Determinants of Dose

Peritoneal dialysis dose can be prescribed empirically and is based on the amount of residual renal function, a patient’s weight and lifestyle constraints.

Residual renal function

The PD prescription should account for residual renal function (RRF). The 2006 KDOQI Updates state that the recommended dialysis dose incorporates the total renal and peritoneal contribution to solute clearance in terms of Kt/Vurea, with a recommended minimum weekly delivered dose of at least 1.7  The recommendations to include RRF are based on a number of studies in PD patients that have demonstrated that RRF independently predicts survival (2–6). In the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD), each 1-unit increase in renal Kt/Vurea produced a 66% decrease in the relative risk of death (5). In patients with preserved RRF, increasing the dialysis dose did not result in any significant improvement in patient outcome. This study also demonstrated that the presence of RRF had an impact on quality of life in PD patients, and was associated with improved physical functioning. Kidney disease symptoms and sleep disorders were also diminished.

In patients who’s RRF does not allow them to achieve the weekly Kt/Vurea target, it is necessary to increase the peritoneal clearance of urea such that the total clearance (peritoneal plus renal) meets or surpasses a minimum total weekly Kt/Vurea of 1.7. As indicated above, the required peritoneal dose (Kpt/Vurea)depends on the RRF and hence renal clearance (Krt/Vurea).  The principal methods to increase Kpt/Vurea in these patients include increasing dwell volumes or increasing frequency of exchanges(6).Although both strategies are similarly effective in increasing Kpt/Vurea, increasing the frequency of exchanges may enhance ultrafiltration to a greater degree. However, increasing the dwell volume is generally preferred unless there are mechanical contraindications. In addition, since adherence to CAPD prescriptions with five daily exchanges is poor, this strategy may be associated with worse quality of life and be more costly. Thus, when more exchanges are needed for increased ultrafiltration, APD is warranted.

Body volume or surface area

Body mass is associated with increased generation of creatinine and urea, and by definition affects normalized clearances. Increasing values of body volume (V) with concomitant decreases in the Krt/V and Kpt/V values will require greater peritoneal clearances.

Estimating Total Body Water and Body Surface Area
V (total body water) can be estimated by either the Watson (7) or Hume (8){C}{C}{C}{C} method in adults using actual body weight (Wt).

Watson method*:
For Men: V=2.447-(0.09516 x Age)+(0.1074 x Height)+(0.3362 x Weight)
{C}{C}{C}{C}
For Women*: V=-2.097+(0.1069 x Height)+(0.2466 x Weight)

Hume method*:
For Men: V= -14.012934+(0.296785 x Weight)+(0.194786 x Height)
For Women: V= -35.270121+(0.183809 x Weight)+(0.344547 x Height)

*Volume in liters, Age in years, Height in centimeters, weight in kilograms.

Body surface area, BSA, values might be needed for calculating clearances (L/wk/1.73 m2 of BSA) or RRF clearances (mL/min/1.73 m2 of BSA) and should be estimated using the DuBois and DuBois method (9), the Gehan and George method (10), or the Haycock method (11)using actual body weight.

For all formulae below, BSA is in square meters (m2), weight is in kilograms, and height is in centimeters.

DuBois and DuBois method: BSA=0.007184 x Weight0.425 x Height0.725
Gehan and George method: BSA=0.0235 x Weight0.51456 x Height0.42246
Haycock method: BSA=0.024265 x Weight0.5378 x Height0.3964

Unfortunately, the relationship between the calculations for V and BSA is not linear (12). When BSA increases linearly as obesity develops, V increases exponentially. There are gender differences in these relationships as well (13). For the same height and BSA, males have a larger V than females.

Example
If the Krt/Vurea is 1.5 per week, then according to the KDOQI recommendation of a total weekly Kt/Vurea of 1.7, only 0.2 Kpt/Vurea is needed per week. Assuming complete urea equilibration (serum to dialysate) at 6 hours, a single 2-L overnight exchange would contribute 14 L per week. If V is 40 L, this contributes a Kpt/Vurea of 14/40 or 0.35 per week. Any ultrafiltrate would add further to total solute removal. That, plus the Krt/Vurea of 1.5, brings the Kprt/Vurea to at least 1.85 satisfying the target requirement.

Lifestyle constraints

The peritoneal dialysis modality impacts adherence and quality of life, which are important considerations in writing a PD prescription. Psycho-social indications such as work, school, social conflicts, the need for a caregiver, and the inability to tolerate large ambulatory volumes should be taken into account prior to initiating PD. Whatever the choice, the patient’s preferences should be a major determinant of the strategy to be undertaken. If patients have concerns about tolerating increased dwell volumes in either CAPD or APD, consideration should be given to increasing nighttime dwell volumes initially since increases in intraperitoneal pressure (IPP) are less for a given dwell volume in the supine or recumbent position compared with either sitting or standing.

Peritoneal transport

One of the predominant determinants of small solute clearance is peritoneal transport. Higher peritoneal transport leads to higher clearances, all other prescription factors being the same. However, peritoneal glucose absorption is also increased and consequently, the osmotic gradient diminishes resulting in reduced ultrafiltration in high transport states. Various studies suggest that high peritoneal transport states are associated with a higher risk of death than low and low average transport. See also Prognostic Value of Transport Status.

References

  1. K/DOQI Clinical practice guidelines for peritoneal adequacy, update 2006. Am J Kidney Dis. 2006;48 Suppl 1:S91-S97. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16813997.
  2. Bargman JM, Thorpe KE, Churchill DN. Relative contribution of residual renal function and peritoneal clearance to adequacy of dialysis: a reanalysis of the CANUSA study. J Am Soc Nephrol. 2001;12(10):2158-2162. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11562415.
  3. Paniagua R, Amato D, Vonesh E, Correa-Rotter R, Ramos A, Moran J, Mujais S. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol. 2002;13(5):1307-1320. Available from: http://www.ncbi.nlm.nih.gov/pubmed/11961019.
  4. Diaz-Buxo JA, Lowrie EG, Lew NL, Zhang SM, Zhu X, Lazarus JM. Associates of mortality among peritoneal dialysis patients with special reference to peritoneal transport rates and solute clearance. Am J Kidney Dis. 1999;33(3):523-534. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10070917.
  5. Termorshuizen F, Korevaar JC, Dekker FW, van Manen JG, Boeschoten EW, Krediet RT. The relative importance of residual renal function compared with peritoneal clearance for patient survival and quality of life: an analysis of the Netherlands Cooperative Study on the Adequacy of Dialysis (NECOSAD )-2. Am J Kidney Dis. 2003;41(6):1293-1302. Available from: http://www.ncbi.nlm.nih.gov/pubmed/12776283.
  6. Blake P, Burkart JM, Churchill DN, Daugirdas J, Depner T, Hamburger RJ, Hull AR, Korbet SM, Moran J, Nolph KD. Recommended clinical practices for maximizing peritoneal dialysis clearances. Perit Dial Int. 1996;16(5):448-456. Available from: http://www.ncbi.nlm.nih.gov/pubmed/8914175.
  7. Watson PE, Watson ID, Batt RD. Total body water volumes for adult males and females estimated from simple anthropometric measurements. Am J Clin Nutr. 1980;33(1):27-39. Available from: http://www.ncbi.nlm.nih.gov/pubmed/6986753.
  8.  Hume R, Weyers E. Relationship between total body water and surface area in normal and obese subjects. J Clin Pathol. 1971;24(3):234-238. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=476961&tool=pm….
  9. Du Bois D, Du Bois E. Clinical calorimetry: Tenth paper a formula to estimate the approximate surface area if height and weight be known. Arch Intern Med. 1916;17(6_2):863-871. Available from: http://dx.doi.org/10.1001/archinte.1916.00080130010002.
  10.  Gehan EA, George SL. Estimation of human body surface area from height and weight. Cancer Chemother Rep. 1970;54(4):225-235. Available from: http://www.ncbi.nlm.nih.gov/pubmed/5527019.
  11. Haycock GB, Schwartz GJ, Wisotsky DH. Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults. J Pediatr. 1978;93(1):62-66. Available from: http://www.ncbi.nlm.nih.gov/pubmed/650346.
  12. Gotch FA, Keen ML. Kinetic Modeling in Peritoneal Dialysis. In: Nissenson AR, Fine RN, eds. Clinical Dialysis. 4th ed. New York: McGraw-Hill Medical Publication; 2005:385-420.
  13. Tzamaloukas AH, Malhotra D, Murata GH. Gender, degree of obesity, and discrepancy between urea and creatinine clearance in peritoneal dialysis. J Am Soc Nephrol. 1998;9(3):497-499. Available from: http://www.ncbi.nlm.nih.gov/pubmed/9513914.

P/N 102491-01 Rev. A 07-2015