Portal de Periódicos da CAPES

Stabilized incidence of diabetic patients referred for renal replacement therapy in Denmark

2006; Elsevier BV; Volume: 70; Issue: 1 Linguagem: Inglês

10.1038/sj.ki.5001516

1523-1755

Vibeke Rømming Sørensen, P. M. Hansen, James Heaf, Bo Feldt‐Rasmussen,

Blood Pressure and Hypertension Studies

Despite an improvement in diabetes care during the last 20 years, the number of diabetic patients starting renal replacement therapy (RRT) has continued to increase in the Western world. The aim was to study the incidence of patients starting RRT in Denmark from 1990 to 2004. Data were obtained from The Danish National Registry; Report on Dialysis and Transplantation, where all patients actively treated for end-stage renal disease have been registered since 1990. The incidence of end-stage renal disease increased until 2001. Thereafter the incidence stabilized on 130 per million people (pmp). The number of diabetic patients starting RRT increased steadily from: 52 (number of patients) in 1990, 113 in 1995, 150 in 2000, 168 in 2001, and 183 in 2002. However, during the years 2003 and 2004 this number was significantly reduced by 15% to 156 and 155, respectively. This was mainly due to a 22% reduction in the number of non-insulin- treated (type II) diabetic patients (number of patients): 98, 82, and 76 in 2002, 2003, and 2004, respectively. The mean age in the background population, the mean age in diabetic patients starting RRT and the incidence of type I and type II diabetes increased during the study period. The encouraging stabilization in the incidence of diabetic patients referred for RRT observed in Denmark could be the result of implementation of a multifactorial and more intensive renoprotective intervention in patients with diabetes and chronic progressive renal disease. Despite an improvement in diabetes care during the last 20 years, the number of diabetic patients starting renal replacement therapy (RRT) has continued to increase in the Western world. The aim was to study the incidence of patients starting RRT in Denmark from 1990 to 2004. Data were obtained from The Danish National Registry; Report on Dialysis and Transplantation, where all patients actively treated for end-stage renal disease have been registered since 1990. The incidence of end-stage renal disease increased until 2001. Thereafter the incidence stabilized on 130 per million people (pmp). The number of diabetic patients starting RRT increased steadily from: 52 (number of patients) in 1990, 113 in 1995, 150 in 2000, 168 in 2001, and 183 in 2002. However, during the years 2003 and 2004 this number was significantly reduced by 15% to 156 and 155, respectively. This was mainly due to a 22% reduction in the number of non-insulin- treated (type II) diabetic patients (number of patients): 98, 82, and 76 in 2002, 2003, and 2004, respectively. The mean age in the background population, the mean age in diabetic patients starting RRT and the incidence of type I and type II diabetes increased during the study period. The encouraging stabilization in the incidence of diabetic patients referred for RRT observed in Denmark could be the result of implementation of a multifactorial and more intensive renoprotective intervention in patients with diabetes and chronic progressive renal disease. Large clinical trials have demonstrated that several therapeutic strategies in the treatment of diabetic patients are effective in slowing or even preventing the progression of end-stage renal disease (ESRD) as well as other diabetic complications.1.Brenner B.M. Cooper M.E. de Z.D. et al.Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.N Engl J Med. 2001; 345: 861-869Crossref PubMed Scopus (6147) Google Scholar, 2.Gaede P. Vedel P. Parving H.H. Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study.Lancet. 1999; 353: 617-622Abstract Full Text Full Text PDF PubMed Scopus (867) Google Scholar, 3.Gaede P. Vedel P. Larsen N. et al.Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes.N Engl J Med. 2003; 348: 383-393Crossref PubMed Scopus (3813) Google Scholar, 4.Lewis E.J. Hunsicker L.G. Clarke W.R. et al.Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.N Engl J Med. 2001; 345: 851-860Crossref PubMed Scopus (5040) Google Scholar, 5.Lindholm L.H. Ibsen H. Dahlof B. et al.Cardiovascular morbidity and mortality in patients with diabetes in the Losartan Intervention for Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol.Lancet. 2002; 359: 1004-1010Abstract Full Text Full Text PDF PubMed Scopus (1463) Google Scholar, 6.Nielsen F.S. Rossing P. Gall M.A. et al.Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy.Diabetes. 1997; 46: 1182-1188Crossref PubMed Google Scholar, 7.Parving H.-H. Lehnert H. Brochner-Mortensen J. et al.The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.N Engl J Med. 2001; 345: 870-878Crossref PubMed Scopus (2938) Google Scholar, 8.Rossing K. Jacobsen P. Pietraszek L. Parving H.H. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial.Diabetes Care. 2003; 26: 2268-2274Crossref PubMed Scopus (225) Google Scholar These studies have shown that intensive glycaemic control, strict control of blood pressure, and blockade of the renin–angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists significantly reduce the risk of development of microalbuminuria and nephropathy in patients with diabetes. This has lead to the development of general recommendations regarding the treatment of patients with diabetes in most countries.9.Molitch M.E. DeFronzo R.A. Franz M.J. et al.Nephropathy in diabetes.Diabetes Care. 2004; 27: S79-S83PubMed Google Scholar Despite this improvement in diabetes care, the number of new diabetic patients starting renal replacement therapy (RRT) has increased in many countries, among which are the United States, Europe, Australia, New Zealand, and Japan.10.Disney A.P. Some trends in chronic renal replacement therapy in Australia and New Zealand, 1997.Nephrol Dial Transplant. 1998; 13: 854-859Crossref PubMed Scopus (19) Google Scholar, 11.Fatica R.A. Port F.K. Young E.W. Incidence trends and mortality in end-stage renal disease attributed to renovascular disease in the United States.Am J Kidney Dis. 2001; 37: 1184-1190Abstract Full Text PDF PubMed Scopus (106) Google Scholar, 12.Stengel B. Billon S. van Dijk P.C. et al.Trends in the incidence of renal replacement therapy for end-stage renal disease in Europe, 1990–1999.Nephrol Dial Transplant. 2003; 18: 1824-1833Crossref PubMed Scopus (219) Google Scholar, 13.Usami T. Koyama K. Takeuchi O. et al.Regional variations in the incidence of end-stage renal failure in Japan.JAMA. 2000; 284: 2622-2624Crossref PubMed Scopus (83) Google Scholar, 14.van Dijk P.C. Jager K.J. 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: 1489-1499Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar This could be due to the increased incidence of non-insulin-dependent (type II) diabetes and lack of effect of the diabetic treatment recommendations. Multipharmacy and lifestyle changes are difficult to comply with and therefore very few patients are able to benefit from such a regimen.15.Lerman I. Adherence to treatment: the key for avoiding long-term complications of diabetes.Arch Med Res. 2005; 36: 300-306Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar In a recent report from the Danish National Registry, Report on Dialysis and Transplantation in Denmark 2004, the reported number of diabetic patients starting RRT has decreased in the last 2 years. We therefore studied the incidence of patients starting RRT in Denmark from 1990 to 2004. The total population in Denmark including Greenland and Faroe Islands increased from 5 237 771 on 1 January 1990 to 5 49 7 759 on 1 January 2004. The mean age in the population increased linearly from 38.1 years to 39.1 years. During the first part of the study period, the percentage of persons in Denmark older than 60 years decreased. However, since 1996 the fraction of persons older than 60 years increased from 19.6 to 20.5%. The prevalence of ESRD, defined as the total number of patients treated with dialysis or having a functioning renal graft, increased every year from 385 per million people (pmp) in 1990 to 752 pmp in 2004. Figure 1 shows the total incidence of ESRD from 1990 to 2004 and the incidence among patients older than 60 years. The total incidence of patients starting RRT was stable since 2001, whereas the incidence among people older than 60 years declined since 2001. Looking into the distribution of various diagnoses during the period, Figure 2 shows that diabetic nephropathy was the single most important cause of ESRD during the entire period. The incidence in diabetic patients (type I and type II) starting RRT increased threefold from 1990 to 2002 (Figure 3). However, during the years 2003 and 2004 the incidence was reduced by 15%. The decreased incidence of patients with diabetes was mainly due to a reduction of patients with type II diabetes whereas the incidence of type I was stable during the last 4 years. The incidence curve with prediction limits for 2003 and 2004 (Figure 4) shows that the decreased incidence in 2004 is significant with P<0.05. In 1990, 18% of the patients starting RRT had diabetic nephropathy. Successively the fraction of diabetic patients increased every year until 1995, from when, the fraction has remained generally stable around 22%. The male/female ratio (63/37) was unchanged during the period and similar in diabetic and non-diabetic patients. Table 1 shows the mean age in type I, type II, and non-diabetic patients during four time intervals. Overall, the mean age of patients starting RRT increased during the study period. In type II diabetic patients the mean age also increased significantly in 2003 and 2004 where the incidence of ESRD owing to diabetes was decreasing. The mean age in type I diabetic patients and non-diabetic patients was not significantly different in 2003–2004 compared to 2000–2002. The differences between the other time periods were all significant.Figure 2Renal diagnoses from 1990 to 2004.View Large Image Figure ViewerDownload (PPT)Figure 3Incidence of diabetic patients starting RRT from 1990–2004 (pmp).View Large Image Figure ViewerDownload (PPT)Figure 4Incidence and 95% prediction limits of diabetic patients with ESRD from 1990–2004.View Large Image Figure ViewerDownload (PPT)Table 1Mean age in patients starting renal replacement therapy from 1990 to 2004 (years (s.d.))1990–19941995–19992000–20022003–2004Patients with type I diabetes47.2±1350.5±13*P<0.05 compared with previous time period.53.8±14*P<0.05 compared with previous time period.51.3±14Patients with type II diabetes62.8±865.3±10*P<0.05 compared with previous time period.66.8±10*P<0.05 compared with previous time period.69.0±9*P<0.05 compared with previous time period.Patients without diabetes54.7±1758.2±17*P<0.05 compared with previous time period.61.7±17*P<0.05 compared with previous time period.61.8±17s.d., standard deviation.* P<0.05 compared with previous time period. Open table in a new tab s.d., standard deviation. The prevalence of diabetes is increasing in Denmark as well as internationally.16.Jones C.A. Krolewski A.S. Rogus J. et al.Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know the cause?.Kidney Int. 2005; 67: 1684-1691Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar, 17.Stovring H. Andersen M. Beck-Nielsen H. et al.Rising prevalence of diabetes: evidence from a Danish pharmaco-epidemiological database.Lancet. 2003; 362: 537-538Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar The incidence of childhood type I diabetes has increased 1.23% annually during the last 30 years in Denmark.18.Svensson J. Carstensen B. Molbak A. et al.Increased risk of childhood type 1 diabetes in children born after 1985.Diabetes Care. 2002; 25: 2197-2201Crossref PubMed Scopus (67) Google Scholar The prevalence of type II diabetes increased 20–60% during the last 20 years and among persons who are 60 years old in Denmark every third man and every fourth woman have either diabetes or impaired glucose tolerance.19.Borch-Johnsen K. Type 2 diabetes. Prevention of a public disease and its consequences.Ugeskr Laeger. 2004; 166: 1316-1320PubMed Google Scholar The prevalence of known diabetes in Denmark has been estimated on the basis of national registers to approximately 100 000 in 1996, 130 000 in 1999, and 150 000 patients in 2004.19.Borch-Johnsen K. Type 2 diabetes. Prevention of a public disease and its consequences.Ugeskr Laeger. 2004; 166: 1316-1320PubMed Google Scholar, 20.Drivsholm T. Ibsen H. Schroll M. et al.Increasing prevalence of diabetes mellitus and impaired glucose tolerance among 60-year-old Danes.Diabet Med. 2001; 18: 126-132Crossref PubMed Scopus (124) Google Scholar, 21.Glumer C. Jorgensen T. Borch-Johnsen K. Prevalences of diabetes and impaired glucose regulation in a Danish population: the Inter99 study.Diabetes Care. 2003; 26: 2335-2340Crossref PubMed Scopus (235) Google Scholar The percentage of patients with ESRD who are older than 60 years has been stable since 1999, comprising approximately 60% of the total number of patients starting RRT. The worldwide prevalence of diabetes has increased dramatically22.King H. Aubert R.E. Herman W.H. Global burden of diabetes, 1995–2025: prevalence, numerical estimates, and projections.Diabetes Care. 1998; 21: 1414-1431Crossref PubMed Scopus (5045) Google Scholar and a concomitant increase in the incidence of diabetic patients requiring RRT has been seen in the Western world. In Europe, the incidence of diabetic patients with ESRD increased form 14.8 pmp in 1991–1992 to 26.9 pmp in 1999–2000.14.van Dijk P.C. Jager K.J. 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: 1489-1499Abstract Full Text Full Text PDF PubMed Scopus (147) Google Scholar In the United States, the incidence of ESRD owing to diabetes increased from 62.5 to 134 pmp during the 1990s.16.Jones C.A. Krolewski A.S. Rogus J. et al.Epidemic of end-stage renal disease in people with diabetes in the United States population: do we know the cause?.Kidney Int. 2005; 67: 1684-1691Abstract Full Text Full Text PDF PubMed Scopus (176) Google Scholar In Denmark, we have now observed a stabilization of the total incidence of ESRD since 2001 and a decreased incidence of diabetic patients starting RRT during the years 2003 and 2004. This was mainly due to a reduction in the incidence of patients registered with type II diabetes. It is likely that some insulin-treated type II diabetic patients in the Danish database have been misclassified as having type I diabetes, because of start of insulin treatment. If this is the case, the true incidence of type I diabetes is less than reported and the observed stable incidence of type I diabetic patients progressing to ESRD is probably underestimated. The stable crude incidence of type I diabetic patients progressing to ESRD is also influenced by the increasing incidence of type I diabetes in the background population and may therefore be further underestimated. As the diagnosis 'diabetic nephropathy' was clinical and only rarely based on kidney biopsy, it cannot be ruled out that some of the patients classified as unknown in the database did have diabetic nephropathy. However, the same groups of persons in the regional centers have been reporting during the entire study period and the methods of registration have been unchanged. Thus, our observations do not seem to be explained by registration bias of diabetic patients starting RRT from 1990 to 2004. Our observations could theoretically be explained by several factors. First, before 1990 diabetic patients were in many cases not offered RRT because of limited capacity in the dialysis units for patients with complicating chronic diseases other than renal failure. In such a scenario, a new steady state should be reached with a higher but stable incidence of RRT patients after a certain period of time. As unlimited access to RRT has been a reality in Denmark for at least 15 years, such a steady state should have been reached many years ago. Secondly, changes in the incidence of diabetes in the study period could play a role. The incidence of both type I and type II diabetes did, however, increase in the background population during the study period, and an increase in the incidence of RRT would therefore be expected. In contrast, the incidence of ESRD due to diabetes stabilized and tended to decrease. Thirdly, changes in the pattern of referral towards not treating elderly diabetic patients could play a role. The percentage of patients older than 80 years when starting RRT has, however, increased linearly from 2% in 1997 to 10% in 2004 and the mean age of diabetic patients starting RRT increased during the entire study period. Furthermore it is the general opinion among Danish nephrologists that the criteria for starting dialysis are similar between the different nephrological centers. As the mean age in the background population increased, neither was this an explanation of the stabilized incidence of RRT owing to diabetes. Random variation is unlikely to explain the observed changes in the incidence of RRT observed during the last 2 years. The incidence in 2003 and 2004 was significantly different than the expected incidence. Furthermore, our observation finds support from other registries where similar trends have been reported. In the United States, the incidence of ESRD owing to diabetes has been stable at approximately 145–150 pmp since 2001.23.U.S. Renal Data System, USRDS 2004 Annual Data Report: Atlas of End-Stage Renal Disease in the United States. National Institute of Diabetes and Digestive and Kidney diseases, Bethesda MD2004Google Scholar A study from Holland also showed stabilization in the total incidence of ESRD since 2001. In that study, the incidence of type II diabetic patients with ESRD was still increasing whereas the incidence of ESRD due to type I diabetes was decreasing.24.Gansevoort R.T. van der H.B. Stegeman C.A. et al.Trends in the incidence of treated end-stage renal failure in The Netherlands: hope for the future?.Kidney Int Suppl. 2004; 92: S7-S10Abstract Full Text Full Text PDF PubMed Google Scholar Finally, in a cohort study of type I diabetic patients in Finland, which aimed at estimating the long-term risk of developing ESRD, it was suggested that the prognosis regarding ESRD had improved during the last four decades.25.Finne P. Reunanen A. Stenman S. et al.Incidence of end-stage renal disease in patients with type 1 diabetes.JAMA. 2005; 294: 1782-1787Crossref PubMed Scopus (223) Google Scholar Our observation of a declining incidence of RRT in diabetic patients could at least in part be due to the more intensive and multifactorial treatment that have been implemented during the last 10–15 years. In the early 1980s, two landmark studies showed that in patients with type I diabetes and proteinuria, treatment of hypertension slowed down the decrease in glomerular filtration rate.26.Mogensen C.E. Long-term antihypertensive treatment inhibiting progression of diabetic nephropathy.Br Med J (Clin Res Ed). 1982; 285: 685-688Crossref PubMed Scopus (697) Google Scholar, 27.Parving H.H. Andersen A.R. Smidt U.M. Svendsen P.A. Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy.Lancet. 1983; 1: 1175-1179Abstract PubMed Scopus (810) Google Scholar Since then, several randomized trials have documented that treatment of hypertension and use of angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists has been effective in slowing or even preventing progression of nephropathy in both type I and type II diabetic patients.1.Brenner B.M. Cooper M.E. de Z.D. et al.Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.N Engl J Med. 2001; 345: 861-869Crossref PubMed Scopus (6147) Google Scholar, 2.Gaede P. Vedel P. Parving H.H. Pedersen O. Intensified multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: the Steno type 2 randomised study.Lancet. 1999; 353: 617-622Abstract Full Text Full Text PDF PubMed Scopus (867) Google Scholar, 6.Nielsen F.S. Rossing P. Gall M.A. et al.Long-term effect of lisinopril and atenolol on kidney function in hypertensive NIDDM subjects with diabetic nephropathy.Diabetes. 1997; 46: 1182-1188Crossref PubMed Google Scholar, 7.Parving H.-H. Lehnert H. Brochner-Mortensen J. et al.The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.N Engl J Med. 2001; 345: 870-878Crossref PubMed Scopus (2938) Google Scholar, 8.Rossing K. Jacobsen P. Pietraszek L. Parving H.H. Renoprotective effects of adding angiotensin II receptor blocker to maximal recommended doses of ACE inhibitor in diabetic nephropathy: a randomized double-blind crossover trial.Diabetes Care. 2003; 26: 2268-2274Crossref PubMed Scopus (225) Google Scholar The implementation of these therapeutic strategies should have the potential to reduce the burden of ESRD due to diabetes, but so far this has only been demonstrated in short-time follow-up. Several reports have also documented that lack of adherence to pharmacological treatment and lifestyle changes is a common problem.15.Lerman I. Adherence to treatment: the key for avoiding long-term complications of diabetes.Arch Med Res. 2005; 36: 300-306Abstract Full Text Full Text PDF PubMed Scopus (106) Google Scholar, 28.Chapman R.H. Benner J.S. Petrilla A.A. et al.Predictors of adherence with antihypertensive and lipid-lowering therapy.Arch Intern Med. 2005; 165: 1147-1152Crossref PubMed Scopus (465) Google Scholar, 29.Rubin R.R. Adherence to pharmacologic therapy in patients with type 2 diabetes mellitus.Am J Med. 2005; 118: 27S-34SAbstract Full Text Full Text PDF PubMed Scopus (307) Google Scholar Serious deficits in the care of diabetic patients with pre-terminal renal failure still exists in the United States as well as in Europe,30.Ismail N. Becker B. Strzelczyk P. Ritz E. Renal disease and hypertension in non-insulin-dependent diabetes mellitus.Kidney Int. 1999; 55: 1-28Abstract Full Text Full Text PDF PubMed Scopus (236) Google Scholar, 31.Rychlik I. Miltenberger-Miltenyi G. Ritz E. The drama of the continuous increase in end-stage renal failure in patients with type II diabetes mellitus.Nephrol Dial Transplant. 1998; 13: 6-10Crossref PubMed Scopus (38) Google Scholar and even better results preventing ESRD might be accessible. Fagerudd et al.32.Fagerudd J. Forsblom C. Pettersson-Fernholm K. Groop P.H. Implementation of guidelines for the prevention of diabetic nephropathy.Diabetes Care. 2004; 27: 803-804Crossref PubMed Scopus (24) Google Scholar studied the implementation of guidelines for prevention of diabetic nephropathy in type I diabetic patients and found that 79% did not achieve the target blood pressure ≤140/≤90 mm Hg. Good glyceamic control defined as Hba1c <7.5% was only registered in 24% of the patients. In our study, we do not have information about duration of diabetes, co-morbidity, blood pressure, or metabolic control and therefore the level of adherence is unknown. We conclude that even though both the mean age and the incidence of type I and type II diabetes in the background population increased, the total incidence of ESRD has been unchanged during the last 4 years, and that the incidence of diabetic patients starting RRT in Denmark has stabilized and possibly declined for the past 2 years. These encouraging observations may be the result of the implementation of a multifactorial and more intensive renoprotective intervention, in most patients with chronic progressive renal diseases, and in particular in patients with diabetes. Data were obtained from The Danish National Registry; Report on Dialysis and Transplantation, where all patients actively treated for ESRD have been registered since 1990. Once a year all regional centers refer data to a central database at the national registry, using identical software programs. The material is checked for errors, and appropriate corrections are made in agreement with the reporting centers. The response rate is 100%. No private clinics exist. A national report is prepared, and data are transferred to the registry maintained by the European Dialysis and Transplantation Association (ERA-EDTA). Data regarding the number and age distribution of the Danish population were obtained from the national database Statistics Denmark. Incidence rates were studied annually from 1990 to 2004. Incidence was expressed as number of patients pmp starting RRT (dialysis or renal transplantation). For analysis, patients were subdivided according to age using a cut-off value of 60 years and to renal diagnoses using ERA-EDTA codes. The incidence was fitted into a linearly model. Using the computer program Statistica 6.0 a linear regression line with the years 1990–2002 on the x axis and the incidence of diabetic patients starting RRT on the y axis was made. The 95% prediction limits were calculated and the incidence of diabetic patients starting RRT in 2003 and 2004 were considered significantly different if they were higher or lower than the line of the 95% prediction limit. We thank The Danish Diabetes Association and the Danish Kidney Association who supported the work.