Effect of Roxadustat on renal adverse events
Eleven trials reported the risk of renal adverse events associated with
oral Roxadustat in the treatment of anemia in CKD. Nine of these trials
included NDD patients and two included DD patients. The pooled results
demonstrated no significant difference in the risk of renal adverse
events observed in NDD (RR = 1.053; CI [0.965 to 1.149]; P = 0.244,
I2 = 0.0%) as well as DD (RR = 2.649; CI [0.201 to
34.981]; P = 0.459, I2 = 41.8%) (Figure 4A)
patients. However, moderate between-trial heterogeneity
(I2 = 41.8%, P = 0.190) was observed in the DD group.
Furthermore, subgroup analysis also suggested that oral Roxadustat did
not demonstrate a significant difference in the risk of renal adverse
events in anemic patients with CKD when compared with placebo (RR=1.088;
CI [0.980 to 1.209]; P = 0.115, I2 = 0.0%) or ESA
(RR = 0.968; CI [0.831 to 1.152]; P = 0.670, I2 =
0.0%) (Figure 4B).
Nine trials evaluated the risk of progression to ESKD associated with
treatment of anemia in CKD patients with oral Roxadustat, of which seven
trials had recruited NDD patients and two trials had DD patients. The
results of pooled analysis indicated that oral Roxadustat did not
enhance the risk of progression to ESKD in patients with anemia in CKD,
irrespective of DD (RR = 1.021; CI [0.917 to 1.136]; P = 0.154,
I2 = 0.0%) and NDD (RR = 1.033; CI [0.928 to
1.150]; P = 0.557, I2 = 0.0%) (Figure 5A) patients.
Moreover, subgroup analysis further illustrated that the risk of ESKD
progression in patients with CKD anemia treated with oral Roxadustat did
not significantly increase, when compared with placebo (RR = 1.062; CI
[0.939 to 1.201]; P = 0.339, I2 = 0.0%) or EAS
(RR = 1.021; CI [0.917 to 1.136]; P = 0.283, I2 =
0.0%) (Figure 5B).
Effect of Roxadustaton hyperkalemia
Fifteen trials reporting the risk
of hyperkalemia associated with oral Roxadustat therapy for anemia in
CKD patients were enrolled in this study, of which nine trials included
NDD patients and six trials had included DD patients. The pooled
analysis demonstrated no statistically significant difference in the
risk of hyperkalemia in the oral Roxadustat therapy group irrespective
of whether the patients were DD patients (RR = 1.145; CI [0.756 to
1.734]; P = 0.524, I2 = 11.6%) or NDD (RR = 1.116;
CI [0.930 to 1.339]; P = 0.236, I2 = 0.0 %)
patients (Figure 6A). Subgroup analysis based on the type of control
intervention further demonstrated no significant difference in risk of
hyperkalemia associated with the use of oral Roxadustat for treatment of
anemia in CKD patients when compared to placebo group
(RR = 1.205; CI [0.980 to
1.483]; P = 0.077, I2 = 0.0%) or the ESA group
(RRĀ = 0.980; CI [0.740 to 1.324]; P = 0.888, I2 =
0.4%) (Figure 6B).
Effect of Roxadustaton hypertension
Fifteen trials reporting the risk of hypertension related to oral
Roxadustat therapy for anemia in CKD patients were enrolled in our
study. Eight of these trials had recruited NDD patients and seven had
recruited DD patients. The pooled results indicated that
a higher risk of hypertension was
observed in NDD (RR = 1.198; CI
[1.042 to 1.377]; P = 0.011, I2 = 36.0%)
patients, but no significant statistical difference was observed in the
risk of hypertension in the oral Roxadustat therapy group for DD
patients (RR = 1.125; CI [1.014 to 1.249]; P = 0.650,
I2 = 10.1%) (Figure 7A). Moreover, subgroup analysis
based on the type of control intervention further demonstrated a higher
risk of hypertension associated with the use of oral Roxadustat for the
treatment of anemia in CKD patients, when compared to the placebo
(RR=1.374; CI [1.153 to 1.638]; P = 0.000, I2 =
0%), but there was no statistically significant difference in the risk
of hypertension in the oral Roxadustat therapy group when compared with
ESA group (RR = 1.125; CI [1.014 to 1.249]; P = 0.877,
I2 = 0.4%)(Figure 7B).