肾炎康复片联合氯沙坦钾治疗原发性IgA肾病（气阴两虚证）的临床观察

目的观察肾炎康复片联合氯沙坦钾治疗原发性IgA肾病（气阴两虚证，IgAN）的临床疗效。方法回顾性分析62例IgAN患者，治疗组32例采用肾炎康复片联合氯沙坦钾治疗，对照组30例单纯应用氯沙坦钾治疗，观察时间为8周。分别监测治疗前0周、治疗后4周和8周的24h尿蛋白定量、IgA、Alb、SCr和中医主症积分，继而进行中西医疗效评价。结果对照组治疗4周后尿蛋白定量下降，Alb升高，SCr、IgA水平降低，中医主症积分减少，与治疗前相比无统计学差异（P〉0．05）；治疗8周后尿蛋白定量明显减少，SCr明显下降，Alb明显升高，与治疗前相比有统计学意义（P〈0．05）。治疗组治疗4周后尿蛋白定量明显下降（P〈0．05）。治疗8周后尿蛋白定量显著下降，Alb显著升高，SCr显著下降，与治疗前相比有统计学意义（P〈0．01）；IgA水平明显降低，中医主症积分明显减少，与治疗前相比有统计学差异（P〈0．05）。治疗组治疗后8周和对照组治疗后8周比较，尿蛋白定量显著下降，Alb显著升高，有统计学意义（P〈0．01）。IgA水平明显降低，中医主症积分明显减少，有统计学意义（P〈0．05）。在西医和中医总的疗效方面，治疗组比对照组有更加确切的疗效，经卡方检验有统计学意义（P〈0．05）。结论肾炎康复片联合氯沙坦钾治疗IgAN（气阴两虚证）疗效显著，与单用氯沙坦钾相比可更有效减少24h尿蛋白定量，提升Alb水平，降低IgA及SCr浓度，改善患者临床症状，从而保护肾功能，延缓IgAN的进展。

加减参芪地黄汤治疗气阴两虚型IgA肾病机理浅析

IgA肾病是一种原发性肾小球疾病,常见分型为气阴两虚型。笔者从IgA肾病的中医、西医认识、中医组方分析,西医药理研究方面进行论述,并举验案说明应用加减参芪地黄汤治疗此病的效果。

The Neglected Significance of Glomerular Density as a 5-year Progression Indicator for IgA Nephropathy

Objective To investigate whether glomerular density （GD） could be an independent prognostic factor for patients of IgA nephropathy with estimated glomerular filtration rate （eGFR） of 30 to 60 ml/min per 1.73 m2, or for patients with time-average proteinuria 〈 0.5 g/d. Methods A total of 173 patients with biopsy-confirmed IgA nephropathy diagnosed from January 2000 to December 2010 were included. All of these patients were followed up for more than 5 years. The endpoint was a 〉 30% of decline in eGFR from baseline after 5-year follow-up. The optimal cut-off value of GD was calculated by ROC curve. Kaplan-Meier method and Cox regression analysis was used for survival analysis. Results A 30% of decline in eGFR occurred in 14.5% of all patients. The optimal diagnostic cut-off value of GD was 1.99/mm2 （AUC = 0.90, sensitivity = 84.0%, specificity = 81.8%） determined by ROC curve. The low GD group （GD 〈 1.99 per mm2） experienced a significant increase in renal endpoint for patients with eGFR of 30 to 60 ml/min per 1.73 m2 （six patients in lower GD group, while one patient in the other group）. For patients with time-average proteinuria 〈 0.5 g/d, the lower GD group showed a higher eGFR decline from baseline （4.5±16.7 ml/min per 1.73 m2 vs. –8.1±21.4 ml/min per 1.73 m2, P = 0.038）; two patients in this group reached the endpoint, while no patients in the higher GD group did. Conclusion GD could be an independent prognostic factor for patients of IgA nephropathy with eGFR at 30 to 60 ml/min per 1.73 m2 of body surface, particularly for those with time-averaged amount of urine protein less than 0.5 g per day.

Existence and significance of hepatitis B virus DNA in kidneys of IgA nephropathy

AIM: To investigate the existence and significance of hepatitis B virus (HBV) DNA in the pathogenesis of IgA nephropathy(IgAN).METHODS: Fifty cases of IgAN with HBV antigenaemia and/or hepatitis B virus antigens (HBAg, or HBsAg, HBcAg)detected by immunohistochemistry in renal tissues were enrolled in our study. The distribution and localization of HBV DNA were observed using in situ hybridization.Southern blot analysis was performed to reveal the state of renal HBV DNA.RESULTS: Among the 50 patients with IgAN, HBs antigenemia was detected in 17 patients (34%). HBAg in renal tissues was detected in 48 patients (96%), the positive rate of HBAg, HBsAg, and HBcAg was 82% (41/50), 58% (29/50),and 42% (21/50) in glomeruli, respectively; and was 94%(47/50), 56% (28/50) and 78% (39/50) in tubular epithelia,respectively. Positive HBV DNA was detected in 72% (36/50)and 82% (41/50) cases in tubular epithelia and glomeruli respectively by in Situ hybridization, and the positive signals were localized in the nuclei of tubular epithelial cells and glomerular mesangial cells as well as infiltrated interstitial lymphocytes. Moreover, 68% (34/50) cases were proved to be HBV DNA positive by Southern blot analysis, and all were the integrated form.CONCLUSION: HBV infection might play an important role in occurrence and progress of IgAN. In addition to humoral immune damages mediated by HBAg-HBAb immune complex,renal tissues of some IgAN are directly infected with HBV and express HBAg in situ, and the cellular mechanism mediated by HBV originating from renal cells in situ may also be involved in the pathogenesis of IgAN.

Effects of yiqi yangyin huoxue therapy on IgA nephropathy: a systematic review and meta-analysis of randomized controlled trials

Objective To assess the efficacy and safety of Yiqi Yangyin Huoxue therapy (YYHT) for the treatment of IgA nephropathy. Methods Databases articles about YYHT in treating IgAN patients were searched through February 2018. Comparisons were YYHT alone or YYHT in combination with western medicine as experimental intervention, and western medicine as the control. Randomized controlled trials (RCTs) were selected. Cochrane collaboration tool was used for assessing risk of bias to evaluate methodologies. RevMan 5.3 software was applied to analyze the data of included trials. Results A total of 21 studies involving 1473 patients were included. Meta-analysis results demonstrated that YYHT alone or YYHT in combination with western medicine were more efficacious than only western medicine in decreasing proteinuria [MD =-0.41, 95% CI (-0.53,-0.29), P < 0.00001] and the urine red blood cells [MD =-7.46, 95% CI (-9.28,-5.64), P < 0.00001]. There also showed improvement in the clinical total effective rate [OR = 2.78, 95% CI (2.14, 3.61), P < 0.00001] between the two groups. Some of the included trials did not report the adverse events. Conclusions Current evidence shows that YYHT can reduce proteinuria and urine red blood cells and improve the total efficacy rate. Since poor quality and publication bias of some included trials, more evidence-based medicine studies needed to define the role of YYHT in the treatment of IgAN.

TCM Differential Treatment of IgA Nephrosis

IgA nephrosis, with an incidence of 38%-49% in the primary glomerulopathy in China, is one of the main causes for the late renal failure. In view of the fact that there are no specific Western remedies for IgA nephrosis characterized by hematuria, the researches on TCM differential treatment of IgA nephrosis have been listed in the major projects of 'the Scientific Technologies in thel0th 5-year plan of China'.

Clinicopathological Analysis of 155 Patients with Persistent Isolated Hematuria

Objectives To reveal etiologies of persistent isolated hematuria （PIH） through ultrastructural pathological examination, to disclose clinicopathological correlation in cases with PIH, and to summarize appropriate management of patients with PIH. Methods we retrospectively studied 155 P1H patients receiving renal biopsy between January, 2003 and December, 2008 in Peking Union Medical College Hospital. All the clinical data and follow-up result were analyzed. Results All subjects included 38 children and 117 adults, with mean age of 11.38±3.25 years for children and 35.17±8.44 years for adults. Thin basement membrane nephropathy （TBMN） was the most common pathology （55.3% of children and 49.6% of adults）, followed by IgA nephropathy （18.4% of children and 32.5% of adults, mainly grade 2-3） and mesangial proliferative glomerulonephritis （MsPGN） without IgA deposition （13.2% of children and 12.8% of adults）. Besides, A1port syndrome （2.6% of children） and membrane nephropathy （2.6% of children and 0.9% of adults） were demonstrated as other causes of PIH. Elevated mean arteral pressure or protein excretion rate, as well as episodic macrohematuria, indicated higher risk for MsPGN rather than TBMN. On the other hand, severity of microhematuria was irrelevant to pathological types of PIH. Totally, 86 patients were followed up and 37 cases therein stayed on track for long term （mean duration 41.11±28.92 months, range 8-113 months）. Most cases had benign clinical course except 3 cases with TBMN, 5 cases with IgA nephropathy, 1 case with MsPGN （without IgA deposition）, and 1 case with Alport syndrome, who developed hypertension or proteinuria. All of them were administered timely intervention. Conclusions Close follow-up should be required as the primary management for PIH. Equally important is careful monitoring for early identification of undesirable predictors; while renal biopsy and other timely intervention are warranted if there is hypertension, significant proteinuria or renal impairment.

Genetic variation of mannose-binding protein associated with glomerular immune deposition in IgA nephropathy

OBJECTIVE: To investigate the relationship between codon 54 gene polymorphism of the host defense molecule, mannose-binding protein (MBP), and the patterns of glomerular immune deposition in IgA nephropathy (IgAN). METHODS: IgAN patients with different patterns of glomerular immune deposition were selected and divided into two groups. Group A consisted of 77 patients with glomerular IgA and C3 deposits, and Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and Clq deposits. Clinical features and laboratory relevant data of all patients were collected. One-hundred and forty healthy adults were recruited as normal controls. The MBP gene codon 54 GGC/GAC polymorphism was investigated by using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotype frequency of GGC/GAC heterozygotes was significantly higher in Group AGM as compared with that of Group A (41.4% vs 19.5%, P

Gene polymorphism in IL-1 receptor antagonist affects its production by monocytes in IgA nephropathy and Henoch-Schonlein nephritis

Objective To define the functional significance of IL-1 receptor antagonist (IL-1ra) gene polymorphism and to investigate, the production of IL-1ra by monocytes from individuals with different genotypes of IL-1.Methods The genotype of IL-1ra was detected by polymerase chain reaction (PCR). Peripheral monocytes obtained from patients with immunoglobin A nephropathy (IgAN), Henoch-Schonlein purpura nephritis (HSPN) and normal subjects were matched in sex and age between the IL1RN-2 allele carriers and non-carriers. The secretion of IL-1ra, IL-1α and IL-1β in the supernatant of GM-CSF (10ng/ml) treated and untreated monocytes were measured by ELISA.Results The secretion of IL-1ra by monocytes stimulated with GM-CSF was significantly higher in the IL1RN-2 allele non-carriers than those of carriers both in IgAN (21.55±3.08 vs 13.85±2.24ng/ml, P<0.001) and HSPN (23.72±6.68 vs 12.67±2.24ng/ml, P<0.01) as well as in normal controls (20.29±1.45 vs 10.51±2.3ng/ml, P<0.001). All showed no significant differences in monocyte secretion of IL-1α and IL-1β by GM-CSF stimulation between the IL1RN-2 allele carriers and non-carriers. Conclusions These results indicate that a functional correlation of the IL1RN-2 allele and IL-1ra production is present in patients with IgAN and HSPN. This gene polymorphism control of IL-1ra production may contribute to the variety of clinical responses to inflammatory stimulation in individuals with different genotype of IL-1ra.

The Short-term Therapeutic Effects of TCM for IgA Nephropathy In Children

Objective: To evaluate the short-term therapeutic effects of TCM for IgA nephropathy in children. Methods: Sixty-two children with primary IgA nephropathy diagnosed for the first time by renal biopsy in the authors’ hospital were randomly divided into a group of 34 cases treated with both TCM and Western medicine and a group of 28 cases treated with Western medicine for six months. The improvements in urinary protein and red blood cell (RBC) were observed and the scores for TCM symptoms and signs were evaluated after 3 months and 6months of treatment. Results: There was no significant difference in the total effective rate between the two groups (χ2=4.743, P>0.05 after treatment for 3 months; and χ2=1.953, P>0.05 after treatment for 6 months). However, the cure plus marked effect rate in the group treated with both TCM and Western medicine was higher than that in the group treated with Western medicine (71.9% vs 45.5%, P<0.05 after treatment for 3 months). At the end of treatment, significant difference were found in the effective rate (9.3% vs 10.5%, χ2=9.653, P<0.01) and in the total score (0.81+1.18 vs 3.42+2.52,t=4.19, P<0.001) between the two groups. Conclusion: Treatment with both TCM and Western medicine can effectively improve the TCM symptoms and signs in child patients with IgA nephropathy, and alleviate hematuria and albuminuria.

Proteins induced by telomere dysfunction are associated with human IgA nephropathy

Aging is one of the contributing risk factors for kidney diseases. Accumulating evidence prompts the view that telomere length in kidney tissue cells is an indicator for organismal aging. Previously identified aging markers （cathelin-related antimicrobial peptide （CRAMP）, stathmin, elongation factor-1α （EF-1α）, and chitinase） were associated not only with telomere driven aging in mice but also with human aging and chronic diseases. This study focuses on the relationship between these biomarkers and IgA nephropathy （IgAN） progression in the Chinese population. For 260 individuals, the four markers are determined in blind datasets using direct enzyme-linked immunosorbent assay （ELISA） and immunofluorescence staining. The expression levels of CRAMP and chitinase increased in blood plasma, urine, and kidney tissues during human IgAN progression. And for the other nephropathy, such as systemic lupus erythematosus （SLE）, diabetic nephropathy （DN）, and focal segmental glomerulosclerosis （FSGS）, there is no protein upregulaUon with telomere shortening. Moreover, a combination of CRAMP and chitinase can distinguish patients with IgAN from healthy individuals with 88.2%/92.5% （plasma） and 74.3%/84.2% （urine） sensitivity/specificity. These data provide the experimental evidence that telomere shortening and related inflammatory proteins are associated with human IgAN, and it could be a new direction for the disease progression study.

Effect of Chinese herbs on immunoglobulin A nephropathy:a randomized controlled trial

OBJECTIVE: The accumulation of extracellular matrix (ECM) is one of the main causes of renal fibrosis. Emerging evidence suggests that the metabolic enzyme of ECM is associated with renal fibrosis. In this study, we applied randomly controlled trial to check the curative effect of Chinese herbs on patients with immunoglobulin A nephropathy (IgAN). METHODS: Twenty-six patients were randomly divided into group A (control group) treated with Western Medicine and group B (treatment group) treated with combination of Traditional Chinese Medicine (TCM) and Western Medicine. Blood and urine tests were done before treatment and after 8-week treatment. RESULTS: The levels of the main composition of ex- tracellular matrix (MC-ECM), the metabolic enzyme of ECM (ME-ECM) and some cytokines in group B decreased more obviously than those in group A after 8-week treatment. So did the level of 24-hour urine protein. However, Metal matrix protease (MMP)-2 and vascular endothelial growth factor in group B increased more obviously than those in group A after 8-week treatment. No effects on the renal function were found in both groups. CONCLUSION: Our study provided important information on using the combination of TCM with Western Medicine to inhibit the progression of renal fibrosis in patients with IgAN.

Clinical and pathological analysis on Traditional Chinese Medicine syndromes in children with immunoglobulin A nephropathy

OBJECTIVE:To evaluate the common Traditional Chinese Medicine(TCM) syndromes and analyze their relationship to clinical and pathological manifestations in children with IgAnephropathy.METHODS:Forty five children diagnosed as having primary IgA nephropathy by renal biopsy for the first time were enrolled in this trial,and their TCM syndromes were evaluated and the distribution of TCM syndromes was observed.All the sick children were growed? according to clinical manifestations and pathological damages,and the differences in TCM syndromes were compared between the groups.RESULTS:The first 5 TCM symptoms were common cold,hyperhidrosis,red dry throat,dark yellow urine and lassitude.In the acute nephritis group,edema and aching pain in loin and knees were significant(P=0.021 and P=0.000).In the severe pathological damage group,edema was obvious(P= 0.004),and 24 h urinary protein was positively correlated with edema(P=0.015) while negatively with common cold(P=0,007).The score of mesangial cell proliferation was correlated with edema,red dry throat and common cold(P=0.006,0.013 and 0.029 respectively).The score of segmental pathological change was positively correlated with edema(P=0.039).CONCLUSION:Common cold,hyperhidrosis,red dry throat,dark yellow urine,lassitude and other symptoms of qi deficiency of the spleen and lung mainly seen in children with IgA nephropathy may bear a close relationship to clinical manifestations and pathological damages.