PD and the Diabetic Patient

Diabetes is the most common cause of end stage renal disease in The United States, accounting for approximately half of all incident dialysis patients1. The vast majority of these patients dialyze using thrice weekly hemodialysis, while only 4.5% use peritoneal dialysis (PD) for renal replacement therapy1. The diabetic patient with ESRD presents many therapeutic challenges, some of which are particularly applicable when PD is selected as the mode of renal replacement therapy (RRT). Though diabetes per se is not a contraindication for PD, the low utilization of PD in diabetics may be due to several perceived therapeutic challenges, including with fluid management, metabolic control (e.g., dyslipidemia, blood sugar) and peritoneal membrane transport characteristics2-8. Despite peritoneal satisfactory ultrafiltration, diabetic patients may have difficulty mobilizing fluid from the interstitial compartment due to low oncotic pressure, since a significant number have proteinuria at the time of initiation of dialysis. Survival data have been inconsistent in this population, with observational studies showing both higher and lower mortality in diabetics using PD, depending on age, gender, and other factors9-12.

Peritoneal Membrane Transport in Diabetic Patients

Peritoneal membrane transport is an important consideration when using PD and plays a role in achieving adequate ultrafiltration (UF). Among diabetic patients, Serlie et al. reported lower transcapillary ultrafiltration (TCUF) compared with non-diabetics, matched for age, sex and duration of continuous ambulatory peritoneal dialysis (CAPD), shortly after initiation of PD6. However, no significant difference was observed one year later. These results suggest that long-term exposure to high glucose concentrations in diabetics prior to CAPD may cause changes in the capillary wall aquaporins, similar to those observed after prolonged exposure to high glucose concentration in non-diabetics. These findings may explain the published discrepancies on the presence or absence of increased peritoneal permeability among diabetic patients13-17. It is possible that differences were observed when diabetics were compared to non-diabetics early in the course of the disease, but not after many years of therapy when both groups could have had abnormally high permeability.

Abnormally high leakage of albumin across capillary walls is also characteristic of diabetic microvascular disease. This increase in capillary permeability is not confined to the renal or retinal capillaries and has been documented in the peritoneal capillaries as well6. Shostak and Gotloib have demonstrated increased permeability in the peritoneal capillaries of diabetic rats, and Krediet et al. have made similar observations in humans18,19. This may be due to a reduction in the fixed negative charges of the capillary basement membrane.

High peritoneal transport inversely correlates with serum albumin concentration (SAC)20, which is a powerful marker of mortality21,22. Nakamoto et al. have confirmed that high peritoneal membrane transport and protein permeability are more common among diabetic patients undergoing PD23. Similarly, Cueto-Manzano, et al. have reported that diabetes mellitus (DM) is significantly more frequent among high transporters and is less frequently associated with low transport24. In their univariate analysis, high peritoneal transport rate, DM, low serum creatinine, low albumin and older age significantly predicted mortality. However, in the multivariate analysis, only DM, low serum creatinine and high peritoneal transport rate were shown as mortality risk factors. Among non-diabetics, high transport did not affect survival. The most important risk factor was DM rather than high peritoneal transport. No difference in peritoneal transport was observed between type I and type II diabetic patients matched for gender, duration of PD and clinical characteristics24.

Despite these issues, many clinicians favor PD in diabetics due to lower infection rates, fewer episodes of hypotension, and the possibility of better residual renal function preservation25.

 References:

  1. U S Renal Data System, USRDS 2012 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2012.
  2. Cotovio P, Rocha A, Rodrigues A. Peritoneal dialysis in diabetics: there is room for more. Int J Nephrol. 2011;2011:914849. Epub 2011 Oct 16.
  3. Kuriyama S. Peritoneal dialysis in patients with diabetes: are the benefits greater than the disadvantages? Perit Dial Int. 2007 Jun;27 Suppl 2:S190-5.
  4. Yao Q, Lindholm B, Heimbürger O. Peritoneal dialysis prescription for diabetic patients. Perit Dial Int. 2005 Feb;25 Suppl 3:S76-9.
  5. Lin JJ, Wadhwa NK, Suh H, Cabralda T, Patlak CS. Increased peritoneal solute transport in diabetic peritoneal dialysis patients. Adv Perit Dial. 1995;11:63-6.
  6. Serlie MJM, Struijk DG, de Blok K, Krediet RT Differences in fluid and solute transport between diabetic and nondiabetic patients at the onset of CAPD. Adv Perit Dial. 1997;13:29-32.
  7. Davenport A, Willicombe MK. Does diabetes mellitus predispose to increased fluid overload in peritoneal dialysis patients? Nephron Clin Pract 114:c60-6, 2010
  8. Gan HB, Chen MH, Lindholm B, Wang T. Volume control in diabetic and nondiabetic peritoneal dialysis patients. Int Urol Nephrol. 2005;37(3):575-9.
  9. Held PJ, Port FK, Turenne MN, Gaylin DS, Hamburger RJ, Wolfe RA. Continuous ambulatory peritoneal dialysis and hemodialysis: comparison of patient mortality with adjustment for comorbid conditions. Kidney Int. 1994 Apr;45(4):1163-9.
  10. Nelson CB, Port FK, Wolfe RA, Guire KE. Comparison of continuous ambulatory peritoneal dialysis and hemodialysis patient survival with evaluation of trends during the 1980s. J Am Soc Nephrol. 1992 Nov;3(5):1147-55.
  11. Schaubel DE, Fenton SS. Trends in mortality on peritoneal dialysis: Canada, 1981-1997. J Am Soc Nephrol. 2000 Jan;11(1):126-33.
  12. Fang W, Yang X, Kothari J, Khandelwal M, Naimark D, Jassal SV, Bargman J, Oreopoulos DG. Patient and technique survival of diabetics on peritoneal dialysis: one-center’s experience and review of the literature. Clin Nephrol. 2008 Mar;69(3):193-200.
  13. Graff J, Fugleberg S, Nielsen SL, Feldt-Rasmussen B. Transperitoneal transport in diabetic and non-diabetic patients on peritoneal dialysis. Clin Physiol. 1999 Nov;19(6):510-8.
  14. Procaccini DA, Querques M, Tappi A, Strippoli P. Peritoneal clearances. Long-term study. ASAIO Trans. 1988 Jul-Sep;34(3):437-40.
  15. Lee HB, Park MS, Chung SH, Lee YB, Kim KS, Hwang SD, Moon C. Peritoneal solute clearances in diabetics. Perit Dial Int. 1990;10(1):85-8.
  16. Lamb EJ, Worrall J, Buhler R, Harwood S, Cattell WR, Dawnay AB. Effect of diabetes and peritonitis on the peritoneal equilibration test. Kidney Int. 1995 Jun;47(6):1760-7.
  17. Rumpsfeld M, McDonald SP, Purdie DM, Collins J, Johnson DW. Predictors of baseline peritoneal transport status in Australian and New Zealand peritoneal dialysis patients. Am J Kidney Dis. 2004 Mar;43(3):492-501.
  18. Shostak A, Gotloib L. Increased peritoneal permeability to albumin in streptozotocin diabetic rats. Kidney Int. 1996 Mar;49(3):705-14.
  19. Krediet RT, Zuyderhoudt FMJ, Boeschoten EW, Arisz L. Peritoneal permeability to proteins in diabetic and non_diabetic continuous ambulatory peritoneal dialysis patients. Nephron. 1986;42(2):133-40.
  20. 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 Mar;33(3):523-34.
  21. Chung SH, Han DC, Noh H, Jeon JS, Kwon SH, Lindholm B, Lee HB. Risk factors for mortality in diabetic peritoneal dialysis patients. Nephrol Dial Transplant. 2010. Retrieved August 6, 2010 from http://www.ncbi.nlm.nih.gov.go.libproxy.wfubmc.edu/pubmed/20466690.
  22. Lowrie EG, Huang WH, Lew NL. Death risk predictors among peritoneal dialysis and hemodialysis patients: A preliminary comparison. Am J Kidney Dis. 1995 Jul;26(1):220-8.
  23. Nakamoto H, Imai H, Kawanishi H, Nakamoto M, Minakuchi J, Kumon S, Watanabe S, Shiohira Y, Ishii T, Kawahara T, Tsuzaki K, Suzuki H: Effect of diabetes on peritoneal function assessed by personal dialysis capacity test in patients undergoing CAPD. Am J Kidney Dis. 2002 Nov;40(5):1045-54.
  24. Cueto-Manzano AM, Correa-Rotter R: Is high peritoneal transport rate an independent risk factor for CAPD mortality? Kidney Int. 2000 Jan;57(1):314-20.
  25. Passadakis PS, Oreopoulos DG. Diabetic patients on peritoneal dialysis. Semin Dial. 2010 Mar-Apr;23(2):191-7.

P/N 101809-01 Rev A 08/2014