apsn - xueqing yu · 2019-09-05 · primary igan confirmed by renal biopsy in the first affiliated...

IgAN Treatment : Current and Perspective

Insights from Chinese Evidences

Xueqing Yu

Department of Nephrology, The First Affiliated Hospital,

Sun Yat-Sen University, Guangzhou

IgAN: the most common primary GN in the world

• Geographical variations in disease prevalence

• More common in young adults (20-39 yr)

• Sex and race difference, familial clustering

- Male: Female 2:1

- Caucasians and Asians are more prone than Blacks

Epidemiology of IgAN

IgAN Clinical Outcome : Big Different

• Slow Progression（30～40%）

– 10 year renal loss 15%～25%

– 20 year renal loss 20％～30％

– 1.5% to ESRD per year

• Rapid progression (＜10%)• Spontaneous remission (＜5 %)• Persistent hematuria (～50%)

KDIGOKidney Disease Improving Global Outcomes

Improve The Prognosis Of Global Kidney Diseases

Toward Global Clinical Practice Guidelines for Kidney Disease

• It is recommended that an ARB or ACE-I be used in both diabetic and non-diabetic adults with CKD and proteinuria >1g/24 hours. (1B)

• It is suggested that a RASI be used in adults with proteinuria 0.5-1.0g/24 hours and in children with proteinuria 0.5-1g/d/1.73m2 (2D).

• It’s suggested to increase dose of ACEI or ARB until proteinuria <1g/d if can be tolerated (2C),

• It’s recommended that a target blood pressure of <130/80mmHg in patients with proteinuria <1g/d, and 125/75 mmHg for those with initial proteinuria >1g/d.

Steroid and Immunosuppressant

• It is recommended that steroid treatment of 6 months in

patients with consistent proteinuria ≥1g/d (with non-response

to 3-6 months ACEI or ARB treatment) (2B).

• It is suggested not treating with corticosteroids combined with

cyclophosphamide or azathioprine in IgAN patients (unless

there is crescentic IgAN with rapidly deteriorating kidney

function. (2D)

• It is suggested not using immunosuppressive therapy in

patients with GFR <30 ml/min per 1.73m2 unless there is

crescentic IgAN with rapidly deteriorating kidney function (2C)

• It is suggested not using MMF in IgAN. (2C)

Study Patient selection Protocols and grouping Follow-up Outcome

Maes BD et al. 2004（n=34)

20<Ccr<70ml/min/, Upro>1g/d,

Grade II to IV by Churg and SobinSBP≥140 or DBP≥90

MMF (2.0/d)/Placebo(21

/13)

CCr，Upro，3ys Follow

up No benefit

Frisch G et al. 2005（n=32)

20<Ccr<80ml/min/Upro>1g/d,

Glomerulosclerosis or tubulointerstitial atrophy and

fibrosis ≥25%BP≥150/90 mmHg

MMF (2.0/d，n=17)/Placebo(17/15)(n=15) for 1yr

Scr,Upro, 3ys Follow

up No benefit

Chen et al2002

（n=62）

Scr<4mg/dl, Upro≥2g/d, Grade IV-V by Lee

No mention BP

OP(n=31, OP 0.8/kg.d) ；MMF(n=31, 1.5~2.0/d) 6

mons

Upro，Follow up

18 mon

reduction Upro

Tang S et alScr<3.4mg/dl, Upro>1g/d,

Haas Grade II-IV<125/85 treated with ACEI/ARB

Control (n=20), ACEI or ARB；

MMF(1.5-2.0/d,n=20),ACEI

or ARB，72weeks

Uprofollow up

for 72 wks

reduction Upro

Cum

ulat

ive

prob

abili

ty o

f rem

issi

on %

Time (months)

Log-rank test: P=0.009

0 2 4 6 9 12

Response rate:

Pred+MMF: 24/30 (80.0%)

Pred: 17/29 (58.6%)

MMF: 12/29 (41.4%)

Pred+MMF:80.0%

Pred:58.6%

MMF:41.4%

Low dose steroid and MMF in IgA nephropathy treatment in China

Challenges in IgAN: diagnosis and therapy

• Clinical patterns：Microscopic haematuria to massive proteinuria

• Pathological patterns ：slightly mesangial proliferative to global sclerosis

• Response to therapies：Sensitive, dependent, or resistant to treatment agents

• Clinical outcomes：stable renal function for lifetime to ESRD

Indications for Treatment of IgAN

Microscopic haematuria

Macroscopic haematuria

Acute kidney injury

Crescentic IgA nephropathy

Proteinuria＞1g/d

Nephrotic syndrome

Hypertension

Progressive fall in GFR

Clinical pattern

Risks of progression

IgAN Database System in SYSUhttp://igan.medidata.cn/

• Real-time data collection system

• Quality control

• Real time Statistics Report Monitoring

• Real-time dynamic multidimensional

Statistic Analysis

• Export data in multiple formats

• Multi-center data management: strict

permission control

Samples and Patients’Databases

• Samples of Kidney diseases：

153 renal units in 30 provinces

patients with KD：29,383

health controls： 30,291

• Patient cohorts：

163 renal units in 30 provinces

registered patients：38,431

Registered Database For Kidney Diseases

datatbase Renal units Patients (n)

IgAN 115 13671

LN 99 4592

PD 89 12807

HD 54 7552

NS 103 1238

REAL-TIME DYNAMIC MULTIDIMENSIONAL STATISTIC ANALYSIS

• Annual patients distribution• Patient birthplace distribution• Sex distribution• Age distribution• BMI• Dyslipidemia• Hyperuricemia• Hypertension• Proteinuria• CKD staging• Scr≥1.5mg/dl• Serum calcium, phosphorus

and iPTH• Clinical manifestation

• Lee classification• Oxford classification• Mesangial hypercellularity• Segmental sclerosis or

glomerular adhesion• Endocapillary

hypercellularity• Crescent• Segmental glomerular

necrosis• Interstitial fibrosis• Tubular atrophy• Arteriolar wall thickness

• Patients survival• Overall• Different levels of

proteinuria• Different levels of

average MAP• Different CKD stage

• Renal survival• Overall• Different levels of

proteinuria• Different levels of

average MAP• Different CKD stage

http://igan.medidata.cn/

Patients Survival in IgAN

Cum survival rates in IgAN patients（%）

Cases 3-year 5-year 10-year 20-year

2119 98.86 98.30 96.96 96.96


Cum Renal survival rates of IgAN patients（%）

Cases 3-year 5-year 10-year 20-year

1939 88.5 81.9 62.2 19.4

Renal Survival Rates in IgAN


Risk Factors on IgAN Progression

• 24 h urinary protein excretion＞1g

• Nephrotic Syndrome

• Microscopic hematuria

• Gross hematuria

• Hypertension

• Acute kidney injury

• Crescent

• Rapidly decrease in GFRhttp://igan.medidata.cn/

Cohort Studies Based on IgAN Database

1 Clinic pathologic features and outcomes of IgAN patients presented with different levels of proteinuria

2 Clinic pathologic features and outcomes of IgAN patients presented with nephrotic syndrome

3 Clinic pathologic features and outcomes of IgAN patients with microscopic hematuria

4 Clinic pathologic features and outcomes of IgAN patients with gross hematuria

5 Clinic pathologic features and outcomes of IgAN patients with acute kidney injury

6 Clinic pathologic features and outcomes of IgAN patients presented with hypertension

7Clinic pathologic features and outcomes of IgAN patients relevant to Circadian Blood Pressure Rhythm, Variability

8 Risk factors and outcomes of IgAN patients with progressive decrease in GFR

9Clinic pathologic features and outcomes of IgAN patients with age >50 years old

10Long-term renal survival in male and femalepatients with IgA nephropathy and related associated factors

11Clinic features and outcomes of IgAN patients presented with different proportions of crescents

12Clinic pathologic features and outcomes of necrotizing IgAN

13Clinic features and outcomes of IgAN patients with renal tubular/interstitial injury

14Clinic pathologic features and outcomes of IgAN patients with vasculitis lesion

15Clinic pathologic features and outcomes of IgAN patients with endothelial proliferation

16Clinic pathologic features and outcomes of IgAN patients with podocyte lesions

• Inclusion criteria：– Primary IgAN confirmed by renal biopsy in The First Affiliated Hospital of Sun

Yat-sen University during January 2006 to December 2011

– Adequate biopsy sample containing ≥ 10 glomeruli

– Age ≥ 14 years

– Willingness to sign the informed consent

• Exclusion criteria：– Secondary IgAN (Hepatitis B-related nephritis、Henoch-Schonlein purpura

nephritis、Lupus nephritis and et al.）– Transplantation-related IgAN– Loss of follow-up– eGFR<15 ml/min/1.73m2

Inclusion and Exclusion Criteria



Gross haematuria

Acute kidney injury


Proteinuria＞1g/d

Nephrotic syndrome

Hypertension


Clinical pattern


Clinical Outcomes of IgA Nephropathy with

Isolated Hematuria

Baseline Data for Patients with Isolated Hematuria

VariableNone-Proteinuria Micro-proteinuria Total

Pn =180 n =76 n = 256

Age(years) 30.49±11.35 28.00±10.41 29.75±11.11 0.102

Female/Male (n) 143/37 54/22 197/59 0.145

Children (n[%]) 16(8.9) 7(9.2) 23(9.0) 0.934

BMI (Kg/m²) 20.14±2.97 20.14±2.77 20.14±2.91 0.985

Duration of IgAN (mo)* 6.49(0.43,251.50) 8.21(0.46,221.90) 6.78(0.43,251.50) 0.781

Macroscopic Hematuria (n[%]) 96(53.3) 41(53.9) 137(53.5) 0.928

Microscopical RBC (+)* ++(+,++++) ++(+,++++) ++(+,++++) 0.738

Hypertension (n[%]) 7(3.9) 1(1.3) 8(3.1) 0.491

Edema (n[%]) 14(7.8) 3(3.9) 17(6.6) 0.261

Hb (g/L) 124.72±14.91 126.16±13.57 125.15±14.51 0.471

Serum Albumin (g/L) 42.22±3.35 41.84±4.33 42.11±3.66 0.512

Serum Uric Acid (µmol/L) 258.63±74.56 275.61±79.61 263.81±76.37 0.116

Total Cholesterol (mmol/L) 4.51±0.99 4.67±0.95 4.56±0.98 0.260

Triglyceride (mmol/L)* 0.82(0.30,8.34) 0.88(0.33,2.64) 0.85(0.30,8.34) 0.334

eGFR (ml/min/1.73m²)* 123.23(90.52,221.86)

111.53(90.08,191.86)

120.20(90.08,221.86)

0.007

VariableNone-Proteinuria Micro Proteinuria Total

Pn =180 n =76 n = 256

Global Sclerosis (%)* 0(0,40.74) 0(0,58.33) 0(0,58.33) 0.337

Segmental Sclerosis (%)* 0(0,28.57) 0(0,35.29) 0(0,35.29) 0.127

MS Proliferation (n[%]) 0.096

Mild 147(81.7) 55(72.4) 202(78.9)

Moderate 33(18.3) 21(27.6) 54(21.1)

Capsular Adhesion (n[%]) 28(15.6) 18(24.3) 46(18.1) 0.099

Crescents Formation (n[%]) 21(11.7) 15(19.7) 36(14.1) 0.090

Endothelial Proliferation (n[%]) 21(11.7) 7(9.5) 28(11.0) 0.610

Podocyte Proliferation(n[%]) 8(4.4) 4(5.4) 12(4.7) 0.998

Tubule Atrophy (n[%]) 0.686

None 77(42.8) 31(41.3) 108(42.4)

Focal 91(50.6) 37(49.3) 128(50.2)

Diffuse 12(6.7) 7(9.3) 19(7.5)

Interstitial Infiltration of Inflammatory Cells (n[%])

0.491

None 83(46.1) 40(54.1) 123(48.4)

Focal 86(47.8) 26(35.1) 112(44.1)

Diffuse 11(6.1) 8(10.8) 19(7.5)

Baseline Data for Patients with Isolated Hematuria

VariableNone-Proteinuria Micro Proteinuria Total

Pn =180 n =76 n = 256

Interstitial Fibrosis (n[%]) 0.023

None 151(83.9) 70(94.6) 221(87.0)

Focal 26(14.4) 3(4.1) 29(11.4)

Diffuse 3(1.7) 1(1.4) 4(1.6)

Thickness of vessel wall (n[%]) 28(15.6) 10(13.5) 38(15.0) 0.678

IgA Intensity (+)* ++(+,++++) +++(+,++++) ++(+,++++) 0.130

IgA Location (n[%]) 0.053

MR 159(93.0) 63(85.1) 222(90.6)

MR & Capillary Loops 12(7.0) 11(14.9) 23(9.4)

Immune Complexes (n[%]) 0.016

IgA 20(11.1) 3(3.9) 23(9.0)

IgA+C3 106(58.9) 37(48.7) 143(55.9)

IgA+IgG 5(2.8) 1(1.3) 6(2.3)

IgA+C3+IgG 49(27.2) 35(46.1) 84(32.8)

Baseline Data For Patients With Ioslated Hematuria

Outcomes of IgAN Patients with HematuriaOutcome Variable None-

ProteinuriaMicro

Proteinuria Total P

eGFR decline＞25% 26(14.4%)* 17(22.4%) 43(16.8%) 0.121

ESRD 0 4(5.3%) 4(1.6%) 0.007

Proteinuria ≥0.5g/24h 13(7.2%) 18(23.7%) 31(12.1%) ＜0.001

New-onset Hypertension 17(9.4%) 10(13.2%) 27(10.5%) 0.377

•The percentage is calculated by outcome cases/ total patients in the corresponding proteinuria group.

112175150219256Number of risk

Renal Survival Of Patients With Isolated Hematuria

Risk Factors on Renal Progression of IgAN Patients With Isolated Hematuria

VariableUnivariateAnalysisRR(95%CI)

Multivariate Analysis RR(95%CI)

Model 1(unadjusted)

Model 2(adjusted)

Urine RBC at baseline + reference reference reference

++++ 4.299(1.250,14.787)* 16.39(2.88,93.09)** 24.34(3.65,162.41)**

Serum albumin at baseline pre 1g/L) 0.913(0.843,0.989)* 0.891(0.818,0.970)** —

Clinical Proteinuria during follow-up（>0.5/24h） 2.543(1.365,4.736)** 3.366(1.698,6.676)** 4.086(1.786,9.345)**

Tonsillitis during follow-up 2.026(1.011,4.060)* — —

Segmental Sclerosis (pre 1%) 1.049(1.007,1.092)* — —

Interstitial Infiltration of inflammatory Cells None reference — reference

Diffuse 3.761(1.489,9.497)** 5.018(1.519,16.577)**

^adjusted by age, sex, eGFR and minimal proteinuria at baseline* P ＜0.05, ** P ＜0.01

IgAN Patients with Gross Hematuria

VariablesGross hematuria Microscopic

hematuria TotalP

n =137 n =119 n = 256

Age(years) 26.58±11.41 33.40±9.58 29.75±11.11 ＜0.001

Female/Male(n) 103/34 94/25 197/59 0.470Children(n[%]) 22(16.1) 1(0.8) 23(9.0) ＜0.001BMI(Kg/m²) 19.60±2.85 20.76±2.86 20.14±2.91 0.001Duration of IgAN(mo)* 6.14(0.46,251.50) 7.59(0.43,174.03) 6.78(0.43,251.50) 0.243Microscopical RBC+)* ++(+,++++) +(+,++++) ++(+,++++) ＜0.001Microalbuminuria(n[%]) 41(29.9) 35(29.4) 76(29.7) 0.928Hypertension(n[%]) 3(2.2) 5(4.2) 8(3.1) 0.478Edema(n[%]) 8(5.8) 9(7.6) 17(6.6) 0.581Tonsillitis (n[%]) 52(38.0) 22(18.5) 74(28.9) 0.001Tonsillitis-Predisposing factor(n[%]) 9(6.6) 1(0.8) 10(3.9) 0.042Upper Respiratory Infection –Predisposing factor(n[%])

79(57.7) 12(10.1) 91(35.5) ＜0.001

Family History of CKD(n[%]) 20(14.6) 6(5.0) 26(10.2) 0.012Serum Albumin(g/L) 41.98±3.84 42.25±3.46 42.11±3.66 0.562Serum Uria acid(µmol/L) 257.39±68.26 271.17±84.43 263.81±76.37 0.167

eGFR(ml/min/1.73m²)*121.67

(90.63,217.23)118.87

(90.08,221.86)124.89

(90.08,221.86)0.517

Clinical Characteristic Of Patients With Gross Hematuria

Pathological Characteristics Of Patients With Gross Hematuria

VariablesGross hematuria Microscopic

hematuria TotalP

n =137 n =119 n =256

Global Sclerosis(%)* 0(0,58.33) 2.33(0,50.00) 0(0,58.33) 0.022

Segmental Sclerosis (%)* 0(0,12.50) 0(0,35.29) 0(0,35.29) 0.486

MS Proliferation (n[%]) 0.519

Mild 106(77.4) 96(80.7) 202(78.9)

Moderate 31(22.6) 23(19.3) 54(21.1)

Capsular Adhesion (n[%]) 27(20.0) 19(16.0) 46(18.1) 0.405

Crescents Formation (n[%]) 22(16.1) 14(11.8) 36(14.1) 0.324

Endothelial Proliferation (n[%]) 11(8.1) 17(14.3) 28(11.0) 0.119

Podocyte Proliferation(n[%]) 7(5.2) 5(4.2) 12(4.7) 0.712

Tubule Atrophy (n[%]) 0.041

None 66(48.5) 42(35.3) 108(42.4)

Focal 61(44.9) 67(56.3) 128(50.2)

Diffuse 9(6.6) 10(8.4) 19(7.5)

Interstitial Infiltration of Inflammatory Cells(n[%])

0.249

None 71(52.6) 52(43.7) 123(48.4)

Focal 53(39.3) 59(49.6) 112(44.1)

Diffuse 11(8.1) 8(6.7) 19(7.5)

Pathological Characteristic Of Patients With Gross Hematuria

VariableGross hematuria Microscopic

hematuria TotalP

n =137 n =119 n = 256

Interstitial Fibrosis(n[%]) 0.047

None 123(91.1) 98(82.4) 221(87.0)

Focal 9(6.7) 20(16.8) 29(11.4)

Diffuse 3(2.2) 1(0.8) 4(1.6)

Thickness of vessel wall(n[%])

17(12.6) 21(17.6) 38(15.0) 0.260

IgA Intensity(+)* ++(+,++++) +++(+,++++) ++(+,++++) 0.922

IgA Location(n[%]) 0.541

MR 121(91.7) 101(89.4) 222(90.6)

MR & Capillary Loops 11(8.3) 12(10.6) 23(9.4)

Immune Complexes(n[%]) 0.695

IgA 11(8.0) 12(10.1) 23(9.0)

IgA+C3 77(56.2) 66(55.5) 143(55.9)

IgA+IgG 2(1.5) 4(3.4) 6(2.3)

IgA+C3+IgG 47(34.3) 37(31.1) 84(32.8)

Summary of Outcomes

Outcome Variable Non-Proteinuria

Micro Proteinuria Total P

eGFR decline＞25% 14(14.6%)* 12(29.3%) 26(19.0%) 0.045

ESRD 0 4(9.8%) 4(2.9%) 0.007

Proteinuria ≥0.5g/24h 8(8.3%) 12(29.3%) 20(14.6%) 0.001

New-onset Hypertension 6(6.3%) 7(17.1%) 13(9.5%) 0.097

microproteinuria: 24hour proteinuria 0.3 ～ 0.5

7154484117137肾无事件人数

Renal Survival Of Patients With Gross Hematuria

3y 6y 9y 12y 15yTotal(137) 100 96 73 60 53

Risk Factors For Renal Progression Of Patients With Gross Hematuria

VariableUnivariate AnalysisRR(95%CI)

Multivariate Analysis RR(95%CI)

Model 1(unadjusted)

Model 2(adjusted)^

Serum uria acid(pre 1µmol/L) 1.007(1.000,1.013)* 1.008(1.001,1.015)* 1.011(1.003,1.019)**

Clinical Proteinuria during follow-up 3.121(1.412,6.898)** 4.363(1.785,10.665)** 4.949(1.748,14.012)**

Segmental Sclerosis(pre 1%) 1.170(1.057,1.295)** — —

Interstitial Infiltration of inflammatory Cells None Reference — reference

Diffuse 4.581(1.341,15.652)* 6.667(1.438,30.914)*

^adjusted by age, sex, eGFR and minimal proteinuria at baseline* P ＜0.05, ** P ＜0.01

The Impact of Hematuria on Patients

Patients of IgAN presenting with isolated hematuria have a potential risk with renal progression

Patients with micro-proteinuria have a similar risk rate with renal progression with those presented gross hematuria.

Proteinuria and diffuse interstitial infiltration of inflammatory cells are important risk factors for patients of IgAN presenting isolated hematuria.

Patients of IgAN presenting isolated hematuria should also monitor the level of urine protein and renal function regularly.



Gross haematuria

Acute kidney injury


Proteinuria＞1g/d

Nephrotic syndrome

Hypertension


Clinical pattern


The Prevalence and risk factors in IgAN Patients

• The prevalence of AKI in our center is 9.59%.

• The clinicopathological injuries were much more severe in AKI-IgAN patients, while had less onset of macroscopic hematuria.

• Acute tubulointerstitial injuries was the most significant intrinsic pathogenic mechanism of AKI in IgAN patients

data was based on：http://igan.medidata.cn/




Acute kidney injury


Proteinuria＞1g/d

Nephrotic syndrome

Hypertension


Clinical pattern


Effect of crescents on the prognosis of IgAN patients

The Profile of crescents in IgAN patients

2006.1.1-2011.12.31 1484 eligible IgAN patients

Crescent: 623 cases (42.0%)

Crescent followed-up: 401cases

Non-crescent: 861 cases

Non-crescent followed-up: 547cases

A flow diagram of the enrollment

The Influence of Crescent on Renal Outcomes of IgA Nephropathy

All crescent non-crescent P

N 948 401 547Gender [n(%)]

MaleFemale

406(42.8)542(57.2)

186(46.4) 215(53.6)

220(40.2)327(59.8) 0.058

Age[yr] 32(26,39) 30(25,38) 33(27,40) <0.001

eGFR [ml/min/1.73 m2] 95(60,123) 85(52,116) 102(67,128) <0.001

SBP [mmHg]DBP[mmHg]

123(112,136)79(70,89)

125(113,139)79(70,89)

122(111,135)79(70,89)

0.0890.368

Hb [g/L] 128(115,140) 125(113,138) 128(116,142) 0.009

UA[umol/L] 349(270,431) 366(294,458) 330(260,419) <0.001

ALB [g/L] 40(37,43) 39(35,42) 40(37,43) <0.001

Chol [mmol/L] 4.9(4.2,5.9) 5.1(4.3,6.0) 4.8(4.2,5.8) 0.022

TG [mmol/L] 1.3(0.9,1.9) 1.4(0.9,2.0) 1.2(0.9,1.8) 0.040

Urine protein [g/24h] 0.60(0.31,1.20) 0.74(0.40,1.54) 0.51(0.27,1.03) <0.001

Urine RBC [n(%)]+

+++++

++++

254(26.9)197(20.9)122(12.9)

51(5.4)

104(26.0)103(25.8)64(16.0)22(5.5)

150(27.6)94(17.3)58(10.7)29(5.3)

<0.001

Comparison between patients with and without crescents

All crescent non-crescent PGlobal glomerulosclerosis[%] 11(0,31) 13(4,31) 9(0,29) 0.002

Segmental glomerulosclerosis[%] 0(0,8) 3(0,9) 0(0,6) <0.001Mesangial hypercellularity [n(%)]

FocalDiffuse

356(37.6)507(48.8)

136(33.9)240(59.9)

220(40.2)267(48.8) 0.001

Endocapillary hypercellularity [%]Focal

Diffuse176(18.6)

11(1.2)106(26.4)10(2.5)

70(12.8)1(0.2) <0.001

Necrosis [n(%)] 71(7.4) 51(12.7) 20(3.6) <0.001Interstitial inflammation [n%]

<25%25%-50%50%-75%≥75%

542(57.2)153(16.1)13(1.4)6(0.6)

250(62.3)73(18.2)6(1.5)5(1.2)

292(53.4)80(14.6)

7(1.3)1(0.2) <0.001

Tubular atrophy [n(%)]<25%

25%-50%50%-75%≥75%

472(49.8)228(24.1)16(1.7)3(0.3)

209(52.1)116(28.9)

9(2.2)1(0.2)

263(48.1)112(20.5)

7(1.3)2(0.4)

<0.001

Interstitial fibrosis [n(%)]<25%

25%-50%50%-75%≥75%

371(39.1)178(18.8)19(2.0)4(0.4)

183(45.6)88(21.9)12(3.0)1(0.2)

188(34.4)90(16.5)

7(1.3)3(0.5) <0.001

Comparison between patients with and without crescents

No. at risk

Crescent 401 264 63

Non-crescent 547 410 188

All 948 674 251

36 months(3yr)

60 months(5yr)

Crescent 93.1 81.3

Non-crescent 95.8 91.2

All 93.3 84.6

Log rank=29.29P<0.001

Cumulative Renal Progression-free Survival Rate (%)

0 12 24 36 48 60 72 84 960

102030405060708090

100

Survival Time(month)Cum

Ren

al P

rogr

essi

on-f r

ee s

urvi

val

CrescentNon-crescent

Renal Survival for IgAN patients with and without crescents

Multivariate Cox regression: the independent risk factors for unfavorable prognosis

HR (95%CI) P value

unadjusted

Crescent 2.23(1.58,3.33) <0.001

adjusted for MEST

Crescent 1.68(1.16,2.46) 0.006Segmentalglomerulosclerosis 2.39(1.59,3.59) <0.001

Tubular Atrophy 4.34(3.34,5.64) <0.001

adjusted for age, gender, eGFR, hypertension, proteinuria, and MEST

Crescent 1.26(0.85,1.86) 0.255Baseline eGFR* 0.96(0.95,0.97) <0.001Proteinuria 1.24(1.10,1.40) <0.001Segmental glomerulosclerosis 2.24(1.48,3.4) <0.001

Tubular Atrophy 1.57(1.14,2.16) 0.006

2000.1.1-2011.12.31 3069 IgAN patients in database

2345 pts

ESRD on admission: 251 ptsSecondary IgA deposite: 17 ptsIncomplete pathology data: 83 pts

2718 pts

No. of glomeruli <10 : 373 pts

748 pts (31.9%) presented crescents

565 pts completed the follow-up

Flow chart of enrollment

Clinical Outcomes of IgA Nephropathy Patients with Different Proportions of Crescents

Variable All <5% 5%-9% 10%-25% ≥25% P

N 565 158 176 182 49

Gender [N(%)] Male

Female 256(45.3) 309(54.7)

72(45.6) 86(54.4)

75(42.6) 101(57.4)

86(47.3) 96(52.7)

23(46.9)26(53.1) 0.837

Age[yr] 32±11 32±11 33±11 31±11 33±14 0.434

eGFR [ml/min/1.73 m2] 81±37 93±37 77±36 79±36 63±39 <0.001

Hypertension [N(%)] 169(29.9) 42(26.6) 51(29.0) 58(31.9) 18(36.7) 0.507

Gross hematuria [N(%)] 71(12.6) 17(10.8) 26(14.8) 24(13.2) 4(8.2) 0.536

Hb [g/L] 124±20 129±17 124±20 123±20 115±20 <0.001

UA [umol/L] 373±132 343±114 387±139 375±121 414±175 0.026

ALB [g/L] 39(36,42) 41(37,42) 39(36,43) 38(35,41) 35(30,39) <0.001

Chol [mmol/L] 5.1(4.3,6.0)

4.8(4.1,5.9)

4.9(4.3,5.8)

5.2(4.4,6.2)

5.7(4.8,6.9) 0.016

Urine protein [g/24h] 0.78(0.40,1.52)

0.56(0.32,1.29)

0.74(0.40,1.39)

0.91(0.40,1.53)

1.12(0.68,2.77) <0.001

Urine RBC+

+++++

++++

182(32.6)153(27.4)94(16.8)19(3.4)

46(29.3)48(30.6)23(14.6)5(3.2)

64(37.0)43(24.9)27(15.6)6(3.5)

58(32.4)47(26.3)35(19.6)

6(3.4)

14(28.6)15(30.6)9(18.4)2(4.1) 0.968

Baseline clinical characteristics of IgAN patients with crescents

Variable All <5% 5%-9% 10%-24% ≥25% P

Cellular crescent [%] 0(0,50) 0(0,100) 0(0,50) 0(0,40) 6(0,53) 0.983

Fibrocellular crescent [%] 17(0,75) 0(0,100) 0(0,100) 40(0,75) 50(14,76) <0.001

Fibrous crescent [%] 1(0,40) 0(0,100) 0(0,63) 20(0,65) 13(0,38) 0.674

Global glomerulosclerosis[%] 12(4,31) 9(0,24) 16(5,38) 11(4,32) 12(6,35) 0.014

Segmental glomerulosclerosis[%] 3(0,9) 1(0,7) 4(0,9) 4(0,12) 0(0,8) 0.031

Diffuse mesangial hypercellularity [N(%)] 447(79.1) 126(79.7) 130(73.9) 149(81.9) 42(85.7) 0.164

Endocapillary hypercellularity [N%] 175(31.0) 40(25.3) 43(24.5) 69(37.9) 23(46.9) 0.012

Necrosis [N(%)] 75(13.7) 21(13.6) 18(10.7) 29(16.5) 7(14.6) 0.474

Interstitial inflammation[N(%)]<25%

25%-50%50%-75%

≥75%

272(48.6)140(25.0)

31(5.5)9(1.6)

84(53.8)23(14.7)

4(2.6)3(1.9)

79(44.9)42(23.9)14(8.0)5(2.8)

87(48.3)58(32.2)

8(4.4)0(0.0)

22(45.8)17(35.4)5(10.4)1(2.1) <0.001

Tubular atrophy [N(%)]<25%

25%-50%50%-75%

≥75%

282(50.4)151(27.0)

30(5.4)10(1.8)

90(57.7)28(17.9)

4(2.6)2(1.3)

85(48.6)51(29.1)12(6.9)5(2.9)

87(48.1)57(31.5)

9(5.0)0(0.0)

20(41.7)15(31.3)5(10.4)3(6.3) 0.004

Interstitial fibrosis [N(%)]<25%

25%-50%50%-75%

≥75%

210(37.6)118(21.1)

12(2.2)5(0.9)

57(36.8)22(14.2)

0(0.0)2(1.3)

65(37.4)31(17.8)

4(2.3)2(1.1)

72(40.0)49(27.2)

5(2.8)0(0.0)

16(32.7)16(32.7)

3(6.1)1(2.0) 0.002

Baseline pathologic characteristics of IgAN patients with crescents

Variable All <5% 5%-9% 10%-25% ≥25% P

N 565 158 176 182 49

RAS Blockade [N(%)] 454(80.4) 129(81.6) 139(79.0) 150(82.4) 36(73.5) 0.505

Immunosuppressivetherapy * [N(%)] 214(37.9) 42(26.6) 51(29.0) 87(47.8) 34(69.4) <0.001

Oral corticosteroid [N(%)]≤0.5mg/kg

1mg/mg

212(37.5)132(23.4)74(13.1)

41(25.9)25(15.8)14(8.9)

51(29.0)36(20.5)14(8.0)

86(47.3)58(32.0)26(14.3)

34(69.4)13(26.5)20(40.8)

<0.001

MP iv. Pulse [N(%)] ≤0.5g>0.5g

99(17.8)89(16.0)10(1.8)

19(12.1)16(10.2)

3(1.9)

18(10.5)17(9.9)1(0.6)

41(22.8)38(21.1)

3(1.7)

21(42.9)18(36.8)

3(6.1)<0.001

Cytotoxic agent [N(%) ]MMFCTXCsA

37(6.5)17(3.0)17(3.0)3(0.5)

5(3.2)2(1.3)1(0.6)2(1.3)

6(3.4)5(2.8)1(0.6)0(0)

15(8.2)8(4.4)7(3.8)0(0)

11(22.4)2(4.1)

8(16.3)1(2.0)

<0.001

*corticosteroid and (or) cytotoxic agents

Treatment of IgAN patients with crescents

Renal Survival for different proportions of glomeruli with crescents

Crescent proportion 60 months (5yr) 120 months (10 yr)

<5% 5%-9%

10%-24% ≥25% Total

93.881.380.570.983.2

69.346.843.835.253.3

Long-term Renal Progression-free Survival (%)

120.0060.000.00

F o llo w-u p tim e (m o n th s )

1.0

0.8

0.6

0.4

0.2

0.0

≥25%-ce ns ore d

10%-24%-

ce ns ore d

5%-9%-ce ns ore d

<5%-ce ns ore d

≥25%

10%-24%

5%-9%

<5%

cre s ce nt proportion

Log rank=11.5P=0.009

No. at risk

<5% 5%-9%

10%-24% ≥25% Total

15817618249565

40473314134

475521

Cum Progression-free Survival

Model 1: age,sex, crescent proportion, segmental sclerosis, extent of mesangial hypercellularity，endocapillary hypercellularity, tubular atrophy.

Variable HR 95% CI P

Segmental glomerulosclerosis (per 5%) 1.19 1.07-1.33 0.002

Diffuse mesangial hypercellularity 1.09 0.69-1.72 0.713

Endocapillary hypercellularity 2.64 1.30-5.34 0.007

Tubular atrophy (per quartile) 1.87 1.39-2.52 <0.001

Crescent proportion (per 5%) 1.08 0.98-1.20 0.108

Multivariate Cox regression (model 1): the independent risk factors for unfavorable prognosis

Model 2: baseline eGFR, hypertention, urine protein+ model1

Variable HR 95% CI P

eGFR<60 ml/min/1.73 m2 5.27 2.22-12.53 <0.001

Hypertension 2.15 1.13-4.09 0.019

Urine protein (g/24h) 1.46 1.18-1.81 0.001

Diffuse mesangial hypercellularity 0.93 0.56-1.52 0.761

Endocapillary hypercellularity 2.22 1.09-4.51 0.028

Segmental sclerosis (per 5%) 1.25 1.11-1.40 <0.001

Tubular atrophy (per quartile) 1.07 0.76-1.51 0.696

Crescent proportion (per 5%) 1.12 1.00-1.24 0.048

Multivariate Cox regression (model 2): the independent risk factors for unfavorable prognosis

Proteinuria on the prognosis

of IgAN patients

The distribution of urine protein in IgAN


26.84%

20.60%

32.35%

20.21%

<0.5g/24h 0.5-1g/24h 1-3g/24h ≥3g/24h

Proteinuria at renal biopsy (g/24h)

Variables All <0.30 0.30-0.50 0.50-1.00 ≥1.00

(n[%]) 951 233(24.5) 174(18.3) 244(25.7) 300(31.5)

Male(n[%]) 397(41.7) 83(35.6) 60(34.5) 103(42.2) 151(50.3)***

Age 32.0(26.0,38.0) 32.0(26.0,37.0) 33.0(27.0,39.0) 31.0(26.0,38.0) 31.0(25.0,40.0)

BMI(kg/m2) 21.7(19.4,24.2) 20.8(18.7,23.0) 20.6(19.3,24.6) 21.7(19.1,24.3) 22.5(20.0,25.0)

Predisposingfactor (n[%]) 236(24.8) 66(28.3) 45(25.9) 63(25.8) 62(20.7)

Systolic pressure(mmHg) 123.0(112.0,136.0)

118.0(109.5,130.0)

120.0(111.0,132.5)

125.0(115.3,135.8)***

129.0(118.0,144.0)***

Diastolic pressure(mmHg) 79.0(70.0,88.0) 75.0(68.0,82.0) 78.0(70.0,86.5)* 80.0(70.0,89.0)*** 81.0(73.0,92.0)***

Hypertension(n[%]) 272(28.6) 44(18.9) 40(23.1) 72(29.5)** 116(38.7)***

Proteinuria (g/24h) 0.58(0.30,1.17) 0.20(0.13,0.25) 0.39(0.33,0.44)*** 0.66(0.57,0.78)*** 1.75(1.22,2.87)***

Microscopic hematuria (n[%]) 613(64.5) 150(64.4) 114(65.5) 162(66.4) 187(62.3)

Gross hematuria (n[%]) 187(19.7) 55(23.6) 46(26.4) 51(20.9) 35(11.7)***

Edema (n[%]) 232(24.4) 33(14.2) 36(20.7) 48(19.7) 115(38.3)***

Hemoglobin (g/L) 127.0(115.0,140.0) 128.0(116.5,141.0) 125.0(113.5,139.3) 128.5(119.0,140.0) 126.0(112.0,140.0)

Anemia (n[%]) 180(18.9) 32(13.7) 33(19.0) 39(16.0) 76(25.4)***

Proteinuria at renal biopsy (g/24h)

Variables All <0.30 0.30-0.50 0.50-1.00 ≥1.00

Total protein (g/L) 67.0(61.0,71.0) 69.0(65.0,73.0) 68.0(64.0,72.0)* 67.0(63.0,72.0)*** 61.0(54.0,67.0)***

Albumin (g/L) 40.0(36.2,42.7) 42.0(40.0,44.0) 41.0(38.0,43.0)** 40.0(37.0,42.0)*** 36.6(31.4,40.0)***

Hypoalbuminema(n[%]) 167(17.6) 11(4.7) 11(6.3) 25(10.3)* 120(40.1)***

Cholestrol (mmol/L) 4.90(4.20,5.90) 4.58(4.00,5.20) 4.50(4.00,5.20) 5.00(4.30,5.90)*** 5.70(4.70,6.90)***

Hypercholesteremia(n[%]) 201(22.1) 20(8.9) 16(9.6) 49(20.9)*** 116(40.8)***

Triglyceride(mmol/L) 1.25(0.86,1.84) 1.05(0.74,1.42) 1.04(0.74,1.59) 1.21(0.88,1.81)*** 1.62(1.09,. 247)***

Hypertriglyceridemia(n[%]) 166(18.2) 16(7.0) 23(13.9)* 37(15.8)** 90(31.6)***

Uric acid(umol/L) 348.0(269.0,429.0)

288.0(224.0,380.5)

320.0(264.8,396.3)**

351.5(277.0,413.5)***

409.0(318.5,499.0)***

Hyperurecimia (n[%]) 220(24.6) 32(14.5) 29(17.1) 43(19.4) 116(41.4)***

Serum creatinine (mmol/L） 80.0(61.0,116.0) 68.0(57.0,90.0) 70.0(59.0,95.5) 80.0(63.0,109.8)*** 106.0(74.0,175.5)***

BUN (mmol/L) 5.30(4.40,7.10) 4.80(4.20,5.80) 4.90(4.20,6.20) 5.40(4.40,6.90)*** 6.50(4.70,9.18)***

eGFR(ml/min/1.73m²)

95.2(60.5,123.1)

111.3(83.9,130.3)

107.5(78.5,127.3)

94.8(63.6,122.1)***

67.8(36.5,105.4)***

Proteinuria at renal biopsy （g/24h）

Variables All <0.30 0.30-0.50 0.50-1.00 ≥1.00

Global glomerulosclerosis (n[%]) 702(73.8) 153(65.7) 113(64.9) 186(76.2)* 250(83.3)***

Segmental glomerulosclerosis (n[%]) 441(46.4) 75(32.2) 66(37.9) 119(48.8)*** 181(60.3)***

Crescent (n[%]) 420(44.2) 67(28.8) 75(43.1)** 118(48.4)*** 160(53.3)***

Necrosis (n[%]) 84(8.8) 15(6.4) 16(9.2) 26(10.7) 27(9.0)

Endothelial proliferation( n[%]) 193(20.3) 44(18.9) 33(19.0) 50(20.5) 66(22.0)

Mesangial proliferation M1(n[%]) 508(54.4) 105(45.9) 93(54.1) 133(55.6)* 177(60.2)

Endocapillary proliferation E1(n[%]) 187(20.5) 44(19.7) 31(18.2) 48(20.7) 64(22.4)

Segmental glomerulosclerosis S1( n[%]) 440(47.3) 73(31.7) 67(39.2) 117(49.4)*** 183(62.5)***

Interstitial fibrosis (n[%])

T0 676(72.7) 202(87.8) 142(83.0) 171(71.3)*** 161(55.7)***

T1 225(24.2) 26(11.3) 26(15.2) 63(26.3)*** 110(38.1)***

T2 29(3.1) 2(0.9) 3(1.8) 6(2.5)*** 18(6.2)***

Interstitial inflammation(n[%])

<25% 234(24.6) 77(33.0) 51(29.3) 62(25.4)* 44(14.7)***

25-50% 549(57.7) 140(60.1) 99(56.9) 149(61.1)* 161(53.7)***

≥50% 168(17.7) 16(6.9) 24(13.8) 33(13.5)* 95(31.7)***

thickening of arterial wall(n[%]) 373(39.2) 74(31.8) 69(39.7) 91(37.3) 139(46.3)***

*compared to < 0.30 g/24h, p<0.05;**为p<0.01;***为p<0.001

proteinuria on renal outcomes of IgAN patients

<0.30g/d 233 229 200 133 45 4

0.30-0.50g/d 174 171 138 72 27 4

0.50-1.00g/d 244 223 183 83 35 4

≥1.00g/d 300 276 173 76 24 8

3 yr 5 yr

All(n=951) 94.3% 86.3%

<0.30g/d(n=233) 99.6% 97.6%

0.30-0.50g/d(n=174) 96.9% 91.0%

0.50-1.00g/d(n=244) 97.3% 89.5%

>1.00g/d(n=300) 85.5% 68.3%

• Median follow-up time: 48.8（34.7,62.7）months，3-year、5-year renal cumulative survival

rate：94.3% and 86.3%

Cox regression model:Hazard ratio of different degrees of proteinuria (SCr doubling or ESRD)

Univariate Model 1 Model 2

HR(95%CI) P HR(95%CI) P HR(95%CI) P

Proteinuria <0.001 <0.001 <0.001

<0.30g/d 1(Ref) 1(Ref) 1(Ref)

0.30-0.50g/d 2.95(1.11,7.86) 0.031 3.15(1.00,9.94) 0.051 2.82(0.87,9.16) 0.085

0.50-1.00g/d 4.41(1.80,10.84) 0.001 4.33(1.55, 12.10) 0.005 3.57(1.22,10.42) 0.020

≥1.00g/d 13.69(5.93,31.60) <0.001 10.60(3.88,28.98) <0.001 7.06(2.50,19.92) <0.001

Model1：proteinuria, age,gender, gross hematuria, hypertension, hyperuricemia, Hypercholesteremia.

Hypertriglyceridemia, serum creatinine;

Model 2：Model1+MEST；

Proteinuria on the Prognosis of IgAN Patients

• IgAN patients with different degrees of proteinuria had

significantly different clinicopathological characteristics at the

time of renal biopsy.

• Degrees of proteinuria at the time of renal biopsy

significantly related to prognosis: proteinuria ≥0.30g/d

carries risk of progression, and ≥0.50g/d is one of

independent risk factors for poor renal outcomes.

Clinicopathological Characteristics and Risk Factors of Patients with Nephrotic IgA Nephropathy

• Prevalence of nephrotic syndrome in IgAN patients was 4.0% (60/1512) in this cohort and 21% are minimal change in pathology.

• Risk factors of NS-IgAN: No presentation of gross hematuria, presence of hypertension, less glomerular sclerosis, lower density of IgA deposition.

• Risk factors of progression of NS-IgAN: Lower eGFR, global glomerular sclerosis more than 25%, interstitial inflammatory cells infiltration>25%.

data was based on http://igan.medidata.cn/




Acute kidney injury


Proteinuria＞1g/d

Nephrotic syndrome

Hypertension


Clinical pattern

Risks of

progression

IgAN and Hypertension

The prevalence of hypertension in IgAN patients• The prevalence of hypertension in patients with IgAN is 6%-49%，but there are

ethic difference.

• In Asian is 22%-33% ，Chinese is about 31%

• Big difference in USA and Europe，France is 10%, USA reported 47%-49%.

• Low prevalence of HBP in children 24%。

• In SYSU IgAN database http://IgAN.medidata.cn/ The prevalence of HBP in

IgAN is 32.7% （1409/4306）.

Wyatt RJ. Am J Kidney Dis. 1984 Sep;4(2):192-200.D'Amico G. Semin Nephrol. 2004 May;24(3):179-96.

Le W. Nephrol Dial Transplant. 2012 Apr;27(4):1479-85.


Risk factors for hypertension in IgANunivariate analysis multivariate analysis

OR 95% CI p value OR 95% CI p value

age 1.053 1.042-1.063 <0.001 1.036 1.023-1.050 <0.001

male 2.089 1.718-2.540 <0.001 1.108 0.816-1.504 0.512

chronic tonsillitis 4.052 2.582-6.356 <0.001 2.749 1.593-4.747 <0.001

smoking 2.015 1.367-2.969 <0.001 0.797 0.485-1.309 0.371

family history of hypertension 1.912 1.318-2.772 0.001 1.338 0.844-2.121 0.216

Impaired glucose metabolism 2.336 1.646-3.316 <0.001 1.134 0.731-1.759 0.574

hyperuricemia 3.428 2.799-4.198 <0.001 1.067 0.804-1.417 0.653

hypoalbumia 2.095 1.658-2.648 <0.001 1.070 0.756-1.514 0.702

hypercholesterolemia 1.625 1.338-1.975 <0.001 1.014 0.710-1.448 0.940

hypertriglyceridemia 2.596 2.108-3.196 <0.001 1.221 0.915-1.631 0.175

HDL-C＜1.04 mmol/l 1.878 1.519-2.322 <0.001 1.076 0.797-1.453 0.632

LDL-C≥3.37 mmol/l 1.419 1.164-1.728 0.001 1.017 0.720-1.438 0.922

eGFR (mL/min/1.73m2) 0.972 0.969-0.975 <0.001 0.983 0.978-0.987 <0.001

hemoglobin (g/l) 0.989 0.984-0.993 <0.001 1.005 0.998-1.013 0.135

univariate analysis multivariate analysis

OR 95% CI p value OR 95% CI p value

proteinuria (g/24h) 1.448 1.334-1.572 <0.001 1.187 1.073-1.312 0.001

Urine red blood cell ≥ 2+ 0.598 0.488-0.734 <0.001 0.805 0.620-1.044 0.103

Glomerular sclerosis (%) 1.040 1.035-1.045 <0.001 1.025 0.997-1.053 0.078

Crescent formation (%) 1.021 1.011-1.032 <0.001 1.005 0.991-1.019 0.463

Capsular adhesion 0.729 0.599-0.887 0.002 0.858 0.658-1.119 0.259

renal necrotizing lesions 0.573 0.385-0.852 0.006 0.619 0.378-1.012 0.056

Segmental sclerosis (S1) 2.283 1.877-2.778 <0.001 1.326 1.021-1.722 0.035

Tubular interstitial fibrosis 5.561 4.479-6.904 <0.001 1.309 0.896-1.913 0.163

Interstitial infiltration >25% 4.828 3.804-6.127 <0.001 1.125 0.775-1.633 0.535

Thickness of vascular wall 3.057 2.504-3.732 <0.001 1.309 1.004-1.708 0.047

Vascular hyaline degeneration 2.631 2.115-3.273 <0.001 1.197 0.893-1.604 0.229

Fibrotic necrosis 10.822 4.211-27.810 <0.001 5.960 1.948-18.239 0.002

capillary thrombosis 3.338 1.263-8.825 0.015 1.191 0.349-4.063 0.780

IgA deposit (+++/++++) 0.811 0.662-0.993 0.043 1.248 0.962-1.619 0.095

Risk factors for hypertension in IgAN

• Average time for follow up 34.7±16.2 months

• Normal blood pressure group, 5 years renal survival is 90.7%，

average renal survival is 81.8 months

• Normal blood pressure group, 5 years renal survival is 51.7%，

average renal survival is 60.8 months

P＜0.001

* data from SYSU IgAN registration system http://igan.medidata.cn ( Jan 1 of 2006 to Dec 31 of 2012)

Influence of hypertension on prognosis


The Effect of Circadian Blood Pressure Rhythms and

Variation on Prognosis of IgA Nephropathy

Distribution of Circadian Blood Pressure Rhythms in IgAN Patients

非杓型62.10%

反杓型25.00%

超杓型12.90%

Non-dipper Types

Extra-dipper

Non-dipperReverse

24-Hr Ambulatory Blood Pressure ProfileOverall Non-dipper Dipper P value

Number of Patients 148 124 24

Daytime systolic BP (mmHg) 121（111.5,131） 120.5（112,131） 122(107,133) 0.860

Daytime diastolic BP (mmHg） 77（71,84） 76.5(71,83) 77(71,84) 0.692

Nighttime systolic BP (mmHg) 113.73±14.39 115.75±14.33 103.29±9.47 0.031

Nighttime diastolic BP (mmHg) 69.70±9.74 70.78±9.87 64.08±6.78 0.048

24-Hr systolic BP (mmHg) 119(110,128) 119 (110.75,129.25) 118(104,128) 0.291

24-Hr diastolic BP(mmHg) 75(69,82) 75(69.75,82) 75(68,82) 0.673

Ratio of nighttime to daytime systolic BP (%) 6.14(1.86,11.03) 4.7(0.75,8.1) 14.03(12.38,18.04) 0.000

Ratio of nighttime to daytime diastolic BP (%) 9.47(5.26,15.38) 8.25(4.36,13.16) 16.91(14.11,17.95) 0.000

Coefficient of variation of 24-Hr systolic BP (%) 10.86±4.22 9.4(7.73,12,24) 10.95(9.3,13.8) 0.056

Coefficient of variation of 24-Hr diastolic BP (%) 14.37±5.36 14.10±5.41 16.46±4.68 0.059

Standard deviation of 24-Hr systolic BP 12.12(10.0,15.27) 11.52（9.41,14.6） 14.68(12.44,17.35) 0.004

Standard deviation of 24-Hr diastolic BP 10.01(8.3,13.6) 9.56(7.88,13.27) 11.78(10.01,14.8) 0.056

Morning peak (n, %) 17,10.6% 13,9.6% 4,15.4% 0.382

Overall Non-dipper Dipper P value


Serum natrium (mmol/l) 140(139,142) 140(139,142) 141 (138,142) 0.549

Serum potassium (mmol/l) 4.08±0.39 4.06±0.39 4.21±0.39 0.099

Serum calcium (mmol/l) 2.27(2.19,2.35) 2.25(2.18,2.34) 2.34(2.29,2.38) 0.013

Serum phosphate (mmol/l) 1.17(1.05,1.29) 1.15(1.04,1.29) 1.17(1.05,1.29) 0.753

Serum CO2 (mmol/l) 25(23,27) 25(23,28) 25(24,26) 0.718

Serum glucose (mmol/l) 4.5(4.2,4.9) 4.4(4.2,4.8) 4.8(4.3,5.0) 0.05

Serum creatinine (µmol/l) 101.5(73.25,158) 111（74.25,174） 89(62.25,109.75) 0.011

eGFR (mL/min/1.73m2) 70.65(38.21,101.4) 64.16(35.36,100.53) 81.88(59.5,115.6) 0.023

CKD stage 1 (n,%) 54,36.5% 44,35.5% 10,41.7%

0.129CKD stage 2 (n,%) 27,18.2% 20,16.1% 7,29.2%

CKD stage 3 (n,%) 45,30.4% 38,30.6% 7,29.2%

CKD stage 4 (n,%) 22,14.9% 22,17.7% 0,0.0%

BUN (mmol/l) 6.95(4.98,10.52) 7.4(5.3,10.8) 5.8(4.2,8.3) 0.042

Baseline Laboratory Characteristics of Dipper and Non-dipper Groups



Uric acid (µmol/l) 427(340,488.75) 435 (346.25,508.75) 386(316.25,441) 0.038

Hyperuricemia (n, %) 89,60.1% 79,63.7% 10,41.7% 0.044

Serum albumin (g/l) 38 (35,40.37) 37.8(34.2,40.2) 38.5(36.5,40.8) 0.295

Hypoproteinemia (n, %) 13,8.8% 12,9.7% 1,4.2% 0.383

Total protein (g/l) 63.95(57.95,68.8) 63.3(55.8,68.8) 67.1(64.4,68.7) 0.066

Cholesterol (mmol/l) 5.15(4.2,6.0) 5.1(4.2,5.9) 5.4(4.3,6.1) 0.207

Hypercholesterolemia (n, %) 72,48.6% 57,45.96% 15,62.5% 0.168

Triglyceride (mmol/l) 1.49(1.06,2.29) 1.51(1.08,2.31) 1.35(1.03,2.2) 0.894

Hypertriglyceridemia (n, %) 55,37.1% 45,36.29% 10,41.7% 0.68

HDL (mmol/l) 1.08(0.89,1.33) 1.07(0.89,1.35) 1.08(0.96,1.33) 0.397

Low HDL (n, %) 68,43.9% 60,46.2% 8,32% 0.134

LDL (mmol/l) 3.03(2.42,3.70) 3.02(2.42,3.7) 3.3(2.43,3.83) 0.446

Low LDL (n, %) 54,36.48 % 43,34.67% 11,45.8% 0.388



Hemoglobin (g/l) 122.55±21 122.17±21.3 124.54±19.73 0.281

Anemia (n, %) 44,29.7% 38,30.6% 6,25.0% 0.58

Serum IgA (g/l) 3.11(2.14,3.59) 2.99 (1.98,3.52) 3.57(3.46,5.16) 0.004

CRP 0.86(0.84,2.71) 0.86(0.84,2.77） 0.86(0.86,2.4） 0.354

Urine protein (g/24h) 1.09(0.5,2.52) 1.12(0.50,2.69) 0.90(0.51,1.68) 0.378

Stratificattion of urine protein (n, %)

0.431

＜0.5g/24h 36,24.3% 31,25.0% 5,20.8%

0.5-1g/24h 36,24.3% 27,21.8% 9,37.5%

1-3g/24h 43,29.1% 37,29.8% 6,25.0%

＞3g/24h 33,22.3% 29,23.4% 4,16.7%

Haematuria (n, %)

0.144≤++ 98,66.2% 79,63.7% 19,79.2%

＞++ 50,33.8% 45,36.3% 5,20.8%

iPTH 70.8(43.2,106.0) 66.1(40.8,111.7) 94.5(65,102.6) 0.134

Pathological Characteristics of Dipper and Non-dipper GroupsOverall Non-dipper Dipper P value


Ratio of global sclerosis (%) 0.25(0.06,0.50) 0.25(0.06,0.52) 0.18(0.02,0.46) 0.323

Crescents (n, %) 68,45.9% 59,47.6% 9,37.5 % 0.364Loops necrosis (n, %) 8,5.4% 7,5.6% 1,4.2% 0.769Mesangial hypercellularity (n, %) 133,89.9% 110,88.7% 23,95.8% 0.762Endocapillary proliferation (n, %) 28,18.9% 27,21.8% 1,4.2% 0.044

Segmental glomerulosclerosis (n, %) 91,61.5% 75,60.5% 16,66.7% 0.814

Renal tubular atrophy/fibrosis (n, %)

T0 85,57.4% 71,57.2% 14,58.3%

0.878T1 38,25.7% 31,25.0% 7,29.2% T2 24,16.2% 21,16.9% 3,12.5% T3 1,0.7% 1,0.8% 0,0%

Interstitial inflammatory cell infiltration (n, %)

<25% 95,64.3% 77,62.1% 18,75% 0.05625%-50% 36,24.3% 30,24.2% 6,25%

≥50% 17,11.5% 17,13.7% 0,0.0% Small artery wall thickening (n, %) 77,52.03% 69,55.6% 8,33.3% 0.045Angiohyalinosis (n, %) 45,30.4% 43,34.7% 2,8.3% 0.01Fibrinoid necrosis (n, %) 2,1.4% 2,1.6% 0,0.0% 0.531Capillary thrombosis (n, %) 1,0.62% 1,7.35% 0,0% 0.659

Immunofluorescence IgA (n, %)

+ 3,2.0% 3,2.4% 0,0%

0.798++ 102,68.9% 86,69.3% 16,66.7% +++ 42,28.4% 34,27.4% 8,33.3%

++++ 1,0.7% 1,0.8% 0,0%

Univariable Multivariable

OR 95% CI P value OR 95% CI P value

Male 0.60 0.24-1.47 0.265

Age (year) 0.99 0.954-1.03 0.667

Hypertension 1.24 0.51-3.05 0.634

Serum creatinine 1.01 1.00-1.02 0.011

eGFR (mL/min/1.73m2) 0.98 0.98-0.99 0.019 0.98 0.97-1.00 0.046

Serum urea nitrogen 1.11 0.97-1.25 0.114

Uric acid 1.01 1.00-1.01 0.036 1.01 1.00-1.02 0.041

Serum IgA 0.62 0.43-0.89 0.011 0.57 0.38-0.87 0.016

Endocapillary proliferation 0.15 0.02-1.21 0.075

Small artery wall thickening 2.51 1.00-6.29 0.050

Angiohyalinosis 5.840 1.31-26.02 0.021 4.98 0.87-28.26 0.48

Logistic Regression of Risk factors on Non-dipper BP in IgAN

Summary

1. Our study found that 83.8%（124/148）IgAN patients manifested disorder of circadian blood pressure rhythms, and almost 25% patients' nighttime blood pressure is abnormally higher than daytime, which is so called non-dipper.

2. Non-dipper IgAN patients presented lower eGFR, higher uric acid, lower serum IgA, more frequently endocapillary proliferation, small artery wall thickening, angiohyalinosis.

3. Relatively lower eGFR, higher uric acid, lower serum IgA, more frequently angiohyalinosis were the independent risk factors on non-dipper in IgAN patients.




Acute kidney injury


Proteinuria＞1g/d

Nephrotic syndrome

Hypertension


Clinical pattern


Total(n=697)

CKD stage 1-2(n=505)

CKD stage3-5(n=192) Pvalue

Age 32(14,74) 30(14,74) 35(15,73) <0.001Male (n, %) 302(43.3) 194(38.4) 108(56.3) <0.001Gross hematuria(n, %) 106(15.2) 94(18.6) 12(6.3) <0.001

Family history of hypertension (n, %) 13(1.9) 5(0.9) 8(4.2) 0.010

Chronic tonsillitis (n, %) 45(6.5) 18(3.6) 27(14.1) <0.001

Drinking history (n, %) 11(1.6) 9(1.8) 2(1.0) 0.736Smoking history (n, %) 25(3.6) 15(3.0) 10(5.2) 0.173

Family history of kidney disease(n, %) 57(8.2) 39(7.7) 18(9.4) 0.536

SAP (mmHg) 125(80,210) 120(85,210) 138.5(80,205) <0.001DAP(mmHg) 80(40,150) 78(40,150) 88(57,140) <0.001MAP(mmHg) 94.3(63.3,170) 92.3(63.3,170) 105.5(66.7,161.7) <0.001Grade of Hypertension (n, %) <0.001

non 671(96.3) 497(98.4) 174(90.6)Grade 1 5(0.7) 1(0.2) 4(2.1)Grade 2 8(1.1) 4(0.8) 4(2.1)Grade 3 13(1.9) 3(0.6) 10(5.2)

Baseline Charactoristics of Different CKD stage groups

Baseline Pathological Charactoristics of Different CKD stage groups

Total CKD stage1-2(n=505)

CKD stage 3-5(n=192) P value

Global sclerosis (n, %) 512(73.5) 330(65.3) 182(94.8) <0.001

Crescent (n, %) 303(43.5) 202(40.0) 101(52.6) 0.003

Loops necrosis (n, %) 53(7.6) 40(7.9) 13(6.8) 0.609

Mesangial proliferation (M1) (n, %) 310(44.5) 226(44.8) 84(43.8) 0.812

Endocapillary proliferation(E1) (n, %) 146(20.9) 107(21.2) 39(20.3) 0.800

Segmental glomerulosclerosis (S1) (n,%) 270(38.7) 165(32.7) 105(54.7) <0.001

Interstitial fibrosis (n, %)

<0.001T0 477(68.4) 432(85.5) 45(23.4)

T1 180(25.8) 70(13.9) 110(57.3)

T2 40(5.7) 3(0.6) 37(19.3)

Total(n=697)

CKD stage 1-2(n=505)

CKD stage3-5(n=192) P value

Interstitial inflammatory cell infiltration (n, %)

<0.001＜25% 565(81.1) 465(92.1) 100(52.1)

25%-50% 108(15.5) 37(7.3) 71(37.0)

≥50% 24(3.4) 3(0.6) 21(10.9)

Thickening of arterial wall( (n, %) 249(35.7) 128(25.3) 121(63.0) <0.001

Angiohyalinosis (n, %) 159(22.8) 92(18.2) 67(34.9) <0.001

Fibrinoid necrosis (n, %) 19(2.7) 8(1.6) 11(5.7) 0.003

Capillary thrombosis(n, %) 11(1.6) 7(1.4) 4(2.1) 0.506

Immunofluorescence IgA (n, %)

0.040

+ 34(4.9) 23(4.6) 11(5.7)

++ 355(50.9) 242(47.9) 113(58.9)

+++ 256(36.7) 199(39.4) 57(29.7)

++++ 52(7.5) 41(8.1) 11(5.7)

IgA deposit(n, %) <0.001

Mesangial 632(90.7) 470(93.1) 162(84.4)

Capillary wall/basement membrane 65(9.3) 35(6.9) 30(15.6)

Univariable

OR 95% CI lower 95% CI upper P value

Age 1.050 1.033 1.068 <0.001

Male 2.061 1.472 2.887 <0.001

Chronic tonsillitis 4.427 2.377 8.246 <0.001

Drinking history .580 .124 2.709 .489

Smoking history 1.795 .792 4.067 .161

Family history of hypertension .876 .091 8.474 .909

Glucose 1.527 .848 2.749 .158

Hyperuricemia 10.350 6.704 15.977 <0.001

Hypoalbuminemia 2.152 1.242 3.728 .006

Chol 2.057 1.431 2.957 <0.001

TG 2.558 1.751 3.737 <0.001

HDL-C＜1.04 mmol/l 2.459 1.681 3.597 <0.001

LDL-C≥3.37 mmol/l 1.477 1.026 2.128 0.036

Hemoglobin (g/l) .968 .959 .976 <0.001

Proteinuria in 24h (g/24h) 1.001 .999 1.002 .291

Microscopic RBC ≥2+ .833 .570 1.217 .345

Global sclerosis 9.652 4.976 18.720 <0.001

OR 95% CI lower

95% CI upper P value

Crescents 1.665 1.191 2.326 0.003

Loops necrosis .844 .441 1.616 .609

Mesangial hypercellularity (M1) .960 .687 1.342 .812

Endocapillary proliferation (E1) .948 .628 1.431 .800

Segmental glomerulosclerosis (S1) 2.487 1.771 3.493 <0.001

Renal tubular atrophy/fibrosis (T1-2) 19.332 12.753 29.303 <0.001

Interstitial inflammatory cell infiltration>25% 10.695 6.961 16.433 <0.001

Small artery wall thickening 5.019 3.519 7.159 <0.001

Angiohyalinosis 2.406 1.657 3.494 <0.001

Fibrinoid necrosis 3.776 1.495 9.536 0.005

Immunofluorescence IgA≥3+ .606 .429 .854 0.004

Logistic Regression of Risk factors

multivariable

OR 95% CIlower

95% CI upper P value

Age 1.100 1.064 1.138 <0.001Male 3.462 1.668 7.186 0.001Hyperuricemia 5.017 2.696 9.334 <0.001HDL-C＜1.04 mmol/l 2.416 1.222 4.776 0.011Hemoglobin(g/l) .964 .948 .981 <0.001global sclerosis 3.055 1.112 8.396 0.030Renal tubular atrophy/fibrosis (T1-2) 5.242 2.574 10.677 <0.001Interstitial inflammatory cell infiltration >25% (n, %)

4.441 2.068 9.537 <0.001

Logistic Regression of Risk factors

Summary1.Patients with lower eGFR were more likely to be older and smoker,

had history of episodes of chronic tonsillitis and hypertension, had higher levels of baseline blood pressure.

2.Pathological change： crescents，segmental glomerulosclerosis，renal tubular atrophy/fibrosis, Interstitial inflammatory cell infiltration >25%, small artery wall thickening, angiohyalinosis, fibrinoidnecrosis.

3. Risk factors of progression of IgAN: age, male, hyperuricemia, HDL-C＜1.04 mmol/l, anemia, global sclerosis ,renal tubular atrophy/fibrosis, Interstitial inflammatory cell infiltration >25%.

- Patient survival

- Renal survival

- Quality of life

The Goal of IgAN Treatment

How to Achieve The Goal

• Correct diagnosis

• Early diagnosis

• Right treatment

• Adequate treatment

• Early prevention

Precision Medicine

•Precision prevention: risk for prevention

•Precision Predictive: outcome and response

•Precision Treatment: target for intervention

CKD Prevalence in Geographic Features

• Chen W, et al. NDT 2009; 24:1205-12 Chen W, et al. NDT 2011;26:1592-9• Liu Q, et al. PLos One 2012;7:e47100 Wei X, et al. Nephrology 2012;17:123-30• Liu K, et al. PLos One. 2013;8:e70767

• CKD in South of China

• CKD in Rural Area

• CKD Periodontal Patients

• CKD in High Altitude Area

• CKD in First Degree Relatives

12.1%

13.6%

18.2%

19.1%

29.7%

Springer Semin Immunopathol 2003;24: 477-93Kidney Int 2004，65: 1544-1547 J Am Soc Nephrol 2005，16: 2088-2097

Pathogenesis of IgA Nephropathy

GWAS study of IgANSusceptible loci MHC 1q32 22q12 Others

IgAN study in Columbia, USA √ √ √

IgAN study in SYSU, China √ not confirmed √

two new loci(17p13,8p23)

Yu XQ, et al. Nat Genet 2012;44:178-82Gharavi AG, et al. Nat Genet 2011;43:321-7

Phase II GWAS: imputation study

(a) Study 2: 12,095 Samples, λ GC = 1.089 (3,112,036 SNPs); λ GC = 1.081 (3,082,471 SNPs, removed 5 IgAN loci)

(5 new loci were discovered and validated) Li Ming, et al. Nature Communications 2015

Multiple susceptible loci from GWAS

Kiryluk K 20142,747 cases, 3,952 controls

Ours 20141,434 cases, 10,661 controls

MH

C

DE

FA

TNF

SF13

HO

RM

AD

2

CF

H

Variables SE Z OR PTotal DEFA1A3 0.023 33.974 0.873 5.59E-09

DEFA1 0.023 15.687 0.914 7.47E-05

DEFA3 0.055 16.699 0.798 4.38E-05

129bp 0.052 3.348 0.909 6.73E-02

124bp 0.028 34.921 0.850 3.43E-09

7bp+ 0.042 0.074 0.989 7.86E-01

7bp- 0.026 33.062 0.863 8.92E-09

215bp 0.024 0.955 0.977 3.28E-01

211bp 0.038 61.821 0.742 3.80E-15

rs2738048 0.072 6.968 0.826 8.30E-03

Association with IgAN Phenotype

Genetic scores of DEFA CNPs associated with renal outcomes

Q5: average GS=9.57;




Q1: average GS=3.06.

DEFA CNV is IgAN Specific or Not?

Validation in other kidney disease populationnon-IgAN nephropathy cohort

IgAN cohort from other populationNon-Chinese IgAN cohort

(500case/ 500control, matched by age, sex and region)

Non-IgAN nephropathy cohort500DN/DKD cases; 500 MN cases;

The same number of controls matched by age, sex and region)

Perform PRTs in those additional samples

Statistical analysis to find out whether the same association can be replicated or not

DN/DKD cohort

Origin

Cases Controls

Sample size

Mean age M/F (%) Sample

sizeMean age

M/F (%)

SouthernChinese 331 57.83 67.2/32.8 329 57.51 68.7/31.3

Singaporean Chinese 475 60.53 58.7/41.3 457 58.06 58.4/41.6

Total 806 59.43 62.2/37.8 786 57.83 62.7/37.3

CN Distributions in DKD cases and controls

Gene/alleles

Cases(n=806)

Control(n=786)

P valueMedian Interquartile

range Mean Interquartilerange

DEFA1A3 7.00 (6.00,8.00) 7.00 (6.00,8.00) 0.952

DEFA1 6.00 (4.00,7.00) 6.00 (4.00,7.00) 0.690

DEFA3 1.00 (1.00,2.00) 2.00 (1.00,2.00) 0.991

215bp 6.00 (5.00,7.00) 6.00 (5.00,7.00) 0.612

211bp 1.00 (0.00,2.00) 1.00 (0.00,2.00) 0.222

Association analysis in DKD adjusted by age and sex

Variants

DKD cohort(806 cases/786 controls)

P ORa(95%CI)

DEFA1A3 0.448 0.98(0.94,1.03)

DEFA1 0.487 0.99(0.94,1.03)

DEFA3 0.778 0.99(0.89,1.09)

215bp 0.884 1.00(0.96,1.05)

211bp 0.158 0.94(0.87,1.02)

MN cohortCases Controls

Origin Sample size

Mean age M/F(%) Sampl

e sizeMean age M/F(%)

Southern Chinese 493 45.97 53.3/46.7 500 45.67 53.2/46.8

CN Distribution in MN cases and controls

Gene/alleles

Cases ControlP value

Mean Interquartilerange Mean Interquartile

rangeDEFA1A3 7.00 (6.00,8.00) 7.00 (6.00,8.00) 3.41×10-1

DEFA1 5.00 (4.00,7.00) 5.00 (4.00,7.00) 6.09×10-1

DEFA3 2.00 (1.00,2.00) 1.00 (1.00,2.00) 1.00×10-2

215bp 6.00 (5.00,7.00) 5.00 (4.00,6.00) 1.03×10-5

211bp 1.00 (0.00,2.00) 2.00 (1.00,2.00) 2.82×10-7

Association analysis in MN adjusted by age and sex

Variants

MN cohort

(493 cases/ 500 controls)

P ORa(95%CI)

DEFA1A3 8.76×10-1 1.00(0.94,1.07)

DEFA1 5.93×10-1 0.98(0.93,1.04)

DEFA3 6.50×10-2 1.16(0.99,1.35)

215bp 6.63×10-4 1.12(1.05,1.20)

211bp 1.11×10-7 0.74(0.67,0.83)

Function study of DEFA1A3 CNVs

IgAN patients (n=100)

Serum/Urine level of HNP1-3 mRNA and proteins

Healthy controls (n=80)

Measuring DEFA1A3 CNVs, including total CN, DEFA3 CN, 211bp CN

Comparison and correlation analysis between DEFA1A3 CNVs and expression level of HNP1-3 mRNA ( white blood cells)/protein(serum)

Western Blot: Total HNP1-3 expression showed no difference in neutrophils isolated from IgAN patients and controls.

HNP1-3

GAPDH

Control IgAN

Control IgAN0.0

0.5

1.0 p=0.3207H

NP

1-

3/GA

PDH

HNP1-3 expression level in neutrophils isolated fromIgAN patients and controls

ELISA: After stimulation of LPS (100ng/ml, 6h) or PMA (20ng/ml, 6h), the extracellular HNP1-3 levels are significantly lower in neurophils isolated from IgAN

patients than controls.

HNP1-3 secretion by neutrophils after stimulated by LPS or PMA

The Effect of HNPs on Cell Proliferation(time-dependent)

HNP1-3 10 μg/mL treated HMC for 0,24,48h,72h,96h in 48-well plates.No significant differences.

0

2

4

6

8

10

12

14

16

0 24h 48h 72h 96h

Cel

l num

ber(

*104

)

ConHNP1-3 10 μg/ml

ElisaC

once

ntra

tion

(pg/

ml)

Time

0

100

200

300

400

500

600

0h 0.5h 1h 3h 6h 12h 24h 48h

************* **

Time (h)

Rel

ativ

e R

NA

leve

l ****

QPCRIL-6 (cell supernatant)

Whole cell lyses

IL-623 Kd

β -actin42 Kd

0h 0.5h 1h 3h 6h 12h 24h 48h

*******

Rel

ativ

e P

rote

in le

vel

Time

HNP1-3 treated HMC for 0,0.5,1,3,6,12,24,48h. *p<0.05, ***p<0.001 vs 0h

The Effect of HNP1-3 on ECM Accumulation

Fn220 Kd Col. I

110 Kd

β -actin42 Kd

Col. III140 Kd

β -actin42 Kd

β -actin42 Kd

Time

Rel

ativ

e pr

otei

n le

vel

Time

Rel

ativ

e pr

otei

n le

vel

Time

Rel

ativ

e pr

otei

n le

vel

*

HNP1-3 10 μg/mL treated HMC for 0,12,24,48h, *p<0.05, vs 0 h

WB

0h 12h 24h 48h0h 12h 24h 48h0h 12h 24h 48h

Col. I Col. IIIFn

Summary• Serum and Urine levels of HNP1-3 are both increased in IgAN patients. Urine

level of HNP1-3 is negatively correlated with DEFA1 CNs (p=0.008) and total DEFA1A3 CNs (p=0.019) in all subjects.

• HAA binding IgA1 was negatively correlated with total DEFA1A3 CNs (r=-0.37, p=0.01) and DEFA1 CNs (r=-0.31, p=0.04) in IgAN patients with higher CNs (CN>6).

• Neutrophils isolated from IgAN patients had lower secretion capability of HNP1-3 as stimulated.

• The expression of interleukin-6 (IL-6) was significantly inhibited as co-cultures with HNP1-3, indicating the potential protective effect of HNP1-3 in IgAN.

Science Translational Medicine: will be online on June 29, 2016

Genetic mapping of susceptibility loci for human diseases

Beyond GWAS: Translational Research

Identification of causal variants

G X G interaction

G X E interaction

Genetic Epidemiology

Risk population

Disease population

Animal model

Translational research Biology

Acknowledgment

• Renal Lab in SYSU Ming LiZhen Ai

Dong XiuqingFan JinjinFeng ShaozhenZhou QinLuo Ning

Li XiaoyanYu JianwenZhou Qian

Liu WentingYin Peiran

Wang MengZhong zhongShi Dianchun

Xu RicongHong Lingyao

• Genome Institute of SingaporeProf. Liu Jianjun

Foo JiaNeeHuiqi Low

Yi LiChanghua Wang

• University of NottinghamProf. John ArmourOmniah Mansouri

Holly Black

• University of LeicesterProf. John Feehally

Barratt JonathanFaculty members

Thank all the hospital units for offering the IgAN and healthy control samples Thank all the subjects and healthy volunteers who participated in this work. Thank all the staff and students of the First Affiliated Hospital, SYSU for assisting with sample collection, DNA extraction and sample storage.

CHINA CKD ALLIANCE

Asia Pacific Chapter Meeting of International Society for Peritoneal Dialysis

(ISPD APC)(2017, Guangzhou)

Asia-Pacific Conference of Nephrology

apsn - xueqing yu · 2019-09-05 · primary igan confirmed by renal biopsy in the first affiliated...

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