Low-dose combination therapy with temocapril and losartan reduces proteinuria in normotensive patients with immunoglobulin a nephropathy.

This study investigates the ability of low doses of angiotensin-converting-enzyme inhibitors, in combination with angiotensin II receptor blockers, to exert antiproteinuric effects in normotensive and proteinuric outpatients with immunoglobulin A (IgA) nephropathy confirmed by biopsy. We performed a prospective, randomized, 6-month study of the effects of temocapril 1 mg (n=10), losartan 12.5 mg (n=10), and both (n=11) on mild-to-moderate proteinuria 0.76+/-0.35 g/day (range, 0.4 to 1.6 g/day) and renal function. The study subjects comprised 31 normotensive and proteinuric outpatients with IgA nephropathy accompanied by normal, or mild-to-moderately reduced but stable renal function (glomerular filtration rate>50 ml/min) without steroid or immunosuppressive therapy. We prospectively evaluated blood pressure, proteinuria, renal function and biochemical parameters before and after 6 months of therapy. The combination therapy significantly reduced proteinuria (63.2%) compared with either temocapril or losartan alone (41.3% and 36.6%, respectively, p=0.04 and 0.01, respectively). Blood pressure was most decreased in the group that received combination therapy. The reduced proteinuria did not correlate with reduced systolic or diastolic blood pressure or mean arterial pressure in any of the groups. The glomerular filtration rate fell during the first 3 months of combined therapy, but became reversible after a further 3 months of therapy. The combination significantly decreased angiotensin II (p <0.01), and this decrease was greater than that by either drug alone. In conclusion, the effectiveness of the combined therapy may have been at least partly due to the greater inhibition of the action of angiotensin II in patients with IgA nephropathy. This strategy apparently reduced mild-to-moderate proteinuria in patients with normotensive IgA nephropathy.     

A case of rapidly progressive IgA nephropathy in a patient with exacerbation of Crohn's disease

ABSTRACT: BACKGROUND: IgA nephropathy has been reported as a renal involvement in Crohn's disease. Crescentic IgA nephropathy, which accounts for fewer than 5% of cases of IgA nephropathy, has a poorer prognosis than other forms of crescentic glomerulonephritis. We recently experienced a case of rapidly progressive IgA nephropathy concurrent with exacerbation of Crohn's disease. Case Presentation. An 18-year-old male diagnosed with Crohn's disease underwent a hemicolectomy 2 years previously. He had maintained a state of Crohn's disease remission with 5-aminosalicylic acid treatment. Four months prior to referral to the nephrology clinic, he experienced non-bloody diarrhea. He simultaneously developed proteinuria and microscopic hematuria with deterioration of renal function. Based on renal biopsy findings, the patient was diagnosed with crescentic IgA nephropathy. Immunostaining for interkeukin-17 in renal tissue and previous exacerbated colonic ulcers was positive. Steroid pulse therapy was administered, followed by high-dose glucocorticoid and oral cyclophosphamide therapy. The patient's renal function recovered and his gastrointestinal symptoms were alleviated. CONCLUSIONS: We report a case of crescentic IgA nephropathy presenting with exacerbation of Crohn's disease, and present a review of the literature focusing on the pathophysiologic relationship between these two conditions.     

Primary IgA nephropathy with nephrotic-range proteinuria in Chinese children

To investigate the clinicopathological features and outcomes of primary IgA nephropathy with nephrotic-range proteinuria in Chinese children. Patients with biopsy-proven IgA nephropathy and nephrotic-range proteinuria between January 2011 and December 2017 were included, and their proteinuria and renal function were followed up. A total of 90 patients were enrolled, and 21.1% (19/90) of them had decreased renal function at diagnosis. Complete remission, partial remission, and no response of proteinuria occurred in 88.6% (70/79), 10.1% (8/79), and 1.3% (1/79), respectively, of the 79 patients who were followed up for 6 to 104 months. 73.7% (14/19) of the patients with decreased renal function at diagnosis recovered to normal level while 26.3% (5/19) of them did not recover or progressed to end-stage renal disease. Two patients with normal renal function at diagnosis progressed to renal insufficiency during follow-up period. By multivariate analysis, the risk for renal function deterioration was significantly higher in the partial remission and no response groups than in the complete remission group. Remission of proteinuria was important for improving renal prognosis in children with IgA nephropathy and nephrotic-range proteinuria. The outcomes for pediatric patients appeared to be better than that reported in adults.     

Prognostic values of serum concentration and urinary excretion of interleukin-1 receptor antagonist and tumor necrosis factor receptors type I and II in patients with IGA nephropathy

Interleukin-1 receptor antagonist (IL-1ra) and tumor necrosis factor soluble receptors (sTNFR) type I and II reducing the activity of IL-1 and TNFalpha may inhibit inflammatory reactions. The aim of the study was to assess whether serum and urine IL-1ra and sTNFR measurements may be useful as the early predicting factors in patients with IgA nephropathy. Twenty seven patients (16 males, 11 females), mean age 41.6 +/- 22.3 years with biopsy-proven IgA nephropathy and nephrotic-range proteinuria were included in this study. Serum concentrations (sIL-1ra, ssTNFR I and II) and urinary excretions (uIL-1ra, usTNFR I and II) of IL-1ra, sTNFR I and II had been measured before the treatment was instituted. After 12 months of therapy with steroids and cyclophosphamide, the patients were divided into two subgroups i.e. R - responders, and NR - nonresponders according to the treatment results. The control groups comprised 8 healthy people. IL-1ra serum concentration and urinary excretion were lower in the patients than in the controls (202 vs 330 ng/ml and 970 vs 1607 ng/mg creatinine respectively; p < 0.05 both). Serum concentrations and urinary excretion rates of sTNFR 1 (5.1 vs 1.7 ng/ml and 4.1 vs 1.1 ng/mg creatinine respectively) and sTNFR II (14.4 vs. 5.0 ng/ml and 8.3 vs. 4.4 ng/mg creatinine respectively) were higher (p < 0.05 each) in the patients than in the controls. The subdivision of patients and their classification according to achieved treatment results showed no statistically significant differences between initial interstitium volume neither concentration of serum total protein, serum creatinine or proteinuria and glomerular filtration rate in R and NR subgroups. Initial IL-1ra serum concentration, its urinary excretion and sTNFR type I and II urinary excretion rates were significantly higher in R than NR (sIL-1ra - 297 vs 167 ng/ml, p < 0.05; uIL-1ra 1360 vs 87 ng/mg Cr, p < 0.01; and ssTNFR I 5.2 vs 2.2 ng/mg Cr, p < 0.05; ssTNF RII14 vs 6 ng/mg Cr, p < 0.05). However, serum concentration and urinary excretion of sTNF R type I and II were significantly higher in R and NR subgroups than in controls (p < 0.05 both), sIL-1ra and uIL-1ra were significantly lower in R and NR than in healthy subjects. The results of evaluations of serum concentration and urinary excretion of IL-1ra showed similar values to control group results only in responders. No statistically significant differences between sIL-1ra or/and uIL-1ra in both R and control groups were found. Increased serum concentration and urinary excretion of IL-1ra correlates with better prognosis for remission of proteinuria and lower risk of deterioration of kidney function. Those assessments may be helpful as a part of initial screening in patients with IgA nephritis and heavy proteinuria. In contrast the evaluation of both serum and urinary TNF RI and II seems to have no predictive value.     

高尿酸血症与IgA肾病临床病理的相关性分析

目的 探讨高尿酸血症与IgA肾病临床病理的相关性.方法 选取2007年1月至2010年12月在吉林大学第一医院肾内科肾活检确诊为IgA肾病患者148例,根据血尿酸水平分为血尿酸正常组(107例)和血尿酸增高组(41例),并对两组年龄、性别、高血压、病程、体重指数、生化指标及病理情况进行比较.结果 二组患者间性别、年龄等差异均无统计学意义(P>0.05).血尿酸增高组患者高血乐发病率、病程(月)、体重指数(kg/m2)、血尿素氮(mmol/L)、肌酐(μmol/L)、TG (mmol/L)及24 h尿蛋白定量(mg/24 h)分别为63.4%、18.90 ±10.12、22.81±3.60、8.93±4.28、155.96±107.72、2.11±1.06和4328.16±1434.25,而血尿酸止常组分别为38.3%、9.46±3.91、15.32±2.54、5.21±2.18、79.52±40.01、1.86±1.20和2885.10±1388.15,两组患者差异均有统计学意义(P值均<0.05).Lee's分级血尿酸增高组I+Ⅱ级占12.2%、IV+V级占39.0%,而血尿酸正常组I+Ⅱ级占25.2%、IV+V级占16.9%,两组患者差异均有统计学意义(P值均<0.05).肾小管间质损害(TIL)分级血尿酸增高组以Ⅲ十Ⅳ级多见,占68.3%,而血尿酸正常组以Ⅱ级多见,占76.6%.肾小动脉病变分级血尿酸增高组以Ⅱ+Ⅲ级多见,占73.2%,而血尿酸止常组以0+I级多见,占69.2%.结论 IgA肾病患者血尿酸水平与24 h尿蛋白定量、血压、肾功能损害相关,血尿酸升高者Lee's分级、TIL分级及肾小动脉病变分级较差.

Abstract：

objective To analyze the correlation between the level of serum uric acid and the clinical and pathological features of IgA nephropathy.Methods Totally 148 patients diagnosed as IgA nephropathy by renal biopsy in our hospital from January 2007 to December 2010 were divided into hyperuricaemic group(41 cases)and non-hyperuricaemic group(107 cases)according to the level of serum uric acid.The clinical parameters and renal pathology grade were compared.Results There were significant differences between hyperuricaemic group and non-hyperuricaemic group in the incidences of hypertension(63.4%vs 38.3%),disease duration[(18.90±10.12)months vs(9.46±3.91)months]and body mass index[(22.81±3.60)kg/m2vs(15.32±2.54)kg/m2](all P<0.05),while no differences in age and sex(both P>0.05).The blood urea nitrogen(BUN)[(8.93±4.28)mmol/L vs (5.21±2.18)mmol/L],creatinine(Cr)[(155.96±107.72)μmol/L vs(79.52±40.01)μmol/L],serum triglycerides[(2.11±1.06)mmoVL vs(1.86±1.20)mmol/L]and 24-hour urine protein amount [(4328.16±1434.25)mg/24 h vs(2885.10±1388.15)mg/24 h]were significantly different between the two groups(all P<0.05).The percentage of Lee's grade I+Ⅱin hyperuricaemic group was 12.2%,and IV+V grade was 39.0%,while percentage of Lee's grade I+Ⅱin non-hyperuricaemic group was 25.2%,and IV+V grade was 16.9%(P<0.05).Tubulointerstitial lesions(TIL)gradeⅢ+IV was more in hyperuricaemic group,which was 68.3%,while TIL grade II was more in non-hyperuricaemic group,which was 76.6%.Renal artery damage grade II+Ⅲ was more in hyperuricaemic group.which was 73.2%,while renal artery damage grade 0+1 was more in non-hyperuricaemic group,which was 69.2%.Conclusion The level of serum uric acid was related with 24-hour urine protein amount,blood pressure and kidney function in IgA nephropathy,and Lee's grade,TIL grade and renal artery damage grade were severe in hyperuricaemic group.     

Antineutrophil cytoplasmic autoantibody (ANCA) positive immunoglobulin A (IgA) nephropathy: Case reports and review of literature

BackgroundThere are reports of circulating antineutrophil cytoplasmic autoantibodies (ANCA) in patients with immunoglobulin A (IgA) nephropathy with an uncertain pathogenic role.Aim of the workTo present the findings of myeloperoxidase (MPO) ANCA-positive patients amid a different course of IgA nephropathy with crescents and to discuss the efficacy of immunosuppressive therapy.Case presentationTwo cases of IgA nephropathy associated with positive ANCA are reported and a review of the literature data is presented. The first patient presented with a progressive nephropathy and significantly impaired renal function at baseline, whereas in the second patient renal function remained stable over 10 years, despite the recurrent exacerbations of the disease. Both patients had extrarenal manifestations (joint pain and/or anemia) and elevated markers of inflammation (erythrocyte sedimentation rate, C-reactive protein) that are not typical features for IgA nephropathy. In the first case, immunosuppressive therapy with corticosteroids and cyclophosphamide resulted in improvement of kidney function. The second case showed the potential efficacy of rituximab as an induction remission and maintenance therapy for ANCA-positive IgA nephropathy.ConclusionWhether the association of IgA nephropathy with ANCA positivity is coincidental or constitutes a novel entity remains debated. Circulating ANCA can be found in patients with IgA nephropathy. They can be truly pathogenic and contribute to kidney damage and may induce overt systemic vasculitis or at least extrarenal signs and symptoms. ANCA-positive IgA nephropathy can respond to immunosuppressive regimens, including rituximab, similar to patients with ANCA-associated vasculitis (AAV).     

血管紧张素转换酶抑制剂对IgA肾病的疗效及影响因素分析

目的 观察血管紧张素转换酶抑制剂（ACEI）对IgA肾病（IgAN）的疗效及其影响因素。方法 131例IgAN患者随机分为治疗组和对照组,治疗组应用ACEI（苯那普利10mg/d)治疗;对照组为非ACEI治疗组;对肾脏病理改变进行Lee氏分级并对各种病变进行半定量分析。结果 治疗组的显效率和总有效率均明显高于对照组（P均＜0.05),治疗1个月后治疗组尿蛋白即有显著下降,3个月时较1个月时仍有明显下降（P＜0.05),6、18个月与3个月时相比差异无显著性;血肌酐和肌酐清除率治疗前后比较无明显变化;对照组尿蛋白1个月时有升高趋势,3个月后较治疗前升高且有显著性（P均＜0.05）;肌酐清除率1个月时略有下降,3个月后与治疗前比较有显著下降（P均＜0.01)。单因素分析显示高血压、肾功能不全、Lee氏Ⅴ级、间质病变Ⅳ级、重度血管病变及肾小球硬化超过75％的患者,应用ACEI的疗效不如无高血压、肾功能正常、Lee氏Ⅰ-Ⅱ级、间质病变Ⅰ级、轻度血管病变和肾小球硬化小于25％的患者。多因素分析显示疗效与系膜增生程度呈正相关,与病程、肾小球硬化率及肾小动脉病变程度呈负相关。结论 应用ACEI治疗IgAN有明显降低蛋白尿和保护肾功能作用,影响疗效的主要因素为系膜增生程度、肾小球硬化率、肾小动脉病变程度及病程。     

CD44在IgA肾病中的表达及临床意义

目的研究CD44在IgA肾病各病变阶段肾组织中的表达及其与临床指标之间的关系,探讨CD44在IgA肾病发病机理中的生物学意义.方法应用免疫组织化学S-P法检测34例IgA肾病肾组织、6例正常肾组织中的CD44的表达情况,同时测定IgA肾病患者的24小时尿蛋白定量、血压、血肌酐(Cr)、肌酐清除率(Ccr)等.分析不同临床分组、病理分级、有无高血压、蛋白尿程度、血Cr水平等对CD44表达的影响.结果 CD44主要于系膜增生、新月体、小管间质炎性细胞浸润的部位表达,于细胞性新月体表达最强.整个球性硬化时,CD44表达近消失.CD44表达与蛋白尿程度正相关(P＜0.05);与血cr水平无明显相关性(P＞0.05);有高血压者CD44表达阳性率92%(23/25),无高血压者为33.3%(3/9),两者比较有显著性差异(P＜0.01).CD44在肾组织中的表达与IgA肾病患者的年龄、性别无相关性.结论 CD44与IgA肾病的活动性进展有关,CD44可作为判定IgA肾病早期进展的可靠指标.     

Rapidly progressive glomerulonephritis. A clinical and pathologic study.

Twenty-nine cases of rapidly progressive glomerulonephritis were reviewed. In all cases there was less than three months between the onset of renal symptoms and renal biopsy. The serum creatinine was greater than 2.5 mg/100 ml at the time of biopsy, and the histology showed a 50 per cent or greater incidence of crescents in the glomeruli. Infectious or febrile episodes were present in 21 cases, microscopic hematuria was noted in 15 and proteinuria exceeding 2.5 g/24 hours in eight. Oliguria less than 500 ml/24 hours was present in 20 cases and dialysis was required in 22. In 10 cases there was sustained improvement; in the remainder the disease progressed or the patient died. The prognosis was related to the number and size of the glomerular crescents. Histologically cases fell into two main groups, one with predominantly extracapillary proliferation and the other with endo- and extracapillary proliferation. In the first group the disease was histologically and clinically more severe, and Immunofluorescence histology was heterogeneous and often non-specific except for three cases in which there were linear immunoglobulin deposits. In the second group the lesions were less severe and immunoglobulin deposits were common. Electron microscopy in 14 cases was confirmatory, and also demonstrated capillary rupture and necrosis of podocytes in some loops. Transition from group I to group II was observed in serial biopsy specimens in one case. The histologic and immunofluorescent heterogeneity suggest that rapidly progressive glomerulonephritis is the end result of several different pathogenetic mechanisms.     

Management of IgA nephropathy

The best treatment of IgA nephropathy (Berger's disease) is not well defined and at present no causal therapy is available. Although initially considered benign, we now recognize it as a common cause of end-stage renal disease and the natural history of IgA nephropathy is quite variable. Standard care includes angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and corticosteroids, in some cases combined with immunosuppressive drugs. The antiproteinuric and renoprotective effects of ACEIs and ARBs in IgA nephropathy have been firmly established. Treatment with corticosteroids is effective in reducing proteinuria and renal injury. The addition of cytotoxic immunosuppressive agents (cyclophosphamide and azathioprine) can be of benefit in patients with a rapidly progressive disease course. Little information is available about the clinical efficacy of tonsillectomy on long-term renal survival in patiens with IgA nephropathy; at present it cannot be recommended. The treatment of the disease is a work in progress; only better knowledge of its pathogenesis will eventually offer novel therapeutic approaches.     

The natural history of immunoglobulin a nephropathy among patients with hematuria and minimal proteinuria

PURPOSE: To determine the natural history of immunoglobulin (Ig) A nephropathy among patients who presented with hematuria and minimal proteinuria, and factors associated with the development of adverse clinical events, such as proteinuria. SUBJECTS AND METHODS: In Hong Kong, all patients who present with isolated hematuria are referred for renal biopsy after urologic diseases are ruled out. We reviewed the clinical course of 72 consecutive patients with histologically confirmed IgA nephropathy who presented with hematuria and minimal proteinuria (0.4 g/day or less). All patients were normotensive and had normal renal function at presentation. Adverse events were defined as proteinuria greater than 1 g per day, hypertension, or impaired renal function (serum creatinine level 120 micromol/L or estimated creatinine clearance < 70 mL per minute).RESULTS: The mean (+/- SD) age at presentation was 27 +/- 8 years; 56 (78%) were female. Nine patients (13%) had grade 2 histologic lesions. During a median follow-up of 7 years, 32 patients (44%) developed adverse events: 24 (33%) developed proteinuria of 1 g per day or more, 19 (26%) became hypertensive, and 5 (7%) developed impaired renal function. Another 30 patients (42%) had persistently abnormal urinalysis examinations. Only 10 patients (14%) had complete resolution of hematuria. The median time for progression from proteinuria (> l g/day) to renal impairment was 84 months (range 56 to 132). In a multivariate analysis, age at presentation (relative risk [RR] per 10 years of age = 2.0; 95% confidence interval [CI], 1.2 to 3.4) and histologic grade (grade 2 versus grade 1, RR = 4.5; 95% CI, 1.7 to 12) were independent predictors of developing an adverse event.CONCLUSIONS: IgA nephropathy that presents with hematuria and minimal proteinuria is usually a progressive disease. Life-long follow-up with regular monitoring of blood pressure and proteinuria is recommended.     

蛋白尿在IgA肾病小管间质损害中的意义

目的探讨蛋白尿对IgA肾病（IgAN）小管间质病理变化的影响.方法对68例IgA肾病患者临床病理资料进行回顾性分析.根据24小时尿蛋白排泄量将68例患者分为A组（21例,＜1 g/24 h）、B组（33例,1.0～3.0 g/24 h）和C组（14例,＞3.0 g/24 h）.小管间质病理损害按Katafuchi R的半定量标准评分.结果蛋白尿程度增加,肾小管间质病理损害明显,组间比较有显著性差异（P＜0.05）.蛋白尿程度与尿视黄醇结合蛋白含量及血清C反应蛋白水平呈显著正相关（r=015302,P＜0102）.结论蛋白尿可能通过促进小管间质的免疫炎症反应,加重小管间质的损伤,是IgA肾病慢性进展的重要影响因子之一.对IgA肾病蛋白尿进行早期干预治疗有重要临床意义.     

IgA-Nephropathie

IgA nephropathy (IgAN) is the most common type of glomerulonephritis in the western world. It usually manifests in young adulthood as an oligosymptomatic disease with recurrent episodes of macrohematuria or persistent microhematuria, mild proteinuria and/or renal failure. Thus, it is not surprising that IgAN is usually a chance finding and would probably never have been discovered in many of those affected. About 20% of the diagnosed patients experience chronic progressive renal failure. Predictors are the extent of proteinuria, hypertension as well as already manifested renal failure at the time of diagnosis. Early identification of this risk group is of eminent importance as an optimal supportive therapy can arrest or at least reduce progression of renal failure. The value of immunosuppressive therapy is comparably less well established, so that it should be reserved for those patients maintaining a high proteinuria or losing renal function despite optimized supportive care.     

Long term follow-up of the effect of captopril on severe proteinuria in hypertensive diabetic patients

We have studied the long term effects of captopril therapy on proteinuria in ten patients with non-insulin-dependent diabetes mellitus with hypertension and nephropathy. There were 7 males and 3 females, with a mean age of 53.3 +/- 10.6 years. After a run-in period of two weeks, therapy with captopril was started. The following parameters were studied: serum glucose, sodium, potassium, cholesterol and triglycerides, glycosylated haemoglobin, renal function and 24 hour urine protein excretion before and at six month intervals for up to 24 months. Average BP fell significantly from 182.5 +/- 28/95 +/- 7.1 to 146 +/- 16.7/76 +/- 18.1 mmHg although no significant changes were seen in the biochemical parameters studied, except a reduction in 24 hour urine protein excretion from 3.86 +/- 2.85 to 0.88 +/- 1.08 g/24 h after 24 months of treatment (P less than 0.01). No correlation was observed between the reduction in proteinuria and any other parameters studied. Our results confirm the reduction of proteinuria in patients with type II diabetes mellitus and stable diabetic nephropathy treated with captopril. This effect was maintained for a period of 24 months.     

Diabetic glomerulopathy in the SHR/N-corpulent rat: role of dietary carbohydrate in a model of NIDDM

Summary We evaluated the course of diabetes and nephropathy in the SHR/N-cp (corpulent) rat characterized by genetic obesity, non-insulin-dependent diabetes (NIDDM), and hypertension, and examined whether the nephropathy in this model is influenced by the type of carbohydrate intake. Two groups of obese and lean SHR/N-cp rats were fed diets containing 54 % carbohydrate, as either sucrose or starch for 3 months (group I) and 9 months (group II). After 3 months on either diet, group I obese rats had higher 2-h response serum glucose levels and urinary glucose excretion than lean rats. Sucrose feeding was associated with greater proteinuria and a higher percentage of abnormal glomeruli in obese rats. Morphometric evaluation of glomeruli (by computerized image analysis) showed greater mean renal corpuscular volume and mesangial fraction in obese than in lean rats fed similar diets. Mean renal corpuscular volume and mesangial fraction were also greater in sucrose-fed obese rats than in starch-fed obese rats. After 9 months, group II obese rats had substantial reductions in serum and urine glucose levels but they were still hyperinsulinaemic and showed more proteinuria than lean rats and a higher percentage of sclerotic glomeruli compared with group I obese rats. At this time, mean mesangial fraction but not renal corpuscular volume was still higher in obese than in lean rats. In group I obese rats, a significant correlation was found between mesangial fraction and urinary protein excretion (r = 0.67, p < 0.05). In group II obese rats, renal corpuscular volume was correlated with percentage of glomerular sclerosis (r = 0.60, p < 0.05). Thus, obese SHR/N-cp rats develop persistent proteinuria and glomerulopathy marked by glomerular enlargement, increased mesangial matrix, and progressive glomerular sclerosis. Sucrose feeding accentuates mesangial expansion and glomerulosclerosis in obese rats. [Diabetologia (1995) 38: 31–38] Received: 14 February 1994 and in revised form: 5 July 1994     

Thiazide diuretics enhance nocturnal blood pressure fall and reduce proteinuria in immunoglobulin A nephropathy treated with angiotensin II modulators

OBJECTIVE: We examined whether thiazide diuretics could restore nocturnal blood pressure (BP) decline and reduce urinary protein excretion in patients with glomerulopathy treated with angiotensin II modulators (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers). METHODS: Twenty-five Japanese outpatients (11 men, 14 women; mean age 43 +/- 12 years) with biopsy-proven immunoglobulin (Ig)A nephropathy, preserved renal function (serum creatinine concentration 相似文献   

IgA肾病病理特征及危险因素分析

目的研究IgA肾病的临床及病理变化特点。方法回顾性分析2005年3月至2009年7月在沈阳军区总院肾内科住院接受肾活检并经免疫病理检查确诊为原发性IgA肾病211例患者的临床及病理资料。结果肉眼血尿发病率38.3%,镜下血尿+蛋白尿发病率45.9%。具有明确的黏膜感染病史者占9.4%,发病前有明确诱因的患者占37.8%。镜下血尿+蛋白尿组水肿发病率11.1%,高血压发病率17.9%,肾功能损害发病率7.2%。211例IgA肾病患者病理分级以IgA肾病Ⅲ级为主,占63.1%。肾小球病理损害评分、系膜增殖程度积分、球性硬化积分、血管病变积分均以蛋白尿组最高(P<0.05),球性硬化积分、肾小管-间质积分以镜下血尿+蛋白尿组最高(P<0.05),对单纯蛋白尿组进行多因素Logistic回归分析显示,血清甘油三酯、高血压升高幅度是单纯蛋白尿组病情进展的危险因素(OR值分别17.063,27.927)。结论镜下血尿+蛋白尿组及单纯蛋白尿组临床及病理改变较重,血清甘油三酯、高血压升高幅度是单纯蛋白尿组病情进展的危险因素。     

IgA肾病合并原发性膜性肾病二例并文献复习

目的探讨IgA肾病合并原发性膜性肾病的临床表现及病理特点.方法分析2例经临床、常规病理检查以及进一步的免疫电镜证实的IgA肾病合并原发性膜性肾病患者的临床表现及病理特点.结果2例患者临床上均可除外继发性肾脏病;免疫电镜证实,IgA沉积于系膜区电子致密物内,IgG沉积于上皮下电子致密物内;2例患者均表现为中～大量的蛋白尿,血尿轻微,肾功能正常.经9个月的随访,肾功能稳定.结论IgA肾病合并原发性膜性肾病较为罕见,临床表现更似于膜性肾病,这两种肾小球疾病合并存在可能对患者的预后并无负面影响.     

Treatment of IgA nephropathy

IgA nephropathy is the most common cause of chronic renal failure among primary glomerulonephritides. During the last decade, there was a remarkable progress in understanding its pathogenesis. A number of therapeutic trials has been published that shed light on its treatment. ACEI and AT1R antagonists (sartans) or their combination represent the cornerstone of therapy of IgA nephropathy. However, this treatment is not given to patients having optimal blood pressure, normal glomerular filtration rate, proteinuria less than 0.3 g/24 h, mild abnormalities in renal biopsy, and stationary course of the disease. The medication is administered in a maximal tolerated dose to patients with active, progressing disease. ACEI and AT1R antagonists are also drugs of the first choice in patients with proteinuric IgA nephropathy. However, if proteinuria does not decrease significantly within 3 months from the beginning of this treatment, administration of glucocorticosteroids is recommended. On the basis of prospective, controlled clinical trials and metaanalyses of other therapeutic studies, it has been concluded that glucocorticosteroids decrease proteinuria and slow down the decline of renal function. A complete remission of proteinuria is the aim of the treatment. The effectiveness of cyclophosphamide in active forms of IgA nephropathy, described in some studies, was not confirmed by metaanalyses. Nevertheless, cyclophosphamide may be effective in some patients with rapidly deteriorating renal function and active morphological findings with cellular extracapillary proliferation.     

IgA Nephropathy with Minimal Change Disease

Background and objectives

Patients with IgA nephropathy typically present with hematuria and subnephrotic proteinuria. Nephrotic syndrome is uncommon in IgA nephropathy, and when present, it is usually associated with severe histologic features, such as endocapillary proliferation, segmental sclerosis, and crescent formation. Rarely, patients with IgA nephropathy present with nephrotic syndrome and only mild mesangial disease. This study sought to better characterize these patients.

Design, setting, participants, & measurements

A retrospective review of cases of IgA nephropathy diagnosed from 2004 to 2011 identified patients with nephrotic range proteinuria and histologically mild IgA nephropathy. Specifically, using the Oxford Classification of IgA Nephropathy, we identified cases that lacked endocapillary proliferation or segmental sclerosis.

Results

The cohort consisted of 17 patients, including 10 men and 15 adults. The median serum creatinine was 0.9 mg/dl (range=0.7–3.1), median 24-hour urine protein was 8.0 g/d (3.0–18.0 g), and 14 patients were fully nephrotic, whereas the remaining 3 patients fulfilled two of three criteria for nephrotic syndrome. Biopsies revealed IgA-dominant or codominant deposits accompanied by mesangial proliferation in 14 patients (82.4%). Electron microscopy showed mesangial deposits and extensive foot process effacement (median=90%). Initial treatment consisted of corticosteroids, although many patients required additional agents to maintain remission status. Over a median follow-up of 20 months (2.2–82 months), 14 patients experienced a complete response, and 3 patients showed a partial response, with a median response time of 2 months (0.5–27 months). At least one relapse of nephrotic syndrome occurred in nine patients (53%). All patients exhibited stable or improved renal function over the follow-up period.

Conclusions

The findings in this cohort and previous studies suggest that rare cases of mild IgA nephropathy with nephrotic range proteinuria exhibit a clinical presentation, biopsy findings, treatment response, and outcome more typical of IgA nephropathy with superimposed minimal change disease. This study favors the view that such cases represent a dual glomerulopathy.