Peritoneal dialysis update 1994.KD Nolph
Department of Internal Medicine, University of Missouri-Columbia, 65212, USA., USA
Each year there are over 400 papers published in the field of peritoneal dialysis. In this review I have touched on only a few highlights of some of the more active areas of investigation and development. The advances in controlling peritonitis rates with the Y-set have been dramatic and have resulted in peritonitis rates in many centers less than one episode per 24 patient months. Technique survivals have also improved with lower peritonitis rates. The enormous literature on new approaches to treatment and new understandings of host defenses are beyond the scope of this review. There are also many advances in peritoneal access. We now have many new types of catheters under investigation such as the Swan-Neck Missouri catheter and the Moncrief-Popovich catheter, with complete burial of the catheter until eventual externalization for CAPD training. There have been major advances in understanding the normal healing of exit sites and the early diagnosis and treatment of exit-site infections. All the extensive literature on catheter development in the management of exit sites will be reviewed elsewhere. I have focused primarily on an update of worldwide demographics, some of the new findings in peritoneal transport, the use of low-calcium solutions, experiences with EPO, new thinking about adequacy and nutrition, and finally, on recent comparisons of CAPD and hemodialysis.
Keywords: Human, Peritoneal Dialysis, adverse effects,utilization,Peritonitis, etiology,
Baxter Healthcare Inc performs an annual worldwide dialysis survey. The following data will represent the status of the worldwide dialysis population as of the end of 1993 according to the Baxter Survey in early 1994.
There were 591,700 chronic dialysis patients worldwide; 29% were in the USA, 23% in Japan and 22% in Europe. The global chronic peritonea] dialysis population was 86,300 and the average annual growth rate of this population since 1990 was estimated at 16%. The percentages of dialysis patients on chronic peritoneal dialysis in various countries monitored ranged from 6 % in Japan to 91% in Mexico. Other examples include 58.8% in New Zealand. 50% in the United Kingdom, 38% in Canada.32 % in Sweden, 17% in USA and 10% in Italy A recent international study by Nissenson et al has shown that non-medical factors such as reimbursement and geography influence these percentages extensively.
According to the Baxter survey, by the end of 1993, the USA chronic peritoneal dialysis population was 29,300; the average annual growth rate since 1990 has been 12%. On a global basis, nearly 17% of patients are on automated peritoneal dialysis techniques (with an automated cycler) and 83% are on CAPD. Automated cycler techniques include continuous cyclic peritoneal dialysis (CCPD) and nightly intermittent peritoneal dialysis (NIPD). Of those on CAPD, nearly 77% use disconnect systems and/or devices such as ultraviolet connectors rather than standard aseptic technique. Disconnect devices are mainly of the Y-set configuration. In the United States, nearly 22% of chronic peritoneal dialysis patients use an automated cycler and nearly 95% use disconnect systems and/or devices.
On a global basis, nearly 40% of chronic peritoneal dialysis patients use a solution containing calcium at 2.5 mEq/1iter. In the USA, over 50% of patients use the 2.5mEq/fiter calcium solution. This calcium concentration is lower than the standard 3.5mEq/liter calcium solution and allows more aggressive Lose of calcium carbonate and calcium acetate phosphate binders with a lower incidence of hypercalcemia.
In 1993, technique failure was attributed to inadequate dialysis in 20%, catheter problems in nearly 25% and peritonitis in 15%.
It has become apparent that patients classified as high transporters by the peritoneal equilibration test (PET) have increased albumin clearances in peritoneal dialysis effluent and are prone to lower serum albumin concentration,. These patients have higher glucose absorption per volume of ultrafiltrate. The greater loads of daily glucose absorption may suppress appetite and decrease dietary protein intake.
High transporters are in need & close monitoring on CAPD and are ideal candidates for oral or intraperitoneal protein supplementation. In another study, high transporters were found to have lower ultrafiltration capacities, higher glucose absorption rates and increased losses of most plasma proteins (including albumin, immunoglobulins, complement components and high density lipoproteins). Thus, patients with high peritoneal transport rates are potentially exposed to augmented, atherogenic plasma lipid profiles and may be prone to nutritional and immunological disturbances.
Recent studies with neutral dextrans, and ionic dextran sulfate and cationic diethylaminoethyl dextran in New Zealand, White rabbits suggest that molecular charge decreases transperitoneal transport, especially for cationic molecules. An electro-negatively charged network (the fibrous glycocalyx) covering the luminal surface of fenestrated capillaries and anionic fixed charges distributed along the subendothelial basement membranes suggest that there is little or no transfenestral passage of macromolecular anionic proteins.
Fenestrations may explain the high permeability of some peritoneal capillaries to non-charged larger molecules such as Vitamin B12 and inulin. The contribution of osmotic induced convection to the transport of macromolecules seems modest. New evidence suggests that macromolecules are mainly transported by transfusion or hydrostatic convection.
New analyses with a three-pore model of microvascular exchange attribute losses of net ultrafiltration to either increased total pore cross-sectional area available for diffusion with an increased transport of glucose to blood and a rapid decrease in the osmotic gradient or to very high lymph flow from the peritoneal cavity (greater than 0.3 milmin.11.73 m2).
Some workers contend, however that it is difficult to differentiate between diffusive and convective transport across the peritoneum even during a hyperlonic exchange. Some question basic concepts of transport models and emphasize the difficulties encountered in fully understanding the transport properties of a biological membrane such as the peritoneum.
New studies support previous reports suggesting that phosphatidylcholine increases net ultrafiltration by reducing lymphatic absorption of fluid from the peritoneal cavity. Recent clinical studies do not support previous findings in rats that intraperitoneal neostigmine decreases lymphatic absorption from the peritoneal cavity.
Intraperilloneal amino-acid based dialysis fluid may enhance peritoneal permeability by generating prostaglandins. While nitroprusside is assumed to increase peritonpal clearances through vasoditatory effects. chloipromazine may increase clearances through surface activity of the drug. Angioterisin II may decrease ultrafiltration by enhancing lymphatic absorption.
Workers continue to explore the relative contributions of lymphatic absorption into the subdiaphragmatic lymphatic system and convective absorption of fluid across the abdominal wall,,,,,,,,. Total absorption from the peritoneal cavity reflects both lymphatic subdiaphragmatic lymphatic absorption and absorption into abdominal wall lymphatics and or capillaries. There may be additional absorption into mesenteric lymphatics and capillaries. The actual contributions of these different pathways remain the subject of intense investigation.
Numerous recent investigations have focused on calcium mass transfer and other findings associated with newer dialysis solutions containing 2.5 instead of 3.5 mEq/litre of calcium,,,,,. Calcium mass transfers are greater with lower calcium containing solutions, especially with hyperlonic exchanges. The use of low-calcium concentrations may reduce the proliferation of peritoneal fibroblasts and the production of cytokines and perhaps minimize the tendencies towards peritoneal fibrosis and sclerosis in the presence of acute inflammation. In CAPD patients with hypercalcemia, high PTH levels and high turnover borne disease, the combination of low-calcium peritoneal dialysis solutions with calcitriol therapy has achieved reductions in the serum parathyroid hormone concentration without increase in serum calcium or phosphorus. The use of low calcium peritoneal dialysis solutions permits substitution of calcium carbonate or calcium acetate in place of aluminium-containing phosphate binders with less risk of hypercalcemia.
Keshaviah feels that concern about adequacy of CAPD should focus on small solute clearances rather than on hypothetical middle molecules, and that urea is an excellent marker solute for assessing small solute clearances. Increasing the number of exchanges in CAPD patients can alleviate uraemic symptoms in patients who have lost residual renal function and had been stable on a lesser number of exchanges. Such manoeuvers mainly impact on the weekly clearances of small molecular weight solutes, which are dependent on dialysate, drain volume. Larger molecular weight solute clearances are more dependent on membrane area and permeability. The weekly urea clearance requirement with intermittent haemodialysis therapy is greater than that for CAPD to yield comparable protein intakes and outcome parameters. One explanation for the greater weekly small solute clearance requirement with intermittent haemodialysis therapy is that the control of peak body fluid concentrations of small molecular weight solutes is important, and an intermittent therapy such as haemodialysis requires greater clearances to maintain the serum concentrations of small solutes at or below the steady state concentration of CAPD (assuming that solute generation rates are identical).
At the same weekly KI urea, CAPD patients have a higher net protein rate (and presumably dietary protein intakes) than do intermittent haemodialysis patients. If the intermittent haemodialysis patients ingested the same amount of protein while receiving the same weekly KTIV urea as CAPD patients, serum urea nitrogen concentrations would be higher in the haemodialysis patients than the steady-state CAPD values for substantial portions of the week (especially the day before the next haemodialysis). Serum urea nitrogen may be a surrogate for small molecular weight toxin(s) that inhibit appetite, and higher concentrations of such a substance or substances may, by inhibiting appetite, reduce these toxic peak concentrations.
Clearly, increasing urea clearances in both CAPD or in haemodialysis increases the net protein catabolic rate (PCR).
I recommend that minimum targets of 50 L / week/1.73 m2 body surface area of creatinine clearance and a weekly KTIV urea of 1.7 are reasonable it protein intakes in excess of 0.9 g/kg normalized body weight are to be achieved in most CAPD patients. The weekly KTIV urea should include the urea clearance by dialysis and by the kidney.
For the weekly creatinine clearance, however, I recommend that the value include the dialysis clearance plus an estimate of the renal creatinine clearance only by glomerular filtration rate. This can be estimated from the mean of renal urea and creatinine, clearances.
A retrospective analysis of the relationship of KT/V urea to outcomes was performed in 16 CAPD patients followed over a five-year period. A direct correlation between KT/V urea and PCR and peripheral nerve conductivity and negative correlations between KT/V urea and number of hospitalization days and peritonitis rates were noted. Weekly KT/V urea values above 1.8 were associated with stable nerve conduction velocities; these deteriorated in patients receiving lower weekly KT/V urea values.
Gotch has suggested that adequate dialysis in CAPD is achieved at a weekly urea clearance only about two-thirds of that required in intermittent haemodialysis. He recommends a weekly KT/V urea value near 2.0 to achieve a net protein catabolic rate equal to 1.1 g/kg normalized body weight. This is in accord with our own studies which suggest that a weekly KTN urea of 1.7 is associated with a net PCR near 0.9 g/kg of normalized body weight in average CAPD patient. Gotch has also presented a rigorous mathematical argument that the dependence of normalized PCR on KTIV urea in CAPD is not a mathematical artifact.
A retrospective analysis of 190 CAPD patients who were followed an average of 12 months revealed that the most powerful predictor associated with a high risk of death was a low serum albumin concentration. Other variables significantly associated with increased probability of death on CAPD were: advancing age, low serum creatinine concentrations and elevated serum cholesterol concentrations. It is important to note that the laboratory data utilized in this study were obtained in the week prior to beginning CAPD. The authors feel that simple laboratory measurements at the time of enrolment in CAPD can predict the relative risk of death for each patient. Future clinical studies are required to see if rigorous attention to adequacy and nutritional status can reverse these risks by altering the laboratory findings on CAPD.
Some CAPD patients are in neutral or positive nitrogen balance with protein intakes as low as 0.7g/kg/body weight/day. Lindholm and Bergstrom feel that CAPD patients generally have lower protein requirements than haemodialysis patients. In CAPD, anabolic effects of glucose absorption from the peritoneal cavity, stable metabolite levels, improved control of acidosis, avoidance of cytokine release due to blood-membrane incompatibility and good middle molecule removal may explain in part why CAPD patients seem to tolerate lower weekly urea clearance sand lower protein intakes than do haemodialysis patients. The peak concentration hypothesis may also explain this paradox. However it is still recommended that CAPD patients be encouraged to ingest at least 1.0 to 1.2 grams of protein per kilogram body weight per day.
Bergstrom and Lindholm have also emphasized that haemodialysis populations have relatively high percentages of patients (when compared to CAPD patients) of low pre-dialysis bicarbonate concentrations associated with lower values of muscle intracellular valine concentrations (probably reflecting catabolic effects of acidosis).
Mean serum albumin concentration has been shown in CAPD patients to correlate inversely with hospital days and directly with technique survival. Initial as well as ongoing serum albumin were predictive of technique failure when low. The strongest predictors of a low serum albumin were diabetes, high peritoneal transport, older age, lower body weight and shorter time on CAPD. More studies are needed to better understand the implications of low serum albumin levels in CAPD patients. In CAPD, low serum albumin concentrations may reflect poor protein intake, enhanced protein losses in dialysate and dilution with salt and water retention. There are also adaptive increases in synthesis. More factors seem to impact on the control of serum albumin concentrations in CAPD than in haemodialysis.
Using the new low-calcium peritoneal dialysis fluid (2.5 mEq/1iter) coupled with calcium carbonate or calcium acetate as phosphate binders appears to achieve good control of serum and phosphorus, decreases in parathyroid hormone concentrations, and improved bone histology in most patients.
Coburn has recommended that dialysate calcium concentration routinely be 2.5 m Eq/litre unless there is a problem with substantial hypocalcemia or unless serum phosphorus levels are normal without the need for any calcium-based phosphate binders.
CAPD patients appear to have an increasing incidence of aplastic bone disease, even more so than haemodialysis patients. Low turnover disorders may comprise 66% of the lesions now being seen in chronic peritoneal dialysis patients. Whereas high turnover disorders represent 62% of the bone histologic findings in haemodialysis patients. Factors contributing to the higher incidence of low turnover disease in peritoneal dialysis patients may be lower PTH hormone concentrations compared to haemodialysis patients, older age, higher prevalence of diabetes and a shorter duration of dialysis. Many of the chronic peritoneal dialysis patients with low turnover bone (a dynamic bone disease) have not been exposed to aluminium and demonstrate the absence of aluminium in bone histology. In such patients, the low turnover bone disease may reflect aggressive parathyroid hormone control. Usually such patients are asymptomatic. Until more is known about the disorder, it is cautioned against efforts to treat the lesion.
Delmez favors oral pulse calcitriol treatment at night for patients on CAPD to decrease parathyroid hormone concentrations. He warned, however, that CAPD patients treated indiscriminately with calcitriol may develop worsening of the low bone turnover state (the clinical consequences of which are unclear). At this time, Delmez favors maintaining serum levels of intact PTH between 1.5 and 2.5 times the upper limits of normal. Calcitriol therapy can be given subcutaneously with impressive decreases in serum PTH,.
There have been numerous studies of EPO treatment in chronic peritoneal dialysis patient,,,,,. The EPO is effective if administered subcutaneously or intraperitoneally. Maximum serum EPO concentrations following intraperitoneal and subcutaneous doses were nearly identical but amounted to only 5% of the maximum concentrations with the comparable intravenous doses. The subcutaneously administered EPO took nearly twice as long as intraperitoneally administered EPO to attain peak serum concentration. Subcutaneous EPO was more bioavailable than intraperitoneal EPO. It is fairly typical to maintain hematocrits between 33 and 35% using EPO doses of 2,000 or 4,000 units weekly or biweekly.
The United States renal data system compared populations selected for peritoneal dialysis or haemodialysis according to co-morbid conditions. Patients selected to peritoneal dialysis were not at greater co-morbid risk due to cardiovascular factors than the haemodialysis patients, as has been commonly proposed. The Michigan registry compared survivals in CAPD and haemodialysis patients in Michigan from 1980 to 1089 (N = 4,288 patients). By 1989, one-third of incident end-stage renal disease (ESRD) patients 20 to 59 years of age were using CAPD at the fourth month of renal replacement. There were no differences in survival between haemodialysis and CAPID for patients with hypertension and other reported causes of end-stage renal disease except for differences noted in patients with glomerulonephritis and diabetic nephropathy. CAPD patients with glornerulonephritis as the cause of their end-stage renal disease had lower mortality rates than their haemodialysis counterparts correcting for differences in risk factors. Among young diabetics, long-term mortality was shown to be lower for patients using CAPD. These death rates wore adjusted for race, sex and year of end-stage renal disease onset.
Maiorca and colleagues provide evidence that suggests that lower technique survivals with CAPD are completely accounted for by dropout related to peritonitis. Patient survivals, in their experience, adjusted for pre-treatment differences in populations are similar for CAPD and haemodialysis.
Rottembourg has extensively reviewed the accumulating evidence that residual renal function is more likely to be better preserved or even improved with CAPD compared to haemodialysis. Gokal has concluded that quality of life comparisons between CAPD and haemodialysis are difficult because of different modality stressors. CAPD may have a marginal advantage over in-centre haemodialysis. Successful transplantation imparts the best quality of life by both objective and subjective parameters.
Each year there are- over 400 papers published in the field of peritoneal dialysis. In this review I have touched on only a few highlights of some of the more active areas of investigation and development. The advances in controlling peritonitis rates with the Y- set have been dramatic and have resulted in peritonitis rates in many centres less than one episode per 24 patient months. Technique survivals have also improved with lower peritonitis rates. The enormous literature on new approaches to treatment and new understandings of host defences are, beyond the scope of this review. There are also many advances in peritoneal access. We now have many new types of catheters under investigation such as the Swan-Neck Missouri catheter and the Moncrief-Popovich catheter, with complete burial of the catheter until eventual externalization for CAPD training. There have been major advances in understanding the normal heating of exit sites and the early diagnosis and treatment of exit-site infections. All the extensive literature on catheter development in the management of exit sites will be reviewed elsewhere.
I have focused primarily on an update of worldwide demographics, some of the new findings in peritoneal & transport, the use of low-calcium solutions, experiences with EPO, new thinking about adequacy and nutrition, and finally, on recent comparisons of CAPD and haemodialysis.