Complications of PD peritonitis PD peritonitis may result in malnutrition due to: \200 \200 \200 Icodextrin Cases of sterile peritonitis have occurred in patients treated with batches of i codextrin \202 uid, attributed to con- tamination with high peptidoglycan concentrations. increased peritoneal protein loss; reduced nutrient intake; acute catabolism. There may be a temporary reduction in ultra \201 ltration during peritonitis due to increa sed peritoneal vascu- larity increasing the transportation status of the membrane as a resu lt of peritoneal in \202 ammation. This may be man- aged by: \200 \200 \200 Mechanical complications of PD Catheter drainage problems Drainage problems may occur becau se of: \200 \200 \200 \200 constipation; malposition/migration of the catheter; abdominal adhesions; catheter occlusio n (e.g. \201 brin, and omental wrapping). shortening dialysis exchanges; hypertonic \202 uids; use of icodextrin for long dwells. CHAPTER 13.4 Peritoneal dialysis 515 Management Management of \202 uid leaks is a period of rest from PD to allow the leak to heal. PD should be recommenced initially with lower volume exchanges with or without omissi on of the ambulant day dwell if the patient is on APD and clearances allow. Persistent leak s require catheter change or surgical repair. Clinical features include slow drainage, which may be pre- dominantly slow drainage out, or alternatively slow in \202 ow (accompanied by slow out \202 ow if \202 uid infusion is possible). Investigations: \200 plain abdominal X-ray (which will show catheter posi- tion and presence of constipation); i njection of radiocontrast down catheter with screening (to show \202 ow of dialyzate and presence of adhesions); CT peritoneography. Hernias in PD Hernias are a relatively common complication of PD. Pre-existing hernias shou ld be repaired before commenc- ing PD. This may be combined with catheter insertion. They m ay also develop after starting PD as a complication of the increase in intra-abdominal pres sure. Sites include: \200 \200 \200 \200 \200 Management Laxatives improve slow drainage due to constipation and sometimes reverse cathet er migration. Heparin is instilled if catheter blockage results from \201 brin or blood, and urokinase may be used if heparin is ineffec- tive. Catheter repositioning may be attemp ted: \200 inguinal; para-umbilical/umbilical; catheter insertion site; other incision sites; ventral hernias. Problems include: \200 \200 radiologically (by passage of guidewire and attempts to move the catheter tip under X-ray s creening); open surgically; laparoscopically. \200 pain; risk of bowel incarceration and strangulation. If surgical intervention is required, partial omentectomy may be performed and the catheter can be sutured into the pelvis. Alternatively, the catheter may be removed and replaced. I f catheter change is required, temporary HD may be avoided by resting from dialysis for the usual catheter heal- ing time if residual renal function is suf \201 cient, or by earlier commencement of PD post surgery using small volume exchanges in supine position (e.g. APD with dry day). In cases of Gram-negative peritonitis one should always consider the possibility of bowel s trangulation as the her- nial ori \201 ce may not always be obvious. Management Management is by surgical repair. This may require a period of discontinuation o f PD and temporary HD. Some PD patients may have adequate residual function to allow a peri od without dialysis. It is also possible to recommence PD very soon after a hernia repair, especially when a mesh repair has been per- formed, with initial use of low dialyzate volum es in the supine position. Fluid leaks Pericatheter leaks Pericatheter leaks may occur early or late after tube inser- tion and may be precipitated by coughing, straining or heavy lifting. Presentation is with \202 uid leaking externally with wetness of the exit site or dressing. Hydrothorax Pleural effusions may occur for a number of reasons on PD. Pulmonary and pleura l disease may occur as in other sub- jects and it is also important to consider \202 uid overload and cardiac failure as causes in PD patients. Abdominal wall leaks Abdominal wall edema may also arise by leaking through the catheter si te or previous abdominal incisions. There may be induration or a spongy feeling of the abdo minal wall skin and peau d \200\231orange appearance. Patients may experience a loss of ult ra \201 ltration without change in transportation characteristics. Abdominal wall leaks ma y be demonstrated by CT perito- neography or MRI. Diaphragmatic leak Effusions may also occur due to peritoneo-pleural leakage of dialyzate w hen dialyzate passes through areas of de \201 - ciency in the diaphragm. This most commonl y occurs on the right side. The presence of an effusion may be identi \201 ed clinically a nd con \201 rmed on chest X-ray. Effusion size varies but may be large enough to cause res piratory dif \201 culties. Thoracocentesis should be performed with \202 uid undergo- in g standard biochemical, microbiological and cytological tests. The presence of low protein in keeping with a transu- date and high glucose content (greater than in blood) sug- gests the diagnosis. Management may include therapeutic pleural aspiration of pleural \202 uid and temporary discontinuation of PD. Occasionally a period of rest and recommencement of PD with initially smaller volumes may be successful. If the effusion recurs, pleurodesis may allow ongoing treat- ment with PD. Genital edema Genital edema is an uncommon but distressing complica- tion of PD. Mechanisms include tracking of \202 uid leaking around the catheter or an incision site via the sub cutaneous tissues or leak via a hernia or patent processus vaginalis. Investigations Diagnosis of any leak and identi \201 cation of the cause may include: \200 \200 \200 CT peritoneogram with intraperitonal contrast; MRI with dialyzate in situ; USS (may identif y the presence of herniae containing dialsate); abdominal scintigraphy (dialyzate containin g radiola- beled tracer). G. WOODROW 516 Other complications of PD Pain with PD exchanges In \202 ow pain In \202 ow pain is the m ost common problem. It may occur soon after commencing PD and disappear with time whilst co ntinuing PD. Persistent in \202 ow pain may relate to the low pH of standard PD \202 uid s and may improve with use of neutral pH solu- tions. An alternative is the use of tidal PD for patients on APD. Pain may relate to movement of the PD catheter out of its correct pos ition which can be diagnosed on AXR. Management includes: \200 \200 regular use of laxatives; patient education about the importance of avoiding con- stipation ; dietary \201 bre supplements. Encapsulating peritoneal sclerosis (EPS) This is a rare but serious complication of long-te rm PD. The incidence increases with time on PD. Patients develop marked \201 brotic thick ening of the perito- neal membrane forming a cocoon surrounding and binding the intestine. It may be preceded by a progressive increase in membrane transportation state. Although typ ically presenting in patients whilst on PD, it may still occur after the patient has been t ransplanted or transfered to HD. Out \202 ow pain Out \202 ow pain is less common. It may be due to peritonitis or be a te mporary phenome- non after commencing PD. Risk factors \200 \200 \200 \200 Back pain Back pain may occur or be exacerbated by the presence of PD \202 uid which alte rs normal posture. Other treatable or serious causes of back pain should be excluded by inv estigation. Reducing volumes of \202 uid in the abdomen during the day, which may involve transfer to APD with reduced daytime dwell volume, or NIPD with a dry daytime period may h elp. long-term exposure to bioincompatible dialysis \202 uid; previous episodes of bacterial p eritonitis; use of acetate as a buffer in dialysis \202 uid; chlorhexidine contamination (used during sterilization of the exchange procedure); previous surgery; malignancy; -blo ckers; autoimmune disease. \200 \200 \200 Hemoperitoneum The presence of blood-stained dialyzate may be alarming for patients. Common ly it is a transient self-limiting event of unknown cause, possibly related to catheter tra uma of the perito- neal membrane. It occurs in women in relation to the menstrual cycle, at times of menstruation and ovulation. Occasionally it is a feature of peritonitis, which sh ould be excluded by microbiological evaluation of a dialyzate sample. Rare causes may inclu de: \200 abdominal malignancy; \200 pancreatitis; \200 hepatobiliary disease; \200 bleeding from a polycystic kidney; \200 liver disease; \200 encapsulating peritoneal sc lerosis. Clinical features \200 \200 \200 \200 \200 \200 bowel obstruction; abdominal pain; hemoperitoneum; weight loss; diarrhea; malnutrition. Malnutrition is common, may be severe and is associated with a high mortality. Clinical fea tures and high index of suspicion are important in making the diagnosis. Investigations Radiological investigations include: \200 \200 \200 plain AXR; ultrasound; CT scanning is the modality of greatest diganostic value Radiological features include: \200 peritoneal calci \201 cation; \200 features of bow el obstruction; \200 thickening of peritoneal membrane. Flushing with heparin-containing dialyzate may help to pre- vent catheter blockage. Constipation Constipation is common in PD due to: \200 older average age of patients on P D; \200 effect of dialyzate on bowel motility; \200 low \201 ber content of diet; \200 constipating medication; \200 electrolyte imbalance. Adverse effects include: \200 \200 \200 EPS may also be diagnosed by appearance of the perito- neum at laparotomy. Patients may hav e elevated in \202 ammatory markers and ongoing sepsis must be excluded where EPS develops soon after an episode of bacterial peritonitis. Management Management of nutrition is crucial. In patients with obstruc- tive symptoms or m alabsorption TPN is often required. It is generally thought that stopping PD is mandatory, though discontinuation of PD may also be a triggering fac- tor for developing EPS in some c ases. reduced \202 uid drainage and ultra \201 ltration; catheter migration; possible increase d risk of peritonitis due to enteric organisms. CHAPTER 13.4 Peritoneal dialysis 517 Immunosuppression: \200 \200 \200 Flanigan M, Gokal R. Peritoneal catheters and exit-site practices towards optimum peritonea l access: a review of current develop- ments. Peritoneal Dial Int 2005; 25: 132 \200\223139 . lacks signi \201 cant evidence base; corticosteroids are most commonly used; other immunos uppressant drugs anecdotally reported to be useful; development of postrenal transplant EPS in patients heavily immunosuppressed casts doubt on role of these drugs; Mujais S, Nolph K, Gokal R, et al. Evaluation and management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ult rafiltration Management in Peritoneal Dialysis. Peritoneal Dialysis Int 2000; 20(Suppl 4): S5 \200\223S21. Piraino B, Bailie GR, Bernadini J, et al. Peritoneal dialysis-related infections recommenda tions: 2005 update. Peritoneal Dial Int 2005; 25: 107 \200\223131. Some reports suggest that tamoxifen may have a bene \201 cial anti \201 brotic effect in EPS, but this is uncon \201 rmed. Surgery: \200 \200 \200 Internet resources International Society of Peritoneal Dialysis: may be indicated for persisting bowel obstruction; earlier studies described high associate d mortality; more recent experience suggests that excellent surgical outcomes can be achiev ed by experienced operators. http://www.ispd.org Peritoneal Dialysis International: http://www.pdiconnect.com Renal Association Clinical Practice Guidelines for PD: Prognosis High mortality in severe cases due to malnutrition and sepsis. Optimal medical an d nutritional management and timely surgical intervention where obstructive symptoms persis t despite conservative measures may be the best current approach and lead to improved survi val rates. http://www.renal.org/guidelines/module3b.html The Renal Registry: http://www.renalreg.org National Kidney Federation Dialysis Outcomes Quality Initiative: Lipid abnormalities in PD Lipid abnormalities are common in renal disease and differ betwee n dialysis modalities. PD is associated with increases in cholesterol and triglyceride conc entrations. VLDL and LDL lipoproteins and lipoprotein (a) increase on PD. Treatment of elev ated serum cholesterol is most com- monly with statins. Fibrates are also effective but req uire dose reduction and carry increased risk of myopathy in PD patients. The effectiveness of lipid-lowering therapy in reducing car- diovascular disease in PD is currently unknown. http://www.kidney.org/professionals/kdoqi/ European Best Practice Guidelines: http://www.ndt-educational.org/guidelines.asp National Institute for Clinical Excellence: http://www.nice.org.uk/ See also Renal replacement therapies in acute kidney injury, p. 328 Dialysis strategies, p. 480 Adeq uacy of dialysis, p. 518 Medical management of dialysis patients, p. 528 Further reading European Best Practice Guidelines for Peritoneal Dialysis. Nephrol Dial Transplant 2005; 20(Suppl 9). R. MACTIER AND G. WOODROW 518 Adequacy of dialysis Introduction Adequacy of dialysis can be de \201 ned as the ability to correct the clinica l features of uremia, promote rehabilitation and prolong survival of patients with ESRD. Di alysis may prevent death in patients with terminal renal failure, and increases in dialysis may improve the clinical status of patients with symptoms of uremia. However, with current techniques for renal replacement, morbidity and mortality remain high. This has led to int erest in objective measures of treatment to quantify and improve outcomes. For many years \200\230adequacy \200\231 has focused on dialytic solute clearances, though more recently h as expanded to include a broader assessment of outcomes and well-being. Therefore, in addit ion to a measurement of the clearance of putative uremic toxins by the dialysis process the assessment of dialysis adequacy should also include a global assessment of the patient \200\231s general well-being, nutrition, hemoglobin concentration, blood pressure and \202 uid status. For practical reasons HD adequacy thus far has been meas- ured using small, easily measured solutes such as urea. The two commonly used measures of HD adequacy are: \200 \200 urea reduction ratio; Kt/Vurea. Urea reduction ratio (URR) This is the simplest method and is the percentage fall in blood urea achieved by a dialysis session. It is measured as follows: \200 (Ureapost/Ureapre) \227 100%. The URR is easy to perform and is the index of dialysis dose which is most widely used in t he UK. URR does not take into account: \200 \200 \200 solute removal via ultra \201 ltration; residual renal function; urea generation during di alysis. Adjustment of dialysis dose to achieve a particular target URR will therefore result in hig her overall urea removal than predicted from the percentage reduction in blood urea. These theoretical drawbacks are not important if the main aim of measuring small solute removal b y HD is to ensure that a minimum target dialysis dose is delivered consist- ently. Kt/Vurea This can be calculated in a number of different ways with mathematical formulas of increas ing complexity. \200 \200 \200 Uremic toxicity Solutes of widely varying molecular size accumulate in patients with renal failure. These substances are believed to be toxic and to result in many of the features of uremia. Most of these substances increase in parallel in uremia, so it is dif \201 cult t o determine which are the most important causes of clinical disease. Retained solutes inclu de: \200 \200 inorganic substances such as electrolytes; small organic molecules (<300 Da) such as urea a nd creatinine; medium molecular weight organic substances, \200\230middle molecules \200 \231 of size 300 \200\2232000 Da; larger substances (up to 50 000 Da) such as 2- microglo bulin ( 2M). K: dialyzer clearance of urea; t: dialysis time; V: patients total body water. Depending on the mathematical method used it is possible to calculate: \200 \200 \200 a single-pool Kt/V (spKt/V); an equilibrated Kt/V (eKt/V); a standardized Kt/V (stdKt/V). The assessment of adequacy has primarily focused on small solute clearances. Blood concentr ations of urea and creatinine increase with deteriorating renal function and are reduced by removal during dialysis. Outcomes do not, however, directly relate to blood concentrations of serum urea and creatinine and, para- doxically, lower values also carry an adverse prog nosis. The serum creatinine concentration depends on both clearance and generation. Creatin ine is generated from muscle metabolism and the rate of generation depends on muscle mass. Low levels may be an adverse prognostic marker, re \202 ecting reduced muscle mass due to malnutri- tion and wasting. Similarly, serum urea is also dependent on generation rates, re \202 ecting protein intake and catabolism, as well as clearance. Each can be calculated using different formulas (see Appendix). These formulas give differe nt results for Kt/V. If Kt/V is being used for comparative audit it is important that the r aw data are collected to allow calculation of URR and Kt/V using a single formula. The seco nd-generation formula for estimating spKt/V, which was reported and validated by Daugirdas, is recom- mended. Single-pool Kt/V This assumes that urea is removed from a single compart- ment during dialy sis and is the easiest to calculate, requir- ing: \200 \200 \200 pre- and postdialysis urea concentrations; duration of dialysis; weight loss during dialysi s. Adequacy of hemodialysis The molecular weights of solutes to be cleared by dialysis range o ver three orders of magnitude, from small (water, urea) to large ( 2M). Adequate clearance of the whole range of molecules by dialysis is important and monitoring of 2M levels may be used in the future to assess dialysis adequacy. Equilibrated (or double-pool) Kt/V This attempts to take into account the amount of rebound in blood urea concentration at the end of dialysis due to redistribution of urea from the multiple body compart- ments. CHAPTER 13.5 Adequacy of dialysis 519 Standardized Kt/V This takes into account more variables including residual renal function but is correspondingly more complex to cal- culate. The true venous blood urea concentration rises rapidly in the \201 rst few minutes after dialysis as the effects of access and cardiopulmonary recirculation dissipate. It continues to rise at a rate higher than that expected from urea gen- eration for up to 30 min as a c onsequence of continued transfer of urea from peripheral body compartments into the bloodst ream. Falsely low measurements of the postdialysis blood urea concentration can occur due t o a combination of: \200 Urea kinetic modeling (formal UKM) Urea kinetic modeling is the most complex measure and in volves analysis of: \200 \200 the fall in blood urea concentration during HD; the rise in blood urea and urea clearance b y residual renal function in the next interdialytic period; the total clearance predicted f rom the dialyzer urea mass transfer area coef \201 cient; blood and dialyzate \202 ow; t ime on dialysis; \202 uid removal during dialysis. the dilutional effect of blood returning from the dialyzer (access recirculation); the dilu tional effect of blood returning via the heart and lungs directly to the \201 stula or ot her access device (cardi- opulmonary recirculation); contamination of the postdialysis bloo d sample by recently administered saline or other intravenous \202 uid. For these reasons the earlier the sample is drawn the higher the apparent delivered dialysis dose. Small var iations in the timing and technique of postdialysis blood sampling can, therefore, result i n clinically important errors in the estimated dose of dialysis. Such variation has been sh own to be common in the past in the USA and UK. The reinfusion method of postdialysis blood sampling should not be performed because of the dilutional effects of the saline washback. Three other methods of postdialy- sis blood sampling are still used: \200 \200 Therefore UKM requires collection of additional data on dialyzer clearance, an interdialyti c urine collection for measurement of urea concentration and volume, and measurement of pre dialysis urea concentration in the sub- sequent dialysis. These data are fed into a compute r program which, assum- ing steady state, calculates Kt/Vurea and normalized protein catabo lic rate. Kt/V measured by formal UKM allows accurate prediction of the effects of changing one particular component of the dialysis prescription (e.g. dialyzer size, dialysis durati on, blood \202 ow rate) on the delivered dialysis dose although this bene \201 t has bee n overstated given the limited number of practical options for changing the dialysis prescr iption. UKM may also give information on the urea generation rate and protein catabolic rat e. If the patient is in a steady state nutritionally, this gives information on current pro tein intake, and may be a useful adjunct to other methods of assessment of nutritional stat us. Stop dialyzate \202 ow method At the end of the dialysis time, stop dialyzate \202 ow b ut keep the blood pump running. After 5 min with no dialyzate \202 ow take a blood sample from anywhere in the blood circuit (i.e. the arterial or venous port). Slow- \202 ow method At the end of the dialysis time turn the blood pump speed down to 100 mL/min. Override alarms to keep the blood pump operating. Wait 15 \200\22330 s and take sa mples from the \200\230arterial \200\231 line sam- pling port. If more than one blood samp le is required, the sample for urea should be the \201 rst one taken. Disadvantages of Kt/V Doubts have been raised as to whether Kt/V is a good index of dialysi s dose since survival rates on HD are higher in patients with larger body size and better n utrition even though this patient group tends to have lower Kt/V values. Non-normalized dia lysis dose (Kt) has been proposed as an alternative and better index of dialysis dose adequ acy to Kt/V since the former index obviates the tendency to accord a higher dialysis dose i n smaller and poorly nour- ished patients. In a large cross-sectional analysis using Kt as the index of dialysis dose, mortality risk was observed to fall if the deliv- ered dialysis dose was a minimum Kt of 42 L in women and 48 L in men. A further dif \201 culty with the use of the Kt/V index for other than thrice-weekly HD is that the signi \201 cance of any weekly Kt/V value depends on the frequency of dialysis since more frequent dialysis therap ies, such as daily HD, will deliver greater small solute removal at the same weekly Kt/V. M ost HD units only measure pre- and postdialysis urea concentrations and a minority undertak e formal UKM rou- tinely. Therefore, to allow comparative audit, the choice is between calc ulation of URR and estimation of Kt/V urea. Simpli \201 ed stop- \202 ow method When you are ready to take the sample turn the blood pump speed slowly down to 50 mL/min. Start counting to \201 ve; if the venous pressure al arm has not already stopped the blood pump when you get to \201 ve, stop the pump manuall y. Table 13.5.1. The effect of urea rebound on URR and Kt/V urea measurements in 70 hemodialys is patients Time of blood urea sampling after HD 0 min 5 min 30 min 4.1 1.7 4.6 1.8 5.1 1.9 Mean urea (mmol/L) Methods of postdialysis blood sampling All measures of urea removal are derived from the ra tio of postdialysis/predialysis blood urea concentrations and so the method of postdialysis blood sampling should be stand- ardized. \200\223 14.9 % 27.3 % % urea rebound 76.9 5.9 74.1 5.9 71.4 6.0 URR 1.55 0.30 1.42 0.24 1.32 0.22 Kt/V urea R. MACTIER AND G. WOODROW 520 Disconnect the arterial line and take a sample from the nee- dle tubing (or the arterial co nnector of the catheter) within 20 s of slowing the blood pump speed to 50 mL/min. If more than one blood sample is required, the urea sample should be the \201 rst one taken. The slow- \202 ow and stop- \202 ow methods were devised to give early postdialysis measureme nts which avoid the effects of access recirculation but do not allow for cardiop- ulmonary recirculation which continues for the \201 rst 2 min after the end of HD using a \201 s tula or graft. The stop- and slow- \202 ow methods will underestimate post- dialysis \200 \230equilibrated \200\231 blood urea concentrations more than the stop dialyzate \202 ow method and consequently overesti- mate urea removal by HD. The stop dialyzate \202 ow met hod has several advantages: \200 Formulas have been validated for predicting 30 min postdi- alysis or \200\230equilibrated \200\231 blood urea from blood samples using either the stop dialyzate \202 ow method or similar sam- pling methods to the slow- \202 ow and stop- \202 ow methods (Appendix). The stop dialyzate \202 ow and slow- \202 ow methods are the two methods included in both G uideline 3.4 of the latest update of the K/DOQI Clinical Practice Guidelines on Haemodialys is Adequacy and the UK Renal Association Clinical Practice Guidelines on HD. Minimum and target dialysis dose in HD The optimal dialysis dose has not been well-de \201 ned but minimum targets of delivered dose measured by URR and Kt/V have been established. A retrospective analysis of the National Co-operative Dialysis Study suggested that a Kt/V of 1.0 was the water- shed between \200\230good \200\231 dialysis (Kt/V >1.0) and inadequa te dialysis (Kt/V <1.0). A large observational study of HD patients showed that variations in URR were associated with signi \201 cant differ- ences in mortality and this study led to the recommenda- tion that the URR should be \211 65%. Subsequent observational studies have generated con \202 ict- ing results and suggest either a reduction in mortality rates with further increments in dialysis dose or no further reduction in mortality rates with a Kt/V >1.3 or URR >70%. These studies led to the setting up of the HEMO study (Table 13.5.2 ). An association between higher dose and lower mortality rates in women but not in men was con \201 rmed using the average URR of incident HD patients in the USA, and eKt/ V of HD patients in the DOPPS data from seven coun- tries. Based upon this evidence the minimum dia lysis dose deliv- ered thrice weekly should be: \200 \200 \200 it avoids the dilutional effects of both access and cardi- opulmonary recirculation; it is a simple two-step process; It is easily reproducible as accurate timing of blood sam- pling is less critical; blood sampling can be performed from either the arte- rial or venous lin e; it is suitable for all forms of vascular access; it is validated in hemodia \201 ltrati on as well as HD; it has been used by all of the HD units in Scotland since 1999 and is the most widely used method in the UK. \200 \200 \200 Equilibrated postdialysis urea concentration Postdialysis rebound in venous blood urea conc entration results from continued return of blood from poorly dia- lysed body \200\230compa rtments \200\231, and is particularly marked after high ef \201 ciency dialysis. Accurate comparison of delivered dialysis dose therefore requires estimation of the equilibrated blo od urea concen- tration and calculation of \200\230equilibrated \200\231 Kt/V. Full re-equ ilibration takes 30 min but it is impractical to ask patients to wait this long for postdi alysis blood sam- pling on a routine basis. The amount of rebound is determined by several factors including the ef \201 ciency of dialysis and the size of the patient. Table 13.5.1 demonstrates the degree of overestimation of dialysis dose if blood sampling does not allo w for urea rebound during the \201 rst 5 min (as measured by the stop dia- lyzate \202 ow method) and \201 rst 30 min after the end of dialysis. URR of 65%; eKt/V of 1.2; spKt/V of >1.3 (calculated from pre- and postdialysis urea concen trations, duration of dialysis and weight loss during dialysis). To achieve a URR >65% or eKt/V >1.2 consistently in the vast majority of the HD population, clinicians should aim for a minimum target URR of 70% or minimum eKt/V of 1.4 in individua l patients. Table 13.5.2 Summary of the HEMO study \201 ndings Prospective randomized controlled trial of 1846 prevalent HD patients. Patients were on dia lysis for a median of 3.7 years at the time of recruitment to the study. 2 \227 2 factoria l study design: high and low \202 ux; high and standard dialysis dose; Study design standard dose goal of an equilibrated Kt/V of 1.05 (URR 65%); or \200 high dose goal of an equilibrated Kt/V of 1.45 (URR 75%). 871 of the 1846 randomized patients died during the study after a mean follow-up period of 2.8 years. Even though dialysis doses were well-separated no difference was observed in: Outcomes primary outcome of all-cause mortality; \200 \201 rst cardiac hospitalization or all-ca use mortality; \200 \201 rst infectious hospitalization or all-cause mortality; \200 \201 rst 15% decrease in serum albumin or all-cause mortality; \200 all non-vascular ac cess-related hospitalizations. Differences in dialysis dose and membrane \202 ux had no effect on the proportion of infe ction-related deaths. Subgroup analysis Survival rates in women randomized to the higher dose group were higher than in women in th e lower dose group after adjusting for different indices of body size. CHAPTER 13.5 Adequacy of dialysis 521 Aiming for these target doses also addresses the concerns raised by recent data suggesting that women and patients of low body weight may have improved survival rates if the URR is m aintained at >70% or the eKt/V is \211 1.4. The achievement of these clinical practice gui delines is dependent on patients \200\231 concordance with treatment. This includes the agr eement of the patient to increase treatment duration if the delivered dialysis dose is inad e- quate after the dialyzer blood \202 ow rate, dialyzate \202 ow rate and dialyzer per formance have been increased to the max- imum that can be achieved. Increased understanding among patients of the bene \201 ts of an adequate dialysis dose should help to improve ou t- comes. The use of 2M to assess adequacy of HD Time-dependent Cox regression analysis o f the HEMO study provides support for the use of 2M to assess ade- quacy of HD: \200 measured, and an aliquot extracted for biochemical analy- sis. Alternatively, individual ba gs may be measured and aliquots taken in volumes proportional to the drained volumes (e.g. 1%) and combined in a \201 nal sample sent for biochemical analysis. 24 h urine samples a re collected according to stand ard procedures. Incomplete collection may occur due to inac curacy of timing of the collection and incomplete collection. Additional error may arise in patients where urine volumes are small and voiding infrequent, and in patients with condit ions leading to incomplete bladder emptying. Methods of assessing small solute removal on PD Dialytic Kt/V urea Since urea clearance is the basis of assessment of HD ade- quacy, there was interest in providing a comparable meas - urement for PD. In HD urea clearance is expressed as the Kt/V for urea per dialysis sessi on. For PD, urea clearance is also expressed as Kt/V, but with values quoted as Kt/V per we ek. Kt is the clearance of solute removed in time t, and is determined from 24 h dialyzate collections. In the expression Kt/V, clearance, Kt, is normalized for body size by division by V, the volume of total body water, which is the volume of distribution of urea. Unlike in HD, in PD the volume V is estimated separately from Kt and biochemical measurements. In clinical prac- tice, V is calculated from equations estimating V from anthropometric and de mographic variables (Appendix). These equations have been developed by regression against t otal body water measured by dilution techniques. The most commonly used equation is that of Watson and Watson. One limitation of anthropometric equations is that there is a degree of inaccuracy in the estimation of total body water in individuals. Also, obesity results in overestimation of V as fat is largely anhydrous, but increasing the weight term of the equa tions will increase estimated V. This leads to underestimation of Kt/V in obese individuals . A further limitation of normalization of clearances to V is that patients with low body w eight resulting from wasting and malnutrition will have lower values for V and thus higher Kt/V. For these patients the optimum clearance required will be greater than that suggested from these calculations. It has been suggested that V should be calculated from ideal weig ht in malnourished patients. mean predialysis serum 2M levels but not dialyzer 2M clearances were associated with al l cause mortality the relative risk of death was 1.11 per 10 mg/L rise in the 2M concentr ation above a reference value of 27 mg/L after adjusting for residual renal function and pr estudy years on dialysis. The apparent disparity between the prognostic effects of serum 2M levels and 2M dialyze r clearances is most likely due to the limited mass removal of 2M in high ef \201 - cien cy dialysis. This is due to intercompartmental transfer resistance of high molecular weight solutes within the patient during HD which results in rebound of serum 2M levels at the end of therapy. In future, 2M levels may also be used to assess the adequacy of dialysis by serving as an indicator of patient outcome and as a surrogate marker of middle molecule removal. Adequacy of peritoneal dialysis Small solute clearances As already alluded to, blood levels of retained solutes are unreliable measures of the ef \201 ciency of dialysis, and the cl earance of small solutes is determined instead. In PD, clearances of urea and creatinine ar e routinely meas- ured. In HD the intermittent nature of the treat ment allows calculation of clearance from the change in blood levels of urea before and after dialysis. This is not possible in PD due to the continuous nature of the therapy, so PD clearances are determine d by collection of drained dialyzate over a 24 h period, and a simultanous 24 h urine colle ction in sub- jects who are not anuric. A blood sample is also taken, which should be midwa y through the dialyzate and urine collection period, espe- cially for \202 uctuating ther apies, i.e. APD. To calculate clearances, it is necessary to know the amount of solute remo ved in 24 h periods by dialysis and by residual renal function. This requires knowledge of \202 uid volumes and their solute concentrations. For dialyzate, the drained volume of di alyzate in a 24 h period is determined and the concentrations of urea, cre- atinine and glu cose in the dialyzate are measured. For APD, the drained volume may be determined from the measurements derived from cycler machines. For CAPD, the \202 uid from all bags may be po oled, the total volume Dialytic creatinine clearance The other standard measure of dialytic clearance in PD is cre atinine clearance. This is determined by measurement of the quantity of cre- atinine remove d in a 24 h dialyzate collection and is calcu- lated in an analogous fashion to urinary cre atinine clearance for measurement of the GFR. It is usually expressed in liters per week an d normalized to 1.73 m2 body surface area (L/1.73 m2/week). Body surface area is determined by anthropometric equa- tions (the formula of DuBois is commonly used). Glucose interferes with some assays for creatinine estima- tion. High dialyzate glucose concentrations may re sult in R. MACTIER AND G. WOODROW 522 spuriously high dialyzate concentrations of creatinine and overestimation of creatinine cle arance. It is important to determine the effect of dialyzate glucose in your local laborato ry, and to measure glucose concen- tration in the collected dialyzate so that an appropriat e correction to dialyzate creatinine concentration can be made. Conversely, in anuric patients, it is more dif \201 cult to achieve clearance targets for creatinine clearance than Kt/V urea by increasing dialysis dose. Kt/V urea or creatinine clearance? The relative merits of urea and creatinine clearances ha ve been debated and are unclear. Neither is superior in performance in re \202 ecting othe r fea- tures of uremia or predicting outcomes. The two measures may vary discordantly in di fferent clini- cal situations. Important factors leading to differences between urea and cr eatinine clearances include PD modality and prescrip- tion, membrane transportation type an d presence of residual renal function. Residual renal function urea and creatinine clearance Residual renal function can make a si gni \201 cant contribution to small solute clearances in PD. Renal clearances of urea and creatinine are measured from 24 h urine collections and values may be added to dialytic cle arances to give total clearances. Renal urea clearances are measured from 24 h urine urea a nd blood urea concentrations and expressed as residual renal Kt/V urea using similar calcul ations to dialytic Kt/V. Creatinine is an imperfect measure of renal function due to tubula r secretion. This leads to overestimation of renal function, which is proportionally greate r with lower clear- ances and especially so for residual renal clearance in patients on dia lysis. To correct for this, \200\230residual renal creatinine clearance \200\231 is calcul ated as the mean of creatinine and urea clearances, as urea is passively reabsorbed in the tubules leading to underestimation of actual renal clearance. Minimum and target dialysis dose in PD There has been huge interest in de \201 ning optima l measures of dialysis, to allow objective determination of ideal dialysis prescription, wi th the aim of reducing the high morbidity and mortality of patients on dialysis, while avoi ding unnec- essarily intrusive dialysis regimes that would reduce patient quality of life w ithout any clinical bene \201 t. Various guidelines have been produced by national and int ernational organizations over time and have been rewrit- ten as advances in the evidence ba se relating to aspects of clearance and patient outcomes have been made. Initial guidelines focused exclusively on small solute clear- ance measurements and were based on the \202 awed assump- tion that control of uremic toxicity is related to total small solute clearanc e, and that clearance of molecules such as urea and creatinine has equivalent impact on out come, whether by dialysis or residual renal function.