| Research BackgroundMembranous nephropathy(MN)is one of the main pathological types leading to adult nephrotic syndrome(NS)or asymptomatic proteinuria.Its typical pathological features are diffusing glomerular basement membrane(GBM)thickening with immune complex deposition under epithelial cells.According to the etiology,MN can be divided into two categories of idiopathic membranous nephropathy(IMN)and secondary membranous nephropathy(SMN),and secondary cases are caused by autoimmune diseases,infections,tumors,drugs,etc.The cases with unknown causes are called IMN.Foreign research reports that IMN accounted for 20%to 40%of adult primary NS,domestic epidemiological journals report that IMN accounted for more than 10%of primary glomerular disease and the incidence rate in recent years is significantly increased.The incidence of IMN is mostly after the age of 40,with the majority of males,and the prevalence of males is more than about 1 times higher than that of females.The onset of this disease is slow.As proteinuria is the main clinical manifestation,60%to 80%of IMN patients present NS,about 40%of them can be found microscopic hematuria and no gross hematuria in the absence of complications.The natural history of IMN is variable.25%of patients may have complete spontaneous remission of proteinuria within 5 years,while 35%may develop end-stage renal disease(ESRD)within 10 years.Reviewing the literature,the factors affecting the prognosis of membranous nephropathy include advanced age,male gender,concomitant hypertension,massive albuminuria,renal insufficiency,and pathological findings with more glomerulosclerosis and heavier tubulointerstitial lesions.As a more common clinical manifestation in IMN-hematuria,especially microscopic hematuria;,its impact on other clinical manifestations,pathological features and the TCM syndrome features of IMN remains to be studied.ObjectivesTo investigate the TCM syndrome,clinical and pathological features of idiopathic membranous nephropathy(IMN)associated with hematuria.MethodsA retrospective study was conducted to select patients who were diagnosed with renal disease in the China Academy of Chinese Medical Sciences Guang' anmen Hospital from January 2006 to December 2016.The patients were diagnosed with IMN and met the inclusion criteria.The patients will be devided into two groups according to whether they were associated with hematuria(High magnification red blood cell count ?3/HP and abnormal red blood cell>70%):the IMN group with hematuria(Group A)(185 cases)and the IMN group without hematuria(Group B)(82 cases).The TCM symptoms,syndrome differentiation,clinical manifestations,and renal pathological data were compared between the two groups to initially investigate the relationship between hematuria and TCM syndromes and clinical pathology within IMN patients.Results1 General information1.1 GenderAmong the patients with hematuria group,106 were males(57.3%),79 were females(42.7%),male to female ratio was 1.34:1;In patients without hematuria,males were 48(58.5%)and females were 34(41.5%).The ratio of male to female was 1.41:1.There was no significant difference in gender between the two groups(P=0.850,>0.05).1.2 AgeIn the hematuria group,the median age of renal biopsy was 52.84(42.90,59.78)years,which was greater than the median age of 49.57(41.46,62.62)years of renal biopsy without hematuria(group B).The difference in age was not statistically significant(P=0.921,>0.05).1.3 Disease courseIn the group with hematuria,the median duration of disease during renal biopsy with hematuria was 5.0(2.0,11.0)months,which was less than that of the group without hematuria(6.0,3.0,12.0 months).The differences in the course of disease between the two groups when receiving renal biopsy were statistically significant(P=0.016;<0.05).2 TCM Symptoms and Syndrome Differentiation2.1 TCM SymtomsComparing the symptoms of TCM with the incidence rate of more than 10%in the two groups,the main symptoms of the two groups ranking in descending order of incidence are as follows:lower extremity edema,urine foam,lumbar acid and back pain,dry mouth,frequent nocturia,cough,poor sleep,dizziness,facial edema,thin stool,yellow urine,bitter mouth and anorexia;in the group with hematuria,the symptom distribution of cough,bitter mouth is less than the group without hematuria:cough(22.2%vs 11.0%),(P= 0.031;<0.05);bitter mouth(15.1%vs 6.1%),(P=0.038,<0.05).The rest of the TCM symptom distribution was not statistically significant(P>0.05).2.2 TCM Syndrome Differentiation2.2.1 General StatisticsThe syndrome differentiation between hematuria group and non-hematuria group:the deficiency syndrome(93.5%vs.91.5%),P=0.548;sthenia syndrome(97.8%vs 97.6%),P=0.888.The two groups of TCM syndrome differentiation were mainly deficiency-excess complex.There was no statistical difference in distribution of syndrome differentiation between the two groups(P>0.05).2.2.2 Deficiency SyndromeThe proportions of deficiency syndrome in hematuria group and non-hematuria group ranking from highest to lowest is:spleen and kidney Qi deficiency syndrome(42.2%vs 46.3%),Qi and Yin deficiency syndrome(23.8%vs 22.0%),liver and kidney Yin deficiency syndrome(16.8%vs 13.4%),lung-kidney Qi deficiency syndrome(10.3%vs 11.0%),spleen-kidney Yang deficiency syndrome(4.9%vs 4.9%);(P all>0.05).2.2.3 Sthenia SyndromeThe proportions of sthenia syndrome in hematuria group and non-hematuria group ranking from highest to lowest is:wetness syndrome(81.1%vs 79.3%),blood stasis syndrome(58.4%vs 59.8%),damp heat syndrome(42.2%vs.41.5%),wet cloud syndrome(0.5%vs 0.0%);(P all>0.05).3 Clinical Information3.1 ComplicationsComparing complications between hematuria group and non-hematuria group:patients with hypertension(62.7%vs 64.6%,P=0.763),patients with dyslipidemia(72.4%vs 68.3%,P=0.491),patients with hyperuricemia(18.4%vs 17.1%,P=0:798),patients with type 2 diabetes(14.1%vs 23.2%,P=0.066),and patients with arteriosclerosis(11.9%vs 13.4%,P=0.727).There was no significt difference in comorbidities between the two groups(P all>0.05).3.2 eGFREstimated glomerular filtration rate(eGFR)medians in patients with hematuria versus those without hematuria:(100 vs 96)mLˇmin-1ˇ1.73m-2.There was no significant difference between the two groups(P=0.066,<0.05).3.3 CKD stagingComparison of staging of CKD in patients with hematuria and without hematuria:CKD stage 1(73.0%vs 58.5%),CKD stage 2(21.1%vs 35.4%),CKD stage 3(4.9%vs 2.4%),CKD stage 4(0.5%vs 3.7%),CKD stage 5(0.4%vs 0.0%);The proportions of CKD1,CKD3,and CKD5 in the hematuria group were more than those in the non-hematuria group.The proportions of CKD2 and CKD4 were less in the hematuria group.The difference between the two groups was statistically significant(P=0.024,<0.05).3.4 Laboratory datas3.4.1 Urine protein quantificationThe comparison of the proportion of proteinuria in nephrotic area between the hematuria group and non-hematuria group is:(48.1%vs 39.0%),the difference was not statistically significant(P=0.169,>0.05);The 24-hour urinary protein quantification of the hematuria group and non-hematuria group is:(3799.50mg/24h vs 3036.00mg/24h).There was no significant difference between the two groups(P=0.585?>0.05).3.4.2 Serum albuminThe median serum albumin in the group with hematuria:24.90(19.08,30.53)g/L was lower than that in the group without hematuria:26.90(20.85,31.5)g/L.The difference was statistically significant(P=0.045,<0.05).3.4.3 Kidney function testsMedian comparison of renal function in patients with hematuria and without hematuria;Serum creatinine(Scr)(68.90 umol/L vs 74.00 umol/L),P=0.091,blood urea nitrogen(BUN)(4.80 mmol/L vs 5.16 mmol/L,P=0.406,serum uric acid(UA)(359.00 umol/L vs 375.00 umol/L),P=0.287;Scr;BUN,and UA were lower in the hematuria group than in the hematuria group,but the difference was not statistically significant(P>0.05).3.4.4 Liver function testMedian comparison of liver function in patients with hematuria and without hematuria:Aspartate aminotransferase(AST)(19.90 U/L vs 19.70 U/L),P=0.486,alanine aminotransferase(ALT)(16.00 U/L vs 16.00 U/L)?P=0.107,and gamma glutamyl transaminase(y-GT)(18.00 U/L vs 22.80 U/L),P=0.001.The y-GT with hematuria group was lower than that without hematuria group,with significant statistical difference(P=0.001,<0.01).There was no significant difference between AST and ALT groups(P>0.05).3.4.5 Lipid test Comparing the median blood lipids in the hematuria group and the without hematuria group:Plasma cholesterol(CHO)(6.97 mmol/L vs 6.97 mmoll/L),P=0.854,plasma triglyceride(TG)(2.09 mmol/L vs 2.25 mmol/L),P=0.585,high-density lipoprotein(HDL-C)(4.42 mmol/L vs 4.22 mmol/L),P=0.363.Low density lipoprotein(LDL-C)(4.22 mmol/L vs 4.43 mmol/L),P=0.363.There was no significant difference between the two groups(P>0.05).4 Pathological data4.1 Kidney pathological stagingComparing the proportion of renal pathological stages in patients with hematuria and without hematuria:Stage I membranous nephropathy(43.1%vs 46.9%),stage ?-?membranous nephropathy(24.9%vs 19.8%),stage II membranous nephropathy(23.8%vs 28.4%),stage ?-? membranous nephropathy(6.1%vs 3.7%),stage ? membranous nephropathy(2.2%vs 1.2%).The difference between the two groups was not statistically significant(P=0.707,>0.05).4.2 Glomerular mesangial lesionsComparing the proportion of mesangial cytopathies in patients with hematuria and those without hematuria:Mesangial area immune complex diversity(45.9%vs 58.2%,P=0.067),mesangial cell proliferation(49.7%vs 40.2%,P=0.152).There was no significant difference between the two groups(P>0.05).4.3 Glomerular sclerosisComparing the proportion of glomerulosclerosis in patients with hematuria and without hematuria:Ischemia(31.4%vs.40.2%,P=0.157),crescent formation(11.4%vs 6.1%,P=0.182),sclerosing(13.5%vs 13.4%,P=0.983),segmental sclerosis(3.8%vs 4.9%,P=0.678).There was no significant difference between the two groups(P>0.05).4.4 Tubular and interstitial lesionsComparing the proportion of tubular and interstitial lesions in patients with hematuria and without hematuria:No obvious lesions(30.5%vs 26.6%,P=0.517),interstitial inflammatory cell infiltration(66.8%vs 64.6%,P=0.725),renal interstitial fibrosis(54.7%vs 17.6%,P = 0.375).There was no significant difference between the two groups(P>0.05).4.5 Renal artery lesionsComparing the proportion of renal arteriopathy in patients with hematuria and without hematuria:No obvious lesions(20.7%vs 12.2%,P=0.098)?small arterial hyalinosis(11.0%vs 2.2%,P=0.006),arteriolar lumen stenosis(3.7%vs 0%,P=0.029)%lumen thickening of small arteries(79.9%vs 88.9%,P=0.075);The proportion of small arterial hyalinosis in the hematuria group was lower than that in the non-hematuria group,with significant statistical differences(P<0.01).The proportion of small arterial stenosis in the hematuria group was lower than that in the non-hematuria group,with statistical difference(P<0.05).There was no significant difference in other renal arteriopathy between the two groups(P>0.05).Conclusion1 Symptoms of TCM and syndrome differentiation of patients with hematuria are basically the same as those without hematuria.2 The gender,age,and clinical manifestations of IMN with hematuria are basically the same as those without hematuria3 Compared with non-hematuria IMN,there was no difference in glomerular and tubulointerstitial lesions with hematuria,but renal arteriole lesions were lighter. |
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