pathological findings of diabetic kidney disease · 12/2/2018  · pathological findings of ....

Pathological findings of

diabetic kidney disease

APSN Continuing Medical Education (CME) Course 2019 in Japan Nagoya Congress Center June 20 (Thu), 20199:45-10:20

Kanazawa Medical University

KENGO FURUICHI

<30

30-44

45-59

60-90

≥90

GFR

(mL/

min

/1.7

3 m

2 )

Albuminuria（mg/g）

A1: <30 A2: 30-300 A3: >300

Stage3

Stage 4

Japanese classification of diabetic nephropathy

Stage2Stage1

*; p<0.05All cause mortality

Cardiovascular eventsKidney events

Wada, Furuichi et al. CEN 2013

N= 4,328Type 2 DM7 years follow up

Event risk in each category

eGFRNormo-albuminuria

Micro-albuminuria

Macro-albuminuria

>90Ref

3.3 11.1

>60 3.0 15.6

>45 0.7 3.4 33.4

>30 1.8 3.1 41.4

<30 6.0 5.8 81.7

eGFRNormo-albuminuria

Micro-albuminuria

Macro-albuminuria

>90Ref

1.0 1.3

>60 1.5 2.1

>45 1.0 1.3 1.9

>30 1.4 1.9 2.4

<30 0.4 0.6 2.0

eGFRNormo-albuminuria

Micro-albuminuria

Macro-albuminuria

>90Ref

1.5 4.4

>60 1.4 1.9

>45 1.6 1.2 4.8

>30 1.2 0.8 4.1

<30 7.6 9.3 5.9

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Pathological findings of diabetic kidney disease

1. What is DKD

2. Pathological variation of DKD

3. DKD and nephrosclerosis

4. Nonproteinuric DKD

CKD with diabetes

DKD

Furuichi K, et al. Clin Exp Nephrol 2018;22:1046-1051

Kidney disease in patients with diabetes

Diabetic nephropathy

Pathological findings of diabetic kidney disease

1. What is DKD in pathology?

2. Pathological variation of DKD

3. DKD and nephrosclerosis

4. Nonproteinuric DKD

Stage 1 Stage 2 Stage 3 Stage 4 Total# of cases 59 87 338 116 600Gender (% of male) 44.0 59.0 70.0 73.0 67.0 Age (yeas old) 54.6 57.6 57.4 61.0 57.9 Height (cm) 153.9 160.4 162.2 163.2 161.7 Weight (Kg) 51.3 60.1 63.7 66.0 63.1 BMI 22.6 23.4 23.9 24.1 23.7 sysBP (mmHg) 133.7 129.7 147.6 152.3 144.6 diaBP (mmHg) 76.0 74.7 80.1 80.2 78.9 Hb (g/dL) 13.2 13.3 12.0 10.3 12.0 UA (mg/dL) 4.5 6.0 6.7 7.5 6.7 TP (g/dL) 6.8 7.1 6.3 5.8 6.3 Alb (g/dL) 4.4 4.0 3.2 2.8 3.3 BS (mg/dL) 201.6 147.6 149.2 113.1 147.4 HbA1c (%) 8.3 8.1 7.7 6.8 7.6 Tcho (mg/dL) 187.1 197.5 226.0 220.1 217.3 TG (mg/dL) 118.1 177.6 172.2 160.4 166.0 eGFR (mL/min/1.73m2) 72.3 71.8 56.3 20.1 53.1 uAlb (g/gCr) 0.0 0.2 2.2 2.7 1.8

Clinical backgroundBased on Japanese classification of diabetic nephropathy 2014

Pathological findings

Glomerular lesions

Diffuse lesion 0-3Nodular lesion 0,1

Subendothelial space widening 0-3Exudative lesion 0,1Mesangiolysis 0,1

Polar vasculosis 0,1Global glomerular sclerosis %

Segmental glomerular sclerosis %Glomerulomegaly 0,1

Interstitial lesions

IFTA 0-3Interstitial cell infiltration 0-3

Vascular lesions

Hyalinosis 0-3Atherosclerosis 0-3

Pathological findings of diabetic nephropathy and nephrosclerosis

Furuichi K, et al. Nephrol Dial Transplant 2018;22:570-582

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

Pathologica changes of diabetic nephropathy.

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

0%20%40%60%80%

100%

1 2 3 4

Score 3Score 2Score 1Score 0

Furuichi K, et al. Clin Exp Nephrol. 2018;22:570-582

GMeg

Diffuse

SubendW

MesLy

PVasNodular

IFTA

ICell

Hyalin

ArterioExudative

p<0.001 ｐ=0.016

Score 0

Score 1

ｐ=0.014

ｐ=0.009

p<0.001

p<0.001

ｐ=0.342

ｐ=0.160

Glomerular diabetic change in early sategindicated poor prognosis.

p<0.001

Furuichi K, et al. , Nephrol Dial Transplant 2018;22:570-582

Nodular lesion

Exudative lesion

Mesangiolysis

Stage 1

Composit kidney eventsStage 2 Stage 3

Stage 1 Stage 2 Stage 3 Stage 4 TotalHR p HR p HR p HR p HR p

Diffuse >100.00 0.00 2.36 0.40 2.41 0.04 4.32 0.15 2.82 0.00Nodular 24.00 0.03 3.55 0.00 1.75 0.00 1.90 0.01 2.43 0.00 Subendo wide 2.89 0.22 2.54 0.05 1.88 0.00 3.21 0.00 2.77 0.38 Exudative 24.00 0.03 1.95 0.19 2.10 0.00 1.37 0.20 2.77 0.00 MesanLy 24.00 0.03 2.66 0.04 2.00 0.00 1.50 0.09 2.57 0.00 PolaVas 1.25 0.79 1.38 0.50 1.60 0.01 1.40 0.22 1.65 0.00 G Sclerosis 1.59 0.68 1.11 0.82 1.40 0.07 1.07 0.89 1.56 0.24 S Sclerosis 1.14 0.90 2.06 0.13 1.67 0.00 1.59 0.06 1.78 0.22 G Megaly 4.92 0.20 1.53 0.35 1.00 0.98 0.87 0.57 1.27 0.05 IFTA 1.09 0.91 2.11 0.18 2.68 0.00 0.36 0.31 3.41 0.88 Interstitial Cell 1.18 0.84 2.11 0.12 3.08 0.00 2.70 0.17 3.60 0.77 Hyalinosis 0.94 0.94 NA 1.00 1.94 0.09 1.81 0.56 2.41 0.74 Atheroscle 1.28 0.75 2.74 0.18 1.53 0.08 2.18 0.28 2.37 0.47

HR for composite kidney event in each pathological findings

Pathological findings of diabetic kidney disease

1. What is DKD in pathology?

2. Pathological variation of DKD

3. DKD and nephrosclerosis

4. Nonproteinuric DKD

Diabetic nephropathy has higher risk in kidney dysfunction than nephrosclerosis

Furuichi K, et al. Clin Exp Nephrol. 2018;22:1046-1051

Increased risk of diabetes

Nephrosclerosis (n = 184)Diabetic nephropathy (n = 600)

Non-CKD

Nephrosclerosis

Diabetic nephropathy

All cause mortality

Composite kidney event

Nephrosclerosis

Diabetic nephropathy

eGFR

chan

ges

(mL/

min

/1.7

3m2 /y

ear) CKD heat map category

カテゴリー G & Y Ogange Red TotalNS

(n=36)DM

(n=103)NS

(n=57)DM

(n=149)NS

(n=91)DM

(n=348)NS

(n=184)DM

(n=600)Age 53.17 54.17 53.60 56.31 57.62 59.63 55.50 57.87

Gender（Male） 0.61 0.53 0.70 0.60 0.65 0.74 0.66 0.67 BMI 26.05 23.25 26.61 23.22 24.22 24.06 25.31 23.72

Sys BP 142.30 131.27 134.95 141.87 141.65 149.52 139.59 144.60 Dia BP 81.55 75.85 81.58 78.88 86.37 79.80 83.89 78.91

Hb 14.40 13.52 14.31 12.83 13.04 11.22 13.70 11.98 eGFR 77.78 82.02 66.06 73.70 36.99 35.78 53.98 53.14 Alb 4.15 4.25 4.09 3.44 3.90 3.08 4.01 3.25

HbA1c 5.90 8.36 5.79 8.41 5.82 7.09 5.83 7.59 Tcho 234.44 196.08 220.85 218.67 213.64 222.45 220.33 217.25

Hematuria 0.42 0.03 0.58 0.30 0.51 0.41 0.51 0.32

Clinical backgroundDiabetic nephropathy and nephrosclerosis

Ｔ-test red p<0.05

Pathological findings

Glomerular lesion

DiffuseNodularSubendo wideExdativeMesanLyPolaVasG SclerosisS SclerosisG Megaly

Interstitial lesionsIFTAInterstitial Cell infiltration

Vascluar HyalinosisAtherosclerosis

Diabetic nephropathy

Nephrosclerosis

Pathological findings of diabetic nephropathy and nephrosclerosis

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* *

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Pathological findings of diabetic nephropathy and nephrosclerosis

NephrosclerosisDiabetic nephropathy

IFTA ICell

Hyalin Arterio

CKD heat map category

GFR≥60

45–5930–45<30

<30 30–299 ≥300Albuminuria

CKD heat map category

PLoS One. 2018 17;13:e0190493

eGFR change of nephrosclerosis

Pathological findings of diabetic kidney disease

1. What is DKD in pathology?

2. Pathological variation of DKD

3. DKD and nephrosclerosis

4. Nonproteinuric DKD

n=526 with T2D & eGFR<60 1:2 propensity score matching: age, gender, DM duration, baseline eGFR

Yamanouchi M, et al. Diabetes Care 2019;42:891-902

Non-proteinuric DN and proteinuric DN

Yamanouchi M, et al. Diabetes Care 2019;42:891-902

Kidney out come Mortality

Log-rank test p<0.001Log-rank test p<0.001

Non-proteinuric

Proteinuric

Non-proteinuric

Proteinuric

Non-proteinuric DN is better prognosis than proteinuric DN

Diabetes Care 2019;42:891-902

Diabetic glomerular changes were minor in non-proteinuric DN.

Nephrosclerosis

CKD with diabetes

DKD

Diabetic nephropathy

Furuichi K, et al. Clin Exp Nephrol 2018;22:1046-1051

Kidney disease in patients with diabetes