Evidence of enhanced uric acid clearance in macrohematuric patients with IgA nephropathy: prognostic significance of macrohematuria

Renal handling of uric acid and clinical prognosis following episodes of macroscopic hematuria (EMH) were examined in 113 patients with IgA nephropathy (IgAN). EMH was observed in 34 out of 113 patients (30.1%). The levels of blood urea nitrogen, proteinuria, serum uric acid, beta 2-microglobulin in sera and the degrees of glomerular sclerosis in renal tissues in macrohematuric patients were significantly decreased than those in patients without EMH. The levels of uric acid clearance (Cua) and fractional excretion of uric acid (FEua) was significantly enhanced in macrohematuric patients (p less than 0.01, p less than 0.05, respectively). There was a significant correlation between the tubular atrophy and the levels of Cua in macrohematuric patients (p less than 0.005). The levels of serum creatinine in macrohematuric patients before and after three years were significantly decreased when compared with microhematuric patients (p less than 0.005). It is concluded that enhanced Cua was related to renal tubular atrophy, and EMH did not clinically influence the glomerular deterioration in patients with IgAN.     

Clinical and pathological features of hyperuricemia in children with IgA nephropathy at a single center

Objective To investigate the clinical, pathological features and risk factors of hyperuricemia in children with IgA nephropathy (IgAN). Methods A retrospective study of 269 primary IgAN children diagnosed between January 1, 2006 to December 31, 2017 at the Children Kidney Disease Center, the First Affiliated Hospital of Sun Yat-sen University, was performed in the hyperuricemia group (uric acid＞350 μmol/L) and the normal uric acid group. The clinical and pathological characteristics were analyzed, and the risk factors of hyperuricemia were analyzed by using multivariate logistic regression analysis. Results There were 185 males and 84 females in the 269 IgAN children with age of (9.2±3.1) years old, among whom there were 70 patients (26.0%) accompanied by hyperuricemia. Clinical indicators such as hypertension, urea nitrogen, serum creatinine, blood lipids, urinary protein in hyperuricemia group were higher than those in normal uric acid group (all P＜0.05), while estimated glomerular filtration rate, serum total protein and albumin were less (all P＜0.05). There were 58 patients (23.0%) and 12 patients (70.5%) associated with hyperuricemia among IgAN children with CKD 1-2 and CKD 3-5. The proportion of hyperuricemia in CKD stage 3-5 IgAN children was statistically higher than that in normal uric acid group (P＜0.01). The hyperuricemia group had a higher proportion of Lee IV and V grade, and a lower proportion of the Lee III grade than the normal uric acid group (all P＜0.05). According to the Oxford pathological classification score, there was no significant difference in total scores of renal lesions, glomerular score, and tubulointerstitial score between the two groups (all P＞0.05). According to the Katafuchi semi-quantitative score, there was no significant difference in the total scores of renal lesions, glomeruli, and tubulointerstitial scores (all P＞0.05), while the hyperuricemia group had higher renal vascular scores than the normal uric acid group (P＜0.01). Multivariate logistic regression analysis showed that hypertension (OR=12.596, 95%CI 1.778-89.243, P=0.011), higher total cholesterol (OR=1.192, 95%CI 1.064-1.336, P=0.002), higher urea nitrogen (OR=1.273, 95%CI 1.104-1.468, P=0.001), proteinuria 3+(OR=1.875, 95%CI 1.309-2.684, P=0.001), proteinuria 4+(OR=1.627, 95%CI 1.241-2.134, P＜0.001) and CKD stage 3 (OR=3.355, 95%CI 1.376-8.181, P=0.008) were the risk factors of hyperuricemia in children with IgAN. Conclusions Twenty-six percent IgAN children patients are accompanied by hyperuricemia, and their clinical parameters and pathological changes are more severe than those in normal uric acid group. Hypertension, higher total cholesterol, higher urea nitrogen, proteinuria 3+/4+ and CKD stage 3 are the risk factors of hyperuricemia in children with IgAN.     

正常血压IgA肾病患者动脉病变的意义

目的:传统观点认为动脉硬化与高血压有关。然而,部分IgA肾病患者,尽管血压正常,但仍有动脉硬化的改变。本研究的目的就是比较血压正常、伴有和不伴有动脉病变的IgA肾病患者的临床病理特点,探讨正常血压IgA肾病患者肾内动脉病变的影响因素及意义。方法:所有患者均经肾活检诊断为原发性IgA肾病,无高血压病史,肾活检前血压<140/90mmHg。动脉病变的定义为活检肾组织光镜下见动脉壁增厚和(或)动脉玻璃样变。符合标准的105例患者,根据动脉病变的有无分为两组,有动脉病变组52例、无动脉病变组53例,分别比较两组的临床病理特点。肾脏动脉病变的半定量分级标准:0:无损害;1:<25%;2:≥25%,<50%;3:≥50%。统计学方法:分别比较两组的临床病理特点,将差异有统计学意义的单因素指标作为多因素分析的入选指标,采用逐步回归方法分析动脉病变的影响因素,以P<0.05作为差异有统计学意义。结果:与无动脉病变组比较,动脉病变组肾活检时的年龄、血肌酐、血尿酸、尿蛋白定量、尿NAG酶、肾小球硬化、肾小管萎缩以及肾间质纤维化的程度显著增高,尿渗透压显著下降。多因素分析的结果表明,肾活检时的血肌酐、尿渗透压、肾小管萎缩及肾间质纤维化是正常血压IgA肾病动脉病变的独立影响因素。动脉病变的程度与血肌酐、肾小管萎缩及肾间质纤维化呈正相关;与尿渗透压呈负相关。结论:血压正常IgA肾病患者的肾内动脉病变,主要与年龄、血肌酐、血尿酸增高等因素有关,常伴有肾小管间质损害。     

Tubular and interstitial expression of ICAM-1 as a marker of renal injury in IgA nephropathy

BACKGROUND: The upregulated renal expression of intercellular adhesion molecule 1 (ICAM-1) is associated with glomerular and interstitial infiltration of leukocytes. AIM: To test the hypothesis that renal expression of ICAM-1 may be predictive in the highly variable IgA nephropathy (IgAN). METHODS: ICAM-1 (CD54) in tubular epithelium and interstitial leukocytes, macrophages (CD14), and T cells (CD3) were assessed using avidin-biotin-peroxidase in renal biopsy specimens from 45 patients with IgAN and from 29 patients with no glomerulonephritis. RESULTS: In IgAN, tubular ICAM-1+ was seen in 25 of 45 (55%) biopsy specimens, associated with glomerular hypercellularity, glomerulosclerosis involving less than 50% of the glomerular area, interstitial cellular infiltration, tubular atrophy, and proteinuria (U = 44, p = 0.005). Interstitial ICAM-1+ leukocytes were correlated with glomerulosclerosis involving less and more than 50% of the glomerular area, tubular atrophy, interstitial fibrosis, and serum creatinine concentration (r = 0.6343, p < 0.001). In patients with an increase of 50% in the serum creatinine concentration, interstitial ICAM-1+ leukocytes and CD14+ and CD3+ cells were significantly more numerous than in patients with a stable creatinine concentration. In patients with no glomerulonephritis, tubular ICAM-1+ was seen in 7 of 29 (24%) biopsy specimens, inversely correlated with the number of normal glomeruli and associated with glomerulosclerosis covering more than 50% of the glomerular area, tubular atrophy, and creatinine. CONCLUSIONS: Tubular and interstitial expression of ICAM-1 can be a marker of tubulointerstitial disturbance in IgAN. Interstitial ICAM-1 may be an adverse predictor of disease progression.     

不同性别成人IgA肾病患者临床特征

目的了解不同性别成人原发性IgA肾病（IgAnephropathy,IgAN）患者的临床特征。方法选择我科1996年3月至2009年11月经肾活检确诊为kAN的成人患者192例,对比分析男性和女性患者各临床表现和病理积分特点。结果成人IgAN患者中,不同性别患者的病程、发病年龄、血胆固醇、清蛋白、血IgA、血C3、尿红细胞计数和估算肾小球滤过率值的差异无统计学意义,但男性收缩压、舒张压、血肌酐、尿素氮、血尿酸及24h尿蛋白定量明显高于女性,差异显著。男性高血压、高尿酸血症、高三酰甘油血症、24h尿蛋白定量〉1g的比例显著高于女性。男女患者的肾小球积分、肾小管间质积分、血管积分及慢性病变、活动性病变积分差异均无统计学意义。肾功能中度损伤的独立危险因素为高尿酸血症（r=9．146,95．0％CI：2．322-36．026,P〈0．01）、总积分（r=2．772,95．0％CI：1．709～4．496,P〈0．01）、肾小球积分（r=0．522,95．0％CI：0．287-0．952,P〈0．05）。结论成人IgAN患者肾活检时男女患者间的肾功能及。肾脏病理改变并无明显差异,但男性患者相关临床病变重,血压、血肌酐、血尿酸及24h尿蛋白定量高,需积极干预延缓其进展。     

Association between obesity and absolute renal risk factors in patients with IgA nephropathy

Objective To investigate the influence of obesity on renal lesion in IgA nephropathy (IgAN) patients by analyzing the association between obesity and absolute renal risk factors (ARR). Method Clinical-pathological data of IgAN patients diagnosed by renal biopsy in General Hospital of Ningxia Medical University were collected retrospectively. According to the body mass index (BMI), patients were divided into non-obese group (BMI＜28, N-OB group) and obese group (BMI≥28, OB group). Their clinical characteristics, pathological index and ARR scores were compared. The relationship of BMI and ARR was analyzed by ordinal logistic regression models. Results (1) A total of 674 IgAN patients with mean age of 35.5±11.3 years were enrolled, including 94 in OB group and 580 in N-OB group respectively. Compared with those in the N-OB group, the proportion of male, age, mean arterial pressure, blood uric acid, blood triglyceride, diabetes mellitus and hypertension increased in OB group (all P＜0.01). Patients in OB group had lower estimated glomerular filtration rate (eGFR) and higher ARR score than those in N-OB group (all P＜0.05). (2) More severe thickening renal small artery wall and hyaline degeneration were observed in the OB group than in the N-OB group (all P＜0.01). There was no statistical difference between the two groups in Lee classification, Oxford classification, mesangial cell proliferation, glomerular sclerosis, crescent formation, renal tubular atrophy, interstitial inflammatory cell in filtration and endothelial cell proliferation. (3) After adjusting for age, sex, blood uric acid, serum albumin, eGFR, low density lipoprotein, glomerular sclerosis, interstitial inflammatory cell infiltration, renal tubular atrophy and vascular wall thickening, BMI was still an independent risk factors for ARR in IgAN patients (OR=1.09, 95%CI 1.03-1.14). Conclusions BMI is an independent risk factors for ARR in IgAN patients. Early prevention and control of obesity and its associated risk factors may improve outcomes of IgAN patients.     

The correlation between serum levels of oxidative stress indicators and renal interstitial fibrosis in patients with IgA nephropathy

Objective To investigate the relationship between serum levels of oxidative stress indicators and the degree of renal interstitial fibrosis in patients with IgA nephropathy (IgAN). Methods Seventy eight patients with confirmed primary IgAN in General Hospital of Ningxia Medical University from January 2013 to December 2014 were enrolled. The patients were divided into T0 group (n=30), T1 group (n=26) and T2 group (n=22) according to the grade of tubular atrophy/interstitial fibrosis of Oxford pathological classification criteria for IgAN in 2009. Meanwhile, thirty cases of health examiner were enrolled as control subjects. The levels of serum malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px) were detected by xanthine oxidase method, thiobarbituric acid spectrophotometry method, ultraviolet spectrophotometry method, chemical colorimetric method, respectively. The levels of serum advanced oxidation protein products (AOPPs), transforming growth factor beta 1 (TGF-β1), monocyte chemotactic protein 1 (MCP-1), transforming growth factor alpha (TGF-α), interleukin 6 (IL-6) and hypoxia inducible factor 1 alpha (HIF-1α) were detected by enzyme linked immunosorbent assay (ELISA) in all groups. Spearman correlation analysis was used to analyze the correlation between serum oxidative stress indicators and traditional risk factors of tubular atrophy/renal interstitial fibrosis. Multivariable linear regression analysis was used to analyze the correlation between oxidative stress indicators and degree of renal tubular atrophy/renal interstitial fibrosis. Results There were differences in serum levels of AOPPs, MDA, SOD, CAT and GSH-Px in IgAN patients with different degrees of renal interstitial fibrosis (all P﹤0.05). With the increase of renal interstitial fibrosis, the levels of AOPPs and MDA increased gradually, while the levels of SOD, CAT and GSH-Px decreased gradually. Serum AOPPs, MDA, SOD, CAT, GSH-Px concentration in IgAN patients were correlated with the mean arterial pressure (MAP), total blood protein (TP), albumin (Alb), Scr, uric acid (UA), 24-hour urinary protein volume and estimated glomerular filtration rate (eGFR). Multivariate regression analysis showed that the AOPPs levels of blood were positively correlated with MAP, Scr, UA and 24-hour urinary protein (all P﹤0.01), and negatively correlated with TP, Alb, eGFR (all P﹤0.05). The serum levels of AOPPs and MDA in IgAN patients were positively correlated with the levels of TGF-β1, MCP-1, TGF-α, IL-6 and HIF-1α. The levels of SOD, CAT and GSH-Px were negatively correlated with the levels of TGF-β1, MCP-1, TGF-α, IL-6 and HIF-1α. Multivariate stepwise regression analysis showed that the degree of renal interstitial fibrosis in IgAN patients was positively correlated with serum AOPPs level (β=0.285, P=0.001), negatively correlated with CAT (β=-0.346, P﹤0.001), GSH-Px (β=-0.303, P﹤0.001). Conclusions The level of serum oxidative stress in IgAN patients is elevated and positively correlated with the degree of renal interstitial fibrosis, suggesting that oxidative stress may be involved in the occurrence and development of renal interstitial fibrosis.     

伴高尿酸血症的IgA肾病临床和病理分析

目的探讨伴有高尿酸血症的IgA肾病的临床和病理特点。方法将经过肾活检明确诊断的原发性IgA肾病110例患者分为2组：尿酸正常组55例，尿酸升高组55例，比较2组临床和病理的差异。结果尿酸升高组与尿酸正常组比较，血尿素氮、血肌酐、24h尿蛋白定量、血总胆固醇、三酰甘油、低密度脂蛋白升高；肾小球损伤加重，肾小管萎缩、肾间质纤维化明显。结论伴有尿酸升高的kA肾病患者临床和病理损伤均重于尿酸正常的IgA肾病，临床上应给与重视。     

Analysis of the clinical pathological characteristics and prognosis of primary IgA nephropathy with hypertension

Objective To investigate the clinic-pathological features and prognostic risk factors of IgA nephropathy (IgAN) with hypertension (HTN). Methods Primary IgAN patients diagnosed with biopsy from January 2016 to December 2017 were recruited. Patients were divided into IgAN with normal blood pressure (IgAN-NTN) group and IgAN with hypertension (IgAN-HTN) group based on the pressure value when performing the kidney biopsy. The clinical and pathological data were collected and compared between the two groups. Kaplan-Meier method was conducted for renal results, whereas the Cox regression model was exploited to analyze the prognostic factors in the progression of IgAN-HTN patients. Results The total number of enrolled patients was 275 cases, 170 (61.82%) of which had normal pressure and 105 individuals (38.18%) resulted in hypertension. The IgAN-HTN group in terms of male proportion, age, systolic pressure, diastolic pressure, serum urea nitrogen, serum creatinine, serum uric acid, 24 h urinary protein, triacylglycerol, complement C4 and so on were higher than those in the IgAN-NTN group (all P＜0.05). The incidence of gross hematuria and the level of estimated glomerular filtration rate (eGFR) were significantly lower than those in the NTN group (all P＜0.001). For the aspect of light microscope pathological manifestations, IgAN-HTN group exhibited more severe histological lesions including glomerular sclerosis, renal tubular atrophy or renal interstitial fibrosis, interstitial vascular injury than IgAN-NTN group (all P＜0.05). Immunofluorescence examination results showed that the deposition ratio of C1q in IgAN-HTN group was higher than that in IgAN-NTN group (P=0.015). By employing Kaplan-Meier method, the cumulative renal survival rate in the HTN group was much lower than that in the NTN group (Log-rank test: χ2=6.456, P=0.011). For the patients in IgAN-HTN group, the cumulative renal survival rate in the dyslipidemia group was much lower than that in the ortholiposis group (Log-rank test: χ2=5.093, P=0.024). There was no significant difference in the cumulative renal survival rate between the blood pressure control group and the unqualified group (Log-rank test: χ2=1.036, P=0.309). As a result of univariate and multivariable Cox regression analysis, total cholesterol, eGFR and 24 h urinary protein were risk factors for renal progression of IgAN patients with hypertension. Conclusions The clinical manifestations and renal pathological changes in patients with IgAN-HTN are more serious than those in IgAN-NTN patients, which result in worse prognosis. IgAN-HTN patients should be paid more attention to the management of serum lipid level during treatment and follow-up.     

Uric acid correlates with the severity of histopathological parameters in IgA nephropathy.

BACKGROUND: Immunoglobulin-A nephropathy (IgAN) is the most common chronic glomerulonephritis worldwide. Many clinical and histopathological risk factors for progression have been found previously. Recently, metabolic risk factors, such as hyperuricaemia and hypertriglyceridaemia, also have been associated with the progression of IgAN. METHODS: In the present study we correlated clinical and metabolic risk factors with histopathological parameters in 202 patients with IgAN. Morphological changes in glomerular, tubulointerstitial and vascular tissue were semiquantitatively graded into three classes. Mesangial proliferation activity and the amount of inflammatory cells were also evaluated by immunohistochemical staining of Ki-67 (MIB-1), CD45 (LCA) and CD68 stainings. Serum uric acid, triglycerides and cholesterol, urine protein excretion (UPE), blood pressure and body mass index (BMI) were measured. Smoking habits and occurrence of diabetes mellitus also were evaluated. The independent role of serum uric acid in the development of renal morphological changes was evaluated in multivariate analysis. RESULTS: Serum uric acid and UPE level correlated with several histological parameters. Uric acid level showed the strongest correlation with tubulointerstitial changes and UPE with glomerulosclerosis. The level of serum triglycerides correlated with interstitial fibrosis and hyaline arteriolosclerosis. Blood pressure correlated with hyaline arteriolosclerosis, glomerulosclerosis and tubulointerstitial changes. BMI and diabetes mellitus correlated with both tubulointerstitial and vascular changes. We found no significant correlations between histopathological parameters and smoking habits or serum cholesterol level. Serum uric acid had independent associations with the presence of tubular atrophy and interstitial fibrosis and inflammation. CONCLUSIONS: We conclude that many metabolic factors are univariately associated with renal morphological findings in IgAN. These same factors are central in the metabolic or insulin resistance syndrome and may have a pathogenetic role in the progression of IgAN. Serum uric acid may have an independent role in development of tubulointerstitial lesions as well as being associated with inflammation in renal tissue of patients with IgAN.     

不同类型血脂异常对IgA肾病临床及病理特征的影响

目的探讨不同类型血脂异常对IgA肾病临床及病理特征的影响。 方法共纳入283例原发性IgA肾病患者,收集临床资料及病理资料进行回顾性分析。将患者分为：高胆固醇(H－TC)组48例( TC≥ 6.22 mmol/L,TG<1.7 mmol/L);高甘油三脂(H－TG)组48例(TG≥2.26 mmol/L,TC<5.18 mmol/L);低高密度脂蛋白(L－HDL)组34例(HDL－C<1.04 mmol/L,TC<5.18 mmol/L,TG<1.7 mmol/L],同时收集IgAN血脂正常者(153例,TG<1.7 mmol/L、TC<5.18 mmol/L、HDL－C>1.04 mmol/L)作为对照组。对各组患者的一般情况、临床指标及病理分型(牛津分型)进行比较,并采用逐步回归分析方法进行多重线性回归分析探讨影响患者肾小球滤过率(eGFR)的因素。 结果H-TC组24 h尿蛋白量高于血脂正常组(Z＝－2.979, P＝0.003),血清白蛋白低于血脂正常组(t＝2.606,P<0.001)。H-TG组,身体质量指数(BMI)、血清尿酸高于血脂正常组(t＝3.982,t＝5.056;P<0.001), eGFR低于血脂正常组(t＝2.011,P＝0.045)。L-HDL组BMI高于血脂正常组(t＝2.946,P＝0.004),eGFR低于血脂正常组(t＝2.498,P＝0.013),肾小管萎缩/间质纤维化程度高于血脂正常组(χ²＝8.284,P<0.017)。回归方程结果显示年龄、收缩压、尿酸与eGFR呈负相关关系(P<0.05),血清TC与eGFR亦呈负相关关系(95%CI：－5.228～－0.312,t＝－2.220,P＝0.027)。血清HDL与eGFR呈正相关关系( 95%CI：1.469～7.468,t＝2.935,P＝0.004),该模型经检验有统计学意义(F＝11.838,P<0.001)。 结论H-TC、H-TG、L-HDL血症均可能加重IgA肾病的临床损害,且L-HDL血症者肾小管间质受损更严重。降低血清TC,提高血清HDL可能有助于IgA肾病患者改善预后。     

Mesangial C3 deposition and decreased serum C3levels in patients with IgA nephropathy

Objective To explore theclinical significance of complementactivation in IgA nephropathy (IgAN) patients and provide new potential therapy targets. Methods Biopsy-proven IgAN patients admitted in our renal center were retrospectively recruited. Demographic, baseline clinical and pathological data were recorded as well as the follow-up results. Patients were divided into three groups, negative, weak positive and strong positive group, according to the intensity of C3 deposition in mesangial area of glomurili. Decreased serum C3 level was defined as C3＜85 mg/dl. Results In this study, 528 IgAN patients were recruited and meanfollow-up time was3 years. There were 119 (22.5%), 164(31.1%), 245(46.4%) patients in the negative, weak positive and strong positive group respectively; 93(21.7%) patients had decreased serum C3 level and 335(78.3%) patients had normal serum C3 level; Significant negative correlation was found between mesangial area of C3 deposition and serum level of C3(r＝-0.209, P＜0.01). Theage or sex were similar among different groups of mesangial C3 deposition. In univariate analysis, higher baselineserum creatinine,uric acid and IgAlevels, and lower estimated glomerular filtration rate(eGFR), body mass index (BMI) levels were associated with a higher grade of mesangial C3 deposition (P＜0.05). Endocapillary hypercellularity and tubular atrophy or interstitial fibrosis were more prominent in patients with higher grade mesangial deposition of C3. Compared with the patients with normal serum C3 level, patients with decreased serum C3 level had lowerwhite blood cells,hemoglobin,triglyceride, cholesterol, eGFR level and higher serum creatinine level(P＜0.05). During the follow-up,a total of 54 patients developed to end stage renal disease (ESRD), the incidence of ESRD was 23.7% in patients with decreased serum C3 level and 8.4% with normal C3 level.Kaplan-Meieranalysis showed that median outcome-free survival timeof patients with decreased serum C3 levelwas significantshorter than patients with normal serum C3 level [(145.0±22.5) months vs (150.8±17.0) months, P＜0.01]. Cox regression proportional hazards models showed that after adjusting by sex, ageand clinical indicators (MAP, eGFR, serum albumin, urine protein and hemoglobin level), decreased serum C3level (HR＝0.97, 95%CI 0.96, 0.99, P＜0.01) remained be an independent riskfactor of ESRD. Conclusions There are different levels of complement activation in patients with IgAN. Complement activation is associated with baseline renal function and clinical outcomes, and decreased serum C3level is an independent riskfactor of ESRD in IgAN patients. Complement activation may be involved in the progression of IgAN.     

Effect of treatment of hyperuricemia with allopurinol on blood pressure,creatinine clearence,and proteinuria in patients with normal renal functions

Background Hyperuricemia has been associated with the development of hypertension, cardiovascular, and renal disease. However, there is no data about the effect of lowering uric acid level on hypertension, renal function, and proteinuria in patients with glomerular filtration rate (GFR) >60 ml/min. We therefore conducted a prospective study to investigate the benefits of allopurinol treatment in hyperuricemic patients with normal renal function. Materials and methods Forty-eight hyperuricemic and 21 normouricemic patients were included in the study. Hyperuricemic patients received 300 mg/day allopurinol for three months. All patients’ serum creatinine level, 24-h urine protein level, glomerular filtration rate, and blood pressure levels were measured at baseline and after three months of treatment. Results A total of 59 patients completed the three-month follow-up period of observation. In the allopurinol group, serum uric acid levels, GFR, systolic and diastolic blood pressure, and C-reactive protein (CRP) levels significantly improved (P < 0.05). However, urine protein excretion remained unchanged (P > 0.05). No correlation was observed between changes in GFR and changes in CRP, or blood pressure in the allopurinol group. No significant changes were observed in the control group (P > 0.05). Conclusion We bring indirect evidence that hyperuricemia increases blood pressure, and decreases GFR. Hence, management of hyperuricemia may prevent the progression of renal disease, even in patients with normal renal function, suggesting that early treatment with allopurinol should be an important part of the management of chronic kidney disease (CKD) patients. Long-term follow-up studies are warranted to identify the benefits of uric acid management on renal function and hypertension.     

Idiopathic IgA nephropathy with diffuse crescent formation

OBJECTIVE: To investigate the clinicopathological features and outcome of idiopathic IgA nephropathy with diffuse crescent formation in Chinese patients. METHODS: Twenty-five patients with diffuse crescentic IgA nephropathy (DCIgAN), 15 males and 10 females with median age of 28.5, and median disease duration of 5.1 months, were studied. Their clinical, laboratory and pathological features and outcome were investigated. Twenty-one were administered pulse immunosuppressive therapy, and 15 were followed up for more than 6 months. RESULTS: 1.14% had total IgA nephropathy, and 16.4% total diffuse crescentic glomerulonephritis. Clinically, most of patients (88%) showed rapidly progressive glomerulonephritis associated with a high level of serum creatinine (418 +/- 264 micromol/l). Gross hematuria was noted in 72%, hypertension in 64%, and nephrotic syndrome in 48%. Pathologically, except for diffuse crescent formation (a median 65% and range 50-95%), we observed segmental necrosis of glomerular capillaries in 60%, glomerular infiltrating cells in 48%, endothelial cells proliferation in 32%, and rupture of Bowmans' capsule in 24%. Severe tubular interstitial damage was also found, tubular atrophy in 64%, interstitial fibrosis in 60%, diffuse interstitial infiltrating cells in 74%, and interstitial vasculitis in 40%. Immunopathologically, four phenotypes were observed; however, IgA associated with IgM deposition was higher than that in patients with general IgA nephropathy (IgAN). In addition, the infiltrating CD4+, CD8+, CD68+ and PCNA+ cells in renal tissue were significantly high compared with that in controls. In a follow-up study, 66.7% of patients had life-sustaining renal function, 4 of them had normal range of serum creatinine (<124 micromol/l), and only 5 were dialysis-dependent. CONCLUSIONS: The patients with crescentic IgA nephropathy mostly show rapidly progressive nephritis associated with more severe pathological changes including glomerular, tubular interstitial and vascular lesions than in patients with general IgAN. The infiltrates in glomeruli may contribute to the crescentic formation, and the intensive immune suppressing treatment is useful to improve renal damage in patients with DCIgAN.     

特发性膜性肾病患者血尿酸与肾小管萎缩的关系

目的:探讨特发性膜性肾病(IMN)患者的血尿酸水平与肾小管萎缩的关系。方法:选取2010年1月至2017年12月本院收治的200例IMN患者,按是否合并肾小管萎缩分为肾小管萎缩组和非肾小管萎缩组。采用logistic回归分析影响IMN患者肾小管萎缩的相关因素。受试者工作特征(ROC)曲线分析血尿酸对诊断IMN患者肾小管...     

Does circulating erythropoietin reflect progression of IgA nephropathy? Comparison with urinary N-acetyl-beta-D-glucosaminidase.

BACKGROUND: Recent reports describe that erythropoietin (Epo) is produced by peritubular interstitial fibroblast-like cells in response to a hypoxic stimulus. We studied serum Epo levels as a possible marker of tubulointerstitial damage in the progression of IgA nephropathy (IgAN), in comparison with urinary (u-) levels of N-acetyl-beta-D-glucosaminidase (NAG), which is mainly derived from proximal tubular cells and is used as a marker of tubular damage. METHODS: Thirty-eight patients with IgA nephropathy (IgAN) with relatively preserved renal function (serum creatinine: sCr, 0.5-2.2 mg/dl) were examined. The severity of glomerulosclerosis and interstitial fibrosis of the renal biopsy tissue was expressed by semiquantitative grading scores. Clinical parameters including serum creatinine (sCr), blood pressures, and 24-h proteinuria levels were obtained at the renal biopsy. Epo was measured by a radioimmunoassay (RIA) of sera obtained in the morning and u-NAG was measured by colorimetric method of 24-h urine samples. RESULTS: The mean Epo level of the patients (17.7+/-6.3 mU/ml) was not different from the control level (19.3+/-3.7 mU/ml). There were no significant correlations between Epo levels and red blood cell (RBC) counts, haematocrit (Hct), or haemoglobin (Hb) levels. The mean u-NAG level of the patients (6.7+/-6.2 U/gCr) was significantly higher than the control level (1.9+/-0.5 U/gCr). There was an inverse quantitative correlation between Epo and u-NAG levels in the patients (P<0.02). The u-NAG levels showed quantitative positive correlations with sCr (P<0.001), u-proteins (P<0.001), systolic (SBP) (P<0.001), and diastolic blood pressures (DBP) (P<0.05). Conversely, Epo levels were inversely correlated with sCr, SBP and DBP (each P<0.05). The patients with higher u-proteins (>2.0 g/day) showed significantly decreased Epo levels (P<0.05) than those with lower u-proteins (<2.0 g/day). The both scores of glomerulosclerosis and interstitial fibrosis were positively correlated with the u-NAG levels (each P<0.001), but were not correlated with the Epo levels. CONCLUSIONS: The significant correlation between u-NAG and serum Epo levels suggests that tubular damage and interstitial cell dysfunction are associated each other in the progression of IgAN. Serum Epo levels bearing inverse correlations with sCr, blood pressure levels and heavy proteinuria seem to reflect clinical severity of IgAN, whereas u-NAG can be more useful progression marker of IgAN bearing correlations with both clinical and histological findings.     

Uric acid metabolism in patients with chronic glomerulonephritis

Serum uric acid (SUA), creatinine clearance (Ccr), urinary excretion of uric acid (UUAV) and uric acid clearance (CUA) were determined in 357 patients with IgA nephritis (IgAN) and 81 patients with membranous nephropathy (MGN) in an attempt to clarify uric acid metabolism in patients with chronic glomerulonephritis, and UUAV/Ccr and CUA/Ccr levels were measured to investigate their correlations. As a result, hyperuricemia that could hardly be explained with a decline of Ccr alone was recognized in many cases, since the patients with hyperuricemia exceeding 7.0 mg/100 ml of SUA registered even as high as 25.5% in IgAN and 33.3% in MGN, whereas those with the Ccr levels higher than 80 ml/min registered 22.3% in IgAN and 38.0% in MGN. Although the SUA level increased and the UUAV and CUA levels decreased along with a decline of Ccr in IgAN, no similar trends were recognized in MGN. When the distribution of UUAV was studied in the patients with the Ccr levels higher than 80 ml/min, the patients whose UUAV levels higher than 800 mg/24 hrs that suggested excessive uric acid production were markedly as low as 3.9% in IgAN and 3.7% in MGN. Thus, the cause of hyperuricemia could not be attributed to an amount in the uric acid production. On the other hand, the patients whose CUA levels lower than 6.0 ml/min in the distribution of CUA that suggested a decrease of uric acid excretion registered 47.4% in IgAN and 63.0% in MGN, respectively, which equally appeared to be a type of lowered excretion in a majority of patients whose hyperuricemia was recognized in IgAN and MGN. The mechanism of the lowered excretion of uric acids from the kidney despite the normal level of Ccr has yet to be clarified.     

代谢综合征对IgA肾病患者病情的影响

目的 观察代谢综合征（MS）对IgA肾病（IgAN）患者病情的影响。 方法 从确诊为IgAN的病例中,以并发MS的118例作为IgAN-MS组;另从同年龄范围的IgAN病例中随机抽取118例无并发MS者作为IgAN-非MS组,对比分析两组患者的临床病理资料。 结果 IgAN-MS组的尿蛋白量、Scr、体质量指数、平均动脉压、血三酰甘油、空腹血糖及血尿酸水平均显著高于IgAN-非MS组（P ＜ 0.05或P ＜ 0.01）;血高密度脂蛋白（HDL-C）水平显著低于IgAN-非MS组（P ＜ 0.01）;高血压、糖代谢异常及脂代谢异常患者的百分率也显著高于IgAN-非MS组（P ＜ 0.01）。IgAN-MS组的病理改变显著重于IgAN-非MS组（P ＜ 0.01）。Spearman相关分析显示MS与尿蛋白量、Scr、肾小球损伤指数及肾小管间质损伤指数均呈正相关（P ＜ 0.01）。 结论 MS是IgAN进展的一个危险因素。     

Clinico-pathological features and renal outcomes of primary IgA nephropathy with IgM deposition

Objective To investigate the clinico-pathological features and renal outcomes of primary IgA nephropathy (IgAN) with glomerular IgM deposition. Methods Primary IgAN diagnosed with biopsy from January 2006 to December 2011 were recruited. Patients were divided into groups according to IgM deposition (Group A) and without IgM deposition (Group B). In addition, Group A was subdivided into two groups based on the position of IgM deposits as the mesangium (Group A1) and both mesangium and capillary wall (Group A2). Renal outcomes were defined as end stage renal disease (ESRD) and/or the doubling of baseline serum creatinine. Clinico-pathological features were retrospectively compared. Kaplan-Meier was conducted for renal outcomes, and Cox regression model was used to analyze the prognostic value of IgM deposition and the position of IgM deposition in the progression of nephropathy in IgAN patients. Results 939 patients were enrolled with 422 (44.9%) having IgM deposition (Group A). Of the 422 patients, 382 patients were divided as Group A1, whereas 40 patients were noted as Group A2. Compared to Group B, hemoglobin, serum protein, albumin and serum IgG levels in group A were significantly lower, and the cholesterol and serum IgM levels were significantly higher (all P＜0.05). There was no significant difference in serum creatinine, estimated glomerular filtration rate (eGFR), urinary protein, blood pressure and uric acid between group A and B. In terms of pathological manifestations, patients in Group A exhibited more severe histological lesions including glomerular sclerosis, S1, M1 and interstitial inflammatory cell infiltration (all P＜0.05). Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A was significantly higher than that in group B (all P＜0.05). By Kaplan-Meier, cumulative renal survival rate has no significant difference between Group A and B (Log-rank test χ2=0.019, P=0.891). Univariate and multivariable Cox regression analysis showed that IgM deposition had no significant effect on the renal progression in IgAN patients. Subgroup analysis showed that patients in Group A2 exhibited higher urine protein, creatinine and blood pressure, and lower eGFR and serum albumin, also had worse histological lesions including M1, E1 and T1-2 of Oxford classification (all P＜0.05), Immunofluorescence showed that the proportion of IgG, C1q and Fg deposition in group A2 was significantly higher than that in group A1 (all P＜0.05). By Kaplan-Meier, renal survival rates calculated from outcomes were lower in Group A2 (Log-rank test χ2=18.207, P＜0.001). In addition, IgM deposited both in the mesangium and capillary wall was a risk factor for renal progression of IgAN patients with IgM deposition by a univariate Cox hazards regression mode and multivariable-adjusted Cox models (HR=3.621, 95%CI 1.924-6.814, P＜0.001; HR=2.309, 95%CI 1.176-4.533, P=0.015 respectively). Conclusions The IgAN patients with IgM deposition relatively had more severe clinico-pathological changes, especially those with IgM deposited both in the mesangium and capillary wall. In this study, IgM deposition was not found to be an independent risk factor for the prognosis of kidney in IgAN patients. However, IgM deposited both in the mesangium and capillary wall was an independent risk factor for renal prognosis in IgAN patients with IgM deposition.     

厄贝沙坦治疗慢性肾功能不全合并高尿酸血症的疗效观察

目的探讨厄贝沙坦治疗慢性肾功能不全合并高尿酸血症的疗效。方法将84例慢性肾功能不全合并高尿酸血症的患者随机分为A、B、C3组,分别给予厄贝沙坦、厄贝沙坦双倍剂量和非血管紧张素受体拮抗剂类降压药治疗,凡影响尿酸代谢的药物均不使用。于治疗前和治疗后15、30、45d检测血尿酸、血压水平及。肾功能。结果A、B两组患者治疗后血尿酸值明显下降,有显著性差异（P〈0．01）,而C组患者治疗前、后血尿酸水平无显著性差异（P〉0．05）。3组患者血压水平均控制在135／85mmHg以下,且血尿酸下降水平与血肌酐的下降水平无相关关系。结论厄贝沙坦降压保护肾功能同时能明显的降低血尿酸水平。