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Tripterygium wilfordii Hook F (a traditional Chinese medicine) for primary nephrotic syndrome

  1. Yizhi Chen1,
  2. Zhixiang Gong2,
  3. Xiangmei Chen1,
  4. Li Tang1,
  5. Xuezhi Zhao3,
  6. Qing Yuan4,
  7. Guangyan Cai1,*

Editorial Group: Cochrane Renal Group

Published Online: 11 AUG 2013

Assessed as up-to-date: 13 AUG 2012

DOI: 10.1002/14651858.CD008568.pub2


How to Cite

Chen Y, Gong Z, Chen X, Tang L, Zhao X, Yuan Q, Cai G. Tripterygium wilfordii Hook F (a traditional Chinese medicine) for primary nephrotic syndrome. Cochrane Database of Systematic Reviews 2013, Issue 8. Art. No.: CD008568. DOI: 10.1002/14651858.CD008568.pub2.

Author Information

  1. 1

    Chinese People's Liberation Army (PLA) General Hospital (301 Hospital), Chinese PLA Medical Academy, Division of Nephrology, State Key Discipline and State Key Laboratory of Kidney Diseases (2011DAV00088), Beijing, China

  2. 2

    Chinese PLA 532 Hospital, Division of Infectious Diseases, Huangshan, Anhui, China

  3. 3

    Shanghai Chang Zheng Hospital, Division of Nephrology, Shanghai Kidney Disease Quality Control Center, Kidney Institute of Chinese PLA, Shanghai, Shanghai, China

  4. 4

    309th Hospital of the People's Liberation Army, Organ Transplant Center, Beijing, China

*Guangyan Cai, Division of Nephrology, State Key Discipline and State Key Laboratory of Kidney Diseases (2011DAV00088), Chinese People's Liberation Army (PLA) General Hospital (301 Hospital), Chinese PLA Medical Academy, Fuxing Road 28, Haidian District, Beijing, 100853, China. caiguangyan@sina.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 11 AUG 2013

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Summary of findings    [Explanations]

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

 
Summary of findings for the main comparison. Summary of findings: Tripterygium wilfordii Hook F (TwHF) versus no TwHF

TwHF versus non-TwHF for primary nephrotic syndrome

Patient or population: patients with primary nephrotic syndrome
Settings:
Intervention: Tripterygium wilfordii Hook F (TwHF)
Comparison: no TwHF

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
Number of participants
(studies)
Quality of the evidence
(GRADE)

Assumed riskCorresponding risk

Non-TwHFTwHF

Complete remission (follow-up: 12 to 16 months)Study populationRR 1.46
(1.18 to 1.80)
293 (4)⊕⊕⊝⊝
Low1,2

436 per 1000637 per 1000
(514 to 785)

Medium risk population

406 per 1000593 per 1000
(479 to 731)

Partial remission (follow-up: 12 to 16 months)Study populationRR 0.77
(0.49 to 1.21)
293 (4)⊕⊕⊝⊝
Low1,2

229 per 1000176 per 1000
(112 to 277)

Medium risk population

257 per 1000198 per 1000
(126 to 311)

Complete or partial remission (follow-up: 12 to 16 months)Study populationRR 1.26
(1.1 to 1.44)
293 (4)⊕⊕⊝⊝
Low1,2

664 per 1000837 per 1000
(730 to 956)

Medium risk population

662 per 1000834 per 1000
(728 to 953)

*The basis for the assumed risk (the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; RR: risk ratio

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate
Very low quality: we are very uncertain about the estimate

 1 Small number of studies and patients, short follow-up, and major concerns with methodological bias.
2 Language bias should be considered because all included studies were conducted in Chinese patients and published in Chinese language.

 Summary of findings 2 Summary of findings: Tripterygium wilfordii Hook F versus prednisone

 Summary of findings 3 Summary of findings: Comparison of TwHF and CPA

 

Background

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of the condition

Primary nephrotic syndrome (NS) is a relatively rare, but important kidney disease in children and adults (Eddy 2003; Hull 2008). It has an annual incidence of 2 to 7/100,000 children (Eddy 2003) and 3/100,000 adults (Hull 2008). There are five main distinct histological variants of primary NS: minimal change nephropathy (MCN); focal segmental glomerulosclerosis (FSGS); membranous nephropathy (MN); mesangioproliferative glomerulonephritis (MsPGN) (immunoglobulin A (IgA) nephropathy and non-IgA nephropathy); and membranoproliferative glomerulonephritis (MPGN). Acute complications related to primary NS include thromboembolism, infection, and acute kidney injury (AKI). Deep and renal vein thromboses could lead to pulmonary embolism. Bacterial and viral infections such as pneumonia and cellulitis are an ongoing threat to the health of immunocompromised patients. Long-term sequelae of primary NS relate mainly to adverse events of immunosuppressive treatments on bones, growth and the cardiovascular system (Eddy 2003; Hull 2008).

 

Description of the intervention

Tripterygium wilfordii Hook F (TwHF) has been used widely in traditional Chinese medicine to treat rheumatoid arthritis and other autoimmune and inflammatory diseases. Results from studies in Chinese patients (Tao 1987; Tao 1989) stimulated further investigation of TwHF for rheumatoid arthritis in western countries (Goldbach-Mansky 2009; Tao 2001; Tao 2002). TwHF has been prescribed as an immunosuppressive agent for primary NS in China for more than 20 years (Chen 1985; Jiang 1994). Preliminary observations suggested that remission was achieved in 8/13 (62%) children with primary NS and maintained in four children (31%) for up to three years (Jiang 1994). A meta-analysis of three studies enrolling 150 adult patients with primary refractory NS indicated that TwHF were associated with a higher complete remission (Odds ratio (OR) 2.81, 95% CI 1.26 to 6.30) and complete or partial remission (OR 3.25, 95% CI 1.20 to 8.76) (Xu 2009a).

Non-standardised TwHF preparations have been reported as causing serious adverse events and death (Wen 1999). A search of the Chinese Biological Medicine (CBM) Database (from 1982 to 1996) identified 38 patients who experienced adverse events related to non-standardised TwHF preparations (Wen 1999). The adverse events included leukopenia (9/38, 24%), aplastic anaemia (5/38, 13%), gastrointestinal tract disturbances (10/38, 26%), liver dysfunction (4/38, 11%), skin lesions such as erythema and papules (5/38, 13%) and other rare complications. Serious adverse events were primarily related to haematological system, and 8/38 (21%) died (leukopenia (4/8, 50%); aplastic anaemia (2/8, 25%); severe liver dysfunction (2/8, 25%)) (Wen 1999). Toxicities caused by non-standardised TwHF preparations which were reported before 1996 were difficult to compare with adverse events reported for standardised TwHF preparations such as ethanol-ethyl acetate and chloroform-methanol extracts of TwHF (Goldbach-Mansky 2009). Peeling the roots of this plant and using a standardised extraction method can fundamentally reduce toxicity and increase tolerability (Tao 2002). More recently, the most common adverse events of standardised TwHF preparations were gastrointestinal tract disturbances, leukopenia, thrombocytopenia, rash, skin pigmentation, and malfunction of reproductive system (Bao 2011). Most of these could be resolved by dose adjustment or drug discontinuation (Bao 2011; Goldbach-Mansky 2009).

 

How the intervention might work

Kupchan 1972 first demonstrated that triptolide and tripdiolide, two diterpenoid triepoxides from TwHF, possess antileukaemic properties. More recently, triptolide and tripdiolide were considered to be the principal active components of TwHF (Tao 1995). Two preparations of TwHF have been used extensively in experimental and clinical studies because of their lower toxicity profiles: chloroform-methanol extract (T2 or TwHF multiglycoside) and ethanol-ethyl acetate extract (Goldbach-Mansky 2009; Sharma 1997; Tao 1998; Tao 2001; Tao 2002; Wan 2010).

Sharma 1997 demonstrated the in vitro inhibitory effect of chloroform-methanol extract on increased glomerular albumin permeability in isolated glomeruli. The protective effect of chloroform-methanol extract on glomerular filtration barriers may be independent from anti-inflammatory and immunosuppressive properties of TwHF (Sharma 1997). Hong 2002 showed that in vitro triptolide could effectively inhibit the pro-inflammatory and immunoregulatory potential of TNF-α activated human renal proximal tubular epithelial cells by inhibiting C3, B7h, and CD40 expression. The chloroform-methanol extract, presumably through reducing production of injurious cytokines, ameliorated proteinuria and acute mesangial injury in Thy1.1 glomerulonephritis rat model (Wan 2005). Triptolide displayed a prominent in vivo anti-proteinuric effect in puromycin aminonucleoside (PAN)-induced nephrosis rat model characterised by improvement of foot process effacement, decrease of podocyte injury marker (desmin) and restoration of nephrin and podocin expression and distribution (Zheng 2008). This in vitro study further confirmed the protective effect of triptolide on immortalised mouse podocytes from PAN-induced disruption of actin cytoskeleton and microfilament-associated synaptopodin and abnormality of nephrin and podocin expression (Zheng 2008). The effects of triptolide may be attributed to the suppression of reactive oxygen species generation and subsequent p38 mitogen-activated protein kinase pathway activation, and restoration of RhoA activity (Zheng 2008).

 

Why it is important to do this review

Although TwHF has been used widely as an immunosuppressive agent for primary NS in China for more than 20 years, the efficacy and safety of TwHF have not been systematically reviewed.

 

Objectives

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

This review aimed to assess the benefits and harms of TwHF for the treatment of primary NS in adults and children, either as a sole agent or combined with other drug therapies.

 

Methods

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Criteria for considering studies for this review

 

Types of studies

All randomised controlled trials (RCTs) investigating the efficacy and safety of TwHF administered to patients with primary NS were considered for inclusion. Quasi-RCTs (studies in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) were excluded. All the included RCTs had a follow-up of at least three months.

 

Types of participants

 

Inclusion criteria

Adult and children diagnosed with primary NS were included. The diagnosis of NS were defined by the authors in each single study. In absence of an explicit definition of primary NS, proteinuria above 3.5 g/24 h was used as the cut-off value for adults, and in children urine protein-creatinine ratio above 200 mg/mmol, proteinuria above 300mg/dL, or protein on urine dipstick above 3+ was used (KDIGO 2012).

 

Exclusion criteria

Patients with secondary NS were excluded.

 

Types of interventions

  • Two preparations of TwHF extracts (ethanol-ethyl acetate extract and chloroform-methanol extract) have been investigated in clinical studies and reported to carry lower toxicity profiles compared with other TwHF preparations. This review considered only ethanol-ethyl acetate extract and chloroform-methanol extract of TwHF. Other TwHF preparations were excluded because of their less favourable toxicity profiles (Tao 2002; Wen 1999).
  • TwHF versus placebo, no treatment, non-immunosuppressive agents (such as angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, anticoagulants, antiplatelet agents, or fish oil), or immunosuppressive drugs (glucocorticoids, alkylating agents, azathioprine, cyclosporine, tacrolimus, mycophenolate mofetil, or leflunomide).
  • TwHF in addition to the listed immunosuppressive and non-immunosuppressive agents versus the same drugs. Co-interventions were permitted where all study arm patients received the same co-interventions.
  • Various doses, frequencies of administration, and therapeutic durations of the same TwHF preparation were included.
  • Any preparations of other traditional Chinese herbal medicines, including single herb, compound herbs, extracts, raw materials, Chinese proprietary medicines, and practitioner-prescribed herbal formulae (individualised treatment) according to the study report, were excluded.

 

Types of outcome measures

 

Primary outcomes

Complete remission, partial remission, and complete or partial remission at the last follow-up. Complete and partial remission were assessed according to the definition provided in each single study. In the absence of an explicit definition of remission, we applied the following parameters (KDIGO 2012).

  • In children
    • Complete remission was defined as urine protein-creatinine ratio < 20 mg/mmol or < 1+ of protein on urine dipstick for three consecutive days.
    • Partial remission was defined as proteinuria reduction of ≥ 50% from the presenting value and absolute urine protein-creatinine ratio of 20 to 200 mg/mmol.

  • In adults

    • Complete remission was defined as proteinuria < 0.3 g/24 h, accompanied by a normal serum albumin concentration and normal serum creatinine.
    • Partial remission was defined as reduction of proteinuria to 0.3 to 3.5 g/24 h and a decrease > 50% from baseline, accompanied by an improvement or normalisation of the serum albumin concentration and stable serum creatinine (change in creatinine < 25%)

 

Secondary outcomes

  • Urinary protein excretion at last follow-up
  • Serum albumin at last follow-up
  • Serum creatinine at last follow-up
  • Adverse events of TwHF

 

Search methods for identification of studies

 

Electronic searches

  • Cochrane Renal Group's specialised register were searched by the Trial Search Coordinator of Cochrane Renal Group in August 2012
  • Cochrane Register of Controlled Trials (CENTRAL) in The Cochrane Library (2012 Issue 8)
  • PUBMED (1966 to August 2012)
  • EMBASE (1966 to August 2012)
  • CBM (Chinese Biological Medical Database) (1978 to November 2010)
  • CNKI (Chinese National Knowledge Infrastructure) (1979 to November 2010)
  • VIP (ChongQing WeiPu Chinese Science and Technology Periodical Database) (1989 to November 2010)
  • WanFang Database (1980 to November 2010)

See Appendix 1 for search strategies used.

 

Searching other resources

We searched the reference lists of relevant studies and related Chinese journals (6 November 2010).

 

Data collection and analysis

 

Selection of studies

The search strategy was applied to obtain titles and abstracts of relevant studies. The titles and abstracts were screened independently by two authors, who discarded studies that were not applicable; however studies and reviews that may have included relevant data or information were retained initially. Two authors independently assessed retrieved abstracts and, if necessary the full text, to determine which satisfied the inclusion criteria. Disagreements were resolved by consultation with a third author.

 

Data extraction and management

Data extraction was conducted independently by two authors using standard data extraction forms. Studies reported in non-English language journals were translated before assessment. Where more than one publication of one study existed, the publication with the most complete data was included. Where relevant outcomes were published only in earlier versions, these data were included in the analyses. Any discrepancies between published versions were to be highlighted. Any further information required from the original investigators was requested by phone or written correspondence and any relevant information obtained was included in this review. Disagreements were resolved by consultation with a third author.

 

Assessment of risk of bias in included studies

The following items were independently assessed by two authors using the risk of bias assessment tool (Higgins 2011). For each item, the judgement (low risk of bias, high risk of bias, or unclear risk of bias) was followed by a description of the design, conduct or observations underlying the judgement (see Appendix 2).

  • Was there adequate sequence generation (selection bias)?
  • Was allocation adequately concealed (selection bias)?
  • Was knowledge of the allocated interventions adequately prevented during the study (detection bias)?
    • Participants and personnel
    • Outcome assessors
  • Were incomplete outcome data adequately addressed (attrition bias)?
  • Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?
  • Was the study apparently free of other problems that could put it at a risk of bias?

 

Measures of treatment effect

For dichotomous outcomes (e.g. remission) results were expressed as risk ratios (RR) with 95% confidence intervals (CI). Where continuous scales of measurement were used to assess the effects of treatment (e.g. urinary protein excretion, serum albumin, serum creatinine), the mean difference (MD) were used, or the standardised mean difference (SMD) if different scales have been used. If possible, we also aimed to determine the applicability of the results to individual patients, such as calculation of absolute risk reductions with therapy in relation to different baseline risk of the event with no therapy or a different therapy. Adverse events were tabulated and assessed using descriptive techniques. Where possible, risk difference with 95% CI was to be calculated for each adverse event, compared with either no treatment or another agent.

 

Unit of analysis issues

Studies with multiple intervention arms were analysed by entering each pair-wise comparison separately. For dichotomous outcomes, both the number of events and the total number of patients were halved. For continuous outcomes, only the total number of participants were halved, while the means and standard deviations were left unchanged (Higgins 2011).

 

Dealing with missing data

Data such as numbers of participants screened, randomised, intention-to-treat, and as-treated and per-protocol populations were evaluated and analysed. Attrition rates (drop-outs, losses to follow-up and withdrawals) were investigated. Issues of missing data and imputation methods (such as last-observation-carried-forward) were critically appraised (Higgins 2011). Participant results missing due to drop-out, intention-to-treat analysis was performed and compared with per-protocol analysis for the dichotomous data; while the continuous data remained unchanged due to the difficulty of application of ITT for this type of data (Moher 2010). For missing statistics such as standard deviations, these studies were not considered in the meta-analysis unless the missing data could be appropriately imputed using methods recommended by the Cochrane Collaboration (Higgins 2011). We also contacted principal investigators to request the missing data.

 

Assessment of heterogeneity

Heterogeneity was analysed using a Chi² test on N-1 degrees of freedom, with an alpha of 0.10 used for statistical significance (Higgins 2011). I² values of 25%, 50% and 75% corresponded to low, medium and high levels of heterogeneity.

 

Assessment of reporting biases

Assessment of publication bias was not conducted because of the small numbers of included studies in the three comparisons.

 

Data synthesis

Data were pooled using the random-effects model but the fixed-effect model was also used to ensure robustness of the model chosen and susceptibility to outliers.

 

Subgroup analysis and investigation of heterogeneity

The following subgroup analyses were planned.

  • Type of NS (steroid-resistant NS (SRNS) or frequently relapsing NS (FRNS)).
  • NS pathology.
  • Age of participants (e.g. children or elderly patients).

 

Sensitivity analysis

  • We conducted sensitivity analyses to explore the influence of diagnostic criteria of NS on the treatment effect.

 

Results

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Description of studies

See Characteristics of included studies and Characteristics of excluded studies.

 

Results of the search

The search strategy identified 2938 citations (6 November 2010) (Figure 1). Of these, 50 studies were considered as potentially eligible. All were conducted in China and reported in Chinese language. A total of 30/50 studies were excluded after further evaluation. We attempted to contact the investigators from the remaining 20 studies to obtain missing data. The authors of two studies could not be contacted and subsequently excluded (10%). We were successful in eliciting responses from 18 studies (90%). Eight of these studies were further excluded after contact with the investigators.

 FigureFigure 1. Flow diagram of study selection

 

Included studies

Our review included 10 RCTs published as full reports (A-Da 2008; Chen 2003; Han 1999; Li 2000; Song 1998; Wen 1993; Yuan 2003; Zhang 2007a; Zhao 1997; Zhao 2009).

 

Baseline characteristics

Age and gender appeared to be balanced in all included studies. Three studies did not report if proteinuria and serum creatinine were comparable at baseline (Li 2000; Wen 1993; Yuan 2003); and seven studies reported comparability at baseline (A-Da 2008; Chen 2003; Han 1999; Song 1998; Zhang 2007a; Zhao 1997; Zhao 2009).

 

Sample size

The 10 included studies randomised a total of 630 patients (345 in the experimental group and 285 in the control group). The median sample sizes was 64 patients (range from 36 to 92).

 

Diagnostic criteria

Eight studies only enrolled patients with primary NS. We contacted the investigators of the remaining two studies and confirmed that all enrolled patients had been diagnosed with primary NS (Li 2000; Zhao 1997). Sensitivity analyses for diagnostic criteria were conducted to detect the potential impact of unpublished information (Li 2000; Zhao 1997).

 

Age

Eight studies enrolled adult patients; one study included elderly patients (Yuan 2003); and one enrolled both adults and children (Li 2000).

 

Clinical conditions

Four studies included patients with primary refractory NS (Chen 2003; Han 1999; Song 1998; Zhao 2009). The remaining six studies included patients with primary NS.

 

Pathologic conditions

Common pathologic diagnoses reported in nine included studies were MCN, FSGS, MsPGN (including IgA nephropathy), MN, and MPGN. One study included only adults with primary IgA nephropathy-induced primary NS (A-Da 2008).

 

TwHF treatment

Initial doses of TwHF ranged from 0.5 mg/kg/d (Wen 1993) to 2.0 mg/kg/d (Song 1998; Zhao 2009), and were administered for four (Chen 2003; Zhao 2009) and eight weeks (A-Da 2008; Song 1998; Zhao 1997).

 

Follow-up

The median follow-up was 12 months (range: 3 to 18 months).

 

Comparisons

A presentation of comparisons in these 10 included studies was presented in additional  Table 1. Nine studies featured two-arm design. Zhao 1997 conducted a three-armed study that compared 34 patients receiving TwHF plus prednisone (0.6 mg/kg/d), 26 patients receiving TwHF, and 26 patients receiving prednisone (1.0 mg/kg/d). The prednisone group (1.0 mg/kg/d) was split into two equal-sized subgroups. Two comparisons were conducted: (A) TwHF plus prednisone (0.6 mg/kg/d) (N = 34) versus prednisone (1.0 mg/kg/d) (N = 13) and (B) TwHF (N = 26) versus prednisone (1.0 mg/kg/d) (N = 13). We conducted primary analyses according to experimental and control interventions:

 

Excluded studies

We excluded 40 studies from this review.

 

Risk of bias in included studies

See Figure 2 and Figure 3.

 FigureFigure 2. Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
 FigureFigure 3. Risk of bias summary: review authors' judgements about each risk of bias item for each included study

 

Allocation

 

Sequence generation

Although all included studies were RCTs, explicit methods of randomised sequence generation was described in only one. A-Da 2008 used a random number table for sequencing. We determined that drawing of lots was used in nine studies by contacting study investigators.

 

Allocation concealment

None of the included studies described allocation sequence concealment methods after contact with study investigators.

 

Blinding

None of the included studies reported blinding methods.

 

Incomplete outcome data

None of the studies described losses to follow-up or treatment withdrawals.

 

Selective reporting

The primary outcome (remission) was reported in all included studies. Secondary outcome data on urinary protein excretion, serum albumin, serum creatinine, and drug-related adverse events were presented in two (20%), two (20%), three (30%), and five studies (50%), respectively.

 

Other potential sources of bias

There was insufficient information to determine other potential sources of bias.

 

Effects of interventions

See:  Summary of findings for the main comparison Summary of findings: Tripterygium wilfordii Hook F (TwHF) versus no TwHF;  Summary of findings 2 Summary of findings: Tripterygium wilfordii Hook F versus prednisone;  Summary of findings 3 Summary of findings: Comparison of TwHF and CPA

Results are presented in  Summary of findings for the main comparison,  Summary of findings 2 and  Summary of findings 3. Subgroup and sensitivity analyses are presented in  Table 2 (TwHF versus non-TwHF) and  Table 3 (TwHF versus prednisone).

 

TwHF versus non-TwHF

Four studies compared TwHF to non-TwHF (Li 2000; Song 1998; Wen 1993; Zhang 2007a).

 

Primary outcomes

TwHF significantly increased complete remission ( Analysis 1.1 (4 studies, 293 participants): RR 1.46, 95% CI 1.18 to 1.80; I² = 3%) and complete or partial remission ( Analysis 1.3 (4 studies, 293 participants): RR 1.26, 95% CI 1.10 to 1.44; I² = 0%). The effect of TwHF on partial remission did not reach statistical significance ( Analysis 1.2 (4 studies, 293 participants): RR 0.77, 95% CI 0.49 to 1.21; I² = 0%).

 

Secondary outcomes

One study (Zhang 2007a) reported no significant difference in urinary protein excretion ( Analysis 1.4 (1 study, 78 participants: MD -0.03 g/24 h, 95% CI -0.21 to 0.15) and serum albumin ( Analysis 1.5 (1 study, 78 participants: MD 0.66 g/L, 95% CI -2.82 to 4.14). Two studies (Song 1998; Zhang 2007a) reported a significant decrease in serum creatinine; however heterogeneity was high (93%) and therefore we did not pool these studies ( Analysis 1.6).

One study (Song 1998) reported three types of adverse events of TwHF: infection, liver transaminase elevation, and leukopenia/bone marrow suppression. There were no significant differences in these adverse events ( Analysis 1.7).

 

Subgroup analyses

We were unable to perform subgroup analyses for pathological diagnosis of NS and age of participants due to lack of data.

 
SRNS or FRNS

Song 1998 included patients with SRNS or FRNS. There were no statistically significant subgroup differences in complete remission (P = 0.37), partial remission (P = 0.81) and complete or partial remission (P = 0.62) ( Table 2).

 
Co-interventions

Wen 1993 and Zhang 2007a compared TwHF + prednisone versus prednisone; Li 2000 and Song 1998 compared TwHF + prednisone + CPA versus prednisone + CPA. There were no statistically significant subgroup differences in complete remission (P = 0.62), partial remission (P = 0.53), and complete or partial remission (P = 0.72).

 

Sensitivity analyses for diagnostic criteria

The diagnosis of primary NS was not confirmed until we contacted the principal investigator in one study (Li 2000). This study was excluded from the sensitivity analysis. There were no significant changes of complete, partial, and complete or partial remission (additional  Table 2).

 

TwHF versus prednisone

Four studies compared TwHF to prednisone (A-Da 2008; Han 1999; Yuan 2003; Zhao 1997).

 

Primary outcomes

There were no significant differences in complete remission ( Analysis 2.1 (4 studies, 223 participants): RR 1.09, 95% CI 0.83 to 1.43, I² = 0%), partial remission ( Analysis 2.2 (4 studies, 223 participants): RR 1.07, 95% CI 0.69 to 1.65, I² = 0%), or complete or partial remission ( Analysis 2.3 (4 studies, 223 participants): RR 1.06, 95% CI 0.92 to 1.22, I² = 14%).

 

Secondary outcomes

Urinary protein excretion, serum albumin, and serum creatinine were not reported.

Two studies (Han 1999; Yuan 2003) showed no significant difference in liver transaminase elevation ( Analysis 2.4.1 (2 studies 101 participants): RR 1.51, 95% CI 0.16 to 14.22; I² = 47%). Yuan 2003 reported no significant difference for leukopenia or bone marrow suppression, elevated blood pressure, elevated blood glucose, femoral head necrosis, and infection. One study (Yuan 2003) reported the risk of psychosis was significantly lower in the TwHF group compared to the prednisone group ( Analysis 2.4.7 (1 study, 37 participants): RR 0.11, 95% CI 0.01 to 0.75).

 

Subgroup analyses

 
SRNS or FRNS

Han 1999 only enrolled patients with SRNS or FRNS. There were no statistically significant subgroup differences in complete remission (P = 0.17), partial remission (P = 0.82) and complete or partial remission (P = 0.06) (additional  Table 3).

 
Pathological diagnosis of NS

A-Da 2008 included only patients with IgA nephropathy-induced primary NS. There were no significant subgroup differences in complete remission (P = 0.53), partial remission (P = 0.51), and complete or partial remission (P = 0.94).

 
Aged participants

Yuan 2003 only enrolled elderly patients. There were no significant subgroup differences in complete remission (P = 0.91), partial remission (P = 0.53), and complete or partial remission (P = 0.60)

 
Co-interventions

A-Da 2008, Yuan 2003 and Zhao 1997 compared TwHF and prednisone; and Han 1999 compared TwHF + cyclosporine versus prednisone + cyclosporine. There were no statistically significant subgroup differences in complete remission (P = 0.17), partial remission (P = 0.82) and complete or partial remission (P = 0.06).

 

Sensitivity analyses for diagnostic criteria

The diagnosis of primary NS was not confirmed until we contacted the principal investigator in one study (Zhao 1997). This study was excluded from the sensitivity analysis. There were no significant changes of complete, partial, and complete or partial remission (additional  Table 3).

 

TwHF versus CPA

Two studies compared TwHF with CPA (Chen 2003; Zhao 2009).

 

Primary outcomes

There were no significant differences in complete remission ( Analysis 3.1 (2 studies, 114 participants): RR 1.06, 95% CI 0.82 to 1.37; I² = 0%), partial remission ( Analysis 3.2 (2 studies, 114 participants): RR 1.02, 95% CI 0.46 to 2.29; I² = 0%), and complete or partial remission ( Analysis 3.3 (2 studies, 114 participants); RR 1.05, 95% CI 0.90 to 1.23; I² = 0%).

 

Secondary outcomes

One study reported no significant differences in urinary protein excretion ( Analysis 3.4 (1 study, 46 participants): MD -0.30 g/24 h, 95% CI -1.34 to 0.74) and serum albumin ( Analysis 3.5 (1 study, 46 participants): MD 1.00 g/L, 95% CI -1.91 to 3.91). This study reported TwHF was associated with a significant decrease in serum creatinine ( Analysis 3.6 (1 study, 46 participants): MD -14.00 μmol/L, 95% CI -26.43 to -1.57).

There were no significant differences in the following adverse events: gastrointestinal discomfort, liver transaminase elevation, menstrual disorders, leukopenia and haemorrhagic cystitis. The risk of hair loss was significantly lower for the TwHF group compared to the CPA group ( Analysis 3.7.5 (2 studies, 114 participants): RR 0.11, 95% CI 0.02 to 0.59; I² = 0%). Subgroup and sensitivity analyses were not performed due to the lack of data.

 

Discussion

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Summary of main results

This systematic review provides some support for the effectiveness of TwHF for the treatment of primary NS; however the quality of evidence was suboptimal because of the small number of included studies enrolling small numbers of participants; short follow-up in each study; only a few studies in each comparison category; and major concerns with methodological bias. TwHF could significantly increase complete remission by 46% (18% to 80%) and complete or partial remission by 26% (10% to 44%). In a population with an expected rate of complete remission of 436/1000, TwHF could increase the number of patients achieving complete remission to 637/1000 (514 to 785). Complete or partial remission could be increased from 664 to 837/1000 (730 to 956). Meta-analyses of head-to-head comparisons demonstrated that there were no significant differences in the primary outcomes when TwHF was compared with either prednisone or CPA. Few studies reported data on secondary outcomes - proteinuria, serum albumin and serum creatinine; one study reported TwHF could significantly decrease serum creatinine compared with CPA. Issues of safety varied considerably and still remain unclear due to the poor reporting of adverse events and the variety of toxicity profiles. Compared to prednisone, TwHF was associated with a lower risk of psychosis. Patients treated with TwHF had a lower risk of hair loss when compared with CPA. However there were no significant differences in other adverse events, including reversible amenorrhoea, leukopenia, liver transaminase elevation, and gastrointestinal discomfort. A double-blind, placebo-controlled study examined the safety and efficacy of TwHF in the treatment of rheumatoid arthritis (Tao 2002). Although the dose in Tao 2002 was 180 mg/d to 360 mg/d for 20 weeks - higher than in any of the 10 included studies (0.5 to 2.0 mg/kg/d for 4 to 8 weeks as initial therapy) - no serious adverse events were observed, and no patients withdrew because of adverse events.

 

Overall completeness and applicability of evidence

All included studies were conducted in Chinese patients and published in Chinese language journals. Evidence is still needed to examine the effects of TwHF for other ethnicities. There was little evidence related to the use of TwHF in children with NS. In Chinese clinical practice many physicians were reluctant to use TwHF for children to avoid reproductive system complications (Li 2000). Pathological variations may differ in response to TwHF treatment; however due to the paucity of evidence we unable to use subgroup analyses to determine whether those variations could convey different responses to TwHF treatment. Although four studies enrolled patients with SRNS or FRNS, heterogeneity in the interventions among these four studies did not allow us to examine the effect of TwHF on patients with SRNS or FRNS.

 

Quality of the evidence

This review included 10 studies (630 participants). Assessment according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group indicated that the results could be considered as low quality level. The suboptimal methodological quality of the included studies was the major contributing factor. No study demonstrated adequate allocation concealment. Effect estimates from studies with inadequate concealment of allocation have been shown to overestimate beneficial effects by 18% (95% CI 5% to 29%) than that from studies with adequate concealment of allocation (Pildal 2007). Blinding was not reported in any study. The outcome measurements were all objective and were not likely to be influenced by lack of blinding; however lack of blinding could introduce potential bias in clinical studies (Higgins 2011). Although primary outcome completeness rates were 100%, this was remarkably lower for secondary outcomes (20% to 50%). Consequently, selective outcome reporting bias should be considered when interpreting the results.

Both the numbers of included studies and participants were relatively small, and all tested comparisons involved no more than four studies. Follow-up duration was no more than 18 months. The paucity of evidence did not allow us to perform subgroup analyses to explore modification effects by age, pathological variations, clinical conditions, and co-interventions. Such modification effects may potentially influence the efficacy of TwHF and should be investigated in the future. None of the included studies were designed to evaluate the efficacy of within intervention differences, such as dose and duration variation. More and better evidence is needed to explore benefits that may be conferred by different doses and durations of TwHF treatment.

 

Potential biases in the review process

Assessment of publication bias was not conducted because of the small number of included studies in the three comparisons. All studies were reported in Chinese language journals. Therefore, publication bias and language bias should be carefully considered when interpreting these results.

 

Agreements and disagreements with other studies or reviews

Xu 2009a meta-analysed results from three studies enrolling 150 adult patients with primary refractory NS. TwHF significantly increased complete remission (OR 2.81, 95% CI 1.26 to 6.30) and complete or partial remission (OR 3.25, 95% CI 1.20 to 8.76). The efficacy of TwHF on primary IgA nephropathy was examined in another meta-analysis of four studies with 188 patients (Chen 2010a). TwHF significantly increased complete remission (RR 1.53, 95% CI 1.09 to 2.16) and complete or partial remission (RR 1.27, 95% CI 1.08 to 1.48).

 

Authors' conclusions

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

 

Implications for practice

Overall, the quality of evidence was suboptimal due to the small number of included studies enrolling small numbers of participants; short follow-up in each study; only a few studies in each comparison category; and major concerns with methodological bias. This review has highlighted the fact that no well-designed RCT has been performed to test the efficacy and safety of TwHF for primary NS. In the majority of the included studies TwHF was used in conjunction with other immunosuppressive agents such as prednisone and CPA. Therefore, the individual effect of TwHF is still unclear. TwHF may have an add-on effect on remission in patients with primary NS. There was insufficient evidence to assess if TwHF was as effective as prednisone or CPA.

 
Implications for research

There is need for more methodologically sound studies with an emphasis on adequate sample size and follow-up. Furthermore, priority should be given to the choice of definite endpoints (all-cause mortality, risk of end-stage kidney disease) rather than surrogate outcomes (decline in kidney function). Recording and reporting adverse events should also be improved in future clinical studies. TwHF should be further directly compared with other widely used immunosuppressive agents after the superiority over placebo or no treatment has been clearly established. Ideally, optimal doses and durations of TwHF treatment that are most beneficial and least harmful to patients of different races, ages, and clinical and pathological severity still remain to be clarified.

 

Acknowledgements

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

We would like to thank the referees for their comments and feedback on this review. We would also like to acknowledge the contribution of Ribao Wei and JIanhui Zhou who helped to prepare this systematic review.

 

Data and analyses

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
Download statistical data

 
Comparison 1. TwHF versus no TwHF

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Complete remission4293Risk Ratio (IV, Random, 95% CI)1.46 [1.18, 1.80]

 2 Partial remission4293Risk Ratio (IV, Random, 95% CI)0.77 [0.49, 1.21]

 3 Complete or partial remission4293Risk Ratio (IV, Random, 95% CI)1.26 [1.10, 1.44]

 4 Urinary protein excretion1Mean Difference (IV, Random, 95% CI)Totals not selected

 5 Serum albumin1Mean Difference (IV, Random, 95% CI)Totals not selected

 6 Serum creatinine2Mean Difference (IV, Random, 95% CI)Totals not selected

 7 Adverse effects1Risk Ratio (IV, Random, 95% CI)Totals not selected

    7.1 Liver transaminase elevation
1Risk Ratio (IV, Random, 95% CI)0.0 [0.0, 0.0]

    7.2 Leukopenia or bone marrow suppression
1Risk Ratio (IV, Random, 95% CI)0.0 [0.0, 0.0]

    7.3 Infection
1Risk Ratio (IV, Random, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. TwHF versus prednisone

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Complete remission4223Risk Ratio (IV, Random, 95% CI)1.09 [0.83, 1.43]

 2 Partial remission4223Risk Ratio (IV, Random, 95% CI)1.07 [0.69, 1.65]

 3 Complete or partial remission4223Risk Ratio (IV, Random, 95% CI)1.06 [0.92, 1.22]

 4 Adverse effects2Risk Ratio (IV, Random, 95% CI)Subtotals only

    4.1 Liver transaminase elevation
2101Risk Ratio (IV, Random, 95% CI)1.51 [0.16, 14.22]

    4.2 Leukopenia or bone marrow suppression
137Risk Ratio (IV, Random, 95% CI)10.45 [0.62, 176.40]

    4.3 Elevated blood pressure
137Risk Ratio (IV, Random, 95% CI)0.16 [0.02, 1.19]

    4.4 Elevated blood glucose
137Risk Ratio (IV, Random, 95% CI)0.27 [0.06, 1.13]

    4.5 Femoral head necrosis
137Risk Ratio (IV, Random, 95% CI)0.19 [0.01, 3.71]

    4.6 Infection
137Risk Ratio (IV, Random, 95% CI)0.24 [0.03, 1.92]

    4.7 Psychosis
137Risk Ratio (IV, Random, 95% CI)0.11 [0.01, 0.75]

 
Comparison 3. TwHF versus CPA

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Complete remission2114Risk Ratio (IV, Random, 95% CI)1.06 [0.82, 1.37]

 2 Partial remission2114Risk Ratio (IV, Random, 95% CI)1.02 [0.46, 2.29]

 3 Complete or partial remission2114Risk Ratio (IV, Random, 95% CI)1.05 [0.90, 1.23]

 4 Urinary protein excretion1Mean Difference (IV, Random, 95% CI)Totals not selected

 5 Serum albumin1Mean Difference (IV, Random, 95% CI)Totals not selected

 6 Serum creatinine1Mean Difference (IV, Random, 95% CI)Totals not selected

 7 Adverse effects2Risk Ratio (IV, Random, 95% CI)Subtotals only

    7.1 Gastrointestinal discomfort
2114Risk Ratio (IV, Random, 95% CI)0.49 [0.24, 1.04]

    7.2 Liver transaminase elevation
2114Risk Ratio (IV, Random, 95% CI)0.69 [0.13, 3.69]

    7.3 Menstrual disorders
114Risk Ratio (IV, Random, 95% CI)1.33 [0.40, 4.43]

    7.4 Leukopenia
2114Risk Ratio (IV, Random, 95% CI)0.32 [0.08, 1.32]

    7.5 Hair Loss
2114Risk Ratio (IV, Random, 95% CI)0.11 [0.02, 0.59]

    7.6 Haemorrhagic cystitis
168Risk Ratio (IV, Random, 95% CI)0.13 [0.01, 2.38]

 

Appendices

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Appendix 1. Electronic search strategies


DatabaseSearch terms

CENTRAL
  1. tripterygium:ti,ab,kw
  2. triptolide:ti,ab,kw
  3. "thundergod vine":ti,ab,kw
  4. "leigong teng":ti,ab,kw
  5. "lei gong teng":ti,ab,kw
  6. (#1 OR #2 OR #3 OR #4 OR #5)
  7. "nephrotic syndrome":ti,ab,kw
  8. MeSH descriptor Nephrosis, Lipoid explode all trees
  9. nephrosis next lipoid:ti,ab,kw
  10. lipoid next nephrosis:ti,ab,kw
  11. "minimal change disease":ti,ab,kw
  12. glomeruloneph*:ti,ab,kw
  13. nephritis:ti,ab,kw
  14. nephropathy:ti,ab,kw
  15. glomerulosclerosis:ti,ab,kw
  16. (FSGS or MsGN):ti,ab,kw
  17. (#7 OR #8 OR #9 OR #10 OR #11 OR #12 OR #13 OR #14 OR #15 OR #16)
  18. (#6 AND #17)

MEDLINE
  1. Tripterygium/
  2. tripterygium.tw.
  3. thundergod vine.tw.
  4. (leigong teng or lei gong teng).tw.
  5. triptolide.tw.
  6. or/1-5
  7. Nephrotic Syndrome/
  8. Nephrosis Lipoid/
  9. nephrotic syndrome.tw.
  10. lipoid nephrosis.tw.
  11. minimal change disease.tw.
  12. minimal change glomerulon$.tw.
  13. minimal change nephr$.tw.
  14. Glomerulonephritis, Membranous/
  15. (membranous adj2 glomerulon$).tw.
  16. (membranous adj2 nephropathy).tw.
  17. extramembranous glomerulon$.tw.
  18. Glomerulosclerosis, Focal Segmental/
  19. focal segmental glomerulosclerosis.tw.
  20. FSGS.tw.
  21. Glomerulonephritis, IgA/
  22. IgA glomerulon$.tw.
  23. IgA nephropathy.tw.
  24. mesangioproliferative glomerulon$.tw.
  25. MsGN.tw.
  26. mesangi$ proliferative glomerulon$.tw.
  27. Glomerulonephritis, Membranoproliferative/
  28. membranoproliferative glomerulon$.tw.
  29. mesangiocapillary glomerulon$.tw.
  30. or/7-29
  31. and/6,30

EMBASE
  1. Tripterygium/
  2. Tripterygium wilfordii extract/
  3. tripterygium.tw.
  4. thundergod vine.tw.
  5. (leigong teng or lei gong teng).tw.
  6. Triptolide/
  7. triptolide.tw.
  8. or/1-7
  9. Nephrotic Syndrome/
  10. Lipoid Nephrosis/
  11. nephrotic syndrome.tw.
  12. lipoid nephrosis.tw.
  13. Focal Glomerulonephritis/
  14. focal segmental glomerulosclerosis.tw.
  15. FSGS.tw.
  16. Immunoglobulin A Nephropathy/
  17. IgA nephropathy.tw.
  18. IgA glomeruloneph$.tw.
  19. Proliferative Glomerulonephritis/
  20. mesangioproliferative glomerulon$.tw.
  21. MsGN.tw.
  22. mesangi$ proliferative glomerulon$.tw.
  23. Membranoproliferative Glomerulonephritis/
  24. membranoproliferative glomerulon$.tw.
  25. mesangiocapillary glomerulon$.tw.
  26. Membranous Glomerulonephritis/
  27. (membranous adj2 glomeruloneph$).tw.
  28. (membranous adj2 nephropathy).tw.
  29. extramembranous glomerulon$.tw.
  30. Minimal Change Glomerulonephritis/
  31. minimal change disease.tw.
  32. minimal change glomerulon$.tw.
  33. minimal change nephr$.tw.
  34. or/9-33
  35. 35. and/8,34



 

Appendix 2. Risk of bias assessment tool


Potential source of biasAssessment criteria

Random sequence generation

Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random).

High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.

Unclear: Insufficient information about the sequence generation process to permit judgement.

Allocation concealment

Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).

High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.

Unclear: Randomisation stated but no information on method used is available.

Blinding of participants and personnel

Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.

High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement

Blinding of outcome assessment

Detection bias due to knowledge of the allocated interventions by outcome assessors.
Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.

High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.

Unclear: Insufficient information to permit judgement

Incomplete outcome data

Attrition bias due to amount, nature or handling of incomplete outcome data.
Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.

High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.

Unclear: Insufficient information to permit judgement

Selective reporting

Reporting bias due to selective outcome reporting
Low risk of bias: The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).

High risk of bias: Not all of the study’s pre-specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified; one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.

Unclear: Insufficient information to permit judgement

Other bias

Bias due to problems not covered elsewhere in the table
Low risk of bias: The study appears to be free of other sources of bias.

High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data-dependent process (including a formal-stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.

Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.



 

What's new

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

Last assessed as up-to-date: 13 August 2012.


DateEventDescription

11 August 2013AmendedContact details updated.



 

Contributions of authors

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

  1. Draft the protocol: Yizhi Chen, Qing Yuan
  2. Study selection: Yizhi Chen, Zhixiang Gong
  3. Extract data from studies: Yizhi Chen, Zhixiang Gong
  4. Enter data into RevMan: Yizhi Chen, Zhixiang Gong
  5. Carry out the analysis: Yizhi Chen
  6. Interpret the analysis: Yizhi Chen, Guangyan Cai, Xiangmei Chen, Xuezhi Zhao, Li Tang, Qing Yuan
  7. Draft the final review: Yizhi Chen, Guangyan Cai, Xiangmei Chen, Xuezhi Zhao, Li Tang, Qing Yuan
  8. Disagreement resolution: Xiangmei Chen
  9. Update the review: Yizhi Chen

 

Declarations of interest

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms

None known.

 

Sources of support

  1. Top of page
  2. Summary of findings    [Explanations]
  3. Background
  4. Objectives
  5. Methods
  6. Results
  7. Discussion
  8. Authors' conclusions
  9. Acknowledgements
  10. Data and analyses
  11. Appendices
  12. What's new
  13. Contributions of authors
  14. Declarations of interest
  15. Sources of support
  16. Index terms
 

Internal sources

  • No sources of support provided, Not specified.

 

External sources

  • This work was partially supported by the National Science and Technology Department 863 Project (2012AA02A512), the National Key New Drug Innovation Project (2013ZX09104-003), the Beijing Science and Technology Project (D13110700470000), and the National Science and Technology Support Program (2011BAI10B00, 2011BAI10B03), China.
    The sponsors had no role in the study design, data collection and analysis, decision to publish, or manuscript preparation.

* Indicates the major publication for the study

References

References to studies included in this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
A-Da 2008 {published data only}
  • A-Da LT, Su JH, Wang ZC. Clinical random control observation of 18 cases of patients with primary IgA nephropathy syndrome treated with tripterygium glycosides tablet. Dangdai Yixue [China Contemporary Medicine] 2008;15(10):12-3.
Chen 2003 {published data only}
  • Chen ZM, Chen ZJ. Clinical analysis of 36 cases of refractory nephrotic syndrome treated by high-dosage Tripterygium glycosides. Zhongguo Quanke Yixue [Chinese General Practice] 2003;6(11):948.
Han 1999 {published data only}
  • Han JH, Mou ZL, Wang JP. Combination of Tripterygium glycosides and cyclosporin A for the treatment of refractory nephrotic syndrome. Linchuang Huicui [Clinical Focus] 1999;14(18):841-2.
Li 2000 {published data only}
  • Li Z, Zhang YF, Liu F. Clinical observation of 48 cases of nephrotic syndrome treated by combined treatment of Tripterygium wilfordii and quadruple chemotherapy. Hainan Yixue [Hainan Medical Journal] 1999;10(6):191-2.
  • Li Z, Zhang YF, Liu F. Clinical observation of 48 cases of nephrotic syndrome treated by combined treatment of Tripterygium wilfordii and quadruple chemotherapy. Yi Xue Wen Xuan [Anthology of Medicine] 2000;19(2):139-40.
Song 1998 {published data only}
  • Song HX, Wang ZT, Chen XT. Clinical study of combined treatment of cyclophosphamide and Tripterygium wilfordii for nephrotic syndrome. Lin Yi Yi Zhuan Xue Bao [Journal of Linyi Medical College] 1998;20(2):109-12.
Wen 1993 {published data only}
  • Wen YQ, Zhu QL, Wang MC, Ren ZQ, Liu ML, Hu GL. Clinical therapeutic analysis of primary nephrotic syndrome treated by prednisone and Tripterygium wilfordii. Zhonghua Shenzangbing Zazhi [Chinese Journal of Nephrology] 1993;9(3):190.
Yuan 2003 {published data only}
  • Yuan DS, Wang YR. Clinical therapeutic analysis of primary nephrotic syndrome in elderly treated by combination treatment of Tripterygium wilfordii and medium dosage prednisone. Zhong Hua Lin Chuang Yi Xue Yan Jiu Za Zhi [Chinese Magazine of Clinical Medicinal Professional Research] 2003;9(12):11475-6.
Zhang 2007a {published data only}
  • Zhang F. Comparison of effects of Tripterygium glycosides plus prednisone with prednisone alone on primary nephrotic syndrome. Zhong Wai Jian Kang Wen Zhai - Yi Yao Yue Kan [World Health Digest - Medical Monthly] 2007;4(8):96-8.
Zhao 1997 {published data only}
  • Zhao DG, Zhao X. Synergism of Tripterygium glycosides and prednisone for the complementary treatment of nephrotic syndrome. Changchun Zhongyiyao Daxue Xuebao [Journal of Changchun University of Traditional Chinese Medicine] 1997;13(4):20-1.
Zhao 2009 {published data only}
  • Zhao L. Comparative observation of effects of Tripterygium glycosides versus cyclophosphamide for the treatment of refractory nephrotic syndrome. Hebei Yi Yao [Hebei Medical Journal] 2009;31(16):2160-1.

References to studies excluded from this review

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Chang 2005 {published data only}
  • Chang H, Li HP. Clinical analysis of 52 patients with nephrotic syndrome treated by Tripterygium glycosides and Fu Fang Dan Shen (active ingredients were Radix Salviae Miltiorrhizae and Lignum Dallbergiae Odoriferae). Zhong Guo Lin Chuang Yi Yao Yan Jiu Za Zhi [Chinese Journal of Clinical Medicine Research] 2005;11(4):14919-20.
Du 2008 {published data only}
  • Du XY. Clinical observation of effects of combined treatment for 50 patients with nephrotic syndrome. Zhong Guo Xian Dai Yao Wu Ying Yong [Chinese Journal of Modern Drug Application] 2008;2(11):98-9.
Han 2001 {published data only}
  • Han SL, Li GX, Zhou LH, Huang S, Ling YS. Clinical therapeutic observation of prednisone plus Tripterygium glycosides in the treatment of nephrotic syndrome (type I). Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2001;2(2):115-6.
Hu 2008 {published data only}
  • Hu GH, Yi ZW, Wang JH, Yao JC. Effect of triptergium wilfordii polyglycosidium on content of Th1 and Th2 in child recurrent nephrotic syndrome. Zhongguo Zhongyao Zazhi [China Journal of Chinese Materia Medica] 2008; Vol. 33, issue 4:441-3. [: CN-00716138]
Huang 2003 {published data only}
  • Huang GH. Therapeutic effect analysis of Tripterygium wilfordii on the treatment of chronic nephrosis. Shiyong Linchuang Yixue [Practical Clinical Medicine] 2003;4(2):48.
Li 2003 {published data only}
  • Li Z, Meng H, Hong J. Clinical observation of 37 patients of nephrotic syndrome treated by combined treatment of Tripterygium wilfordii, Radix Astragali Mongolici, and quadruple chemotherapy. Zhongguo Quanke Yixue [Chinese General Practice] 2003;6(3):248.
Lin 2005 {published data only}
  • Lin X, Yang FF, You YW, Chen LX, Wang J, Li SL. Clinical efficacy of double dosage of Tripterygium wilfordii with intermittent maintenance therapy in treatment of primary nephrotic syndrome. Youjiang Minzu Yixueyuan Xuebao [Journal of Youjiang Medical College for Nationalities] 2005;27(3):282-4.
Liu 2003a {published data only}
  • Liu AM, Wang YP, Dai YW, Yang C, Tang HY. Clinical observation of the re-treatment after relapse in children with primary nephrotic syndrome. Zhejiang Zhongyi Zazhi [Zhejiang Journal of Traditional Chinese Medicine] 2003;38(3):334.
Liu 2003b {published data only}
  • Liu CM, Liu Y, Xu K. Clinical therapeutic observation of Tripterygium glycosides for the treatment of nephrotic syndrome. Guizhou Yiyao [Guizhou Medical Journal] 2003;27(5):442-4.
Liu 2010 {published data only}
  • Liu ZH, Yuan F, Wang YF. Tripterygium wilfordii combined with prednisone in the treatment of refractory primary nephrotic syndrome. Zhong Guo Yi Xue Chuang Xin [Medical Innovation of China] 2010;7(3):1-2.
Lu 2003 {published data only}
  • Lu XT. Combined Tripterygium wilfordii and prednisone for the treatment of nephrotic syndrome. Xiandai Zhongxiyijiehe Zazhi [Modern Journal of Integrated Traditional Chinese and Western Medicine] 2003;12(10):1058.
Ma 1991 {published data only}
  • Ma P. Effect of Tripterygium wilfordii combined with small-dosage prednisone on nephrosis syndrome. Linchuang Huicui [Clinical Focus] 1991;6(5):210-1.
Mo 2009 {published data only}
  • Mo XX. Effect of Tripterygium wilfordii combined with leflunomide on refractory nephrosis syndrome. Zhongguo Shequ Yishi [Chinese Community Doctors] 2009;11(10):54-5.
Pang 1999 {published data only}
  • Pang W, Fu HF, Tang DS. Clinical observation of integrated traditional Chinese and western medicine in treatment of nephrotic syndrome. Guangzhou Yixueyuan Xuebao [Academic Journal of Guangzhou Medical College] 1999;27(3):43-5.
Song 2008 {published data only}
  • Song B. Comparison between the therapeutic effects of cyclophosphamide and Tripterygium wilfordii hook on children refractory nephrotic syndrome. Zhong Guo Shi Yong Yi Yao [China Practical Medicine] 2008;3(14):7-8.
Sun 2008 {published data only}
  • Sun XH, Li HJ, Han W, Li BH. Observation on the therapeutic effect of the prednisone, Tripterygium wilfordii, ligustrazin in old age primary nephrotic syndrome. Xin Jiang Yi Ke Da Xue Xue Bao [Journal of Xinjiang Medical University] 2008;31(6):676-8.
Tang 2004 {published data only}
  • Tang XL, Hong SJ, Tang LL. Clinical therapeutic observation of combined Tripterygium wilfordii and ticlopidine in treatment of refractory nephrotic syndrome. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2004;5(1):27.
Wang 1996 {published data only}
  • Wang KL, Wang DM. Effects of combination of prednisone and Tripterygium wilfordii in 30 patients with primary nephrotic syndrome. Da Li Yi Xue Yuan Xue Bao [Journal of Dali Medical College] 1996;5(4):36-7.
Wang 2000 {published data only}
  • Wang HW, Chen JH. Comparison of effects of Tripterygium wilfordii and prednisone in treatment of nephrotic syndrome in elderly. Youjiang Minzu Yixueyuan Xuebao [Journal of Youjiang Medical College for Nationalities] 2000;22(6):883-4.
Wang 2001 {published data only}
  • Wang QY, Zhao XH, Zhou WY, Wang XY. Clinical study of combined Tripterygium wilfordii and Shu Xue Tong injection in treatment of refractory nephrosis in adults. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2001;2(10):606-7.
  • Wang QY, Zhou WY, Zhao XH. Clinical study of combined Tripterygium wilfordii and Shu Xue Tong injection in treatment of refractory nephrosis in adults. Heilongjiang Yi Xue [Heilongjiang Medical Journal] 2001;14(3):212.
Wang 2002 {published data only}
  • Wang LN, Tang XZ, Chen PP. Clinical therapeutic observation of prednisone plus Tripterygium wilfordii for the treatment of nephrotic syndrome. Zhongguo Zhongxiyi Jiehe Shenbing Zazhi [Chinese Journal of Integrated Traditional and Western Nephrology] 2002;3(7):418-9.
Wang 2005a {published data only}
  • Wang DY. Clinical therapeutic observation of combined Tripterygium wilfordii and lumbrokinase in the adjunctive treatment of primary nephrotic syndrome. Jiangxi Yiyao [Jiangxi Medical Journal] 2005;40(Suppl):694-6.
Wang 2005b {published data only}
  • Wang KM, Lai XH, Xu RF. Tripterygium wilfordii for the treatment of refractory primary nephrotic syndrome. Zhongguo Zhongxiyi Jiehe Zazhi [Chinese Journal of Integrated Traditional and Western Medicine] 2005;15(6):341-2.
Wang 2006 {published data only}
  • Wang YL. Clinical observation of integrated traditional Chinese and western medicine in treatment of nephrotic syndrome. Zhongyuan Yikan [Central Plains Medical Journal] 2006;33(10):60-1.
Wen 1996 {published data only}
  • Wen JF, Cao JX. Observation of effects of Tripterygium wilfordii and heparin on nephrotic syndrome. Zhongguo Xiandai Yixue Zazhi [China Journal of Modern Medicine] 1996;6(2):42.
Xiao 2003 {published data only}
  • Xiao HQ, Ding GH, Zhang JE, Zhang QH, Li T, Luo CX. Comparison between the therapeutic effects of Tripterygium wilfordii and cyclophosphamide on primary nephrotic syndrome. Linchuang Huicui [Clinical Focus] 2003;18(18):1039-40.
  • Xiao HQ, Zhang JE, Ye CY. Effects of Tripterygium wilfordii on primary nephrotic syndrome. Lin Chuang Shen Zang Bing Za Zhi [Journal of Clinical Nephrology] 2001;1(3):131-3.
Xiao 2007 {published data only}
  • Xiao YC. Clinical therapeutic observation of 56 patients with primary nephrotic syndrome treated by Tripterygium wilfordii. Shi Yong Quan Ke Yi Xue [Applied Journal of General Practice] 2007;5(4):312-3.
Xu 1998 {published data only}
  • Xu ZH, Hou CA, Chen Y, Xue QZ. Clinical observation of integrated traditional Chinese and western medicine in treatment of nephrotic syndrome. Shi Yong Zhong Xi Yi Jie He Za Zhi [The Practical Journal of Integrating Chinese with Modern Medicine] 1998;11(1):62.
Xu 2009b {published data only}
  • Xu YZ, Huang ZQ, Tang R. Effect of Tripterygium wilfordii together with prednisone in treatment of elderly primary nephrotic syndrome. Zhongguo Jiceng Yiyao [Chinese Journal of Primary Medicine and Pharmacy] 2009;16(5):781-2.
Yang 1995 {published data only}
  • Yang XH, Yu RF. Therapeutic observation of 40 patients with primary nephrotic syndrome and infection. Shiyong Yixue Zazhi [Journal of Practical Medicine] 1995;11(11):725-6.
Yang 2002 {published data only}
  • Yang LR. Combination of Tripterygium wilfordii and levamisole for the treatment of 41 patients with nephrotic syndrome. He Nan Yi Yao Xin Xi [Henan Medical Information] 2002;10(14):58-9.
Yang 2010 {published data only}
  • Yang J, Fan LH. Therapeutic observation of Tripterygium wilfordii and prednisone in the treatment of primary nephrotic syndrome. Zhong Guo Shi Yong Yi Yao [China Practical Medical] 2010;5(16):161-2.
Ye 2010 {published data only}
  • Ye YJ. Therapeutic observation of effect of combined leflunomide and tripterygium on refractory nephrotic syndrome. Jilin Yixue [Jilin Medical Journal] 2010;31(6):773.
Zhai 2004 {published data only}
  • Zhai XS, Zhou TG, Zou Y, Chen T. Clinical therapeutic analysis of 32 patients with nephrotic syndrome treated by Tripterygium wilfordii and prednisone. Xian Dai Yi Yao Wei Sheng [Modern Medicine Health] 2004;20(21):2246-7.
Zhang 2007b {published data only}
  • Zhang CF, Wang Z, Wang ML, Hua MN. Therapeutic analysis of 70 patients with nephrotic syndrome. Zhong Guo Shi Yong Yi Yao [China Practical Medical] 2007;2(36):137-8.
Zhang 2010 {published data only}
  • Zhang X, He XM, Du WB, Zhao CL. Effect of Tripterygium wilfordii combined with moiety prednisone on treatment of the aged nephrosis syndrome. Zhongguo Jiceng Yiyao [Chinese Journal of Primary Medicine and Pharmacy] 2010;17(5):623-5.
Zheng 1987 {published data only}
  • Zheng DH, Su P, Fang JY, Wei HM. Clinical therapeutic observation of 26 patients with nephrotic syndrome treated by Tripterygium wilfordii and urokinase. Huazhong Yixue Zazhi [Central China Medical Journal] 1987;11(2):77-8.
Zhong 2002 {published data only}
  • Zhong ZH, Lu JJ, Cai CD. Clinical analysis of 30 patients with refractory nephrotic syndrome treated by prednisone and Tripterygium wilfordii. Zhong Guo Zong He Lin Chuang [Clinical Medicine of China] 2002;18(5):435-6.
Zhou 1999 {published data only}
  • Zhou YC. Tripterygium wilfordii in combination with small-dosage prednisone for the treatment of nephrotic syndrome. Hebei Yixue [Hebei Medicine] 1999;5(4):14-6.
Zhou 2000 {published data only}
  • Zhou YZ. Clinical therapeutic observation of integrated traditional Chinese and western medicine in treatment of primary nephrotic syndrome. Hebei Zhongyi [Hebei Journal of Traditional Chinese Medicine] 2000;22(8):620-1.

Additional references

  1. Top of page
  2. Abstract
  3. Summary of findings
  4. Background
  5. Objectives
  6. Methods
  7. Results
  8. Discussion
  9. Authors' conclusions
  10. Acknowledgements
  11. Data and analyses
  12. Appendices
  13. What's new
  14. Contributions of authors
  15. Declarations of interest
  16. Sources of support
  17. Characteristics of studies
  18. References to studies included in this review
  19. References to studies excluded from this review
  20. Additional references
  21. References to other published versions of this review
Bao 2011
  • Bao J, Dai SM. A Chinese herb Tripterygium wilfordii Hook F in the treatment of rheumatoid arthritis: mechanism, efficacy, and safety. Rheumatology International 2011;31(9):1123-9. [MEDLINE: 21365177]
Bonilla-Felix 1999
Chen 1985
  • Chen SY. Effect of Tripterygium wilfordii on the remission of proteinuria in patients with nephrotic syndrome. Zhongguo Zhongxiyi Jiehe Zazhi [Chinese Journal of Integrated Traditional and Western Medicine] 1985;5(3):164-6, 132. [MEDLINE: 3157498]
Chen 2010a
  • Chen YZ, Gao Q, Zhao XZ, Chen XM, Zhang F, Chen J, et al. Meta-analysis of Tripterygium wilfordii hook F in the immunosuppressive treatment of IgA nephropathy. Internal Medicine 2010;49(19):2049-55. [MEDLINE: 20930429]
Eddy 2003
Goldbach-Mansky 2009
  • Goldbach-Mansky R, Wilson M, Fleischmann R, Olsen N, Silverfield J, Kempf P, et al. Comparison of Tripterygium wilfordii Hook F versus sulfasalazine in the treatment of rheumatoid arthritis: a randomized trial. Annals of Internal Medicine 2009;151(4):229-40, W49-51. [MEDLINE: 19687490]
Gulati 1999
Haas 1997
  • Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: A comparison of renal biopsy findings from 1976-1979 and 1995-1997. American Journal of Kidney Diseases 1997;30(5):621-31. [MEDLINE: 9370176]
Higgins 2011
  • Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane-handbook.org.
Hong 2002
  • Hong Y, Zhou W, Li K, Sacks SH. Triptolide is a potent suppressant of C3, CD40 and B7h expression in activated human proximal tubular epithelial cells. Kidney International 2002;62(4):1291-300. [MEDLINE: 12234299]
Hull 2008
ISKD 1978
  • Anonymous. Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney International 1978;13(2):159-65. [MEDLINE: 713276]
Jiang 1994
  • Jiang X. Clinical observations on the use of the Chinese herb Tripterygium wilfordii Hook for the treatment of nephrotic syndrome. Pediatric Nephrology 1994;8(3):343-4. [MEDLINE: 7917863]
KDIGO 2012
  • KDIGO. Idiopathic membranous nephropathy. Kidney International - Supplement 2012;2:186-97.
Korbet 1996
Kupchan 1972
  • Kupchan SM, Court WA, Dailey RG, Jr, Gilmore CJ, Bryan RF. Triptolide and tripdiolide, novel antileukemic diterpenoid triepoxides from Tripterygium wilfordii. Journal of the American Chemical Society 1972;94(20):7194-5. [MEDLINE: 5072337]
Moher 2010
  • Moher D, Hopewell S, Schulz KF, Montori V, Gotzsche PC, Devereaux PJ, et al. CONSORT 2010 explanation and elaboration: updated guidelines for reporting parallel group randomised trials. BMJ 2010;340:c869. [MEDLINE: 20332511]
Pildal 2007
  • Pildal J, Hrobjartsson A, Jorgensen KJ, Hilden J, Altman DG, Gotzsche PC. Impact of allocation concealment on conclusions drawn from meta-analyses of randomized trials. International Journal of Epidemiology 2007;36(4):847-57. [MEDLINE: 17517809]
Sharma 1997
  • Sharma M, Li JZ, Sharma R, Artero M, Ge X, McCarthy ET, et al. Inhibitory effect of Tripterygium wilfordii multiglycoside on increased glomerular albumin permeability in vitro. Nephrology Dialysis Transplantation 1997;12(10):2064-8. [MEDLINE: 9351066]
Srivastava 1999
  • Srivastava T, Simon SD, Alon US. High incidence of focal segmental glomerulosclerosis in nephrotic syndrome of childhood. Pediatric Nephrology 1999;13(1):13-8. [MEDLINE: 10100283]
Tao 1987
  • Tao XL, Dong Y, Zhang NZ. A double-blind study of T2 (tablets of polyglycosides of Tripterygium wilfordii hook) in the treatment of rheumatoid arthritis. Zhonghua Nei Ke Za Zhi [Chinese Journal of Internal Medicine] 1987;26(7):399-402, 44-5. [MEDLINE: 3322706]
Tao 1989
  • Tao XL, Sun Y, Dong Y, Xiao YL, Hu DW, Shi YP, et al. A prospective, controlled, double-blind, cross-over study of Tripterygium wilfordii hook F in treatment of rheumatoid arthritis. Chinese Medical Journal (English) 1989;102(5):327-32. [MEDLINE: 2509153]
Tao 1995
  • Tao X, Cai JJ, Lipsky PE. The identity of immunosuppressive components of the ethyl acetate extract and chloroform methanol extract (T2) of Tripterygium wilfordii Hook. F. Journal of Pharmacology & Experimental Therapeutics 1995;272(3):1305-12. [MEDLINE: 7891348]
Tao 1998
Tao 2001
  • Tao X, Cush JJ, Garret M, Lipsky PE. A phase I study of ethyl acetate extract of the Chinese antirheumatic herb Tripterygium wilfordii hook F in rheumatoid arthritis. Journal of Rheumatology 2001;28(10):2160-7. [MEDLINE: 11669150]
Tao 2002
Wan 2005
  • Wan Y, Gu L, Suzuki K, Karasawa T, Fujioka Y, Han GD, et al. Multi-glycoside of Tripterygium wilfordii Hook f. ameliorates proteinuria and acute mesangial injury induced by anti-Thy1.1 monoclonal antibody. Nephron. Experimental Nephrology 2005;99(4):e121-9. [MEDLINE: 15722645]
Wan 2010
  • Wan Y, Sun W, Zhang H, Yan Q, Chen P, Dou C, et al. Multi-glycoside of Tripterygium wilfordii Hook F. ameliorates prolonged mesangial lesions in experimental progressive glomerulonephritis. Nephron. Experimental Nephrology 2010;114(1):e7-14. [MEDLINE: 19816047]
Wen 1999
  • Wen ZH, Xu WH, Lai SL. Causal relationship of adverse reactions with tripterygium in 38 patients. Zhongyao Xinyao Yu Linchuang Yaoli [Traditional Chinese Drug Research & Clinical Pharmacology] 1999;10(1):50-3.
Xu 2009a
Zheng 2008