| Research backgroundMembranous nephropathy(MN)is a group of diseases characterized by the deposition of immune complex under epithelial cells and diffuse thickening of glomerular basement membrane(GBM).According to the pathogenesis,MN can be divided into primary membranous nephropathy,secondary membranous nephropathy and idiopathic membranous nephropathy(IMN).IMN is the most common type of MN,and it is also the most common renal cause of massive proteinuria in Chinese adults.At present,studies show that the natural course of IMN is various,about 30%of patients can spontaneously and completely relieve,about 30%of patients can partially relieve,the remaining 30%-40%of patients have progressive renal function decline,and then develop into end stage renal disease.Therefore,IMN is not a benign disease.Early diagnosis,accurate assessment of prognosis and effective treatment are the main tasks in clinical practice.Hyperuricemia(HUA)is a common biochemical abnormality,which is caused by the excessive production of urate and/or the reduction of urine acid excreted by the kidney.Several studies have shown that hyperuricemia is related to the pathogenesis and progress of hypertension,IgA nephropathy,diabetic nephropathy,polycystic kidney disease and other chronic kidney diseases,but the relationship between hyperuricemia and morbidity of membranous nephropathy is not clear.The main clinical manifestation of IMN is nephrotic syndrome,which can be classified as "edema","lumbago","turbid urine" in traditional Chinese medicine.Modern researchers combine the renal pathological manifestations of IMN to carry out syndrome differentiation and treatment from macro and micro perspectives,which makes the application of traditional Chinese medicine in IMN treatment more extensive and accurate,showing that traditional Chinese medicine has certain advantages in IMN treatment.However,the knowledge of IMN with hyperuricemia in traditional Chinese medicine needs to be further improved.The purpose of this study is to explore the characteristics of TCM syndromes and clinical pathology of IMN with hyperuricemia,to further evaluate the correlation between hyperuricemia and TCM syndromes,clinic and pathology,and to enrich the understanding of IMN in TCM,so as to provide a certain basis for the diagnosis and treatment of TCM.ObjectiveTo investigate the TCM syndrome,clinical and pathological characteristics of IMN with hyperuricemiaMethodsA single center,retrospective cohort study was conducted in this study.Patients who were diagnosed as IMN by renal biopsy and met the inclusion criteria from the nephrology department of Guang'an men Hospital,Chinese Academy of traditional Chinese medicine between January 2006 and June 2019 were observed and study.According to the level of serum uric acid,303 patients were divided into hyperuricemia group(100 cases)and normal uric acid group(203 cases).By collecting and comparing the general data,TCM syndrome data,clinical data and pathological data of the two groups,the TCM syndrome,clinical and pathological characteristics of patients with hyperuricemia IMN were preliminarily discussed.Results1 General data1.1 GenderThe proportion of male and female in hyperuricemia group and normal uric acid group were(53.00%vs 47.00%)and(52.7%vs 47.3%)respectively,and there was no significant difference between the two groups(P>0.05).1.2 Age of onsetThe mean age of onset in hyperuricemia group and normal uric acid group were 51.71±13.82 years and 49.25±13.17 years,respectively.The two groups were mainly middle-aged and old-age groups.The hyperuricemia group may have the trend of higher incidence age and higher incidence age ratio,but there was no significant difference between the two groups(P>0.05).1.3 Course of diseaseThe median course of disease(interquartile distance)in hyperuricemia group and normal uric acid group were 4.00(11.50)months and 5.75(10.25)months respectively,and there was no significant difference between the two groups(P>0.05).2 TCM syndrome data2.1 The main symptoms of TCMThe main TCM symptoms of hyperuricemia group and normal group of blood uric acid include edema,foam urine,fatigue,waist acid,abdominal distention,dry mouth,bitter taste and shortness of breath.The proportion of bitter taste in hyperuricemia group was higher(P<0.05),and there was no significant difference in other TCM symptoms(P>0.05).2.2 TCM Syndrome Distribution(1)General distribution of TCM Syndrome Types:in 303 cases of IMN,the proportion of the patients with simple deficiency syndrome,primary asthenia-secondary sthenia syndrome and simple excess syndrome were 3.96%,96.04%and 0.00%respectively.Comparison between hyperuricemia group and normal blood uric acid group:simple deficiency syndrome(5.00%vs 3.45%),primary asthenia-secondary sthenia syndrome(95.00%vs 96.55%),and there was no significant difference between the two groups(P>0.05)(2)Deficiency syndrome:comparison between hyperuricemia group and normal blood uric acid group:deficiency of spleen and kidney qi(38.00%vs 30.54%),deficiency of lung and kidney qi(9.00%vs 14.29%),deficiency of spleen and kidney yang(18.00%vs 15.27%),deficiency of liver and kidney yin(12.00%vs 14.29%)and deficiency of both qi and Yin(23.00%vs 25.62%).The distribution of deficiency of spleen and kidney qi in the group with hyperuricemia was higher than normal uric acid group(P<0.05),and there was no statistical difference in other deficiency syndrome between the other two groups(P>0.05)(3)Superficiality excess syndrome:comparison between hyperuricemia group and normal uric acid group:water-dampness syndrome(30.00%vs 36.95%),dampness-heat syndrome(63.00%vs 52.70%),blood stasis syndrome(58.00%vs 55.67%)and dampness-turbid syndrome(7.00%vs 10.34%).The distribution proportion of dampness-heat syndrome in hyperuricemia group was higher than normal uric acid group(P<0.05),and there was no statistical difference in other superficiality excess syndrome between the two groups(P>0.05).3 Clinical data3.1 Complications(1)Hypertension:the proportion of grade 1 hypertension in hyperuricemia group was lower than that in normal uric acid group(28.00%vs 31.53%),and the proportion of grade 3 hypertension was higher than that in normal uric acid group(36.00 vs 20.69%),with significant difference between the two groups(P<0.05).(2)Other complications:comparison between hyperuricemia group and normal uric acid group:dyslipidemia(81.00%vs 71.92%),type 2 diabetes(23.00%vs 27.57%),coronary heart disease(26.00%vs 23.65%),arteriosclerosis(38.00%vs 28.08%),and there was no significant difference between the two groups(P>0.05).3.2 Renal functionThe median(interquartile distance)of renal function indexes in hyperuricemia group and normal uric acid group:serum creatinine(Scr)[86.70(42.75)vs 67.85(34.90)]?mol/L,blood urea nitrogen(BUN)[6.18(4.52)vs 5.07(2.89)]mmol/L,estimated glomerular filtration rate(eGFR)[82.10(38.77)vs 97.35(30.80)]ml·min-1·1.73m-2.Comparison with hyperuricemia group,Scr,BUN levels were higher,eGFR was significantly lower,and the difference between the two groups was statistically significant(P<0.05,P<0.05,P<0.01,respectively).Compared with normal uric acid group,proportion of chronic kidney disease(CKD)in hyperuricemia group was lower in stage 1 and higher in stage 2,with statistical difference between the two groups(P<0.05).The proportion of CKD stage 2 in hyperuricemia group was higher than other stages(P<0.05).Spearman correlation analysis showed that there was a positive correlation between the degree of hypertension and CKD stage(P<0.01).3.3 Other biochemical indexesThe levels of cholesterol(TC)[6.80(2.92)vs 6.00(2.56)]mmol/L and low-density lipoprotein(LDL-C)[4.66(2.01)vs 3.42(1.97)]mmol/L in hyperuricemia group were higher than those in normal uric acid group,with statistical difference between the two groups(P<0.05).There was no significant difference in the level of albumin(ALB),Alanine aminotransferase(ALT),aspartate Aminotransferase(AST),triglyceride(TG)and high density lipoprotein-cholesterol(HDL-C)between the two groups(P>0.05).3.4 HemoglobinThe levels of hemoglobin(HGB)in hyperuricemia group and normal uric acid group were 136.58±15.60g/L and 143.30±23.16g/L,respectively.There was no significant difference between the two groups(P>0.05).3.5 Urine protein quantificationThe 24h-UTP levels of hyperuricemia group and normal uric acid group were 3.42(4.59)g/24 h and 3.18(3.35)g/24h respectively,and there was no significant difference between the two groups(P>0.05).3.6 Urine red blood cell countThe number of cases with red blood cells ?5/HP by high power microscopy in hyperuricemia group and normal blood uric acid group were 29(29.00%)and 52(25.62%),respectively.There was no significant difference between the two groups(P>0.05).4 Pathological data4.1 Pathological stageHyperuricemia group and normal uric acid group were mainly concentrated in stage I(39.00%vs 46.80%)and stage ?(51.00%vs 48.60%).There was no significant difference between the two groups(P>0.05)4.2 ImmunofluorescenceIgG(88.00%vs 93.60%)and complement C3(70.00%vs 62.07%)were mainly deposited in hyperuricemia group and normal uric acid group,with a small amount of IgM,IgA and Clq deposition,and there was no significant difference between the two groups(P>0.05).4.3 Glomerular lesionThe proportion of glomerular sclerosis and segmental sclerosis in hyperuricemia group were higher than that in normal uric acid group(28.00%vs 12.32%,11.00%vs 5.91%respectively),with statistical difference between the two groups(P<0.05).In addition,there was no significant difference in the proportion of mesangial hyperplasia,crescent formation and ischemic sclerosis between the two groups(P>0.05)4.4 Renal interstitial lesionThe proportion of renal interstitial fibrosis and inflammatory cell infiltration in hyperuricemia group were higher than those in normal uric acid group(86.00%vs 72.91%,89.00%vs 78.82%respectively),with statistical difference between the two groups(P<0.05).4.5 Renal tubular lesionsFocal atrophy was dominant both in hyperuricemia group and normal uric acid group(63.00%vs 61.08%),and there was no significant difference between the two groups(P>0.05).4.6 Renal vascular lesionThe proportion of no obvious lesions in arterioles in hyperuricemia group was significantly lower than that in normal group(9.00%vs 25.12%),and the proportion of hyaline degeneration in arterioles was higher than that in normal group(33.00%vs 16.75%),with statistical differences between the two groups(P<0.01,P<0.05 respectively).There was no significant difference in the proportion of arteriolar wall thickening between two groups(P>0.05).ConclusionsCompared with IMN with normal blood uric acid,IMN with hyperuricemia has the following characteristics:(1)TCM syndrome:the main symptoms are edema and foam urine.Deficiency of spleen and kidney qi is the most common deficiency syndrome,and dampness-heat syndrome is the most common superficiality excess syndrome;(2)Clinical feature:often accompanied by poor basic renal function,hypercholesterolemia,and prone to serious hypertension;(3)Renal pathology:glomerular sclerosis,segmental sclerosis,interstitial fibrosis,interstitial inflammatory cell infiltration and hyalinization of arterioles are more common. |
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