categorization of the diabetic nephropathy by tervaert classification in clinical setting
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Categorization of the diabetic nephropathy by Tervaert classification in clinical setting. Filipa Moreno*, Ana Pinho**, Renata Dias*, Ramon Vizcaino* *Anatomic Pathology Department – Santo Antonio Hospital, Oporto, Portugal **Nephrology Department – Faro Hospital, Faro, Portugal. - PowerPoint PPT PresentationTRANSCRIPT
Categorization of the diabetic nephropathy by Tervaert classification in
clinical settingFilipa Moreno*, Ana Pinho**, Renata Dias*,
Ramon Vizcaino*
*Anatomic Pathology Department – Santo Antonio Hospital, Oporto, Portugal**Nephrology Department – Faro Hospital, Faro, Portugal
Diabetic Nephropathy
Diabetic Nephopathy (DN) is the most common cause of end-stage renal disease (ESRD)
The percentage of patients with ESRD who have Diabetes Mellitus, specially Type II patients, have increseased over the past decade
The incidence of Diabetes Mellitus is rising world wide
It is estimated that 20-40% of all diabetic patients will develop diabetic nephropathy
What is the Diabetic Nephropathy?
Clinical syndromeClinical syndrome• Persistente proteinuria • Hypertension• Progressive decline in renal function
Pathologic renallesions
Pathologic renallesions
• Diabetic microangiopathy – of basement membrane (BM) material• Difuse glomerulosclerosis – difuse in mesangial matrix and thickening of the capillary walls • Nodular glomerulosclerosis – Kimmelstiel-Wilson lesions • Insudative lesions – hyalinosis • Atubular glomeruli• Difuse linear reaction for IgG along the BM
Diabetic Nephropathy
Glomerular-Thickening of glomerular basement membrane (GBM)-Mesangial expansion-Nodular glomerulosclerosis (Kimmelstiel-Wilson lesions)
Interstitial-Thickening of tubular basement membrane (TBM)-Arteriolar hyalinosis
Diagnostic histopathologic lesionsDiagnostic histopathologic lesions
Tervaert’s Pathologic Classification of Diabetic Nephropathy
Similar histologic lesionsSimilar renal complications
Type I DN Type I DN Type II DN Type II DN
Tervaert’s Pathologic Classification of Diabetic Nephropathy
Class I Glomerular Basement Membrane Thickening
• Biopsy shows no or only mild, nonspecific changes by light microscopy
• Changes do not meet the criteria of classes II through IV• Absence of mesangial expansion,
nodular KW lesions and glomerulosclerosis
• GBM, measured with EM is, on average• Thicker than 430 nm in males • Thicker than 395 nm in females
Class I – H & E 400x
Class II Mesangial Expansion
II a – MildII b – Severe
• Mild or severe mesangial expansion, not meeting the criteria for class II or IV
• Mesangial expansion – increase in extracellular material in the mesangium such that the width of the interspace exceeds two mesangial cell nuclei in at least two glomerular lobules
• Mild – expanded mesangial area < mean area of a capillary lumen
• Severe - expanded mesangial area > mean area of a capillary lumen
Class II a – PAS 400x
Class II b – PAS 400x
Class III Nodular Sclerosis – Kimmelstiel-Wilson lesions.
• At least one convincing Kimmelstiel-Wilson lesion is found
• The biopsy specimen does not have more than 50% global glomerulosclerosis (Class III)
• Kimmelstiel-Wilson lesion – focal, lobular, round to oval mesangial lesions with an acellular, hyaline/matrix core, rounded peripherally by sparse, crescent-shaped mesangial nucleiClass III – PAS 400x
Class IV Advanced Diabetic Glomerulosclerosis
• Advanced DN
• More than 50% global glomerulosclerosis
• The is clinical or pathological evidence that the sclerosis is attributable to DN
Class IV – PAS 400x
Tervaert’s Pathologic Classification of Diabetic Nephropathy
To assess the reliability and prognostic value of the Tervaert’s pathologic classification of
diabetic nephropathy in renal biopsies performed on type 2 diabetes mellitus patients
with an atypical clinical presentation of renal disease
Objective
Methods
Senior Pathologist>10 years experience(A – Gold standard)
Senior Pathologist>10 years experience(A – Gold standard)
Intermediate Pathologist3 years experience
(B)
Intermediate Pathologist3 years experience
(B)
Junior Pathologist1st year of practice
(C)
Junior Pathologist1st year of practice
(C)
Blinded inter-observer and blinded for clinical outcome categorization of DM biopsies
Study design
Population•Single-center study in a tertiary referral hospital for renal pathology•Retrospective evaluation of 710 consecutive renal biopsies•Selection of Diabetic Nephropathy (DM) positive biopsies
Exposure & Comparison
Methods Categorization with Tervaert Classification
Methods Study analysis
Outcomes
• Primary: Start dialysis • Secondary: Death (censored death not related with diabetic disease)
Time
• Between biopsy data and outcome (Cohort retrospective)
Results
• Testing of the different baseline characteristics among classes• Evaluation of Tervaert’s classification reproducibility • Survival analysis by classes - Kaplan Meier
Results Characterization of the Population
Table 1 Baseline data at the moment of biopsy**
** All patients had Type II diabetes mellitus
Results Reproducibility
Table 2 Senior Pathologist (A – Gold standard) vs Intermediate Pathologist experience (B)
Global Kappa – 0.82
Table 3 Senior Pathologist (A – Gold standard) vs Junior Pathologist experience (C)
(A)Classes II III IV
(B) II 9 1 1III 1 14 -IV - 1 3
kappa= 0.85
(A)Classes II III IV
(C) II 8 1 1III 2 13 -IV - 2 3
kappa=0.79
Results Renal survival
At 5 years follow-up
Renal survival•II= 98.4% •III= 54.3% •IV= 36.2%
Figure 1 Kaplain Meier curves by Tervaert Classification DN
Discussion
1. Recruitment
2. Allocation
3. Maintenance
4. Blind or objective assessment of outcomes
5. Results analysis
Study validity
Recruitment
• The setting was appropriate, given the study goals.
• The participants were at a similar stage in terms of progression of their disease.
• The participants were not representative of all Tervaert’s Pathologic Classification of Diabetic Nephropathy with pure nephropathy diabetic
Problems
Biopsies are performed only when clinical course is not typical for diabetic nephropathy
• The biopsies do not represent the pathologic range of DN in type II diabetic patients
• The biopsies only represent patients with atypical clinical course
• A wide range of non-diabetic renal disease may be present
Recruitment
Allocation
• The participants were consistently allocated to Tervaert’s classes
• The measurements of baseline data were accurate and similar for
the different classes
• The differences between classes were documented
at the biopsy date
Problems
The pathologic findings in diabetic nephropathy differ substantially between type I and type II diabetic patients
• Kidney lesions underlying renal dysfunction are more heterogeneous in type II patients
• In Type I patients, the most important renal structure changes occur in the glomeruli
• Type II patients are more complex and only a minority have histopathological patterns similar to the typical DN of Type I patients
Allocation
Problems
The mechanisms underlying the associations between cause, natural history and histopathological pattern in the
DN of Type II patients are inadequately defined
• Only a percentage of samples from type II diabetic patients with proteinuria have typical diabetic glomerulopathy
• The association between the clinic and pathologic findings is not always linear in Type II patients
• Differences found between class IIb and III may only be due to different pathogenic processes and not progression of disease
Allocation
Maintenance
• The participants remained in the groups they were initially allocated to
• The participants / investigators were blind to participants categorization
with Tervaert Classification /clinical baseline data, respectively
• Clinical co-intervention during the follow-up period was unknown
• Completeness of follow-up was high and similar in allocated groups
• Compliance and contamination problems were probably absent
Assessment of outcomes
• The outcome assessors were unaware of participants
categorization with Tervaert Classification (Blind assessment of
outcomes)
• The assessment of outcomes was objective (start dialysis date)
• The death not related with diabetic disease was censored
Results
• Survival analyses include all participants allocated by exposure
factor
• Reasonable precision (low confidence limits)
• There was consistency with other studies
• No adjusted analyses was needed for confounders
Mazzucco, G. et al. Different patterns of renal damage in type 2 diabetes melitus: a multicentric
study on 393 biopsies. AJKD 39 (4), 713-720 (2002)
Se Won Oh et al. Clinical implications of pathologic diagnosis and classification for diabetic nephropathy. Diabetes research and clinical practice 97 418–424 (2012)
Conclusions
•In our study, Tervaert classification proved to be user friendly, accurate and clinically useful
•There was a good inter-observer reproducibility
•A uniform and consistent classification of DN will improve the communication between renal pathologists and clinicians, allowing better clinical management.
•Our findings corroborate the results from experimental centers
•Larger and more significant trials are therefore recommended
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