Active and chronic phases of Berger's disease (IgA nephropathy)

Berger's disease, or IgA nephropathy, is generally considered as pursuing a chronic course, often with recurrent attacks of gross hematuria or persistent microscopic hematuria. However, little attention has been paid to the acute changes that may accompany this nephropathy, and there are few reports of follow-up renal biopsy studies in these patients. We have had the opportunity to study two patients with Berger's disease (IgA nephropathy) in whom initial and follow-up renal biopsy studies were available. Both of these patients presented clinically with gross hematuria and moderately heavy proteinuria. In both cases, the initial renal biopsy disclosed diffuse mesangial proliferation associated with crescent formation, while follow-up biopsy disclosed only mild mesangial proliferation and no crescents. In one case electron microscopy revealed prominent subendothelial and small mesangial deposits in the initial biopsy, which became almost solely large mesangial in the second biopsy. The other case demonstrated only mesangial deposits in both biopsies.     

IgA肾病伴部分性新月体形成的临床病理分析

目的：探讨原发性IgA肾病伴部分性新月体形成的临床和病理特点。方法：选取79例经肾活检确诊伴部分性新月体形成IgA肾病患者,分析其临床和病理特点,并根据新月体形成所累及肾小球的比例分组：≥10%为A组,31例;≤10%为B组,48例。结果：（1）临床表现：79例均有血尿＋蛋白尿,蛋白尿〉1g/24h者48例（60.8%）;两组比较,A组蛋白尿〉1g/24h28例（89.3%）,B组蛋白尿〉1g/24h20例（41.7%）,A组大量蛋白尿、肉眼血尿、高血压、肾衰竭发生率均高于B组（P〈0.05）。（2）病理表现：79例新月体形成累及肾小球3.3%～29.0%,均以细胞性为主,几乎均有肾小球硬化、内皮细胞及系膜细胞增生、球囊黏连、灶性肾小管萎缩、以及炎性细胞浸润;两组比较A组中、重度系膜细胞及内皮细胞增生、炎性细胞浸润,细胞新月体所占比例均较B组明显;病理改变硬化肾小球占55例（69.6%）。结论：IgA肾病伴部分性新月体形成患者临床均有血尿＋蛋白尿,尤其大量蛋白尿;病理改变以局灶节段性肾小球硬化常见;炎性细胞浸润、内皮细胞及系膜细胞增生等活动性病变易见并影响新月体形成;新月体的多少及纤维化程度影响临床病理表现,≥10%较≤10%严重。     

IgA nephropathy. Evaluation of prognostic factors in patients with moderate disease

Previous studies of IgA nephropathy have demonstrated a number of prognostically significant clinical and pathological factors in groups of patients with the full histological spectrum of the disease. Whether these factors can be applied to a group of IgA nephropathy patients with disease of moderate degree is unknown. Forty patients (9 females, 31 males) with grade III IgA nephropathy (no more than 10% obsolete glomeruli and little or no interstitial fibrosis) were evaluated with respect to age, sex, degree of proteinuria, history of recurrent gross hematuria, hypertension, extent and type of segmental glomerulosclerosis, demonstration of IgG and/or IgM in deposits, presence of peripheral capillary deposits, whether or not there were crescents, and extent of vascular sclerosis. The mean age was 29.6 +/- (SD) 13.1 years. Sixteen patients presented with recurrent gross hematuria, and 24 had microscopic hematuria and proteinuria as the initial manifestation. Hypertension was seen in 5 patients. The mean serum creatinine concentration was 1.09 +/- 0.47 mg/dl (96.4 +/- 41.5 mumol/l), and the mean 24-hour urinary protein was 1.5 +/- 1.3 g. Nine patients had proteinuria greater than or equal to 2.0 g/24 h. Thirty-two patients demonstrated segmental glomerulosclerosis in their biopsies, 13 of which had more than 10% of the glomeruli involved. Seven patients developed established renal failure (Cr greater than or equal to 2.0 mg/dl; 176.8 mumol/l). The 60-and 100-month renal survival rates were 96 and 52%. Life table analysis disclosed that only the degree of proteinuria (greater than or equal to 2.0 g/24 h; p less than 0.05) and the extent of segmental glomerulosclerosis (p less than 0.025) were of prognostic significance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Factors predicting progression of IgA nephropathies

The difficulties in defining the natural history of primary IgA nephropathy (IgAN) depend upon the pre-selection of patients for renal biopsy, a true individual variability - ranging from asymptomatic to rapidly progressive forms - as well as the use of different classifications of the renal lesions and statistical analyses sometimes carrying incorrect modalities. Long-term natural history studies have demonstrated that the rate of progression has an extremely wide range, from 5 to 25% after 10 years and 25-50% at 20 years, and complete remission is reported as well in 5 to 30% of cases. A geographic variability has been confirmed in a tri-continental study, explainable only partly by the earlier referral. Among the factors predicting progression, the more frequent in cohorts showing worse actuarial survival at 10 years are those associated with the advanced phases of renal damage, as increased creatinine level, arterial hypertension and nephrotic range proteinuria. A multivariate statistical approach showed the relevance of proteinuria during follow-up (percent duration of massive proteinuria or proteinuria at 1 year) more than proteinuria at the onset. Mean blood pressure value (MAP) and proteinuria during follow-up were independent predictors of end-stage CKD. Note the predictive value of severe microscopic hematuria in several studies. As far as histological features are concerned, strong independent predictors of progression at Cox multivariate analysis are the severity of glomerular sclerosis and interstitial fibrosis. The presence of crescents was a risk factor in almost all studies at univariate analysis, but did not maintain a significant predictor value at multivariate analysis. Conversely the association between crescents and tuft adhesions, possibly resulting from previous segmental necrosis, was found to be a significant risk factor. The extent of mesangial proliferation and parietal expansion of deposits was not significantly associated to unfavourable prognosis at multivariate analysis. The analysis of risk factors for progression of IgAN related to Henoch-Schoenlein purpura (HSP) failed to demonstrate any prognostic value for the presence and severity of extra-renal signs of vasculitis or presence of triggering factors. At multivariate Cox analysis, age and mean proteinuria during follow-up were powerful independent prognostic predictors. Proteinuria at baseline was not significantly related to renal progression, nor were hypertension or impaired renal function at onset. It is of interest that data at onset and at renal biopsy (renal function impairment, hypertension, nephrotic-range proteinuira) were not significantly related with renal detrimental progression. Neither had prognostic value the finding of crescents involving up to 75% of glomeruli.     

IgA nephropathy in children: significance of glomerular basement membrane deposition of IgA

Seventeen children with IgA nephropathy were grouped according to the absence (group I, n = 10) or presence (group II, n = 7) of glomerular basement membrane (GBM) deposition of IgA to determine whether GBM deposition of IgA correlated with laboratory or pathologic data at diagnosis or clinical status at follow-up. Children in group II had significantly (p less than 0.01) more proteinuria at diagnosis than children in group I. The percentage of glomeruli demonstrating crescent formation was significantly (p less than 0.05) higher in group II biopsies. Chronic changes of fibrous crescents, segmental sclerosis, global obsolescence, tubular atrophy, and interstitial fibrosis were also significantly (p less than 0.001) more common in group II biopsies. After a mean follow-up period of 2 years, all children in group II have persistent proteinuria of more than 1 g/24 h, and 3 of 5 have renal insufficiency (2 require dialysis). In contrast, 2 of 9 group I children have proteinuria exceeding 1 g/24 h, and only 1 has renal insufficiency. We conclude that, as compared to children with IgA localized to the mesangium, children with IgA nephropathy and GBM deposition of IgA have a higher urinary protein excretion at the time of diagnosis, more severe histologic alterations including a greater percentage of glomeruli demonstrating crescent formation, more chronic changes of segmental or global sclerosis, tubular atrophy, and interstitial fibrosis. Such children usually have persistent proteinuria and are more likely to develop progressive renal disease.     

Clinicopathological correlations in nephrotic children with IgA nephropathy

Background. The prognostic significance of nephrotic syndrome (NS) in children with IgA nephropathy (IgAN) is unclear. Methods. NS was found in eight children with IgAN (mean onset age, 9.3 years). The clinicopathological findings of these eight children were investigated. Results. Five patients presented with macroscopic hematuria, while the remaining three were discovered in a school urinary screening program or by chance urinalysis. Six patients developed NS at the onset, and two developed NS later in the course of IgAN. All patients were treated with corticosteroids. At the end of follow-up, heavy proteinuria persisted in four children, one of whom had renal dysfunction at the onset of NS and developed end-stage renal failure, and two of whom developed NS after the onset of IgAN. Proteinuria decreased to less than 1 g/day 3 months after NS in four patients, two of whom showed disappearance of proteinuria afterward. Renal biopsy specimens revealed mesangial proliferation and crescent formation in all patients. The degree of persisting proteinuria was correlated with the presence of glomerular sclerosis, fibrous crescents, tubulo-interstitial changes on light microscopy, and depositions of C3 on immunofluorescence microscopy. Conclusions. Children who developed NS after the onset of IgAN developed renal dysfunction; the prognosis of those who showed chronic histopathological changes on renal biopsy specimens was poor, even in these young children. Received: April 17, 2000 / Accepted: July 4, 2000     

Mesangial changes in IgA nephropathy in children

The mesangial changes in 92 renal biopsy specimens from 81 children with IgA nephropathy were correlated with the clinical and the other renal biopsy findings. Three types of mesangial changes were identified: mesangial hypercellularity was predominant compared with the increase in matrix in 34 biopsy specimens (type A), the degrees of mesangial hypercellularity and matrix increase were similar in 36 (type B) and matrix increase was predominant in 22 (type C). The interval between the onset of disease and biopsy was significantly shorter in biopsies with type A mesangial changes (P less than 0.01) and significantly longer in those with type C (P less than 0.01). Serial pathologic observations revealed that predominant mesangial hypercellularity was almost exclusively seen in the initial biopsy but predominant matrix increase was usually seen in the follow-up biopsy. The percentage of glomeruli showing sclerosis was significantly higher in biopsies with type C mesangial changes (P less than 0.05). At the latest follow-up, 58% of the patients showing type A and 57% showing type B lost their proteinuria, whereas only 9% showing type C lost their proteinuria (P less than 0.01). These findings suggest that predominant mesangial hypercellularity is characteristic of the early lesion of childhood IgA nephropathy, and progression of disease leads to gradual decrease of mesangial cellularity and increase of matrix with sclerosis.     

伴有新月体形成的原发性IgA肾病的临床与病理特点及预后分析

目的观察伴有新月体形成的原发性IgA肾病的临床、病理特点,分析其对激素及环磷酰胺治疗的反应。 方法收集包头医学院第一附属医院1997年8月至2015年04月收治的80例经肾活检确诊为原发性IgA肾病并伴新月体形成的患者,并依据新月体累及的肾小球比例进行分组,新月体占受累肾小球比例≥50% (A组) 24例;新月体累及的肾小球比例<50%(B组) 56例。肾小球系膜增生、肾小管间质病变采用R.Katafuchi标准积分量化。对两组的临床及病理特点进行比较。治疗方案：将A、B两组再分为单纯糖皮质激素(激素)治疗组,激素＋环磷酰胺治疗组,分别比较不同治疗方案对各组的疗效。A、B组各有24例患者接受了随访。应用SPSS软件进行统计学分析。 结果①临床方面：32例(40%)患者有镜下血尿＋蛋白尿,76例(95%)患者尿蛋白≥2 g/24 h,32例(40%)患者有肉眼血尿;水肿、高血压、肾功能异常者超过半数。A组尿蛋白量及血清肌酐明显高于B组(t＝1.890,t＝2.570; P<0.05),血清白蛋白及肾小球滤过率明显低于B组(t＝2.681, t＝3.014;P<0.05)。②病理方面：所有受累肾小球的新月体面积百分比为5.92%～88.9%,其中A组为52.6%～88.9%, B组为5.92%～48.9%;与B组比较A组肾小管间质损害更严重,两组比较差异有统计学(P<0.05)。③治疗情况：A组及B组经激素或激素＋环磷酰胺治疗后,尿蛋白定量均明显减少(P<0.05) ;单纯激素治疗后A组血清肌酐较治疗前有明显下降(t＝3.243,P<0.05)。随访2～4年时,A组8例患者出现血清肌酐升高,达透析指征,1例死亡;B组2例患者出现血清肌酐升高(1例原有轻度升高,1例新出现血清肌酐升高)。 结论IgA肾病患者随着新月体占受累肾小球比例的增加,肾小管间质病理损害及临床表现亦逐渐加重且预后不佳;激素治疗可减少伴有大新月体形成的原发性IgA肾病的蛋白尿并有可能改善其肾功能。     

Recurrence of IgA nephropathy with crescents in kidney transplants

Crescentic IgA nephropathy is an uncommon finding in native kidneys (3%-5%) and in renal transplants. This study was performed to determine the frequency of relapsing crescentic IgA nephropathy after kidney transplantation. Over a 15-year period, 42 patients (25 men, 17 women) of age range 17 to 59 years with biopsy-proven IgA nephropathy in their native kidneys were entered into this retrospective study, because they had undergone kidney transplantation and had sequential allograft biopsies during their follow-up. Mean follow-up after transplantation was 8.9 years (range, 1-15 years). In their native kidneys, 5 patients (12%) had more than 20% crescents, and only 2 (5%) had more than 50% of glomeruli involved. As expected, 52.4% of recipients showed recurrent mesangial IgA deposits in their kidney grafts. The 2 patients with diffuse crescentic IgA nephropathy in their native kidneys experienced acute graft dysfunction at 15 and 47 months. Graft biopsy showed recurrent IgA deposits with cellular crescents in 30% and 20% of glomeruli, respectively. Despite corticosteroid pulse therapy, graft failures occurred 2 and 27 months later. No crescentic proliferation was observed during follow-up in any other case. Only 5 other grafts failed because of chronic allograft nephropathy, without any relationship to the relapse of IgA deposits. These data suggested for the first time that only diffuse crescentic IgA nephropathy in the native kidneys was associated with the occurrence of crescents in the kidney transplants, a finding that raises the possibility of a particular subgroup of IgA nephropathies.     

Loss of renal graft due to recurrent IgA nephropathy with rapidly progressive course: an unusual clinical evolution

Recurrence of IgA nephropathy following renal transplantation has been described in 40-50% of patients, and it usually has a good outcome. We present the case of a 54-year-old man with IgA nephropathy who developed terminal renal failure in 1985, 3 years after the onset of the disease. In March 1986 he received a cadaveric renal allograft following treatment with ciclosporin and steroids. Eight months later he developed microhaematuria and proteinuria and 10 months later he developed acute nephritic syndrome and rapidly progressive renal failure. Renal biopsy disclosed an IgA nephropathy with epithelial crescents in 60% of glomeruli. Treatment with plasma exchange and cyclophosphamide was unsuccessful and the patient lost his graft and returned to regular haemodialysis 15 months after renal transplantation.     

Histological alterations in renal specimens as indicators of prognosis of IgA nephropathy.

A retrospective clinicopathological study of 66 patients with IgA nephropathy was undertaken to determine the prognostic significance of various renal histopathological alterations and clinical parameters. At the latest follow-up, after a period of 60 to 72 months following biopsy, 18 patients had serum creatinine concentration above 1.8 mg/dl. When the entire patients were evaluated as a whole, the extents of interstitial broadening and glomerular sclerosis were correlated significantly with the final status of renal function: proteinuria of more than 1.0 g per day and mildly impaired renal function at the time of biopsy were also associated with unfavourable outcome. However, when the patients with initially normal renal function, i.e. serum creatinine level below 1.2 mg/dl, were evaluated separately, the initial amount of proteinuria, but none of the other parameters, had a prognostic significance in the subsequent course of renal function. These findings suggest that proteinuria of more than 1.0 g per day as an early event often indicates the progression of IgA nephropathy, and lead to a postulation that renal histopathological changes become more significant prognostic indicators in the relatively advanced stage of the disease.     

Renal survival rate of IgA nephropathy

In an attempt to identify prognostic indicators in IgA nephropathy, we evaluated the relationship between clinical and histological findings and changes in renal function in 81 patients with IgA nephropathy whose creatinine clearance was more than 80 ml/min at the time of renal biopsy. The incidence of patients whose creatinine clearance decreased to less than 60 ml/min during the follow-up period was calculated with the life table method to designate the renal survival rate. This rate was compared according to the clinical and histological findings at the time of renal biopsy. In conclusion, a statistically significant decrease in the renal survival rate was observed in patients with proteinuria of more than 1.0 g/day, hypertension, severe diffuse proliferative glomerulonephritis, diffuse proliferative glomerulonephritis with focal crescents and glomerular deposition of IgM and/or fibrinogen-related antigen.     

Effects of methylprednisolone pulse therapy on progressive IgA nephropathy]

In order to estimate the effects of methylprednisolone pulse therapy on progressive IgA nephropathy, clinical parameters in eight patients with the disease were compared between before and after the therapy. In this study progressive IgA nephropathy was defined as follows; 24 hour urinary protein excretion was (++) or more and renal biopsy carried out just before the therapy revealed crescents, inevitably including cellular crescents, in 10% or more glomeruli observed. Methylprednisolone 1000 mg a day was intravenously administered for three consecutive days and the therapy was repeated with an interval of 4 days. The additional third course was given in two patients, in whom significant decrease in urinary protein had not been obtained after the original two courses of the therapy. Oral prednisolone 20 mg a day started simultaneously was tapered one month later to maintenance daily doses of 5-10 mg. After the pulse therapy urinary protein excretion was significantly decreased in every patient with a mean decrease from 2.3 +/- 0.5 (0.8-5.5)g to 1.1 +/- 0.3 (0-2.8)g (p less than 0.05). Glomerular filtration rate (GFR) was increased from 83 +/- 11 (31-115) ml/min to 96 +/- 10 (44-130) ml/min (p less than 0.05). In the initial biopsy crescents were observed in 25 +/- 7 (19-57)% of glomeruli observed and 20-100% of these were composed of cellular crescents. Complete loss of cellular crescents in 6 patients and a marked decrease from 73% to 33% in another were demonstrated by the second biopsies performed after the pulse therapy. These results suggested that the methylprednisolone pulse therapy significantly reduced urinary protein excretion and improved renal function through suppression of new crescent formation as well as transformation of cellular crescents to fibrocellular or fibrous crescents.     

Long-standing spontaneous clinical remission and glomerular improvement in primary IgA nephropathy (Berger's disease)

Of the 244 cases of IgA nephropathy diagnosed at Necker Hospital before 1981, 9 patients (3.7%) developed spontaneous clinical remission of long duration. Three of these 9 patients presented with gross hematuria, while in the others the disease was discovered by the finding of proteinuria at routine urinalysis. During the disease course 5 patients had recurrent episodes of gross hematuria, lasting several years in 4. At the time of the first biopsy all patients had hematuria and permanent proteinuria. In 1 patient, renal biopsy showed only an increase in mesangial matrix while in the others segmentary lesions were observed, affecting less than 30% of the glomeruli in 6. Diffuse mesangial deposits of IgA were present in all. During the follow-up, proteinuria and microscopic hematuria gradually decreased and completely disappeared within 4-14 years after the onset of the disease. A repeat biopsy performed during remission in 4 patients showed, in 3, an improvement of glomerular lesions and a significant decrease in IgA mesangial deposits in parallel with clinical recovery. As in other types of 'primary' glomerulonephritis, these data indicate that the initial disorder in IgA nephropathy may be spontaneously reversible even after a long course of the disease.     

Renal disease in pregnancy. Three controversial areas: mesangial IgA nephropathy, focal glomerular sclerosis (focal and segmental hyalinosis and sclerosis), and reflux nephropathy

Whether gestation has adverse effects on the course of renal disease is controversial. Three diseases regarding which conflicting opinions are especially noteworthy are IgA nephropathy, focal and segmental hyalinosis and sclerosis, and reflux nephropathy. We analyzed 102 pregnancies in 65 women with IgA nephropathy, noting hypertension in 63% of the gestations (severe in 18%), decreases in renal function in 22%, and biopsy evidence demonstrating a significantly greater amount of glomerular proliferation and crescents as well as focal and segmental hyalinosis and sclerosis when the renal histology from women who were pregnant and those who had never conceived were compared. Our experience with glomerular sclerosis is limited to 28 gestations in 15 patients, but the clinical findings resemble those of women with IgA nephropathy who conceived. Finally, we analyzed 227 pregnancies in 95 women with normal renal function and reflux nephropathy comparing results to 118 gestations in 42 patients with evidence of dysfunction (serum creatinine SCr greater than 1.25 mg/dL). Women with preserved function had good outcomes in general, whereas hypertension (36%) and an accelerated decline in function (8%) were observed in the groups that had moderate renal insufficiency in the initial stage of pregnancy. Increased proteinuria was the best predictor of progression of reflux nephropathy in both groups.     

The spectrum of acute renal failure in IgA nephropathy

Background: Acute renal failure rarely complicates the course of IgA nephropathy. In this study, we have tried to define the mode of presentation, the spectrum of morphology, and the prognostic factors for renal outcome. Methods: Twenty patients with biopsy-proven IgA nephropathy who developed acute renal failure were identified from 2000 to 2009 at a medical center in Taiwan. The patients' records were retrospectively reviewed with respect to clinical presentation, morphology of renal biopsy, and outcomes. Results: On histology, glomerular crescents were present in 11 patients (55%), acute tubular necrosis was identified in 11 patients (55%), acute interstitial nephritis was seen in 4 patients (20%), and extensive tubular red blood cell casts were present in 4 patients (20%). At the end of follow-up, 2 patients (10%) had died, 11 patients (55%) were in remission, and 7 patients (35%) developed end-stage renal disease. The prognostic factors for renal outcome were peak serum creatinine, dialysis support requirement, morphology (prominent glomerular/tubular injury), percentage of glomeruli affected by crescents, and interstitial infiltration (p = 0.04, <0.001, 0.013, 0.05, 0.02, respectively). Conclusions: Our findings suggested that there were four pathogenic mechanisms involved in IgA nephropathy with acute renal failure including (1) crescentic IgA nephropathy; (2) acute tubular necrosis associated with microhematuria and red blood cell casts occluding tubules; (3) acute tubular necrosis not related to microhematuria; and (4) acute interstitial nephritis, apparently induced by drugs. In general, patients with prominent tubular injury had a much higher remission rate than patients with prominent glomerular injury.     

Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy

Discriminant analysis of clinical markers before renal biopsy in patients with IgA nephropathy is described. Sixty eight patients with IgA nephropathy (IgA nephropathy group) and 66 patients with other chronic glomerulonephritis (non-IgA nephropathy group) were examined. The discriminant analysis was applied to separate those two groups by using twenty clinical parameters as well as binding capacity of serum IgA to the glomeruli of renal specimens. Binding of serum IgA of patients to the glomeruli obtained from patients with IgA nephropathy was performed using avidin-biotin immunofluorescence. Among twenty clinical markers, the levels of serum IgA and creatinine, and degree of microhematuria in IgA nephropathy group were significantly higher than those in non-IgA nephropathy group Furthermore, the positive incidence of serum IgA binding of IgA nephropathy group was significantly higher than that of serum IgA binding of non-IgA nephropathy group. The correct classification rate were 79.10% using five clinical markers including serum IgA, microhematuria, serum C4, quantitation of proteinuria and degree of proteinuria. It is indicated that the levels of serum IgA and the binding of serum IgA to the glomeruli were considered to be major markers for clinical diagnosis of patients with IgA nephropathy It was concluded that the discriminant analysis before renal biopsy was useful for diagnosis of IgA nephropathy.     

贫血加重IgA肾病患者的临床和病理改变

目的 分析IgA肾病合并贫血患者的临床病理特征.方法 收集经肾活检确诊的IgA肾病患者临床资料409例,按照贫血与否分为非贫血组和贫血组,回顾性分析两组患者的临床和病理资料.结果 与非贫血组比较,贫血组患者的肾小球损伤和肾小管间质萎缩程度较重、24 h尿蛋白增多和eGFR降低.Spearman相关分析结果显示,血红蛋白、eGFR与肾脏病理损伤呈负相关(P＜0.05),血尿酸、24h尿蛋白与肾脏病理损伤呈正相关(P＜0.05).多因素Logistic回归分析发现贫血是肾小管间质萎缩的独立危险因素.结论 IgA肾病合并贫血患者的临床和病理损伤重于IgA肾病非贫血的患者,贫血参与IgA肾病的进展.     

Superimposition of poststreptococcal acute glomerulonephritis on the course of IgA nephropathy

A 17-year-old male with poststreptococcal acute glomerulonephritis (PSAGN) superimposed on the course of IgA nephropathy is presented. The histological findings of the first renal biopsy showed mild IgA nephropathy with a mesangial deposition of IgA and C3. Eighteen months later, acute nephritic syndrome with hypocomplementemia and rising antihyaluronidase titer occurred 10 days following the onset of an upper respiratory infection. The second renal biopsy revealed severe diffuse endocapillary proliferative and exudative glomerulonephritis with cellular crescents in 70% of the glomeruli. Immunofluorescence showed granular staining of C3 alone along the capillary walls. The pre-existing IgA deposits had disappeared. Typical 'humps' were observed by electron microscopy. The symptoms were gradually resolved by intensive steroid and anticoagulant therapy. Five months after the episode of acute nephritic syndrome, the patient was clear of symptoms except for mild proteinuria and hematuria. The third renal biopsy at that time showed morphologic changes similar to those of the first renal biopsy with mild mesangial IgA deposits.     

Treatment of severe IgA nephropathy in children

We treated ten children with severe IgA nephropathy (IgAN) [proteinuria > 1g/day, hypertension, renal insufficiency, segmental sclerosis, crescent formation and/or glomerular basement membrane (GBM) deposition of IgA] with prednisone and azathioprine for 1 year. Following the year of therapy, seven of the ten children underwent a repeat kidney biopsy. All biopsies were scored for activity (percentage of glomeruli demonstrating crescent formation, degree of mesangial proliferation and interstitial infiltrate; maximum score = 9) and chronicity (percentage of glomeruli demonstrating fibrous crescents, segmental sclerosis, global sclerosis, and degree of tubular atrophy and interstitial fibrosis; maximum score = 12). After 1 year of therapy, the protein excretion of all the children decreased significantly (P<0.01) from 4052±3190 mg/day to 1692±1634 mg/day. The activity score decreased significantly (P<0.01) from 4.35±0.94 prior to therapy to 2.28±0.75 after therapy while the chronicity score was unchanged (5.42±1.7 vs 5.85±2.0). The percentage of glomeruli demonstrating cellular crescents decreased (P<0.05) from 21.2±21.7% prior to therapy to 0.94±2.4% after therapy. Mesangial deposition of IgA persisted but GBM deposition of IgA was less prominent after therapy. During the follow-up period (mean 2.6 years, range 9 months–7.5 years), one child required brief retreatment for biopsy-confirmed recurrence of active disease, two children have developed renal insufficiency due to progressive scarring in the absence of inflammation, while the remaining seven are stable. We suggest that treatment with prednisone and azathioprine may be beneficial in children with severe IgAN and that a controlled clinical trial is warranted.