Diabetes is one of the primary causes of end stage renal disease (ESRD) with roughly 40% of CKD patients presenting with diabetes, deeming itself to be an important condition in the ESRD populations (1). Compared to non-diabetic patients, diabetic patients have a higher risk for comorbidities and complications, including cardiovascular disease, inadequate fluid balance, a decreased quality of life, and a decline in reserved renal function (2,3). Diabetic patients also suffer from worse outcomes related to morbidity and mortality along with high technique failure rates after dialysis initiation (2,4). When determining a peritoneal dialysis (PD) prescription for a diabetic patient, all of these parameters must be taken into consideration. 

Regarding dialysis adequacy, the K/DOQI workgroup recommends a target Kt/Vurea of at least 1.7 per week in all PD patients (5). In the ADEMEX study, which evaluated PD prescription outcomes based on clearance, the diabetic subgroup had identical results to the whole group demonstrating that diabetic patients could potentially follow the K/DOQI recommendations for Kt/Vurea targets (6). Overall, the Kt/Vurea should be tailored to each individual patient’s response.  

The PD prescription for all patients, including diabetic patients should be based on the treatment goals for the individual patient, kinetic modelling, and patient’s preference. Clinical evaluation including hydration, nutrition, hypertension, and glycemic control should be incorporated. The four main factors that affect peritoneal clearance are patient transport type, total dialysate volume, dwell time, and ultrafiltration volume. When evaluating the PD prescription one month after starting on PD, the recommended test must be used to measure peritoneal transport, ultrafiltration, and clearance. The most common tests are the Peritoneal Equilibration Test, or PET, and a 24-hour batch collection. The PET measures transport status and ultrafiltration while the 24-hour batch measures peritoneal clearance, residual renal function, and ultrafiltration. It can also monitor nutritional status (7).  

The management of volume in patients with diabetes on peritoneal dialysis is affected by several factors, including the degree of residual renal function, peritoneal membrane small-solute transport, salt and water intake, blood sugar control, comorbidity, and nutritional status. 

• As with non-diabetic PD patients, transport type in diabetics is patient-specific and should be considered when determining appropriate dwell times for clearance and ultrafiltration.   
• With dialysate volume, more volume can help to increase urea clearance. Volume can be adjusted by increasing the number of exchanges or the volume of individual dwells.  
• Individualizing dwell times for maximal UF is critical. Dwell time should be based on transport type and clinical needs. Based on the modeled ultrafiltration profiles of an average transporter, the peak ultrafiltration times vary from 3 hours, with 1.5% dextrose solution, to 6 hours with 4.25% dextrose solution (8). Most of the diabetic patients tend to be high transporters and have been shown to have evidence of intraperitoneal inflammation (9) and do less well on continuous ambulatory peritoneal dialysis (CAPD) (10). The principal strategies to manage the prescriptions for diabetic’s patients may include the use APD to deliver shorter dwell times as well as higher dialysate glucose concentrations to avoid reabsorption of fluid. Additionally, the studies have showed that compared with CAPD, APD might reduce glucose fluctuation in diabetic PD patients (11,12).  
• Dialysate glucose may be increased to augment UF; however, this needs to be done cautiously because of concerns regarding glucose exposure in these patients. Glucose as an osmotic agent is associated with hyperglycemia, hyperinsulinemia, and obesity, and is a poor option in diabetics because glucose is rapidly absorbed (13). It is important to note that the ratio of net UF volume per gram of glucose absorbed is higher with short cycles than with the longer cycles of CAPD (14). Average systemic glucose absorption from repeated exposure to PD solutions ranges between 100 and 300 g/day (8). The caloric intake from a CAPD regimen can be estimated by multiplying the amount of total glucose absorbed (60–80%) by 3.7 (conversion factor for gram to kcal). Whereas, the caloric intake from shorter automated PD dwells is estimated to be lower at 40–50% (15).  Thus, adjusting the dextrose strength of the dialysate can help achieve optimal UF; and, when appropriate, icodextrin can be considered for long dwells.  
• Icodextrin is an alternative PD solution osmotic agent which lacks the metabolic effects of glucose, is absorbed slower than glucose, and allows for prolonged peritoneal ultrafiltration with enhanced fluid removal (3,13). The modification of the prescription by including the use of an icodextrin exchange during the day may provide sustained UF over a longer dwell, despite the fast transport status, because it makes use of the effectively increased peritoneal surface area in this patient population (16). Thus, icodextrin has been suggested to be an appropriate osmotic agent in diabetic patients due to its ability to reduce serum insulin levels, improve insulin sensitivity, and better control glucose in diabetic patients (2,13).  

Euvolemia is an important adequacy parameter in peritoneal dialysis (PD) patients. Diabetic peritoneal dialysis patients have been reported to have faster peritoneal solute transport and may be at risk of reduced ultrafiltration volumes, leading to fluid overload. It is also suggested that diabetic peritoneal dialysis patients have an expanded extracellular volume (17).  An important aspect of fluid balance in PD patients is sodium removal. Sodium removal is largely dependent on sodium sieving and ultrafiltration rate. Additionally, sodium removal correlates heavily with ultrafiltration volume for all solution types. Sodium sieving occurs particularly when using high glucose concentrations. Sieving impairs sodium removal in too short cycles, and reabsorption in too long cycles. Thus, maximizing the PD prescription for time to peak UF also maximizes sodium removal.  

Furthermore, the adjustment of the prescription for diabetic PD patients should be based on frequent blood glucose determinations and hemoglobin A1c (HA1c). Therapeutic actions that include stepwise addition of oral hypoglycemic agents and insulin, based on individual assessment of PD patients should be considered to manage the hyperglycemia. In addition to peritoneal dialysis prescription adjustments, it may be necessary to incorporate dietary counseling such as dietary salt and fluid restriction may help reduce the use of hypertonic glucose solution and thus facilitate the blood glucose control in diabetic patients undergoing peritoneal dialysis. Also, oral nutritional supplements, hypolipidemic drugs for control of serum lipids, and education on the limitation of simple sugars and saturated fats depending on the patient’s nutritional status (18,19). Reduction of urinary and peritoneal protein loss and preservation of RRF with early initiation of ACEIs or ARBs after the start of PD therapy are also important. A decrease in proteinuria with the use of angiotensin converting enzyme inhibitors (ACEIs) in patients with diabetic nephropathy is well recognized (20,21). With better glycemic control, improved nutrition, improved fluid balance, may aid in preservation of residual renal function. 

 References:

1. United States Renal Data System. 2016 USRDS Annual Data Report: Epidemiology of Kidney Disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, 2016.; 2016. 
2. Yao Q, Lindholm B, Heimbürger O. Peritoneal dialysis prescription for diabetic patients.Perit Dial Int. 2005;25 Suppl 3:S76-9. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16048263. 
3. Kuriyama S. Peritoneal dialysis in patients with diabetes: are the benefits greater than the disadvantages?Perit Dial Int. 2007;27 Suppl 2:S190-5. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17556303. 
4. Cotovio P, Rocha A, Rodrigues A. Peritoneal dialysis in diabetics: there is room for more.Int J Nephrol. 2011;2011:914849. Available from: http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3195540&tool=pmcentrez&rendertype=abstract. 
5. K/DOQI Clinical practice guidelines for peritoneal adequacy, update 2006.Am J Kidney Dis. 2006;48 Suppl 1:S91-7. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16813997. 
6. Paniagua R, Amato D, Vonesh E, et al. 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. 
7. Hemodialysis Adequacy Peritoneal Dialysis Adequacy Vascular Access A Curriculum for CKD Risk Reduction and Care Kidney Learning System (KLS)TM2006 Updates Clinical Practice Guidelines and Recommendations. Available from: www.kidney.org. 
8. Danielski M, Ikizler TA, McMonagle E, et al. Linkage of hypoalbuminemia, inflammation, and oxidative stress in patients receiving maintenance hemodialysis therapy.Am J kidney Dis. 2003;42(2):286-294. 
9. Lambie M, Chess J, Donovan KL, et al. Independent effects of systemic and peritoneal inflammation on peritoneal dialysis  survival.J Am Soc Nephrol. 2013;24(12):2071-2080. 
10. Brimble KS, Walker M, Margetts PJ, Kundhal KK, Rabbat CG. Meta-analysis: peritoneal membrane transport, mortality, and technique failure in peritoneal dialysis.J Am Soc Nephrol. 2006;17(9):2591-2598. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16885406. 
11. Skubala A, Zywiec J, Zełobowska K, Gumprecht J, Grzeszczak W. Continuous glucose monitoring system in 72-hour glucose profile assessment in patients with end-stage renal disease on maintenance continuous ambulatory peritoneal dialysis.Med Sci Monit. 2010;16(2):CR75-83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20110918. 
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13. Paniagua R, Ventura M-J, Avila-Díaz M, et al. Icodextrin improves metabolic and fluid management in high and high-average transport diabetic patients.Perit Dial Int. 2009;29(4):422-432. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19602608. 
14. Twardowski ZJ, Nolph KD, Khanna R, Gluck Z, Prowant BF, Ryan LP. Daily clearances with continuous ambulatory peritoneal dialysis and nightly peritoneal dialysis.ASAIO Trans. 1990;32(1):575-580. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3778773. 
15. Heimbürger O, Waniewski J, Werynski A, Lindholm B. A quantitative description of solute and fluid transport during peritoneal dialysis.Kidney Int. 1992;41(5):1320-1332. Available from: http://www.ncbi.nlm.nih.gov/pubmed/1614047. 
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17. Davenport A, Willicombe MK. Does Diabetes Mellitus Predispose to Increased Fluid Overload in Peritoneal Dialysis Patients?Nephron Clin Pract. 2010;114(1):c60-c66. Available from: https://www.karger.com/DOI/10.1159/000245070. 
18. Rocco M V, Ikizler TA. Nutrition. In: Daugirdas JT, Blake PG, Ing TS, eds.Handbook of Dialysis. 4th ed. Lippincott Williams & Wilkins; 2015:535-554. 
19. Tzamaloukas AH, Friedman EA. Diabetes. In: Daugirdas J, Blake PG, Ing T, eds.Handbook of Dialysis. 4th ed. Lippincott Williams & Wilkins; 2007:490-507. 
20. Viberti G, Mogensen CE, Groop LC, Pauls JF. Effect of captopril on progression to clinical proteinuria in patients with  insulin-dependent diabetes mellitus and microalbuminuria. European Microalbuminuria Captopril Study Group.JAMA. 1994;271(4):275-279. 
21. Weidmann P, Boehlen LM CM et al. Effects of different antihypertensive drugs on human diabetic proteinuria.Nephrol Dial Transpl. 1993;8(5824). 

P/N 102539-01 Rev A 03/2020