PET -A Simpler Approach for Determining Prescriptions for Adequate Dialysis Therapy


Zbylut J. Twardowski

Fast Pet test is a modijied version of original PET. Only one dialysate sample for glucose and creatinine is taken from the total drained dialysate and a blood sample at the end of the test exchange. It can be used both for diagnostic and prognostic purposes. The Pet and clearance measurements are complementary studies which can guide in dialysis prescription.

Key words

Adequacy of dialysis, peritoneal equilibration test, clearance, fast PET

From

the Division of Nephrology, Department of Medicine, University of Missouri, Harry S. Truman Veterans Administration Hospital, Dalton Research Center, Columbia, Missouri.

Optimal dialysis

The relationship between the amount of dialysis and clinical results is presented in Figure I. According to this theoretical approach optimal dialysis is defined as the amount of dialysis yielding clinical results which cannot be further improved. The results would be measured by comparison of longevity, morbidity, and general wellness in dialysis patients to those in general population. By the amount of dialysis I accept not only the dose of dialysis (average weekly clearance/standard body surface area, or weekly KT IV , or volume of peritoneal dialysis solution per week), but also weekly distribution of dialysis sessions (continuous, infrequent intermittent, daily, nightly, or twice daily). Such an evaluation has not been performed yet. There are three possible outcomes of such a study (if it is ever done): I) constant increase in dialysis would give consistently better results but at some point the improvement would be so small that the benefits would not be easily discernible; 2) best maximum would be an amount of dialysis beyond which further increases in amount of dialysis would not result in further improvement; and 3) overdialysis would occur when increasing dialysis beyond a given point cause clinical deterioration. Do we provide optimal dialysis? There is no answer to this question but it is very likely that we are far from optimal dialysis.

Adequacy of dialysis

Because we are forced to keep the cost and time of dialysis within reasonable limits we do not even attempt to provide optimal dialysis, we only try to provide merely adequate dialysis. According to Webster ' optimal' means most desirable or satisfactory, 'adequate' means sufficient for a specific requirement, barely sufficient or satisfactory .But what does adequate dialysis mean, how much dialysis is 'barely sufficient or satisfactory'? The term is frequently used in two ways (Table I): 1) A dialysis prescription fulfilling certain criteria, and 2) The condition of a patient achieved with a particular prescription. This outcome constitutes a criterion of dialysis adequacy.

During the early years of chronic hemodialysis, a definition of adequate dialysis was based on clinical grounds, particularly on the absence of symptoms and signs of uremia (1). In the early 1970s the definitions were based on a mixture of clinical symptoms and laboratory data (2,3). These definitions used a priori criteria of adequacy and were supposed to predict long term results of dialysis. The National Institutes of Health (NIH) sponsored National Cooperative Dialysis Study (NCDS) used the overall morbidity and mortality as decisive objective criteria for the relative values of different dialysis prescriptions (4). This approach used an a posteriori (from the actual results) criterion of dialysis adequacy. It was found that more dialysis decreased morbidity but no attempt was made to establish the optimal prescription.

Adequate peritoneal dialysis

The adequacy of peritoneal dialysis prescriptions has never been tested in well controlled prospective studies. The adequacy of peritoneal dialysis is judged mainly by a priori clinical and laboratory criteria (Tables II and III). The adequately dialyzed patient 'feels well and looks good', maintains hematocrit above 25% (without anabolic steroids or erythropoietin), has stable or increasing nerve conduction velocity (if not diabetic), and exhibits well controlled blood pressure. Manifestations of inadequate dialysis are usually subtle and often develop insidiously. Most commonly, inadequate dialysis results in such symptoms as insomnia, and anorexia leading to poor nutrition with wasting and loss of lean body weight. Blood urea nitrogen may be low because of poor protein intake, but creatinine level is usually high. There is no particular creatinine level at which all patients develop symptoms of underdialysis. According to my personal experience, serum creatinine level above 20 mg% are associated with subtle symptoms ofunderdialysis in the majority of peritoneal dialysis patients; however, serum creatinine levels above 15 mg% may be associated with inadequate dialysis, especially in nonmuscular persons (5).

A controversial issue is whether other symptoms and signs of uremia should indicate inadequate dialysis. Control of serum phosphorus to prevent secondary hyperthyroidism by dialysis alone without phosphate binders is umealistic, thus, hyperphosphatemia and hyperparathyroidism are not considered as indicating inadequate dialysis. Serositis may occur in otherwise adequately dialyzed patients and generally is not considered as indicating inadequate dialysis.

Minimum adequate clearances

Even after several decades of research, there is no general agreement on adequate body clearances of uremic toxins. Elsewhere in this proceedings dialysis prescription based on urea kinetics is presented. In 1978 Boen et al. postulated a combined (renal and peritoneal) creatinine clearance of 5.5 ml/min (7.92 I/day, or 55.44 L/week) for adequate peritoneal dialysis in a standard patient with body surface area (BSA) of 1.73 m2 (6). My personal experience indicates that anuric patients fulfilling criteria of adequate dialysis have at least a peritoneal creatinine clearance of 4.0-5.0 ml/min/ 1.73 m2 (5.8 7.2 L/ day; 40-50 L/week). There is no doubt in my mind that we are far from the possibility of over dialysis and that the clearance closer to the upper numbers would be desirable. Still the recommended clearance value is lower than that postulated by Boen et at. , but a higher clearance seems to be realistic only in patients with small body surface areas.

Adequate ulrafiltration

Adequate ultrafiltration on CAPD is defined as ability to generate at least 5.5 ml ultrafiltration per 1 g of absorbed glucose or 1500 ml of ultrafiltration with glucose infusions of 270 280 g/ day ( e .g. , with 2 L infusion volume and 2 exchanges of 2.5% solution +2 exchanges of 4.25% solution; or with 3 L volumes and 2 exchanges of 2.5% solution + 1 exchanges of 4.25% ).

Peritoneal equilibration test

The peritoneal transport rate is an important factor which detennines the patient response to various fonns of peritoneal dialysis (7,8). Categorization of patients according to the peritoneal transport characteristics is based on the results of 103 peritoneal equilibration tests in our total patient population (7) .Excellent reproducibility was seen after tests were standardized for length of preceding exchange, times of inflow and drainage, patient position, methods of obtaining and processing samples and laboratory assays. Wide variations were found in the study population. The test proved to be very useful for diagnostic and prognostic purposes, and dialysis regimen planning. (7,8). As the consequence of several year experience with the results of the unabridged equilibration test a simplified, abridged, equilibration test was developed (9). Baseline tests are perfonned soon after patients begin CAPD and the test is repeated as needed for diagnostic purposes. Even the abridged protocol is designed to provide for a maximal level of accuracy and reproducibility and internal control. However, it is realized that the PET protocol is labor intensive, requiring measurement of glucose and creatinine in 3 dialysate samples and in one blood sample, precise timing of dialysate flows and over 4 hours of nurse-patient interaction. As a result, the PET protocol is, in many dialysis centers, perfonned infrequently or not at all.

Many discussions with peritoneal dialysis professionals convinced me that it would be desirable to design a test that is less precise but is very easy to perfonn (10). The availability of such a test might result in more widespread use of peritoneal transport testing with clinicians becoming familiar with the technique. The increased data base, together with the improved skills of the clinicans should offset any modest decrease in precision. Therefore, I considered a further simplication of the Peritoneal Equilibration Test by using a shorter (2 hour) dwell time and only dialysate to plasma ratio for urea or only dialysate glucose. The disadvantage of such a test would be the lack of internal control and the risk of a larger error in case of imprecise timing (10). As a further compromise I proposed a test that might be widely accepted due to its short time commitment and simplicity but with some internal control and smaller error in case of imprecise timing -the FAST Pet (11).

The test is standardized regarding the preceding exchange and the test exchange. Only one dialysate sample for glucose and creatinine is taken from the total drained dialysate after 4 hour dwell and a blood sample is taken at the end of the test exchange (II). Results are compared to those in Table IV. If the test is performed properly the values for glucose, creatinine, and drain volume should fall within the same ranges and transport categories. In diabetics with high serum glucose levels (>3OO mg/dl) the results of glucose concentration and drain volume are not useful for transport classification and are inconsistent with creatinine values permission) portrays creatinine dialysate to plasma ratios, dialysate volume, and creatinine clearance versus dwell time in patients with extremely low and high transport rates using dialysis solution with a 2.5% glucose concentration. In patients with low transport rates, peak ultrafitration occurs late during dwell time and net utlrafiltration is still obtained after a long dwell time. Also, D/P ratios increase almost linearly during the dwell, consequently clearances per exchange increase also almost linearly throughout the long dwell exchange. In these patients total dialysis time is crucial for adequate clearances and they benefit from continuous regimens such as CAPD or CCPD with diurnal exchanges. Because of a well maintained dialysate/plasma concentration gradient for an extended period during dwell, clearances per unit time are augmented relatively little by rapid exchange techniques such as IPD or tidal peritoneal dialysis (TPD). Consequently, intermittent techniques require long treatment times for adequate clearances. On the contrary , the patients with high peritoneal transport rates have poor ultrafiltration on standard CAPD with dwell times exceeding 4 hours. In these patients peak ultrafiltration occurs early during the dwell time and is followed by dialysate absorption. If dialysate is drained after a 4 hour dwell, there is minimal or no net ultrafiltration. Also, the mass transfer of small molecular weight solutes in long-dwell exchanges decreases proportionately with the reduction in drain volume. After several hours of dwell, the clearance per exchange is less than in patients with low peritoneal transport rates (crossing point in Figure 2). Reducing the dwell time in patients with Ultrafiltration and clearance patterns in relation to solute transport

Figure 2 (reproduced from reference lO, with high transport rates captures maximum ultrafiltration while maintaining near complete equilibration of small molecular weight solutes and so increases net solute removal. These patients benefit from techniques utilizing rapid exchanges and may achieve adequate clearances with intermittent peritoneal dialysis regimens of relatively short duration. Patients with transport rates between these two extremes have intermediate patterns.

Prognostic values of baseline equilibration test

Table V summarizes the prognostic usefulness of the baseline peritoneal equilibration test. The patients with high peritoneal transport are ideal candidates for regimens with short dwell exchanges (NIPD, NTPD, DAPD)I. The patients with high average transport are excellent candidates for any peritoneal dialysis prescription. Most patients with low average peritoneal transport can be maintained on the standard dose CAPD; however, many of them may require a modified prescription (high dose CAPD, high dose CCPD) when residual renal function becomes negligible, particularly if they have high body surface area. These patients have excellent ultrafiltration with moderate dialysis solution glucose concentrations. Finally, patients with low peritoneal transport rates usually have excellent utltrafiltration with low dialysis solution glucose concentration and are very likely to develop symptoms of inadequate dialysis on standard CAPD when their residual renal function becomes negligible. These patients are not good candidates for regimens with short dwell exchanges.

PET versus clearances for determining peritoneal dialysis prescriptions

The PET is a simple and only approximate measure of peritoneal dialysis performance. It cannot completely replace clearance measurements but it is a useful guide in choosing dialysis prescription in the majority of patients. On the other hand clearance alone is insufficient as a guide for choosing regimen and technique (intermittent vs continuous, short vs long dwell exchanges) .Moreover, PET is very useful in diagnosing the cause of insufficient dialysis or ultrafiltration (9). The PET and clearance measurements are complementary studies which can guide in dialysis prescription.

Stepwise approach to PD prescription

Figure 3 presents stepwise approach to peritoneal dialysis prescription. Usually I start with a standard schedule of four 2 L exchanges in most patients. In patients with well preserved residual renal function (endogenous creatinine clearance >5.0 ml/min) the total dialysis solution inflow is decreased to below 7.5 L per day. The peritoneal equilibration test is performed in all patients and serves as a prognosticator of a patient's response to various peritoneal dialysis regimens.

The patient is followed closely and the prescription is modified to preferred when the residual renal function becomes negligible and/ or criteria of adequate dialysis are not fulfilled. If preferred prescription does not deliver adequate dialysis, daily creatinine clearance is measured and the prescription modified as needed. If dialysis is inadequate by clinical and laboratory criteria despite creatinine clearance over 40 L/week/ 1.73 m2 BSA, a higher dose of dialysis is recommended.

References

  1. Pendras JP , Erickson R V. Hemodialysis: a successful therapy for chronic uremia. Ann Intern Med 1966; 64: 293-311.
  2. De Palma JR, Abukurah A, Rubini ME: ' Adequacy' of haemodialysis. Proceedings of the European Dialysis and Transplant Association 1972; 9: 265 70.
  3. Twardowski Z. The adequacy of haemodialysis in treatment of chronic renal failure. Acta Med Pol 1974; 15: 227-43.
  4. Parker TF, Laird NM, Lowrie EG. Comparison of the study groups in the National Cooperative Dialysis Study and a description of morbidity, mortality, and patient withdrawal. Kidney Int 1983; 23 (SuppI13): S-42-S-49.
  5. Twardowski ZJ, Nolph KD. Opinion: Peritoneal dialysis-how much is enough? Seminars in Dialysis 1988; 1: 75-76.
  6. Boen ST, Haagsma-Schouten WAG, Birnie RJ .Longterm peritoneal dialysis and a peritoneal dialysisindex. Dial Transplant 1978; 7: 377-80.
  7. Twardowski ZJ , Nolph KD , Khanna R, Prowant BF , Ryan LP, Moore HL, Nielsen MP. Peritoneal equilibration test. Perit Dial Bu111987; 7: 138-47.
  8. Twardowski ZJ, Khanna R, Nolph KD. Peritoneal dialysis modifications to avoid CAPD dropouts. In: Khanna R, Nolph KD, Prowant B, Twardowski ZJ , Oreopoulos Do ed. Advances in Continuous Ambulatory Peritoneal Dialysis. Perit Dial Bull Inc 1987; 171-78.
  9. Twardowski ZJ .Clinical value of standardized equilibration tests in CAPD patients. Blood Purif 1989; 7: 95-108.
  10. Twardowski ZJ .Nightly peritoneal dialysis ( why? who? how? and when?). ASAIO Transactions 1990; 36: 8-16.
  11. TwardowskiZJ. The Fast-PET. Seminars in Dialysis. 1990; 3: (In press). 1 See page 47 for Peritoneal Dialysis Glossary.
Corresponding author:
Zbylut J. Twardowski M.D. , Division of Nephrology, MA 436 Health Sciences Center, University of Missouri, Columbia, MO 65212, U.S.A.