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Long term outcome of IgA nephropathy single center experience Hematuria

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					Dear Reviewers,


I would like to submit the attached manuscript entitled “Long term outcome of IgA
nephropathy- A single center experience”, for consideration for possible publication in the
Acta Nephrologica by Taiwan Society of Nephrology.

     This work has not been published before in whole or part and is not under consideration
for publication elsewhere. Hopefully, this manuscript will be acceptable to you and to the
reviewers. Your favorable consideration will be highly appreciated.


Sincerely,


Shuo-Kai Su, MD
Division of Nephrology, Department of Internal Medicine, Taichung Veterans General
Hospital, Taichung 407, Taiwan



Corresponding Author:
Kuo-Hsiung Shu, MD
Division of Nephrology, Department of Internal Medicine, Taichung Veterans General
Hospital, Taichung 407, Taiwan
Tel: 886-4-23592525-3040
Fax: 886-4-23594980
E-mail: khshu@vghtc.gov.tw




1
Long term outcome of IgA nephropathy- A single center experience
IgA 腎病變長期追蹤結果-單一醫學中心的經驗
Shuo-Kai Su1, Mei-chin Wen4, Chi-Hung Cheng1,2, Ming-Ju Wu1,2, Cheng-Hsu Chen1,3,
Tung-Min Yu1, Ya-Wen Chuang1, Shih-Ting Huang1, Kuo-Hsiung Shu1, 2
Div. of Nephrology, Dept. of Internal Medicine, Taichung Veterans General Hospital1, Institute of
Medicine, Chung-Shan Medical University2, School of Medicine, China Medical University3,
Taichung, Dept of pathology, Taichung Veterans General Hospital4
蘇碩凱 1,文美卿 4,鄭志雄 1,2,吳明儒 1,2,陳呈旭 1,3,游棟閔 1,莊雅雯 1,黃士婷 1,徐國雄 1,2

台中榮總腎臟科 1,中山醫學大學醫學院 2, 中國醫藥大學醫學院 3,台中榮總病理部 4




Short running title: Long term outcome of IgA nephropathy




Corresponding author: Kuo-Hsiung Shu, MD, Division of nephrology, Department of
Medicine, Taichung Veterans General Hospital, No 160, Section 3, Chung-Kang Road,
Taichung, 407, Taiwan
Tel: 886-4-23592525 ext 3040
Fax: 886-4-23594980
E-mail: khshu@vghtc.gov.tw
Abstract:
2
Abstract:

Background: IgA nephropathy (IgA N) is the most common primary glomerulonephritis in

worldwide. The long-term outcome and the prognosis factors of IgA N have rarely been


addressed in Taiwanese patients.


Methods: We retrospectively reviewed our kidney biopsy database of the past 25 years. Cases

with biopsy-proven IgA N were identified and medical charts reviewed. Patients with


inadequate data were excluded. A proportion of cases ( 157 patients) have adequate biopsy


tissue to give further pathological classification according to the criteria suggested by Haas et


al 2. The patients were divided into subgroups according to their outcome at last follow-up.


Group of “stable” includes patients in remission (normal renal function, no more hematuria


defined as RBC < 2/HPF, and proteinuria < 0.2 gm/day) and patients with stable renal


function without signs of progression (variation of serum creatinine level less than 10% with


or without hematuria /proteinuria). Group of progression includes patients with deteriorating


renal function (serum creatinine increased by more than 10%) and patients with end-stage


renal disease (ESRD). We compare the differences of several parameters, such as initial level


of creatinine, proteinuria, pathological subclass, between two groups.


Results: A total of 436 cases (male: female=241:195; 55.5%: 44.5%) with a mean follow-up


duration of 7.06.1 years (median: 5.5 years) were enrolled for the study. The mean age at


biopsy was 35.413.7 years, while the duration of apparent disease onset to biopsy was



3
1.42.7 years (median: 0.3 years). At last follow-up, 256 cases (58.7%) had various degree of

renal function deterioration. Compared to patients in remission or with stable renal function,


the progressive groups had higher baseline serum creatinine (3.23.7 vs 1.30.7 mg/dl,


p<0.0001), higher urine protein (2.52.6 vs. 2.4 4.0 gm/day, p< 0.0001), and higher

incidence of hepatitis C virus infection (14.3% vs. 4%, p<0.005). The progressive groups also


tended to have higher grade of Haas sub-classification (21.8% with subclass 5, compared to


1.1% in the stable groups, p<0.0001).


Conclusion: we conclude that a significant proportion of IgA N patients may progress to renal

insufficiency in the long run. Baseline characteristics including laboratory exam at onset and


pathological finding may predict long-term outcome and deserve intensive treatment.




Key words: IgA nephropathy, prognosis, risk factor.




4
摘要:


背景:A 型免疫球蛋白腎病 ( IgA 腎病) 為世界最常見的原發性腎絲球腎炎,臺灣人罹


患 IaA 腎病之長期追蹤結果及其預後因子,至今仍不十分清楚。


方法:此為回溯性研究,從過去台中榮總 25 年來接受腎臟切片的資料庫中,挑出 IgA 腎


病的病例。腎炎皆由組織學證明,以調閱病例方式進行研究。若資料不足則剔除。其中


一部分的病理分級是根據 Haas et al 2 所提出的評量方式。


結果:共 436 位病人被納入此研究,男:女=241:195 (55.5%: 44.5%),平均追蹤 7.06.1


年 (中位數: 5.5 年)。接受腎臟切片的平均年齡是 35.413.7 年,從


有症狀到接受切片的時間為 1.42.7 年 (中位數: 0.3 年)。至最後追蹤時,256 位病人

(58.7%)有各種程度不一的腎功能不全。與腎功能穩定或是痊癒的病人相較,這 256 個病


人最初的血清肌酐酸較高 (3.23.7 vs. 1.30.7 mg/dl, p<0.0001), 最初尿蛋白較高


(2.52.6 vs. 2.4 4.0 gm/day, p< 0.0001),較高比例有 C 型肝炎帶原(14.3% vs. 4%,

p<0.005)。在 Haas sub-classification 有較高的比例級別較高 (21.8% 為第五級, 穩定組則


僅有 1.1% 為第五級, p<0.0001)。


結論: 我們在長期追蹤 IgA 腎病變時發現,有相當比例的病人腎功能衰退,諸多實驗數


據譬如初始腎功能,尿蛋白,以及腎臟病理嚴重程度,將可預測日後腎功能衰退情況,


對這些病人有必要採進一步積極之治療,以期防止病情持續惡化。


關鍵字: IgA 腎病,預後,風險因子。

研究參與及致謝: 台中榮民總醫院生物統計小組



5
Introduction:

Primary IgA nephropathy (IgA N) is the commonest glomerulonephritis among patients


undergoing renal biopsy worldwide. The possible pathogenic mechanism includes abnormal


structure and deficient clearance of IgA antibody, but no definite conclusion is made so far.


The prevalent rate is different between western countries and Asian countries1. This is partly


due to different strategy for biopsy. In United Kingdom, Canada and United States, the


common practice is performing biopsy until proteinuria increased or renal function worsened.


Early detection of abnormal urine analysis and more aggressive practice for biopsy all make


higher prevalence in Asian countries1. Several risk factors were identified, such as


hypertension, proteinuria, pathologic classification1. Antihypertension medication,


immunosuppressant agent are the cornerstone of therapy1. Although it has been studied


extensively in the western countries, the clinical features as well as the long-term outcome


have not been well-established in Taiwan.




6
Materials & Methods: We retrospectively reviewed our kidney biopsy database of the past

25 years (1982-2008). Cases with biopsy-proven IgA N were identified and medical charts


reviewed. Patients with inadequate data were excluded. A proportion of cases ( 157 patients)


have adequate biopsy tissue to give further pathological classification according to the criteria


suggested by Haas et al 2. The patients were divided into subgroups according to their


outcome at last follow-up. Group of “stable” includes patients in remission (normal renal


function, no more hematuria defined as RBC < 2/HPF, and proteinuria < 0.2 gm/day) and


patients with stable renal function without signs of progression (variation of serum creatinine


level less than 10% with or without hematuria /proteinuria). Group of progression includes


patients with deteriorating renal function (serum creatinine increased by more than 10%) and


patients with end stage renal disease (ESRD). Parameters, such as initial renal function,


amount of proteinuria, duration from symptom onset to biopsy, hematuria, chronic hepatitis,


age, sex, pathologic classification, were analyzed. Prednisolone, immunosuppressant


(cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil ), angiotensin


converting enzyme inhibitor ( ACEI), angiotensin receptor blocker ( ARB), pentoxiphylline,


and dipyridamole in various combinations were the mainstay of therapy. To evaluate the effect


of aggressive treatment with immnumosuppressants, patients with a daily proteinuria > 1gm


were analyzed while those with a proteinuria < 1 g/day were excluded because the later were


presumed to have a better prognosis and were rarely treated aggressively. We used



7
Mann-whitney U test for analyzing the difference of categorical variants between stable and


progressive groups, Yate’s correction of contingency and Pearson chi-square test for


continuous variants. Fisher’s exact test is used to analyze the data from medication effect for


patients with daily proteinuria more than one gram. The renal survival data were shown as


Kaplan-Meier survival curves and further comparison between groups were performed by


using a Log-Rank test.




8
Result:

From 1982 to 2008, 5558 cases of kidney biopsies have been performed. Of these, 712 cases


(12.8%) were proved to be IgAN. The medical charts were available in 440 cases. Four


patients were excuded de to insufficient data. Of the 436 patients male gender accounts for


55.9%. The mean follow-up duration was 6.986.07 years (median: 5.53 years, from 0 year to


24.79 years). The mean age at biopsy was 35.413.7 years, while the duration of apparent


disease onset to biopsy was 1.382.67 years (median: 0.28 years). Three hundreds and seven

patients (69.93%) had sub-nephrotic range proteinuria, while 99 patients (22.55%) had


nephrotic range proteinuria, 221 patients (50.34%) had serum creatinine > 1.5mg/dl while 48


patients (10.93%) had ESRD. Other demographic data were shown in Table 1 and 2. The


patients number of pathologic class (1 through 5) is 32 (13.6%), 56 (23.7%), 68 (28.8%), 48


(20.3%), and 32(13.6%), respectively. The prevalence of HBV and HCV infection were 60


patients (14.4%) and 35 patients (10.5%) respectively. Fifty-four patients (12.4%) had


complete remission, while 126 patients (28.9 %) had stable renal function at last followed up.


These two subgroups were classified as “Stable “group. The “progressive” group consisted of


125 patients (28.7%) who had progressive renal failure and 131patients (30.4%) who were


ESRD at last follow-up. The comparison of clinical parameters between the “Stable” group (n


=180) and “Progressive” group (n =256) was depicted in Table 3. The progressive group had


higher baseline serum creatinine (3.223.69 vs. 1.300.70 mg/dl, p<0.0001) and higher initial



9
urine protein excretion (2.542.58 vs. 2.354.02 gm/day, p< 0.0001, 52.2% patients had

>1gm/day proteinuria) and more patients with hypertension (49.69% vs. 27.8%, p< 0.0001).


At last follow up, the progression group also had more proteinuria (1.91 2.15 vs. 1.011.98

gm/day, P<0.0001). Interestingly, the progressive group had higher prevalence of hepatitis C


virus infection (14.3% vs. 4%, p<0.005). Pathologically, the progressive groups also tended to


have higher grade of Haas sub-classification (21.8% with subclass 5, compared to 1.1% in the


stable groups, p<0.0001). The correlation between pathological class and outcome were


presented in Table 5. There was no significant difference in other parameters, such as IgA


level, gender, prevalence of chronic hepatitis B and hematuria (data not shown). Logistic


regression analysis showed that patients with worse initial renal function, higher Hass’s

classification and initial proteinuria ≧ 1gm independently predicted disease progression


( Table 6). The 5,10,20 years renal survival were 80.5 %, 70.0 %, 36.9%, respectively (Figure


1). The impact of hypertension, pathological classification and proteinuria on renal survival


were shown in Figure 2, 3, 4 respectively. The medication prescribed was shown in Table 7.


Of the patients with an initial proteinuria > 1 mg/day, prednisolone and cyclophoaphamide


were used more frequently in “stable “ patients, compared the “progressive” group (65.9% vs.


47.7%; 11.8% vs.4%, respectively, in table 8), implying a possible therapeutic effect of theses


two drugs in stabilizing renal function.




10
Discussion:

In the current study, the mean age at biopsy is 35.4 years old implying that IgA N is a disease


of younger population. Male accounted for 55.5% of the patients which was similar to most of


the studies. The median duration between apparent onset and biopsy was only 0.3years


indicating that most patients were diagnosed relatively early. In view of a similar pre-biopsy


duration between the stable and progressive groups (Table 3), a lead-time bias might not exist.


However, the progressive group had a longer period of follow-up (Table 4). IgA N is a


lifelong progressive disease. So it is no surprised that the longer the duration of follow-up, the


more the possibility would the disease progress.


In our study, the percentage of gross hematuria (36.4%) was less than that of microscopic


hematuria (50%). Microscopic hematuria is a more common finding in Asian countries 3


probably due to routine screening for school-age children or on army recruits, thus milder


cases can be discovered. In contrast, in North American, the opposite result was obtained


indicating a different policy and timing of renal biopsy 3. The relationship of disease


progression and degree of hematuria has been extensively discussed. Although patients with


persistent microscopic hematuria were associated with a worse outcome compared to patients


experienced episodes of gross hematuria, in some series 4,5, Nicholls et al, in contrast,


demonstrated a relationship between hematuria (red blood cells >105/ml) and crescents 6.


Multivariate analysis in other studies 4, 7, 8 also considered high number of erythrocyte in urine



11
is a risk factor for progression. In our study, initial degree of hematuria was not associated


with poor prognosis (Table 3). In contrast, most of the studies revealed that the baseline serum


creatinine level is predictive for disease progression 4-7; in which, an initial level > 1.5 mg/dl


appeared to be a poor prognostic factor. A serum creatinine of 3 mg/dl was found to be a


no-return point 9. In our study, patient in progressive group had mean baseline serum


creatinine value of 3.22 3.69 mg/dl, which is at around the “no return point” and was

significantly higher than the stable group.


The degree of proteinuria had been proved to be predictive for prognosis in many reports 10-13.


A daily urine protein >3.5gm or with nephrotic syndrome usually indicates poor prognosis 4, 6,

7
    while others suggested that proteinuria> 1gm /day is a cut-off point for disease progression 4,

11-13
        . In our study, the mean values of proteinuria in both groups were greater than 1gm/day.


Although it is significantly higher in the “progressive” group (Table 4). Logistic regression

analysis also demonstrated that a ≧1gm/day is an independent risk factor for disease


progression (Table 6). After treatment, amount of proteinuria decreased in both groups,


although that of the progressive group was still higher (Table 4). The decrement of proteinuria


was larger in stable group. Whether the degree of proteinuria decrement can be deserved as a


good prognostic factor will need further confirmative studies. Nevertheless, effort in reducing


proteinuria should be an important part of therapy in IgA N.


Hypertension is generally accepted as a risk factor of disease progression. Higher blood



12
pressure at presentation (> 140/90 mmhg) was associated with higher percentage of sclerotic


glomeruli and lower GFR 8. Hypertension itself is unfavorable for all chronic kidney disease


(CKD) and vicious cycle exits between them 11. Our finding is that the progression group had


higher proportion of patients with hypertension which is in line with previous reports 14, 15, 16.


Patients presented with hypertension were associated with inferior renal survival (Figure 2).


Given that both ACEI and ARB have antihypertensive and proteinuria-lowering effect, these


agents have been drug of choice in IgA N patients 17, 18. As can be seen in Table 5, almost half


of our patients received either of these two agents. For patients with proteinuria of more than


one gm/day, although ACEI or ARB were used in almost equal percentages, hypertension


were more common in progress group (Table3 & 8), again underscored the importance of BP


control in the management of IgA N.


It has been well documented that IgA N could be secondary to chronic hepatitis B and


alcoholic liver cirrhosis. The prevalence of HBV surface antigen was increased in IgA N


patients in a previous study 19. In another study, IgA N was the most common in among


patients with HBV associated GN 20. In mainland China, where is also an endemic region of


HBV infection, the prevalence of HBV carriage was 18% in patients with IgA N. HBV DNA


could be identified in the nuclei of tubular epithelium, glomerular mesangial cells and


interstitial lymphocytes in such patients 21. In Taiwan, the prevalence of HBV carriage was


about 15-20% which is similar to the prevalence of our patient group (14.4%). From this point



13
of view, HBV infection might not play an important role in the pathogenesis of IgA N in our


series.


On the other hand, the most common GN correlated with HCV is mesangiocapillary


glomerulonephritis. Interestingly, the prevalence of HCV in our study is higher than that of


general population (10.5% vs. 2-4%). Moreover, the progression group had higher proportion


of patients with HCV infection compared to the stable group (14.3% vs. 4.0%, p<0.005, Table


3). The relationship between HCV and IgA N is not conclusive yet. Whether IgA N represents


another extrahepatic manifestation of HCV infection remains to be tested in the future. In IgA


N with HCV infection, less intensive treatment, such as immunosuppressant, might be


prescribed in an attempt not to provoke virus replication. This practice might have rendered


the IgA N out of control, thus leads to disease progression.


Semiquantitative severity grading method described by Pirani and Salinas-Madrigal 22, or


histological grading system by Hass et al 23, were commonly used by the majority of studies.


Although there are many studies which intended to correlated prognosis and histological


finding, diversity of results were obtained, probably de to retrospective study in nature,


enrolling patient in various stages, various duration of follow-up and the lack of standard


treatment 24. In our study, only eighteen patients (19.6%) with subclass 4 or 5 were in stable


group, compared to 62 patients (43.6%) with subclass 4 or 5 were in progressive group (Table


6 ). Thus Haas classification appeared to be valuable in predicting high risk group in our study.



14
Combination with other strong risk factors such as hypertension or proteinuria should predict


the outcome more precisely.


The beneficial effect of prednisolone and cyclophosphamide were proved by many studies


already 25-29. Prednisolone and cyclophosphamide were used more frequently in stable group


(Table 8) implying that use of prednisolone and cyclophosphamide may accounted for better


prognosis in this group.


In conclusion, we have characterized the clinical features of IgA N in Taiwan from our kidney


biopsy registry data which, to the best of our knowledge, is one of the biggest in this country.


Several prognostic factors were identified and potentially could be the targets in the


management of IgA N.




Acknowledgment:


The authors wish to thank Ms. Hui- Ching Ho and the Biostatistics Task Force of


Taichung Veterans General Hospital, Taichung, Taiwan, ROC for their statistical analysis and


preparation of the figures.




15
Table 1 Categorical demographic data ( n=436)
Variable                                          %
Male gender                                     55.5
Gross hematuria                                 36.4
Microscopic hematuria                            50
Hypertension                                    40.5
HBV hepatitis                                   14.4
HCV hepatitis                                   10.5
Hass's subclass
  Class I                                       13.6
  Class II                                      23.7
  Class III                                     28.8
  Class IV                                      20.3
  Class V                                       13.6
Daily urine proteitn at onset
     < 1+, negative, trace                      39.4
     1~3+                                       33.9
     ≧3+                                        26.7




16
Table 2 Continuous demographic data ( n= 436)
Age at biopsy ( y/o)                   35.4 ± 13.7, (33.2, 7.62-73.7)
Duration from symptom to biopsy ( yrs) 1.4 ± 2.7, (0.3, 0.0-20.1)
Follow-up ( yrs)                       7.0 ± 6.1, (5.5, 0.00-24.8)
Serum creatinine at onset ( mg/dl)     2.5 ± 3.0, (1.3, 0.3-17.5)
GFR at onset (ml/min)                  62.2 ± 39.4, (63.3, 3.1-295.7)
Serum creatinine at final (mg/dl)      3.3 ± 3.8, (1.4, 0.4-20.9)
GFR-final (ml/min)                     52.5 ± 37.8, (53.9, 2.1-199.2)
IgG (mg/dl)                            1124.8 ± 418.4, (1140.0, 126.00-2710.0)
IgA (mg/dl)                                   332.6   ± 152.5, (311.0, 18.0-1350.0)
IgM (mg/dl)                                   125.5   ± 79.4, (107.5, 7.80-895.1)
IgE (mg/dl)                                   299.8   ± 805.2, (56.1, 0.00-5805.0)
Daily urine protein at onset (gm/day)         2.5 ±   3.2, (1.4, 0.0-30.3)
Daily urine protein at final (gm/day)         1.5 ±   2.1, (0.8, 0.0-13.5)
Data were expressed as mean  SD (median, range)




17
Table 3 Comparison of categorical variables between stable and progressive groups
Variable                       stable (n=180)           Progressive (n=256) P-value
Male gender (%)                57.8                     53.1                  0.388
Hepatitis B carrier (%)        14.8                     14.4                  1.0
Gross hematuria Positive (%)   40.0                     34.0                  0.237
Micohematuria Positive (%)     50.6                     50.0                  0.986
Hypertension (%)               27.8                     49.6                  <0.0001
Hepatitis C carrier (%)        4.0                      14.3                  <0.005




18
Table 4: Comparison of continuous variables between stable and progressive group
Variable                                Stable (n=180)     Progressive (n=256) P-value
Age at biopsy (y/o)                     32.4 ± 13.1        37.3 ± 13.5             < 0.0001
Duration from symptom to biopsy (yrs)   1.2 ± 2.3          1.5 ± 2.9               0.743
Duration of follow-up (yrs)             6.4 ± 6.1          7.5 ± 6.0               0.025
Scr* at onset ( mg/dl)                  1.3 ± 0.7          3.2 ± 3.7               < 0.0001
Scr* at final (mg/dl)                   1.1 ± 0.5          4.9 ± 4.3               < 0.0001
IgG (mg/dl)                             1099.6 ± 441.7     1141.1± 400.2           0.609
IgA (mg/dl)                             334.3 ± 164.0      332.2 ± 144.6           0.993
IgM (mg/dl)                             133.8 ± 68.6       119.3 ± 86.7            0.007
IgE (mg/dl)                             441.5 ± 1009.1     179.8 ± 552.2           0.042
Proteinuria at onset (gm/day)           2.4 ± 4.02         2.5 ± 2.6               < 0.0001
proteinuria at final (gm/day)           1.01 ± 2.0         1.91 ± 2.2              < 0.0001
* Serum creatinine




19
Table 5 Correlation between clinical and pathological classification *
Hass's subclass         Stable ( n= 180)             Progression ( N=256) P-value

1                       21.7                         8.5
2                       23.9                         23.2
3                       34.8                         24.6                < 0.0001
4                       18.5                         21.8
5                       1.1                          21.8
* based on pathological grading proposed by Haas et al ( Ref   )




20
Table 6 Factors that predict disease progression by Logistic regression analysis

      Varialbe          Group      Odds ratio 95% CI of odds ratio       P value

     Initial eGFR     <60 ml/min       1.0
                         ≧60          0.35            0.19-0.63          <0.001
 Hass's subclass
                       Class 1         1.0
                      Class2+3         2.2            0.91-5.06          <0.079
                      Class 4+5       4.44           1.67-11.81          <0.003
Initial proteinuria
                      <1 gm/day       1.00
                      ≧1 gm/day       1.20            0.63-2.31           0.577




21
Table 7 Treatment of patients
Medication                               N/%
prednisolone                             203 (46.1%)
cyclophosphamide                         23 (5.2%)
azathioprine                             18 (4.0%)
cyclosporine                             30 (6.8%)
mycophenolate mofetil                    26 (5.9%)
dipyridamole                             138 (31.3%)
pentoxiphylline                          151 (34.3%)
angiotensin      convertase     inhibitor/ 206 (46.8%)
anigiotensin receptor blocker
herb                                     8 (1.8%)
others                                   118 (26.8%)
no treatment                             13 (2.9%)




22
Tab 8 Effect of therapy in patients with proteinuria > 1gm/day
medication                      stable(n=85)          progression (n=174)   P-value
prednisolone                    65.9                  47.7                  0.009
cyclophosphamide                11.8                  4                     0.036
azathioprine                    4.7                   4.6                   1.0
cyclosporine                    4.7                   9.8                   0.246
mycophenolate mofetil           3.5                   8.0                   0.267
dipyridamole                    25.9                  33.9                  0.244
pentoxyphilline                 35.3                  42.5                  0.327
aCEI, ARB                       54.1                  53.4                  1.0
* presented as percentage




23
Figure 1




                                         100%
                                         90%
       Cumulative Proportion Surviving




                                         80%
                                         70%
                                         60%
                                         50%        years     survival (%)
                                                    1         95.2
                                         40%
                                                    5         85.1
                                         30%        10        70.1
                                                    20        36.9
                                         20%
                                         10%
                                          0%
                                                0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

                                                                               Years




Figure 2:
24
                                  100%
                                  90%
Cumulative Proportion Surviving




                                  80%
                                  70%
                                  60%
                                  50%
                                  40%                                                 Normotension, n=258

                                  30%
                                  20%
                                          P <0.0001
                                  10%
                                          0.0.00010                      Hypertension, n=177
                                   0%     .0001
                                      0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

                                                                    Years




Figure 3:
25
                                  100%
                                  90%
Cumulative Proportion Surviving



                                  80%                                              Class 1 (n=32)
                                  70%                                                       Class 2 (n=55)

                                  60%
                                  50%                P value
                                                                                    Class 3 (n=67)
                                            2 vs.4   0.001
                                  40%
                                            2 vs.5   <0.0001
                                  30%       3 vs.5   0.028

                                  20%
                                                                                  Class 4 (n=48)
                                  10%        Overall
                                             P = 0.0004                                    Class 5 (n=32)
                                   0%
                                         0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26

                                                                        Years




Figure 4:
26
                                  100%
                                  90%
Cumulative Proportion Surviving



                                  80%                                        Proteinuria < 1gm/day (n=164)
                                  70%
                                  60%
                                                                            Proteinuria 1-3 gm/day (n=140)
                                  50%                  P value
                                             1 vs 2   0.0002
                                  40%        1 vs 3   <0.0001
                                             2 vs 3   0.016
                                  30%
                                  20%                            Proteinuria >3 gm/day (n=111)

                                  10%       Overall:
                                            P < 0.0001
                                   0%
                                         0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25

                                                                         Years




Figure legend

27
Figure 1: The survival curve of total patients


Figure 2: A significant difference in renal survival was found between patients with and


without hypertension


Figure 3: Survival analysis according to Haas’s classification of renal pathology


Figure 4: A statistically significant difference was found among patients with different amount


of proteinuria at presentation.




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