Dialysis in diabetic nephropathy

Author 
Lionel U Mailloux, MD, FACP 

Section Editors 
Jeffrey S Berns, MD 
David M Nathan, MD 

Deputy Editor 
Alice M Sheridan, MD 

Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Oct 2013. | This topic last updated: Sep 4, 2012.

INTRODUCTION  — Although the development and progression of diabetic nephropathy may be retarded by normalization of the blood pressure (preferably with an angiotensin converting enzyme inhibitor) and strict control of the plasma glucose concentration, many patients still progress to end-stage renal disease [ 1-3 ]. Important determinants of progression include the severity of histologic disease and the absolute amount of proteinuria [ 4 ].

Diabetes is the most common cause of new patients requiring renal replacement therapy, accounting for approximately 45 percent of cases in the United States [ 5,6]. Although less frequent in other countries, 34 and 30 percent of incident dialysis patients have diabetes in Germany and Australia, respectively [ 7 ]. An increasing incidence has also been noted in non-German European countries, as reported from data from 10 registries in Europe [ 8 ]. However, the incidence appears to have stabilized in Denmark, which may be due to the widespread implementation of intensive renoprotective measures [ 9 ].

In the United States and Puerto Rico, although the total number of total number of patients who develop end-stage renal disease due to diabetes continues to increase, the risk of developing end-stage renal disease appears to be decreasing among patients who have diabetes [ 6 ]. Although the reasons for the decline in risk are not known, improved glycemic and blood pressure control and the use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may play a role [ 2,6,10 ].

PATIENT SURVIVAL  — Patient survival in diabetics on maintenance dialysis is lower than that seen in nondiabetics with end-stage renal failure due to chronic glomerular disease or hypertension [ 5,11,12 ]. As noted in the 2009 USRDS database, only approximately 30 percent of patients with diabetes survived five years after initiation of hemodialysis [ 13 ]. Survival also varies inversely with age, being best in young patients with good blood pressure control and no clinically evident cardiac disease [ 5,14 ].

However, these survival data may be overly optimistic as it is based upon information from the United States Renal Data system, a data base that excludes patients who have died within the first 90 days of the initiation of dialysis. When such individuals are included in mortality studies, the survival rate of diabetics requiring dialysis remains poor, even in dialysis centers located in countries with relatively high survival rates. As an example, among 84 consecutive patients with type 2 diabetes requiring dialysis in a center in France, 27 (32 percent) died at a mean follow-up of 211 days [ 15 ].

Cardiovascular disease is the most common cause of death, accounting for more than one-half of cases [ 16-18 ]. In addition to the presence of significant cardiovascular disease prior to the initiation of dialysis, the tissue deposition of advanced glycosylation end products (AGEs) may also enhance cardiovascular mortality once dialysis is begun. (See "Patient survival and maintenance dialysis" and "Overview of diabetic nephropathy" .)

The adequacy of dialysis and a decrease in nutritional status may also be contributors to the worse outcome in diabetics. The morbidity associated with insufficient dialysis in diabetics may be mediated through anorexia, leading to decreased caloric and protein intake. The potential importance of malnutrition is suggested by the observation that the increase in mortality (when compared to nondiabetics) largely disappears if reductions in the plasma albumin and creatinine concentrations (that primarily reflect inadequate intake) are taken into account [ 19 ]. (See "Kt/V and the adequacy of hemodialysis" and "Assessment of nutritional status in end-stage renal disease" .)

Death by withdrawal from dialysis is also more likely to occur in patients with diabetes [ 20,21 ]. (See "Patient survival and maintenance dialysis" and "Withdrawal from and withholding of dialysis" .)

DIALYSIS VERSUS RENAL TRANSPLANTATION  — In the 2009 USRDS report relating to diabetics with end-stage renal disease, adjusted patient survival at five years after kidney transplantation in diabetics ranged from 67 to 77 percent at five years [ 13 ]. These less than optimal results, due largely to extrarenal vascular disease, are still markedly better than those seen with either hemodialysis or peritoneal dialysis, which is approximately 30 percent at five years [ 13 ]. Transplantation is also associated with a better quality of life and a higher degree of rehabilitation [ 22,23 ]. Because of these substantial benefits, renal transplantation should be offered to any suitable diabetic patient with end-stage renal disease. (See "Renal transplantation in diabetic nephropathy" .)

Some of the benefit associated with renal transplantation is clearly related to patient selection. Those patients who receive a transplant are usually younger and less likely to have type 2 diabetes or extrarenal vascular disease. However, the improved outcome with transplantation is seen even if the evaluation of dialyzed patients is limited to relatively healthy subjects who are candidates for transplantation (but not transplanted for some reason). Thus, factors in addition to selection bias must also be important. It is possible, for example, that the restoration of near normal renal function following transplantation retards the progression of microvascular disease by reducing the circulating levels of advanced glycosylation end products (as noted previously) [ 24 ]. This mechanism of possible benefit has been difficult to prove. (See "Patient survival after renal transplantation" .)

HEMODIALYSIS VERSUS PERITONEAL DIALYSIS  — Choice of a dialysis modality in diabetics is dependent in part upon the following factors which apply to nondiabetics as well.

Comorbid conditionsHome situationIndependence and motivation of the patientAbility to tolerate volume shifts — Diabetic patients with autonomic neuropathy are often more likely to have hypotensive episodes during hemodialysis. (See"Hemodynamic instability during hemodialysis: Overview" .) Fluid removal is more gradual with peritoneal dialysis and therefore hypotension is not a problem unless the patient becomes volume depleted.Status of the vasculature and/or abdomen — Older patients with type 2 diabetes are more likely to have severe peripheral vascular disease that limits the ability to create and sustain adequate vascular access for hemodialysis. Unfortunately, these are often the same patients who are unable to perform peritoneal dialysis due to concomitant illnesses.Risk and history of infection

Among diabetics with adequate manual dexterity and visual acuity, we continue to recommend peritoneal dialysis as an option for maintenance dialysis. Diabetic patients with unstable cardiac hemodynamics, severe vascular disease, and/or advanced neuropathy are most often treated with in-center hemodialysis. Few studies have specifically analyzed the efficacy of peritoneal dialysis in these patients. Very few diabetic patients choose home hemodialysis which is generally associated with the highest survival rates. (See "Home hemodialysis" .)' and (see "Outcomes associated with nocturnal hemodialysis" ).

Survival  — If dialysis is required, most studies, after adjustment for comorbid factors, have NOT found a survival difference between hemodialysis and peritoneal dialysis in diabetic patients [ 25,26 ].

Initial reports suggested that peritoneal dialysis was associated with a better outcome [ 16,27-31 ]. In the Michigan experience, the risk ratio for mortality for diabetics treated with peritoneal dialysis was 0.40 to 0.70 when compared to diabetics treated with hemodialysis [ 27,31 ].In contrast, data from the USRDS case-mix study suggest that mortality may actually be increased in diabetic patients treated with peritoneal dialysis rather than hemodialysis. One report found that the increase in risk was limited to elderly diabetic patients, who may have had more underlying peripheral vascular disease [ 32 ]. A subsequent study of prevalent patients for three successive years found that patients treated with peritoneal dialysis had a 19 percent higher mortality rate than any form of hemodialysis: this increase in risk was greatest in diabetics of any age and in nondiabetics above age 55 [ 33 ]. 

There are, however, potential problems with these data. They were obtained at a time when the delivery of dialysis was inadequate, the importance of residual renal function was poorly understood, and the importance of comorbid conditions was not taken into account.A subsequent very large study attempted to assess the impact of multiple risk factors, including diabetes, on survival after initiation of either hemodialysis or peritoneal dialysis. Utilizing data from 398,940 patients who initiated dialysis between the years 1995 to 2000, some patient characteristics included the following: 12 percent used PD for initial therapy; 45 percent were diabetic; 51 percent were older than 65 years of age, and 55 percent had at least one comorbidity [ 34 ]. Mortality risk was significantly higher on hemodialysis than PD among younger diabetics with no comorbidity (1.22, age between 18 and 44 years). By comparison, hemodialysis was associated with a lower mortality risk in older diabetics with either no comorbidity (RR of 0.92 and 0.86 for ages 45 to 64 and greater than 65 years, respectively) or a baseline comorbidity (0.82 and 0.80 for ages 45 to 64 and greater than 65 years, respectively). No difference in survival with either modality was observed among younger diabetic patients with baseline comorbidity.

Few diabetic patients perform home hemodialysis, the single modality with the highest patient survival rate [ 35 ]. (See "Home hemodialysis" .)

INSULIN THERAPY IN PERITONEAL DIALYSIS  — Maintenance of glycemic control in diabetic patients with end-stage renal disease may be complicated by a variety of factors that either increase or decrease insulin requirements. More insulin may be required because of insulin resistance and the glucose load absorbed from the hypertonic dialysate. A 1.5 percent dialysate solution, for example, has a glucose concentration of 1500 mg/dL (83 mmol/L), well above that in the plasma. On the other hand, less insulin is often required because of decreased carbohydrate intake (if the patient is inadequately dialyzed) and prolongation of the duration of action of insulin resulting from reduced renal and hepatic clearance. (See "Carbohydrate and insulin metabolism in chronic kidney disease" .)

A discussion of the use of various agents to maintain serum glucose levels in peritoneal dialysis patients is presented separately. (See "Management of hyperglycemia in diabetics with end-stage renal disease" .)

DIALYSIS DOSE AND ACCESS ISSUES

Dialysis dose and vascular access issues are discussed in detail separately. (See "Adequacy of peritoneal dialysis" and "Kt/V and the adequacy of hemodialysis" and"Arteriovenous fistulas and grafts for chronic hemodialysis access" .)

SUMMARY AND RECOMMENDATIONS

Diabetes is the most common cause of end-stage renal disease in patients requiring renal replacement therapy, accounting for approximately 45 percent of cases in the United States. Although less frequent in many other countries, diabetes is also a common cause of end-stage renal disease throughout the world. (See 'Introduction' above.)Survival in diabetic patients on maintenance dialysis is lower than that seen in nondiabetics with end-stage renal failure due to chronic glomerular disease, hypertension, or other causes of end-stage renal disease. Cardiovascular disease is the most common cause of death, accounting for more than one-half of cases. (See 'Patient survival' above.)Compared with dialysis, kidney transplantation is associated with increased patient survival and a better quality of life. We recommend transplantation rather than dialysis to any diabetic patient with end-stage renal disease who is eligible for a renal allograft, ideally before dialysis is even initiated if possible ( Grade 1A ). (See 'Dialysis versus renal transplantation' above.)Among diabetics with adequate manual dexterity and visual acuity, we continue to offer peritoneal dialysis as an option for maintenance dialysis. Diabetic patients with unstable cardiac hemodynamics, severe vascular disease, and/or advanced neuropathy are most often treated with in-center hemodialysis. Few studies have specifically analyzed the efficacy of peritoneal dialysis in these patients. Very few diabetic patients choose home hemodialysis which is generally associated with the relatively highest patient survival rates. (See 'Hemodialysis versus peritoneal dialysis' above.)

REFERENCESPerneger TV, Brancati FL, Whelton PK, Klag MJ. End-stage renal disease attributable to diabetes mellitus. Ann Intern Med 1994; 121:912.Finne P, Reunanen A, Stenman S, et al. Incidence of end-stage renal disease in patients with type 1 diabetes. JAMA 2005; 294:1782.Rosolowsky ET, Skupien J, Smiles AM, et al. Risk for ESRD in type 1 diabetes remains high despite renoprotection. J Am Soc Nephrol 2011; 22:545.Ruggenenti P, Gambara V, Perna A, et al. The nephropathy of non-insulin-dependent diabetes: predictors of outcome relative to diverse patterns of renal injury. J Am Soc Nephrol 1998; 9:2336.United States Renal Data System. Excerpts from the USRDS 2009 annual data report: Atlas of end-stage renal disease in the United States. Am J Kidney Dis 2010; 55(Suppl 1):S1.Centers for Disease Control and Prevention (CDC). Incidence of end-stage renal disease attributed to diabetes among persons with diagnosed diabetes --- United States and Puerto Rico, 1996-2007. MMWR Morb Mortal Wkly Rep 2010; 59:1361.United States Renal Data System. Excerpts from the USRDS 2006 annual data report: Atlas of end-stage renal disease in the United States. Am J Kidney Dis 2007; 49(Suppl 5):S1.Van Dijk PC, Jager KJ, Stengel B, et al. Renal replacement therapy for diabetic end-stage renal disease: data from 10 registries in Europe (1991-2000). Kidney Int 2005; 67:1489.Sørensen VR, Hansen PM, Heaf J, Feldt-Rasmussen B. Stabilized incidence of diabetic patients referred for renal replacement therapy in Denmark. Kidney Int 2006; 70:187.Nishimura R, Dorman JS, Bosnyak Z, et al. Incidence of ESRD and survival after renal replacement therapy in patients with type 1 diabetes: a report from the Allegheny County Registry. Am J Kidney Dis 2003; 42:117.Wolfe RA, Gaylin DS, Port FK, et al. Using USRDS generated mortality tables to compare local ESRD mortality rates to national rates. Kidney Int 1992; 42:991.United States Renal Data System. Excerpts from the USRDS 2005 annual data report: Atlas of end-stage renal disease in the United States. Am J Kidney Dis 2006; 47(Suppl 1):S1.www.usrds.org, accessed May 2010.Locatelli F, Pozzoni P, Del Vecchio L. Renal replacement therapy in patients with diabetes and end-stage renal disease. J Am Soc Nephrol 2004; 15 Suppl 1:S25.Chantrel F, Enache I, Bouiller M, et al. Abysmal prognosis of patients with type 2 diabetes entering dialysis. Nephrol Dial Transplant 1999; 14:129.Tzamaloukas AH, Yuan ZY, Balaskas E, Oreopoulos DG. CAPD in end stage patients with renal disease due to diabetes mellitus--an update. Adv Perit Dial 1992; 8:185.Brunner FP, Selwood NH. Profile of patients on RRT in Europe and death rates due to major causes of death groups. The EDTA Registration Committee. Kidney Int Suppl 1992; 38:S4.Dikow R, Ritz E. Cardiovascular complications in the diabetic patient with renal disease: an update in 2003. Nephrol Dial Transplant 2003; 18:1993.Lowrie EG, Lew NL, Huang WH. Race and diabetes as death risk predictors in hemodialysis patients. Kidney Int Suppl 1992; 38:S22.Mailloux LU, Bellucci AG, Napolitano B, et al. Death by withdrawal from dialysis: a 20-year clinical experience. J Am Soc Nephrol 1993; 3:1631.Nelson CB, Port FK, Wolfe RA, Guire KE. The association of diabetic status, age, and race to withdrawal from dialysis. J Am Soc Nephrol 1994; 4:1608.Grenfell A, Bewick M, Snowden S, et al. Renal replacement for diabetic patients: experience at King's College Hospital 1980-1989. Q J Med 1992; 85:861.Khauli RB, Steinmuller DR, Novick AC, et al. A critical look at survival of diabetics with end-stage renal disease. Transplantation versus dialysis therapy. Transplantation 1986; 41:598.Makita Z, Bucala R, Rayfield EJ, et al. Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure. Lancet 1994; 343:1519.Passadakis P, Thodis E, Vargemezis V, Oreopoulos D. Long-term survival with peritoneal dialysis in ESRD due to diabetes. Clin Nephrol 2001; 56:257.Jaar BG, Coresh J, Plantinga LC, et al. Comparing the risk for death with peritoneal dialysis and hemodialysis in a national cohort of patients with chronic kidney disease. Ann Intern Med 2005; 143:174.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; 3:1147.O'Donoghue D, Manos J, Pearson R, et al. Continuous ambulatory peritoneal dialysis and renal transplantation: a ten-year experience in a single center. Perit Dial Int 1992; 12:242, 245.Dumler F, Schmidt RJ, Cruz C, et al. Single center success with a high risk peritoneal dialysis population. Adv Perit Dial 1992; 8:105.Mailloux LU, Bellucci AG, Wilkes BM, et al. Mortality in dialysis patients: analysis of the causes of death. Am J Kidney Dis 1991; 18:326.Wolfe RA, Port FK, Hawthorne VM, Guire KE. A comparison of survival among dialytic therapies of choice: in-center hemodialysis versus continuous ambulatory peritoneal dialysis at home. Am J Kidney Dis 1990; 15:433.Held PJ, Port FK, Turenne MN, et al. Continuous ambulatory peritoneal dialysis and hemodialysis: comparison of patient mortality with adjustment for comorbid conditions. Kidney Int 1994; 45:1163.Bloembergen WE, Port FK, Mauger EA, Wolfe RA. A comparison of mortality between patients treated with hemodialysis and peritoneal dialysis. J Am Soc Nephrol 1995; 6:177.Vonesh EF, Snyder JJ, Foley RN, Collins AJ. The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis. Kidney Int 2004; 66:2389.Zimmerman SW, Sollinger H, Wakeen M, et al. Renal replacement therapy in diabetic nephropathy. Adv Ren Replace Ther 1994; 1:66.