Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients

Julia M. Steinke, Michael Mauer, Christine Aebi, Mimi Belmonte, Keith Drummond, Robert Gardiner, Michael Kramer, Diane Laforte, Constantin Polychronakos, Alicia Schiffrin, Atul Sharma, Samy Suissa, Khalil Khoury, Jan Braaten, Kenneth Faught, Paul Czernichow, Marie Claire Gubler, Claire Levy-Marchal, Philippe Passa, Rebecca Carpenter & 7 others Blanche Chavers, Youngki Kim, Krishna Saxena, Joseph Sockalosky, Marty Spencer, Michael Steffes, Robert Vernier

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Diabetic Nephropathy (DN) remains the leading cause of end stage renal disease (ESRD) in the Western world, responsible for nearly half of all new ESRD cases in the USA (1). DN develops in 20-25% of patients with type 1 diabetes (T1DM) (2) and, although risk of DN is clearly related to glycemic control (3,4), other variables including genetic propensity (5) are needed to explain why only a minority T1 DN patients progress to ESRD. The clinical manifestations of DN including increasing levels of urinary albumin excretion (AER), rising blood pressure (BP) and falling glomerular filtration rates (GFR) are closely related to renal structural abnormalities of DN (5,6). These glomerular, tubular, vascular and interstitial lesions are strongly correlated with these functional abnormalities especially when non-linear analysis models are used (6,7). This is because DN's natural history is one of clinical silence for years to decades during which time serious underlying renal lesions may be developing. Once the clinical manifestations, including the development of persistent microalbuminuria [(MA); (AER 20-200 μ/ min)] are present, the structural injury is often far advanced (8). Moreover the nature of the renal lesions changes following the development of overt proteinuria so that the further decline in GFR is now associated with focal and global glomerular sclerosis and tubulo-interstitial injury which probably accelerates the GFR decline towards ESRD (7). Since interventions at these late stages of disease may only slow but not completely arrest the inexorable progression towards renal failure (9), understanding early natural history becomes important. Since DN structurally and functionally is a progressive disease; it is reasonable to presume that patients that either do not develop the earlier lesions of DN or develop them very slowly will not progress within their lifetime to stages of advanced renal structural injury and ESRD. We therefore considered it important to understand the early natural history of diabetic nephropothy and formed the International Diabetic Nephropathy Study Group (IDNSG) in order to investigate the early stages of ON in young TlDM volunteers. The design of the Natural History Study (NHS) (9) has been reported. The IDNSG participating institutions included 3 university centers (McGill University, Montreal, Canada with affiliations with the University of Sherbrooke, Sherbrooke, Canada, the Ottawa Civic Hospital, and the Childrens Hospital of Eastern Ontario; the Department of Pediatrics, University of Minnesota Medical School with affiliations at St Paul Children's Hospital and the International Diabetes Center in Minneapolis; the Robert Debré Höspital in Paris with affiliations with Höspital Saint Louis). The data coordinating center for the NHS was in the Department of Epidemiology and Biostatistics at McGill University and light microscopy readings were carried out at INSERM Unité 192 at the Höpital Necker-Enfants Malades in Paris. Patients could be included if they had type 1 diabetes for 2-20 years, had onset of diabetes before age 31, had AER less than 100 μg/min and GFR ≥ 90 ml/min/1.73m2 (9). Patients also had to be normotensive for their age and sex and have no other significant renal or systemic disease. Quarterly studies included measurements of blood pressure, (BP), urinary albumin excretion rate (AER), hemoglobin A1C (HbA1C), GFR, and renal plasma flow (RPF). Renal biopsies were performed at baseline and after 5 years in the study. The primary goal of the study was to determine the clinical predictors of the baseline biopsy and baseline clinical and renal structural predictors of the changes between the baseline and the 5 year biopsy. The longitudinal structural studies are still in analysis and the paper will mainly review the cross sectional studies that hove been completed to date.

Original languageEnglish (US)
Pages (from-to)958-963
Number of pages6
JournalPediatric Endocrinology Reviews
Volume5
Issue numberSUPPL. 4
StatePublished - Aug 1 2008

Fingerprint

Diabetic Nephropathies
Natural History
Glomerular Filtration Rate
Kidney
Chronic Kidney Failure
Albumins
Paris
Type 1 Diabetes Mellitus
Biopsy
Canada
Wounds and Injuries
Accidental Falls
Biostatistics
Blood Pressure
Renal Plasma Flow
Western World
Nonlinear Dynamics
Sclerosis
Ontario
Medical Schools

Keywords

  • Diabetes
  • Kidney
  • Natural history

Cite this

Steinke, J. M., Mauer, M., Aebi, C., Belmonte, M., Drummond, K., Gardiner, R., ... Vernier, R. (2008). Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients. Pediatric Endocrinology Reviews, 5(SUPPL. 4), 958-963.

Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients. / Steinke, Julia M.; Mauer, Michael; Aebi, Christine; Belmonte, Mimi; Drummond, Keith; Gardiner, Robert; Kramer, Michael; Laforte, Diane; Polychronakos, Constantin; Schiffrin, Alicia; Sharma, Atul; Suissa, Samy; Khoury, Khalil; Braaten, Jan; Faught, Kenneth; Czernichow, Paul; Gubler, Marie Claire; Levy-Marchal, Claire; Passa, Philippe; Carpenter, Rebecca; Chavers, Blanche; Kim, Youngki; Saxena, Krishna; Sockalosky, Joseph; Spencer, Marty; Steffes, Michael; Vernier, Robert.

In: Pediatric Endocrinology Reviews, Vol. 5, No. SUPPL. 4, 01.08.2008, p. 958-963.

Research output: Contribution to journalArticle

Steinke, JM, Mauer, M, Aebi, C, Belmonte, M, Drummond, K, Gardiner, R, Kramer, M, Laforte, D, Polychronakos, C, Schiffrin, A, Sharma, A, Suissa, S, Khoury, K, Braaten, J, Faught, K, Czernichow, P, Gubler, MC, Levy-Marchal, C, Passa, P, Carpenter, R, Chavers, B, Kim, Y, Saxena, K, Sockalosky, J, Spencer, M, Steffes, M & Vernier, R 2008, 'Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients', Pediatric Endocrinology Reviews, vol. 5, no. SUPPL. 4, pp. 958-963.
Steinke, Julia M. ; Mauer, Michael ; Aebi, Christine ; Belmonte, Mimi ; Drummond, Keith ; Gardiner, Robert ; Kramer, Michael ; Laforte, Diane ; Polychronakos, Constantin ; Schiffrin, Alicia ; Sharma, Atul ; Suissa, Samy ; Khoury, Khalil ; Braaten, Jan ; Faught, Kenneth ; Czernichow, Paul ; Gubler, Marie Claire ; Levy-Marchal, Claire ; Passa, Philippe ; Carpenter, Rebecca ; Chavers, Blanche ; Kim, Youngki ; Saxena, Krishna ; Sockalosky, Joseph ; Spencer, Marty ; Steffes, Michael ; Vernier, Robert. / Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients. In: Pediatric Endocrinology Reviews. 2008 ; Vol. 5, No. SUPPL. 4. pp. 958-963.
@article{83dea082232a4e62808d502a27d25da8,
title = "Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients",
abstract = "Diabetic Nephropathy (DN) remains the leading cause of end stage renal disease (ESRD) in the Western world, responsible for nearly half of all new ESRD cases in the USA (1). DN develops in 20-25{\%} of patients with type 1 diabetes (T1DM) (2) and, although risk of DN is clearly related to glycemic control (3,4), other variables including genetic propensity (5) are needed to explain why only a minority T1 DN patients progress to ESRD. The clinical manifestations of DN including increasing levels of urinary albumin excretion (AER), rising blood pressure (BP) and falling glomerular filtration rates (GFR) are closely related to renal structural abnormalities of DN (5,6). These glomerular, tubular, vascular and interstitial lesions are strongly correlated with these functional abnormalities especially when non-linear analysis models are used (6,7). This is because DN's natural history is one of clinical silence for years to decades during which time serious underlying renal lesions may be developing. Once the clinical manifestations, including the development of persistent microalbuminuria [(MA); (AER 20-200 μ/ min)] are present, the structural injury is often far advanced (8). Moreover the nature of the renal lesions changes following the development of overt proteinuria so that the further decline in GFR is now associated with focal and global glomerular sclerosis and tubulo-interstitial injury which probably accelerates the GFR decline towards ESRD (7). Since interventions at these late stages of disease may only slow but not completely arrest the inexorable progression towards renal failure (9), understanding early natural history becomes important. Since DN structurally and functionally is a progressive disease; it is reasonable to presume that patients that either do not develop the earlier lesions of DN or develop them very slowly will not progress within their lifetime to stages of advanced renal structural injury and ESRD. We therefore considered it important to understand the early natural history of diabetic nephropothy and formed the International Diabetic Nephropathy Study Group (IDNSG) in order to investigate the early stages of ON in young TlDM volunteers. The design of the Natural History Study (NHS) (9) has been reported. The IDNSG participating institutions included 3 university centers (McGill University, Montreal, Canada with affiliations with the University of Sherbrooke, Sherbrooke, Canada, the Ottawa Civic Hospital, and the Childrens Hospital of Eastern Ontario; the Department of Pediatrics, University of Minnesota Medical School with affiliations at St Paul Children's Hospital and the International Diabetes Center in Minneapolis; the Robert Debr{\'e} H{\"o}spital in Paris with affiliations with H{\"o}spital Saint Louis). The data coordinating center for the NHS was in the Department of Epidemiology and Biostatistics at McGill University and light microscopy readings were carried out at INSERM Unit{\'e} 192 at the H{\"o}pital Necker-Enfants Malades in Paris. Patients could be included if they had type 1 diabetes for 2-20 years, had onset of diabetes before age 31, had AER less than 100 μg/min and GFR ≥ 90 ml/min/1.73m2 (9). Patients also had to be normotensive for their age and sex and have no other significant renal or systemic disease. Quarterly studies included measurements of blood pressure, (BP), urinary albumin excretion rate (AER), hemoglobin A1C (HbA1C), GFR, and renal plasma flow (RPF). Renal biopsies were performed at baseline and after 5 years in the study. The primary goal of the study was to determine the clinical predictors of the baseline biopsy and baseline clinical and renal structural predictors of the changes between the baseline and the 5 year biopsy. The longitudinal structural studies are still in analysis and the paper will mainly review the cross sectional studies that hove been completed to date.",
keywords = "Diabetes, Kidney, Natural history",
author = "Steinke, {Julia M.} and Michael Mauer and Christine Aebi and Mimi Belmonte and Keith Drummond and Robert Gardiner and Michael Kramer and Diane Laforte and Constantin Polychronakos and Alicia Schiffrin and Atul Sharma and Samy Suissa and Khalil Khoury and Jan Braaten and Kenneth Faught and Paul Czernichow and Gubler, {Marie Claire} and Claire Levy-Marchal and Philippe Passa and Rebecca Carpenter and Blanche Chavers and Youngki Kim and Krishna Saxena and Joseph Sockalosky and Marty Spencer and Michael Steffes and Robert Vernier",
year = "2008",
month = "8",
day = "1",
language = "English (US)",
volume = "5",
pages = "958--963",
journal = "Pediatric endocrinology reviews : PER",
issn = "1565-4753",
publisher = "YS Medical Media Ltd.",
number = "SUPPL. 4",

}

TY - JOUR

T1 - Lessons learned from studies of the natural history of diabetic nephropathy in young type 1 diabetic patients

AU - Steinke, Julia M.

AU - Mauer, Michael

AU - Aebi, Christine

AU - Belmonte, Mimi

AU - Drummond, Keith

AU - Gardiner, Robert

AU - Kramer, Michael

AU - Laforte, Diane

AU - Polychronakos, Constantin

AU - Schiffrin, Alicia

AU - Sharma, Atul

AU - Suissa, Samy

AU - Khoury, Khalil

AU - Braaten, Jan

AU - Faught, Kenneth

AU - Czernichow, Paul

AU - Gubler, Marie Claire

AU - Levy-Marchal, Claire

AU - Passa, Philippe

AU - Carpenter, Rebecca

AU - Chavers, Blanche

AU - Kim, Youngki

AU - Saxena, Krishna

AU - Sockalosky, Joseph

AU - Spencer, Marty

AU - Steffes, Michael

AU - Vernier, Robert

PY - 2008/8/1

Y1 - 2008/8/1

N2 - Diabetic Nephropathy (DN) remains the leading cause of end stage renal disease (ESRD) in the Western world, responsible for nearly half of all new ESRD cases in the USA (1). DN develops in 20-25% of patients with type 1 diabetes (T1DM) (2) and, although risk of DN is clearly related to glycemic control (3,4), other variables including genetic propensity (5) are needed to explain why only a minority T1 DN patients progress to ESRD. The clinical manifestations of DN including increasing levels of urinary albumin excretion (AER), rising blood pressure (BP) and falling glomerular filtration rates (GFR) are closely related to renal structural abnormalities of DN (5,6). These glomerular, tubular, vascular and interstitial lesions are strongly correlated with these functional abnormalities especially when non-linear analysis models are used (6,7). This is because DN's natural history is one of clinical silence for years to decades during which time serious underlying renal lesions may be developing. Once the clinical manifestations, including the development of persistent microalbuminuria [(MA); (AER 20-200 μ/ min)] are present, the structural injury is often far advanced (8). Moreover the nature of the renal lesions changes following the development of overt proteinuria so that the further decline in GFR is now associated with focal and global glomerular sclerosis and tubulo-interstitial injury which probably accelerates the GFR decline towards ESRD (7). Since interventions at these late stages of disease may only slow but not completely arrest the inexorable progression towards renal failure (9), understanding early natural history becomes important. Since DN structurally and functionally is a progressive disease; it is reasonable to presume that patients that either do not develop the earlier lesions of DN or develop them very slowly will not progress within their lifetime to stages of advanced renal structural injury and ESRD. We therefore considered it important to understand the early natural history of diabetic nephropothy and formed the International Diabetic Nephropathy Study Group (IDNSG) in order to investigate the early stages of ON in young TlDM volunteers. The design of the Natural History Study (NHS) (9) has been reported. The IDNSG participating institutions included 3 university centers (McGill University, Montreal, Canada with affiliations with the University of Sherbrooke, Sherbrooke, Canada, the Ottawa Civic Hospital, and the Childrens Hospital of Eastern Ontario; the Department of Pediatrics, University of Minnesota Medical School with affiliations at St Paul Children's Hospital and the International Diabetes Center in Minneapolis; the Robert Debré Höspital in Paris with affiliations with Höspital Saint Louis). The data coordinating center for the NHS was in the Department of Epidemiology and Biostatistics at McGill University and light microscopy readings were carried out at INSERM Unité 192 at the Höpital Necker-Enfants Malades in Paris. Patients could be included if they had type 1 diabetes for 2-20 years, had onset of diabetes before age 31, had AER less than 100 μg/min and GFR ≥ 90 ml/min/1.73m2 (9). Patients also had to be normotensive for their age and sex and have no other significant renal or systemic disease. Quarterly studies included measurements of blood pressure, (BP), urinary albumin excretion rate (AER), hemoglobin A1C (HbA1C), GFR, and renal plasma flow (RPF). Renal biopsies were performed at baseline and after 5 years in the study. The primary goal of the study was to determine the clinical predictors of the baseline biopsy and baseline clinical and renal structural predictors of the changes between the baseline and the 5 year biopsy. The longitudinal structural studies are still in analysis and the paper will mainly review the cross sectional studies that hove been completed to date.

AB - Diabetic Nephropathy (DN) remains the leading cause of end stage renal disease (ESRD) in the Western world, responsible for nearly half of all new ESRD cases in the USA (1). DN develops in 20-25% of patients with type 1 diabetes (T1DM) (2) and, although risk of DN is clearly related to glycemic control (3,4), other variables including genetic propensity (5) are needed to explain why only a minority T1 DN patients progress to ESRD. The clinical manifestations of DN including increasing levels of urinary albumin excretion (AER), rising blood pressure (BP) and falling glomerular filtration rates (GFR) are closely related to renal structural abnormalities of DN (5,6). These glomerular, tubular, vascular and interstitial lesions are strongly correlated with these functional abnormalities especially when non-linear analysis models are used (6,7). This is because DN's natural history is one of clinical silence for years to decades during which time serious underlying renal lesions may be developing. Once the clinical manifestations, including the development of persistent microalbuminuria [(MA); (AER 20-200 μ/ min)] are present, the structural injury is often far advanced (8). Moreover the nature of the renal lesions changes following the development of overt proteinuria so that the further decline in GFR is now associated with focal and global glomerular sclerosis and tubulo-interstitial injury which probably accelerates the GFR decline towards ESRD (7). Since interventions at these late stages of disease may only slow but not completely arrest the inexorable progression towards renal failure (9), understanding early natural history becomes important. Since DN structurally and functionally is a progressive disease; it is reasonable to presume that patients that either do not develop the earlier lesions of DN or develop them very slowly will not progress within their lifetime to stages of advanced renal structural injury and ESRD. We therefore considered it important to understand the early natural history of diabetic nephropothy and formed the International Diabetic Nephropathy Study Group (IDNSG) in order to investigate the early stages of ON in young TlDM volunteers. The design of the Natural History Study (NHS) (9) has been reported. The IDNSG participating institutions included 3 university centers (McGill University, Montreal, Canada with affiliations with the University of Sherbrooke, Sherbrooke, Canada, the Ottawa Civic Hospital, and the Childrens Hospital of Eastern Ontario; the Department of Pediatrics, University of Minnesota Medical School with affiliations at St Paul Children's Hospital and the International Diabetes Center in Minneapolis; the Robert Debré Höspital in Paris with affiliations with Höspital Saint Louis). The data coordinating center for the NHS was in the Department of Epidemiology and Biostatistics at McGill University and light microscopy readings were carried out at INSERM Unité 192 at the Höpital Necker-Enfants Malades in Paris. Patients could be included if they had type 1 diabetes for 2-20 years, had onset of diabetes before age 31, had AER less than 100 μg/min and GFR ≥ 90 ml/min/1.73m2 (9). Patients also had to be normotensive for their age and sex and have no other significant renal or systemic disease. Quarterly studies included measurements of blood pressure, (BP), urinary albumin excretion rate (AER), hemoglobin A1C (HbA1C), GFR, and renal plasma flow (RPF). Renal biopsies were performed at baseline and after 5 years in the study. The primary goal of the study was to determine the clinical predictors of the baseline biopsy and baseline clinical and renal structural predictors of the changes between the baseline and the 5 year biopsy. The longitudinal structural studies are still in analysis and the paper will mainly review the cross sectional studies that hove been completed to date.

KW - Diabetes

KW - Kidney

KW - Natural history

UR - http://www.scopus.com/inward/record.url?scp=54949144323&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54949144323&partnerID=8YFLogxK

M3 - Article

VL - 5

SP - 958

EP - 963

JO - Pediatric endocrinology reviews : PER

JF - Pediatric endocrinology reviews : PER

SN - 1565-4753

IS - SUPPL. 4

ER -