Primary nephrotic syndrome (NS) is a relatively rare kidney disease (diagnosed in up to 7/100,000 children and 3/100,000 adults annually). However the resulting kidney damage causes loss of proteins in urine (proteinuria) leading to low level albumin in the bloodstream, which can cause raised lipids and severe, generalised swelling. Primary NS can also lead to blood clotting (thromboembolism), infection, and acute kidney injury, and may become life threatening. Treatment for primary NS aims to relieve symptoms, avoid complications, and prolong life. Immunosuppressive treatments are of importance for primary NS. In China, a traditional Chinese herbal medicine, Tripterygium wilfordii Hook F (TwHF) has been used for over two decades as an immunosuppressive agent to decrease proteinuria and preserve kidney function. TwHF is prescribed alone or in combination with corticosteroids or other immunosuppressive agents such as cyclophosphamide (CPA).
In this review we investigated the use of TwHF as an immunosuppressive therapy for patients with primary NS. We only considered two standardised TwHF extracts which have lower toxicity profiles and fewer adverse effects than other non-standardised preparations. We reviewed the evidence from 10 randomised studies enrolling 630 Chinese patients with primary NS. Of these, four studies (293 patients) reported that when TwHF was used there was a significantly increased number of patients achieving complete, and complete or partial remission without increasing adverse events. There were no significant differences in complete, partial, or complete or partial remission when TwHF was compared with prednisone in four studies (223 patients). There were also no significant differences in complete, partial, or complete or partial remission when TwHF was compared with CPA in two studies (114 patients). One study reported TwHF significantly improved kidney function (decreased serum creatinine) when compared with CPA. TwHF was associated with a lower risk of psychosis than prednisone; and there was less likelihood of hair loss when compared to CPA. The quality of evidence was poor; there were only 10 studies, enrolling a total of 630 patients; follow-up was short; the maximum number of studies included in a comparison was four; and we had major concerns over the quality of the included studies. TwHF may have an add-on effect on remission in patients with primary NS; however there is insufficient evidence to assess if TwHF is as effective as prednisone or CPA.
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. More methodologically sound and sufficiently powered studies, with adequate follow-up would help to better inform management options for the use of TwHF for primary NS. TwHF should be further directly compared with other widely used immunosuppressive agents after the superiority over placebo or no treatment has been clearly established.
Tripterygium wilfordii Hook F (TwHF), a traditional Chinese herbal medicine used as an immunosuppressive agent, has been prescribed in China for patients with primary nephrotic syndrome (NS) for more than two decades. Although patients with primary NS in China have benefited from TwHF treatment, its properties have not yet been fully understood.
To assess the benefits and harms of TwHF for patients with primary NS.
We searched the Cochrane Renal Group's specialised register (August 2012), Cochrane Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 8), EMBASE (1966 to August 2012), and MEDLINE (1966 to August 2012). We also searched 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), and reference lists of articles (6 November 2010).
Only randomised controlled trials (RCTs) were included. Two standardised preparations of TwHF were investigated: ethanol-ethyl acetate extract and chloroform-methanol extract. All other TwHF preparations were excluded because of reported toxicities. Other traditional Chinese herbal medicines were also excluded. All included RCTs had a follow-up of at least three months.
Data extraction and risk of bias assessment were undertaken independently by two authors. Where details of randomised sequence generation and allocation concealment were absent or inadequately reported, we contacted original study investigators for verification and details of the procedure. For dichotomous outcomes (remission and drug-related adverse events) we used risk ratio (RR) with 95% confidence intervals (95% CI) and mean difference (MD) for continuous outcomes (urinary protein excretion, serum albumin and serum creatinine).
Ten studies enrolling 630 participants were included. 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. Four studies (293 participants) contributed to the comparison of TwHF versus non-TwHF. TwHF significantly increased complete remission (RR 1.46, 95% CI 1.18 to 1.80) and complete or partial remission (RR 1.26, 95% CI 1.10 to 1.44) without escalating the adverse events profile at the last follow-up (12 to 16 months). Four studies (223 participants) compared TwHF with prednisone. There were no statistically significant differences between complete remission, partial remission, and complete or partial remission. Two studies (114 participants) contributed to the comparison of TwHF versus cyclophosphamide (CPA) at the last follow-up (3 to 12 months). There were no statistically significant differences between complete, partial, or complete or partial remission. One study (46 participants) reported TwHF was associated with a significantly lower serum creatinine compared with CPA (MD -14.00 μmol/L, 95% CI -26.43 to -1.57). No serious adverse events of TwHF were observed. One study (37 participants) reported TwHF was associated with a significantly lower risk of psychosis when compared to prednisone (RR 0.11, 95% CI 0.01 to 0.75), and two studies showed a significantly lower risk of hair loss with TwHF when compared to CPA ((2 studies, 114 participants): RR 0.11, 95% CI 0.02 to 0.59).