IgA nephropathy (IgAN) is the most common primary glomerular disease, and one major cause of malignant hypertension (MHT) secondary to renal parenchymal disease. The clinical conditions and severity of renal lesion have been reported to be more serious when IgAN is accompanied by MHT, but risk factors of MHT in IgAN analyzed from Traditional Chinese Medicine (TCM) perspective are still unclear.

To explore the TCM-related factors and pathogenesis associated with MHT in IgAN patients.

From 518 cases of primary IgAN who were diagnosed by renal biopsy in First Medical Center of Chinese PLA General Hospital during December 2013 to September 2021, a sample of 12 cases accompanied by MHT (IgAN-MHT group) computed by PASS 15.0 were selected for correlation power analysis, and they were matched at a ratio of 1∶5 with other randomly selected 85 cases without MHT (IgAN group) . Clinical, pathological and TCM syndromes between the two groups were compared. Lasso regression was used to screen 93 TCM syndromes, among which those with significant associations with IgAN-MHT were identified by multivariate Logistic regression.

Compared with IgAN group, IgAN-MHT group had higher prevalence of headache and dizziness or nausea and vomiting as the first clinical manifestations, and clinically diagnosed nephrotic syndrome, higher levels of baseline mean arterial pressure, highest systolic and diastolic blood pressure, blood urea nitrogen, serum creatinine, serum inorganic phosphorus, serum magnesium, and quantitatively estimated 24-hour urinary protein excretion, higher prevalence of CKD stages 3-5, blood stasis syndrome, subtypes of qi-deficiency syndromes (including mental fatigue and lack of strength, limb fatigue, tibia and leg weakness, dizziness, headache with nausea, and vomiting) , subtypes of yin-deficiency syndromes (including blurred vision and eye floaters) , subtypes of blood stasis syndromes (including nail cyanosis, and dark purple tongue) , and intrarenal arteriosclerosis (P<0.05) . Moreover, IgAN-MHT group had lower prevalence of abnormal urine test results as the first clinical manifestations, previous hypertension and clinical diagnosed chronic nephritic syndrome, as well as lower levels of mean serum IgM and IgG levels, and eGFR (P<0.05) . Both groups had no significant difference in the prevalence of interstitial fibrosis/tubular atrophy (T) lesions among the two groups (P<0.05) . The common TCM syndrome in IgAN-MHT group was qi-yin deficiency syndrome combined with blood stasis syndrome. Correlation analysis showed that IgAN-MHT was positively associated with blood stasis syndrome (P<0.05) ; in IgAN-MHT group, male and quantitatively estimated 24-hour urinary protein excretion was positively associated with qi-deficiency syndrome (P<0.05) ; serum inorganic phosphorus and potassium was negatively associated with yin-deficiency syndrome (P<0.05) , and renal tubular atrophy/interstitial fibrosis was positively associated with blood stasis syndrome (P=0.040) . Multivariate Logistic regression analysis showed that headache〔OR=7.895, 95%CI (1.643, 37.935) , P=0.010〕, blurred vision〔OR=5.499, 95%CI (1.207, 25.053) , P=0.028〕, dry mouth with desire for drink 〔OR=10.079, 95%CI (2.289, 44.373) , P=0.002〕, and nail cyanosis〔OR=18.312, 95%CI (2.179, 153.884) , P=0.007〕 were associated with MHT in IgAN.

IgAN-MHT patients had worse renal function and more serious renal pathological damage. The common TCM syndrome in IgAN-MHT was qi-yin deficiency syndrome with blood stasis syndrome. The clinical and pathological indices of IgAN-MHT patients had a certain level of correlation with qi-deficiency syndrome, yin-deficiency syndrome and blood stasis syndrome. The subtypes of TCM syndromes, such as headache, blurred vision, dry mouth with desire for drink, and nail cyanosis were the influencing factors of MHT in IgAN. Early detection, diagnosis and treatment, concern for and improvement of symptoms related to syndromes of qi-deficiency, yin-deficiency, and blood stasis, may contribute to decreased risk of MHT in IgAN.