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Epidemiology and risk factors for chronic kidney disease in Chinese patients with biopsy-proven lupus nephritis M. Sui,1 X. Ye,2 J. Ma,1 C. Yu,3 S. Zhao,1 X. Liu,1 L. Li,1 J. Cao,4 X. Jia1 and R. Xie1 1
Departments of Nephrology, 2Haematology and 3Cardiology, First Affiliated Hospital of Harbin Medical University, and 4Endemic Disease Control,
Harbin Center for Disease Prevention and Control, Harbin, China
Key words chronic kidney disease, epidemiology, lupus nephritis, risk factor. Correspondence Rujuan Xie, Department of Nephrology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, China. Email: [email protected] Received 11 March 2015; accepted 9 June 2015. doi:10.1111/imj.12840
Abstract Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). It is the most common secondary glomerulonephritis leading to end-stage renal disease. Aim: The purpose of this study is to evaluate the epidemiology and risk factors of chronic kidney disease (CKD) in Chinese patients with LN. Methods: Clinical, laboratory, renal histopathology, treatment and outcome data were collected and retrospectively analysed in LN patients with or without CKD. Results: At the end of the study, 94 (45.63%) patients were identified as having CKD among 206 individuals with renal biopsy-proven LN. Renal function, represented by serum creatinine and estimated glomerular filtration rate, was significantly decreased in the CKD patients (P = 0.008 and P < 0.001, respectively) at the time of the kidney biopsy. Compared with the non-CKD group, significantly increased proportions of hypertension (P < 0.001), serositis (P = 0.042) and anti-histone antibody positivity (P = 0.004) were detected in the CKD patients. Renal pathological activity and chronicity index scores were significantly increased in the CKD group (P < 0.001 for all). Finally, hypertension (hazard ratio (HR) 2.432, 95% confidence interval (CI) 1.575–3.754, P < 0.001), antihistone antibody (HR 2.907, 95% CI 1.837–4.600, P < 0.001), and tubular atrophy (HR 1.248, 95% CI 1.007–1.547, P = 0.043) were independent risk factors for CKD. Conclusions: Hypertension, anti-histone antibody and tubular atrophy are independent risk factors for CKD in Chinese LN patients.
Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple systems. Lupus nephritis (LN) is associated with a poor prognosis.1 The incidence of chronic kidney disease (CKD) in SLE patients remains high. CKD is associated with a high risk of mortality, endstage renal disease (ESRD) and cardiovascular disease.2 Impressive gains in outcome have been possible with immunosuppressive regimens, with recent studies from North America and Europe reporting a 10-year renal survival rate of 80% to 90%.3 Some studies even report the maintenance of normal renal function in 90% of patients.4,5 However, other studies demonstrated worse outcomes, with 5-year renal survival rates of 48% to 65% and 10-year survival rates of 21% to 35%.6,7 M. Sui and X. Ye contributed equally to this work. Funding: The presented work was supported by the National Natural Science Foundation of China (Grant 81370831). Conflict of interest: None.
However, few studies have assessed the risk factors for CKD in Chinese patients with LN. In this paper, we retrospectively analysed the clinicopathologic characteristics, response to treatment and risk factors for CKD in 206 LN patients.
Methods Patients In this single-centre retrospective study, 206 patients with biopsy-proven LN were enrolled from January 2002 to August 2013 at the 1st Affiliated Hospital of Harbin Medical University. Patients with the following criteria were included: (i) 16 years old or older, (ii) fulfillment of the American College of Rheumatology revised criteria for SLE8 and (iii) at least 12 months of follow up. Patients were excluded if they had persistent severe renal dysfunction (creatinine clearance less than 20 mL/min), active infections, diabetes or pregnancy. The research
© 2015 Royal Australasian College of Physicians
1167
Sui et al.
complied with the Declaration of Helsinki and approved by the ethics committee of Harbin Medical University. CKD was defined according to the Kidney Disease (glomerular filtration rate (GFR) < 60 mL/min/1.73/m of body surface area for 3 months or more).9 All patients were divided into two groups (with or without CKD) at the end of the study.
Collection of clinical laboratory and histological data Hypertension was defined as a blood pressure of ≥140/ 90 mmHg or the use of any antihypertensive medications. In addition, the antinuclear antibodies profile was detected by the European Union immunoblot assay. Complement factor 3 (C3) and complement factor 4 (C4) were determined by nephelometry. Renal histopathology was classified according to the World Health Organisation and International Society of Nephrology/Renal Pathology Society.10 Pathological parameters, such as activity index (AI) and chronicity index, were approached by a modification of the criteria proposed by Austin et al.11,12 involving semi-quantitative scoring of specific renal pathological features by two renal pathologists. Differences in scoring between the two pathologists were resolved by re-reviewing the biopsies and reaching a consensus.
Treatment regimen The patients were treated in accordance with the clinical routine for LN.13 Patients with severe necrotising crescentic glomerulonephritis and diffuse pulmonary alveolar haemorrhage were also treated with methylprednisolone (MP, 7–15 mg/kg per day, 3 days) pulse therapy.
Statistical analyses Analysis was performed with SPSS19.0 (Chicago, IL, USA). Quantitative data are expressed as the mean ± SD, and categorical variables are expressed as percentages. Baseline characteristics for patients were compared using t-tests or Mann–Whitney U-tests for continuous variables as appropriate and χ2 tests for categorical variables. The Cox proportional hazards model was used to estimate the hazard ratio (HR), and 95% confidence intervals (CIs) were used to identify the predictive factors for CKD. Initially, each possible baseline factor was assessed by univariate analysis, and those that exhibited a P-value < 0.05 were considered for further analysis. Subsequently, the independent risk of baseline factors for CKD was assessed by Cox proportional hazard regression multivariate analyses. The requirement for keeping the variables in the final Cox model included statistical significance with a P-value < 0.05. A P-value < 0.05 was considered significant.
Results Baseline demographic, clinical and laboratory profiles At the end of the study, we identified 94 (45.63%) patients with CKD from 206 LN patients. The patients’ characteristics at the time of the kidney biopsy are presented in Tables 1 and 2. Renal function at the time of the
Table 1 Comparison of clinical parameters between patients with and without chronic kidney disease in lupus nephritis patients at the onset Characteristics
Assessment of response to treatment The criteria for remission and relapse were developed according to the definition by the Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on SLE Response Criteria.14 Response status was assessed as complete remission (GFR ≥ 90 mL/min/ 1.73/m or >25% increase from baseline, urinary proteinto-creatinine ratio 5 RBC/HPF and/or cellular casts.
Female (%) Age at LN (years) Follow-up period (years) Hypertension (%) Fever (non-infection) (%) Malar rash (%) Photosensitivity (%) Oral ulcer (%) Alopecia (%) Arthritis (%) Serositis (%) Neurologic disorder (%) Anaemia (%) Leukocytopenia (%) Thrombocytopenia (%) SLEDAI
Without CKD (n = 112)
With CKD (n = 94)
P-value
105 (93.75%) 32.01 ± 11.36 5.60 ± 1.93 17 (15.18) 26 (23.21) 58 (51.79) 16 (14.29) 36 (32.14) 36 (32.14) 62 (55.36) 24 (21.43) 16 (14.29) 70 (62.50) 55 (49.11) 19 (16.96) 17.20 ± 5.9
83 (88.30) 31.14 ± 12.44 5.74 ± 1.73 51 (54.26) 24 (25.53) 41 (43.62) 23 (24.47) 21 (22.34) 19 (20.21) 42 (44.68) 33 (35.11) 11 (11.70) 63 (67.02) 44 (46.81) 19 (20.21) 20.25 ± 6.7
0.350 0.600 0.588
Epidemiology and risk factors for chronic kidney disease in Chinese patients with biopsy-proven lupus nephritis M. Sui,1 X. Ye,2 J. Ma,1 C. Yu,3 S. Zhao,1 X. Liu,1 L. Li,1 J. Cao,4 X. Jia1 and R. Xie1 1
Departments of Nephrology, 2Haematology and 3Cardiology, First Affiliated Hospital of Harbin Medical University, and 4Endemic Disease Control,
Harbin Center for Disease Prevention and Control, Harbin, China
Key words chronic kidney disease, epidemiology, lupus nephritis, risk factor. Correspondence Rujuan Xie, Department of Nephrology, First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin 150001, China. Email: [email protected] Received 11 March 2015; accepted 9 June 2015. doi:10.1111/imj.12840
Abstract Background: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). It is the most common secondary glomerulonephritis leading to end-stage renal disease. Aim: The purpose of this study is to evaluate the epidemiology and risk factors of chronic kidney disease (CKD) in Chinese patients with LN. Methods: Clinical, laboratory, renal histopathology, treatment and outcome data were collected and retrospectively analysed in LN patients with or without CKD. Results: At the end of the study, 94 (45.63%) patients were identified as having CKD among 206 individuals with renal biopsy-proven LN. Renal function, represented by serum creatinine and estimated glomerular filtration rate, was significantly decreased in the CKD patients (P = 0.008 and P < 0.001, respectively) at the time of the kidney biopsy. Compared with the non-CKD group, significantly increased proportions of hypertension (P < 0.001), serositis (P = 0.042) and anti-histone antibody positivity (P = 0.004) were detected in the CKD patients. Renal pathological activity and chronicity index scores were significantly increased in the CKD group (P < 0.001 for all). Finally, hypertension (hazard ratio (HR) 2.432, 95% confidence interval (CI) 1.575–3.754, P < 0.001), antihistone antibody (HR 2.907, 95% CI 1.837–4.600, P < 0.001), and tubular atrophy (HR 1.248, 95% CI 1.007–1.547, P = 0.043) were independent risk factors for CKD. Conclusions: Hypertension, anti-histone antibody and tubular atrophy are independent risk factors for CKD in Chinese LN patients.
Introduction Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple systems. Lupus nephritis (LN) is associated with a poor prognosis.1 The incidence of chronic kidney disease (CKD) in SLE patients remains high. CKD is associated with a high risk of mortality, endstage renal disease (ESRD) and cardiovascular disease.2 Impressive gains in outcome have been possible with immunosuppressive regimens, with recent studies from North America and Europe reporting a 10-year renal survival rate of 80% to 90%.3 Some studies even report the maintenance of normal renal function in 90% of patients.4,5 However, other studies demonstrated worse outcomes, with 5-year renal survival rates of 48% to 65% and 10-year survival rates of 21% to 35%.6,7 M. Sui and X. Ye contributed equally to this work. Funding: The presented work was supported by the National Natural Science Foundation of China (Grant 81370831). Conflict of interest: None.
However, few studies have assessed the risk factors for CKD in Chinese patients with LN. In this paper, we retrospectively analysed the clinicopathologic characteristics, response to treatment and risk factors for CKD in 206 LN patients.
Methods Patients In this single-centre retrospective study, 206 patients with biopsy-proven LN were enrolled from January 2002 to August 2013 at the 1st Affiliated Hospital of Harbin Medical University. Patients with the following criteria were included: (i) 16 years old or older, (ii) fulfillment of the American College of Rheumatology revised criteria for SLE8 and (iii) at least 12 months of follow up. Patients were excluded if they had persistent severe renal dysfunction (creatinine clearance less than 20 mL/min), active infections, diabetes or pregnancy. The research
© 2015 Royal Australasian College of Physicians
1167
Sui et al.
complied with the Declaration of Helsinki and approved by the ethics committee of Harbin Medical University. CKD was defined according to the Kidney Disease (glomerular filtration rate (GFR) < 60 mL/min/1.73/m of body surface area for 3 months or more).9 All patients were divided into two groups (with or without CKD) at the end of the study.
Collection of clinical laboratory and histological data Hypertension was defined as a blood pressure of ≥140/ 90 mmHg or the use of any antihypertensive medications. In addition, the antinuclear antibodies profile was detected by the European Union immunoblot assay. Complement factor 3 (C3) and complement factor 4 (C4) were determined by nephelometry. Renal histopathology was classified according to the World Health Organisation and International Society of Nephrology/Renal Pathology Society.10 Pathological parameters, such as activity index (AI) and chronicity index, were approached by a modification of the criteria proposed by Austin et al.11,12 involving semi-quantitative scoring of specific renal pathological features by two renal pathologists. Differences in scoring between the two pathologists were resolved by re-reviewing the biopsies and reaching a consensus.
Treatment regimen The patients were treated in accordance with the clinical routine for LN.13 Patients with severe necrotising crescentic glomerulonephritis and diffuse pulmonary alveolar haemorrhage were also treated with methylprednisolone (MP, 7–15 mg/kg per day, 3 days) pulse therapy.
Statistical analyses Analysis was performed with SPSS19.0 (Chicago, IL, USA). Quantitative data are expressed as the mean ± SD, and categorical variables are expressed as percentages. Baseline characteristics for patients were compared using t-tests or Mann–Whitney U-tests for continuous variables as appropriate and χ2 tests for categorical variables. The Cox proportional hazards model was used to estimate the hazard ratio (HR), and 95% confidence intervals (CIs) were used to identify the predictive factors for CKD. Initially, each possible baseline factor was assessed by univariate analysis, and those that exhibited a P-value < 0.05 were considered for further analysis. Subsequently, the independent risk of baseline factors for CKD was assessed by Cox proportional hazard regression multivariate analyses. The requirement for keeping the variables in the final Cox model included statistical significance with a P-value < 0.05. A P-value < 0.05 was considered significant.
Results Baseline demographic, clinical and laboratory profiles At the end of the study, we identified 94 (45.63%) patients with CKD from 206 LN patients. The patients’ characteristics at the time of the kidney biopsy are presented in Tables 1 and 2. Renal function at the time of the
Table 1 Comparison of clinical parameters between patients with and without chronic kidney disease in lupus nephritis patients at the onset Characteristics
Assessment of response to treatment The criteria for remission and relapse were developed according to the definition by the Renal Disease Subcommittee of the American College of Rheumatology Ad Hoc Committee on SLE Response Criteria.14 Response status was assessed as complete remission (GFR ≥ 90 mL/min/ 1.73/m or >25% increase from baseline, urinary proteinto-creatinine ratio 5 RBC/HPF and/or cellular casts.
Female (%) Age at LN (years) Follow-up period (years) Hypertension (%) Fever (non-infection) (%) Malar rash (%) Photosensitivity (%) Oral ulcer (%) Alopecia (%) Arthritis (%) Serositis (%) Neurologic disorder (%) Anaemia (%) Leukocytopenia (%) Thrombocytopenia (%) SLEDAI
Without CKD (n = 112)
With CKD (n = 94)
P-value
105 (93.75%) 32.01 ± 11.36 5.60 ± 1.93 17 (15.18) 26 (23.21) 58 (51.79) 16 (14.29) 36 (32.14) 36 (32.14) 62 (55.36) 24 (21.43) 16 (14.29) 70 (62.50) 55 (49.11) 19 (16.96) 17.20 ± 5.9
83 (88.30) 31.14 ± 12.44 5.74 ± 1.73 51 (54.26) 24 (25.53) 41 (43.62) 23 (24.47) 21 (22.34) 19 (20.21) 42 (44.68) 33 (35.11) 11 (11.70) 63 (67.02) 44 (46.81) 19 (20.21) 20.25 ± 6.7
0.350 0.600 0.588
