim for the greatest possible reduction in overt proteinuria with ACEI and/or ARB. Modera te salt restriction (4 \200\2236 g/24 h (Na+<100 mmol/day)) increases the antiproteinuric e ffect of ACEI and ARB. Glycemic control Aim for an HbA1C \211 6.5%. Prevention of AKI It is important to be aware of the potential risks to renal function in diabetic patients and to try to avoid or minim ize their impact. Salt Salt intake should be restricted to 4 \200\2236 g/day (for better blood pressure contr ol). Dyslipidemia Aim for an LDL-cholesterol concentration of \211 3 mmol/L (100 mg/dL). Dietar y advice is necessary. Statins need to be used in many patients to reach the tar- get LDL-c holesterol. In patients on chronic hemodialysis, treatment with statins should be restricte d to those with a speci \201 c indication (e.g. after myocardial infarction), since no cli nical bene \201 t has been proven, even in patients with high LDL-cholesterol. Dehydration Loss of sodium and extracellular water (e.g. from diarrhea) may lead to worseni ng kidney function, particularly in patients taking ACEIs, ARBs and diuretics. Patients sho uld provisionally stop diuretics if there is a risk of dehydration. Drugs Avoid drugs that can worsen renal function: \200 \200 Pharmacological treatment of diabetes Patients with CKD 3 \200\2235 are at risk of hypoglyc emia because of: \200 \200 NSAIDs; aminoglycosides. decreased renal clearance of insulin and sulfonylureas; impaired renal gluconeogenesis. Diagnostic imaging When iodinated contrast agents must be used (e.g. for a CT scan or angio graphy) the following preventative meas- ures should be considered: \200 \200 Type 1 diabetes Insulin needs may change with decreasing renal function, since CKD is assoc iated with insulin resistance and there is decreased renal clearance with advancing CKD. Ty pe 2 diabetes A number of different oral hypoglycemic drugs are availa- ble (Table 12.3.1). The bene \201 ts of intensive therapy are independent of the type of treatment administer ed. stop NSAIDs, aminoglycosides and metformin; give IV hydration with 0.9% saline or 1.4% sodi um bicar- bonate (1 mL/kg/h for 6 \200\22312 h before and after); use a low osmolal contras t agent; use the smallest volume of contrast agent possible; consider the use of oral or IV acetylcysteine (ef \201 cacy is not established). \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.