QJM Advance Access published August 19, 2014
End stage renal disease and survival in people with diabetes: a national database linkage study Samira Bell1, Emma H. Fletcher2 , Inez Brady2, Helen C. Looker2 , Daniel Levin2, Nicola Joss3, Jamie P Traynor4, Wendy Metcalfe4, Bryan Conway5, Shona Livingstone2, Graham Leese6, Sam Philip7, Sarah Wild8, Nynke Halbesma8, Naveed Sattar9, Robert S. Lindsay9, John McKnight10, Donald Pearson11, Helen M. Colhoun2 On behalf of the Scottish Diabetes Research Network and Scottish Renal Registry 1
Renal Unit, Ninewells Hopsital, NHS Tayside, Dundee, DD1 9SY
2
Diabetes Epidemiology Unit, University of Dundee, Mackenzie Building, Kirsty Semple Way, Dundee DD2 4BF
3
NHS Highland, Raigmore Hospital, Inverness IV2 3UJ
4
Scottish Renal Registry, Cirrus House, Marchburn Drive, Glasgow Airport Business Park, Abbotsinch Paisley PA3 2SJ Centre for Cardiovascular Science, University of Edinburgh, The Queens Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ
6
Scottish Diabetes Research Network, Ninewells Hospital and Medical School, Dundee DD1 9SY
7
Grampian Diabetes Research Unit, Woolmanhill Hospital, Aberdeen AB25 1LD
8
Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG
9
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA
10
Metabolic Unit, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU
11
NHS Grampian, Aberdeen Royal Infirmary, Eday Road, Aberdeen, AB15 6XS
Corresponding author: Dr Samira Bell Renal Unit Ninewells Hospital Dundee DD1 9SY Telephone number: +44 (0) 1382 660 111 Fax number: +44 (0) 1382 383802 Email: [email protected]
Running Title: ESRD and survival in Scottish diabetics Abstract word count: 266, Word count: 2163
© The Author(s) 2014. Published by Oxford University Press on behalf of the Association of Physicians. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 1
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5
Abstract Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end stage renal disease (ESRD) requiring renal replacement therapy (RRT). Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. Results: Point prevalence of Chronic Kidney Disease (CKD)5 in 2008 was 1.63% of 19,414
diabetes (T2DM) (Odds ratio for DM type 0.97, p=0.77, on adjustment for duration Whilst 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (Odds ratio for DM type 0.83, p=0.432). Diabetic nephropathy was the Primary Renal Diagnosis (PRD) in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI 1.92, 2.38) in T2DM. Conclusion: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning.
2
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people with type 1 diabetes (T1DM) compared to 0.58% of 167,871 people with type 2
Introduction The prevalence of diabetes worldwide has increased dramatically in recent years and is projected to reach over 552 million cases by 2030(1). In Scotland the recorded prevalence of diabetes has increased substantially from 2.6%(2) in 2003 to 4.7%(3) in 2011. This increase in prevalence of diabetes is projected to lead to a significant increase in patients with end stage renal disease (ESRD) requiring renal replacement therapy (RRT)(4). Incidence of new patients commencing RRT in 2011 in Scotland was 96 per million population(pmp) with 24% of patients with diabetes as their primary renal diagnosis (PRD) between 2007-2011(5). United Kingdom (UK) Registry incidence was 108 pmp with 25% diabetes as PRD in their 2011 incident cohort (6) . In the UK renal registry co-morbidity data are reported in 55% of all those with RRT and among these 35% either have diabetes as the PRD or report it as a co-
resources and to gauge whether outcomes in those with diabetes are changing, accurate estimates of current prevalence among those with diabetes would be useful but this cannot be directly obtained from current reports. The aim of this study was, firstly, to examine the prevalence of patients with chronic kidney disease (CKD) 5 and patients receiving RRT in all diabetics within Scotland, UK and ascertain the PRD of these patients. Secondly, we examined survival in these patients and whether PRD was related to survival after the initiation of RRT. Methods All patients diagnosed with diabetes until 31st May 2008 in Scotland, UK were included in the analysis. Data were linked between the following relevant datasets: Scottish Renal Registry (SRR)(5), the Scottish Care Initiative-Diabetes Collaboration (SCI-DC)(8) and the National Records of Scotland death data by the National Health Service Information Services Division. Records for all those ever registered as having diabetes in the SCI-DC database by 31st May 2008 were extracted and linked to the SRR and National Records of Scotland
3
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morbid condition(7). However in order to predict this future burden on healthcare and
death data. Diabetes type was determined by the clinician recording the diagnosis on the SCI-DC database but with the additional requirement that the prescription history did not contradict this (i.e. no evidence of lengthy period of diabetes before insulin and no coprescribing of non-metformin oral diabetes drugs (9). Data sources All patients with diabetes are registered on a single nationwide clinical record system; the SCI-DC database which was rolled out nationwide from 2002 onwards. Registration occurs automatically when a patient is diagnosed with diabetes and assigned a corresponding Read code for diabetes in a primary care practice or a hospital-based diabetes clinic. Read codes are standardised codes used to record clinical data in primary care in the UK and are used to evaluate clinical performance, inform payment tariffs in primary care and allow inclusion
General Practitioner practices in Scotland are linked to the register and so the database is estimated to capture over 99% of all patients nationally assigned a Read code for diabetes. The SRR records the assigned PRD, methods of treatment and outcomes of all patients receiving RRT in Scotland. Patients are registered when RRT is first commenced. The SRR was started in 1991 and was back-filled to 1960 when regular and routine RRT was initiated, using the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) registry. The SRR currently captures data from all of the nine adult and one paediatric renal unit in Scotland in addition to all 24 satellite dialysis units thereby achieving 100% national coverage. The PRD is recorded by the nephrologist responsible for the care of the patient using ERAEDTA PRD codes. PRDs were grouped into five categories – primary glomerulonephritis, interstitial nephropathies, multisystem disease, diabetic nephropathy and ‘not known and other’ (10). The ‘not known and other’ group constitutes mostly those patients for whom it has not been possible to determine the PRD. A PRD of diabetic nephropathy is often based
4
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into the national retinopathy screening programme. All but five of approximately 1,000
on the clinical judgement of the nephrologist and not proven by a renal biopsy. Renal biopsy in only performed when there is clinical doubt about the diagnosis of diabetic nephropathy due to the potential risks involved. Point prevalence Data from individuals who were alive and diagnosed with diabetes on or before the 31st May 2008 were analysed to provide the point prevalence in order to allow examination of the current level of renal disease burden. Individuals were identified as having CKD5 (eGFR75
481
6
1.25
41282
306
0.74
41763
312
0.75
Total
19414
316
1.63
167871
972
0.58
187285
1288
0.69
16
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Total Number
Both types
Table 2. Survival by year from first RRT and type of diabetes Years since first RRT
Percentage alive (95% CI)
Type I diabetes
Type II diabetes
Both types
0
100.00 (100, 100)
100.00 (100, 100)
100.00 (100, 100)
1
83.8 (79.0, 89.0)
71.9 (68.4, 75.5)
75.0 (72.0, 78.0)
2
67.4 (61.0, 74.6)
52.1 (48.1, 56.5)
56.0 (52.5, 59.7)
3
54.8 ( 47.6, 63.2)
34.4 ( 30.3, 39.1)
39.6 (35.9, 43.7)
4
47.7 (39.7, 57.2)
24.2 (20.2, 29.0)
30.0 (26.2, 34.3)
17
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Table 3. Survival by year from first RRT with respect to PRD for those with type 2 diabetes Years since first RRT
Percentage alive (95% CI)
Diabetic Nephropathy
Primary Glomerulonephritis
Interstitial Nephropathies
Multisystem Diseases
Not Known and Other Causes of CKD5
0
100.00 (100, 100)
100.00 (100, 100)
100.00 (100, 100)
100.00 (100, 100)
100.00 (100, 100)
1
74.04 ( 69.53, 78.84)
84.26 ( 72.49, 97.93)
79.40 ( 68.24, 92.38)
59.43 ( 50.48, 69.97)
70.68 ( 61.27, 81.54)
2
51.79 ( 46.42, 57.77)
66.64 ( 51.53, 86.19)
66.28 ( 53.22, 82.55)
42.80 ( 33.88, 54.08)
52.87 ( 42.49, 65.79)
3
35.65 ( 30.22, 42.07)
49.98 ( 32.98, 75.75)
40.03 ( 26.25, 61.04)
23.05 ( 15.36, 34.60)
36.00 ( 25.72, 50.40)
4
24.78 ( 19.60, 31.34)
44.43 ( 27.61, 71.49)
30.88 ( 17.66, 53.99)
17.96 ( 10.47, 30.82)
17.60 ( 9.03, 34.32)
18
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Figure 1. Identification of records included in study
31st May 2008
206,303 individuals with diabetes
188,360 individuals
17,943 (8.7%) without eGFR status
187,285 individuals in study
1,075 (0.01%) with forms of diabetes not relevant to the study
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Figure 2. Primary causes of renal disease in those with type 1 diabetes and type 2 diabetes receiving RRT* * Among those with type 2 diabetes, Multisystem Diseases comprise of the following: Renal vascular disease - type unspecified (32%); renal vascular disease due to hypertension (no primary renal disease) (23%); myelomatosis/light chain deposit disease (11%); and renal vascular disease due to other cause (11%)
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List of Acronyms Type 1 Diabetes (T1DM) Type 2 Diabetes (T2DM) End Stage Renal Disease (ESRD) Renal Replacement Therapy (RRT) Chronic Kidney Disease (CKD) Primary Renal Diagnosis (PRD) Scottish Care Initiative-Diabetes Collaboration (SCI-DC) Scottish Renal Registry (SRR) estimated Glomerular Filtration Rate (eGFR)
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End stage renal disease and survival in people with diabetes: a national database linkage study Samira Bell1, Emma H. Fletcher2 , Inez Brady2, Helen C. Looker2 , Daniel Levin2, Nicola Joss3, Jamie P Traynor4, Wendy Metcalfe4, Bryan Conway5, Shona Livingstone2, Graham Leese6, Sam Philip7, Sarah Wild8, Nynke Halbesma8, Naveed Sattar9, Robert S. Lindsay9, John McKnight10, Donald Pearson11, Helen M. Colhoun2 On behalf of the Scottish Diabetes Research Network and Scottish Renal Registry 1
Renal Unit, Ninewells Hopsital, NHS Tayside, Dundee, DD1 9SY
2
Diabetes Epidemiology Unit, University of Dundee, Mackenzie Building, Kirsty Semple Way, Dundee DD2 4BF
3
NHS Highland, Raigmore Hospital, Inverness IV2 3UJ
4
Scottish Renal Registry, Cirrus House, Marchburn Drive, Glasgow Airport Business Park, Abbotsinch Paisley PA3 2SJ Centre for Cardiovascular Science, University of Edinburgh, The Queens Medical Research Institute, 47 Little France Crescent, Edinburgh, EH16 4TJ
6
Scottish Diabetes Research Network, Ninewells Hospital and Medical School, Dundee DD1 9SY
7
Grampian Diabetes Research Unit, Woolmanhill Hospital, Aberdeen AB25 1LD
8
Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh EH8 9AG
9
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA
10
Metabolic Unit, Western General Hospital, Crewe Road South, Edinburgh EH4 2XU
11
NHS Grampian, Aberdeen Royal Infirmary, Eday Road, Aberdeen, AB15 6XS
Corresponding author: Dr Samira Bell Renal Unit Ninewells Hospital Dundee DD1 9SY Telephone number: +44 (0) 1382 660 111 Fax number: +44 (0) 1382 383802 Email: [email protected]
Running Title: ESRD and survival in Scottish diabetics Abstract word count: 266, Word count: 2163
© The Author(s) 2014. Published by Oxford University Press on behalf of the Association of Physicians. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. 1
Downloaded from by guest on September 3, 2015
5
Abstract Background: Increasing prevalence of diabetes worldwide is projected to lead to an increase in patients with end stage renal disease (ESRD) requiring renal replacement therapy (RRT). Aim: To provide contemporary estimates of the prevalence of ESRD and requirement for RRT among people with diabetes in a nationwide study and to report associated survival. Methods: Data were extracted and linked from three national databases: Scottish Renal Registry, Scottish Care Initiative-Diabetes Collaboration and National Records of Scotland death data. Survival analyses were modelled with Cox regression. Results: Point prevalence of Chronic Kidney Disease (CKD)5 in 2008 was 1.63% of 19,414
diabetes (T2DM) (Odds ratio for DM type 0.97, p=0.77, on adjustment for duration Whilst 83% of those with T1DM and CKD5 and 61% of those with T2DM and CKD5 were receiving RRT, there was no difference when adjusted for age, sex and DM duration (Odds ratio for DM type 0.83, p=0.432). Diabetic nephropathy was the Primary Renal Diagnosis (PRD) in 91% of people with T1DM and 58% of people with T2DM on RRT. Median survival time from initiation of RRT was 3.84 years (95% CI 2.77, 4.62) in T1DM and 2.16 years (95% CI 1.92, 2.38) in T2DM. Conclusion: Considerable numbers of patients with diabetes continue to progress to CKD5 and RRT. Almost half of all RRT cases in T2DM are considered to be due to conditions other than diabetic nephropathy. Median survival time for people with diabetes from initiation of RRT remains poor. These prevalence data are important for future resource planning.
2
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people with type 1 diabetes (T1DM) compared to 0.58% of 167,871 people with type 2
Introduction The prevalence of diabetes worldwide has increased dramatically in recent years and is projected to reach over 552 million cases by 2030(1). In Scotland the recorded prevalence of diabetes has increased substantially from 2.6%(2) in 2003 to 4.7%(3) in 2011. This increase in prevalence of diabetes is projected to lead to a significant increase in patients with end stage renal disease (ESRD) requiring renal replacement therapy (RRT)(4). Incidence of new patients commencing RRT in 2011 in Scotland was 96 per million population(pmp) with 24% of patients with diabetes as their primary renal diagnosis (PRD) between 2007-2011(5). United Kingdom (UK) Registry incidence was 108 pmp with 25% diabetes as PRD in their 2011 incident cohort (6) . In the UK renal registry co-morbidity data are reported in 55% of all those with RRT and among these 35% either have diabetes as the PRD or report it as a co-
resources and to gauge whether outcomes in those with diabetes are changing, accurate estimates of current prevalence among those with diabetes would be useful but this cannot be directly obtained from current reports. The aim of this study was, firstly, to examine the prevalence of patients with chronic kidney disease (CKD) 5 and patients receiving RRT in all diabetics within Scotland, UK and ascertain the PRD of these patients. Secondly, we examined survival in these patients and whether PRD was related to survival after the initiation of RRT. Methods All patients diagnosed with diabetes until 31st May 2008 in Scotland, UK were included in the analysis. Data were linked between the following relevant datasets: Scottish Renal Registry (SRR)(5), the Scottish Care Initiative-Diabetes Collaboration (SCI-DC)(8) and the National Records of Scotland death data by the National Health Service Information Services Division. Records for all those ever registered as having diabetes in the SCI-DC database by 31st May 2008 were extracted and linked to the SRR and National Records of Scotland
3
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morbid condition(7). However in order to predict this future burden on healthcare and
death data. Diabetes type was determined by the clinician recording the diagnosis on the SCI-DC database but with the additional requirement that the prescription history did not contradict this (i.e. no evidence of lengthy period of diabetes before insulin and no coprescribing of non-metformin oral diabetes drugs (9). Data sources All patients with diabetes are registered on a single nationwide clinical record system; the SCI-DC database which was rolled out nationwide from 2002 onwards. Registration occurs automatically when a patient is diagnosed with diabetes and assigned a corresponding Read code for diabetes in a primary care practice or a hospital-based diabetes clinic. Read codes are standardised codes used to record clinical data in primary care in the UK and are used to evaluate clinical performance, inform payment tariffs in primary care and allow inclusion
General Practitioner practices in Scotland are linked to the register and so the database is estimated to capture over 99% of all patients nationally assigned a Read code for diabetes. The SRR records the assigned PRD, methods of treatment and outcomes of all patients receiving RRT in Scotland. Patients are registered when RRT is first commenced. The SRR was started in 1991 and was back-filled to 1960 when regular and routine RRT was initiated, using the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) registry. The SRR currently captures data from all of the nine adult and one paediatric renal unit in Scotland in addition to all 24 satellite dialysis units thereby achieving 100% national coverage. The PRD is recorded by the nephrologist responsible for the care of the patient using ERAEDTA PRD codes. PRDs were grouped into five categories – primary glomerulonephritis, interstitial nephropathies, multisystem disease, diabetic nephropathy and ‘not known and other’ (10). The ‘not known and other’ group constitutes mostly those patients for whom it has not been possible to determine the PRD. A PRD of diabetic nephropathy is often based
4
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into the national retinopathy screening programme. All but five of approximately 1,000
on the clinical judgement of the nephrologist and not proven by a renal biopsy. Renal biopsy in only performed when there is clinical doubt about the diagnosis of diabetic nephropathy due to the potential risks involved. Point prevalence Data from individuals who were alive and diagnosed with diabetes on or before the 31st May 2008 were analysed to provide the point prevalence in order to allow examination of the current level of renal disease burden. Individuals were identified as having CKD5 (eGFR75
481
6
1.25
41282
306
0.74
41763
312
0.75
Total
19414
316
1.63
167871
972
0.58
187285
1288
0.69
16
Downloaded from by guest on September 3, 2015
Total Number
Both types
Table 2. Survival by year from first RRT and type of diabetes Years since first RRT
Percentage alive (95% CI)
Type I diabetes
Type II diabetes
Both types
0
100.00 (100, 100)
100.00 (100, 100)
100.00 (100, 100)
1
83.8 (79.0, 89.0)
71.9 (68.4, 75.5)
75.0 (72.0, 78.0)
2
67.4 (61.0, 74.6)
52.1 (48.1, 56.5)
56.0 (52.5, 59.7)
3
54.8 ( 47.6, 63.2)
34.4 ( 30.3, 39.1)
39.6 (35.9, 43.7)
4
47.7 (39.7, 57.2)
24.2 (20.2, 29.0)
30.0 (26.2, 34.3)
17
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Table 3. Survival by year from first RRT with respect to PRD for those with type 2 diabetes Years since first RRT
Percentage alive (95% CI)
Diabetic Nephropathy
Primary Glomerulonephritis
Interstitial Nephropathies
Multisystem Diseases
Not Known and Other Causes of CKD5
0
100.00 (100, 100)
100.00 (100, 100)
100.00 (100, 100)
100.00 (100, 100)
100.00 (100, 100)
1
74.04 ( 69.53, 78.84)
84.26 ( 72.49, 97.93)
79.40 ( 68.24, 92.38)
59.43 ( 50.48, 69.97)
70.68 ( 61.27, 81.54)
2
51.79 ( 46.42, 57.77)
66.64 ( 51.53, 86.19)
66.28 ( 53.22, 82.55)
42.80 ( 33.88, 54.08)
52.87 ( 42.49, 65.79)
3
35.65 ( 30.22, 42.07)
49.98 ( 32.98, 75.75)
40.03 ( 26.25, 61.04)
23.05 ( 15.36, 34.60)
36.00 ( 25.72, 50.40)
4
24.78 ( 19.60, 31.34)
44.43 ( 27.61, 71.49)
30.88 ( 17.66, 53.99)
17.96 ( 10.47, 30.82)
17.60 ( 9.03, 34.32)
18
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Figure 1. Identification of records included in study
31st May 2008
206,303 individuals with diabetes
188,360 individuals
17,943 (8.7%) without eGFR status
187,285 individuals in study
1,075 (0.01%) with forms of diabetes not relevant to the study
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Figure 2. Primary causes of renal disease in those with type 1 diabetes and type 2 diabetes receiving RRT* * Among those with type 2 diabetes, Multisystem Diseases comprise of the following: Renal vascular disease - type unspecified (32%); renal vascular disease due to hypertension (no primary renal disease) (23%); myelomatosis/light chain deposit disease (11%); and renal vascular disease due to other cause (11%)
Downloaded from by guest on September 3, 2015
List of Acronyms Type 1 Diabetes (T1DM) Type 2 Diabetes (T2DM) End Stage Renal Disease (ESRD) Renal Replacement Therapy (RRT) Chronic Kidney Disease (CKD) Primary Renal Diagnosis (PRD) Scottish Care Initiative-Diabetes Collaboration (SCI-DC) Scottish Renal Registry (SRR) estimated Glomerular Filtration Rate (eGFR)
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