Chronic kidney disease (CKD) is a worldwide public health problem, stage 4 CKD is a critical stage during the course of CKD, marking the significant decline of kidney function and the obvious appearance of symptoms. Although fermented cordyceps sinensis powder has been used in the treatment of chronic kidney disease for a long time, its prognostic effect on CKD, especially the curative effect of stage 4 CKD, lacks evidence-based medical evidence.

To explore the long-term prognosis of stage 4 CKD patients treated with fermented cordyceps sinensis powder and the potential related factors affecting the prognosis.

A total of 631 patients diagnosed with stage 4 CKD in the nephrology Department of Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine from 2013 to 2022 were collected. Based on standardized integrated Chinese and Western medicine treatment, patients were divided into cordyceps treatment group (339 cases) and integrated Chinese and Western medicine treatment group (252 cases) according to whether fermented cordyceps sinensis powder was used. Data such as patients' basic information, whether they were accompanied by diabetes, the occurrence and time of endpoint events, the time of diagnosis of stage 4 CKD, and relevant laboratory indicators at diagnosis were collected. After eliminating baseline differences between groups with propensity score matching, COX regression analysis was conducted to analyze potential prognostic factors. Survival curve was drawn by Kaplan-Meier method, and the difference of survival between groups was compared by Log-rank test.

A total of 378 patients were included after matching at a ratio of 1:1. Multivariate Cox proportional hazard regression analysis showed that the using of fermented cordyceps sinensis powder (HR=0.79, 95%CI=0.64-0.98, P=0.030), the increased level of estimated glomerular filtration (HR=0.97, 95%CI=0.94-1.00, P=0.025) and serum albumin (HR=0.97, 95%CI=0.96-0.99, P=0.002) prolonged the survival time of stage 4 CKD patients; male (HR=1.37, 95%CI=1.09-1.71, P=0.006), the increased level of brain natriuretic peptide (HR=1.00, 95%CI=1.00-1.00, P=0.003), blood phosphorus (HR=2.44, 95%CI=1.63-3.67, P<0.001) and 24 h urinary protein (HR=1.00, 95%CI=1.00-1.00, P<0.001) shortened the survival time of patients with stage 4 CKD. The results of survival curve analysis showed that cumulative survival rate of cordyceps treatment group was higher than that of integrated Chinese and Western medicine treatment group (HR=0.70, 95%CI=0.57-0.86, P<0.001). The cumulative survival rate in the low protein level subgroup was higher in the cordyceps treatment patients than in the integrated Chinese and western medicine treatment patients (HR=0.67, 95%CI=0.52-0.85, P<0.001). In the high urinary protein level subgroup, there was no significant difference in cumulative survival between the two treatment groups (P=0.518) .

Long-term use of fermented cordyceps sinensis powder can prolong the progression of renal function in patients with stage 4 CKD, and can play a better clinical effect under the premise of active control of urinary protein. Relatively low levels of brain natriuretic peptide and serum phosphorus, and relatively high levels of serum albumin are also potential factors for good prognosis in patients with stage 4 CKD.