| ObjectiveWe analyzed the baseline and follow-up data of lupus nephritis patients according to the proportion of crescent body and TCM manifestations,in order to improve the understanding of lupus nephritis with crescent,and provide more references for clinical diagnosis,treatment and prognosis.MethodsThe patients diagnosed with lupus nephritis by renal biopsy from January 1,2006 to December 31,2016 in Guangdong Provincial Hospital of Traditional Chinese Medicine were divided into 3groups:group C0(without crescent),group Cl(proportion of crescent<25%)and C2 group(proportion of crescent≥25%).Then we compared the clinicopathological characteristics and prognostic survival of the 3 groups.We also collected the four diagnosis data of 202 LN patients,carryed out TCM manifestations,and analyzed the relationship between TCM syndromes and prognosis of LN patients.Results①General clinical features:A total of 172 women were involved(85.1%),with a male/female ratio of 1:5.7.The median age was 27.0(22.8,37.3)years and the median course of disease was 9.5(2.0,54.25)months.Edema was the most common first symptom(45.1%).CKD stages were higher in the group C1 and C2 groups than that in group C0(all P<0.001).Anemia was more severe and the prevalence of hypoproteinemia and hypertension were higher in group C2(all P<0.05).There was no statistical difference in sex,age,course of disease,initial symptoms,the prevalence and of hyperuricemia,diabetes,heart failure,infection,AKI,nephrotic syndrome,hypothyroidism and allergic history in the three groups(P>0.05).②Baseline clinical examination:Serum creatinine and c-ANCA positive rate increased according to the increase of crescents in the three groups,and decreased in accordance with eGFR and hemoglobin conversely.Compared with patients without crescent,patients in group C1 and C2 had more severe urinary occult blood,higher anti-dsDNA positive rate and lower erythrocyte count(all P<0.05).There was no significant decrease in the white blood cell count,neutrophil count and platelet count in LN patients with crescents,although hemoglobin decreased according to the increase of crescents,and the red blood cell count in the crescent body group was lower.Serum uric acid and CRP levels in group C2 were higher than those in C0.The average titer levels of PR3-ANCA、MPO-ANCA and anti-GBM antibody were negative in three groups,and there was also no significant difference in other biochemical and immunological indexes.③Baseline pathological features:There were no type Ⅰ and Ⅵ LN patients in 202 patients,and type Ⅳ was the most(41.1%).The rate of patients with type Ⅳ(including type Ⅳ+Ⅴ)was as high as 95.9%in group C2,which was significantly higher than those in the group C1(43.1%)and C0(all P<0.001).Cellular crescent was mainly seen in patients with proliferative type(including type Ⅲ,Ⅳ and those with combined type Ⅴ,P=0.001),while fibrous crescent was more common in type Ⅴ(P=0.004),and cellular fibrous crescent was not significantly different in different type(P=0.078).Mesangial hyperplasia,capillary endothelial hyperplasia and platinum ear structure were more common in patients in groups C1 and C2 than those in groups C0(all P<0.05).While segmental/spherical sclerosing glomeruli ratio and various immunofluorescence levels were the same among the three groups.The pathological score AI、CI increased one by one from group C0 to group C2(all P<0.05),and TIL score and TIL grade in group C2 were higher than those in the other two groups(all P<0.05).④TCM manifestations:Toxin heat incandescent syndrome was rare(12 cases,5.9%)in TCM syndromes,the other four types were equivalent.All patients had both blood stasis syndrome.Patients had dampness turbid syndrome(73.3%)more than those with dampness and heat syndrome(26.7%).There was no significant difference between the distribution of TCM syndromes in the three groups.⑤Treatment:199 patients were treated with glucocorticoids,the other 3 without hormone therapy were patients without crescent.107 patients with massive MP therapy,there were 38 in group C2(79.2%),which higher than those in C1(55.4%)and C0(37.1%)(all P<0.05).185 patients received additional immunosuppressive therapy,those received CTX pulse therapy(61.4%)was the highest(23.3%),those received MFF followed(23.3%).There was 81.5%of patients received CTX pulse therapy in group C2,which was higher than C1(58.5%,P=0.002)and C0(50.6%,0.001).Patients treated with cytosolic therapy in group C2 were less than that in C1(10.4%vs 32.3%,P=0.006),and was similar compared with group C0.149 patients received routine treatment with hydroxychloroquine.All patients were treated with traditional Chinese herbs during hospitalization,and 182 patients were treated with additional proprietary Chinese medicine.Patients in group C2 received most drugs in the class of tonifying kidney and releasing turbidity,which followed by group C1,and the least in group C0(35.4%,18.5%,5.6%,P<0.05).⑥Factors associated with crescent formation:The outcome of Spearman correlation analysis showed that the proportion of crescent was positively correlated with blood creatinine,CKD stage,serum uric acid,anemia degree,CRP,anti dsDNA antibody,urine occult blood,segmental sclerosing glomerulus ratio,mesangial hyperplasia degree,platinum ear structure formation,AI,CI,TIL score and grade,initial symptom,hypertension history,infection history,taking drugs in the class of tonifying kidney and releasing turbidity,and was negatively correlated with eGFR,erythrocyte count,HDL-C,anti-Sm antibody,and treatment with cyclosporine.The proportion of crescent was strongly correlated with AI(|rs|≥0.6),and moderately correlated with CKD stage,Mesangial hyperplasia,CI,and TIL score(0.4≤|rs|<0.6).⑦Prognosis:The median follow-up time was 65.5(43.0,89.0)months,with 38 end-point events(18.8%)occurring.group C2 had the highest incidence of end-point events,followed by group C1 and the lowest in group C0(35.4%,20.0%,9.0%,P<0.05).The results of Kaplan-Meier survival curve analysis showed that there were significant differences in the renal cumulative survival rate among the three groups(Log-rank test:x2=14.968,P=0.001),the renal cumulative survival rate in Cl and C2 were both lower than that in the group C0(P=0.040,P=0.001),and there was no statistical difference between C1 and C2(P=0.079).The renal survival rate of LN patients with spleen and kidney yang deficiency syndrome was lower than that of spleen and kidney qi deficiency syndrome(Log-rank test:x2=23.792,P<0.001),qi and yin deficiency syndrome(Log-rank test:x2=20.506,P<0.001)and liver and kidney yin deficiency syndrome(Log-rank test:x2=5.895,P=0.015).The renal survival rate of patients with toxin heat incandescent syndrome was lower than those with spleen and kidney qi deficiency syndrome(Log-rank test x2=4.983,P=0.026)and qi and yin deficiency syndrome(Log-rank test:x2=4.302,P=0.038),and was no statistical difference with patients with liver and kidney yin deficiency syndrome.LN patients with deficiency of spleen and kidney qi,deficiency of qi and yin,deficiency of liver and kidney yin and different additional syndromes had no significant difference in renal survival rate.⑧Risk factors for poor prognosis:The results of univariate Cox regression analysis showed that male,SCr,eGFR,CKD stage,BUA,RBC,hemoglobin,urine protein quantification,ratio of crescent,ratio of segmental/spherical glomerulosclerosis,AI,CI,TIL grade,hypertension,heart failure,infection,AKI,nephrotic syndrome,spleen-kidney yang deficiency syndrome,toxin heat incandescent syndrome were the risk factors for renal prognosis in LN patients.The results of multiple factors Cox regression analysis suggested that male(HR=4.351,P=0.036),SCr(HR=1.005,P<0.001),hypertension(HR=5.531,P<0.001),infection(HR=7.127,P=0.003)were independent risk factors for poor renal outcomes in LN patients.After multivariate correction,the proportion of crescent and TCM manifestations were not an independent risk factor for poor renal prognosis(P>0.05).ConclusionCLN patients had poor baseline renal function,serious clinical manifestations and kidney injury,high incidence of endpoint events,low cumulative renal survival rate,LN patients with spleen and kidney yang deficiency syndrome as well as toxin heat incandescent syndrome had poor renal prognosis.Male,creatinine,hypertension,and infection were independent risk factors for poor prognosis of LN.Proportion of crescent and TCM manifestations were not an independent risk factor for poor renal prognosis after multivariate correction.Long-term prognosis of LN patients with different crescent proportions was comparable.But there are different controversies at present,and further studies are needed to verify the relationship between proportion of crescent and LN long-term prognosis. |
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