Crescentic glomerulonephritis in children

Data on patients with crescentic glomerulonephritis (>50% glomeruli with crescents), referred to the Hospital for Sick Children during the past 13 years, were reviewed. Thirty patients (13 male, 17 female) aged 3.7–15.7 years (mean 9.5) were evaluated. Initial clinical features included: oedema (24/30), hypertension (19/30), gross haematuria (15/30), oliguria (15/30) and a decreased glomerular filtration rate (GFR<30 ml/min per 1.73 m²) (22/30). Henoch-Schönlein purpura was present in 9 patients, microscopic polyarteritis in 3, polyarteritis nodosa in 1, Wegener's granulomatosis in 1, systemic lupus erythematosus in 1, post-streptococcal glomerulonephritis in 2, mesangiocapillary glomerulonephritis in 7, anti-glomerular basement membrane glomerulonephritis in 2, and 4 were idiopathic. In 10 patients 50%–79% of glomeruli were affected by crescentic changes (group 1) and in the remaining 20, 80% or more (group 2). The crescents were cellular, fibrocellular or fibrous, and the degree of sclerosis was assessed. Patients in both groups were treated with plasma exchange, corticosteroids, anticoagulants, cyclophosphamide and azathioprine in different combinations. On follow-up, 3 patients were dead, 1 was lost to follow-up, 12 were on dialysis/transplant programmes, 4 had a GFR of less than 30 and 10 a GFR of more than 30 ml/min per 1.73 m². In our experience, 50% progressed to end-stage renal failure. The interval between disease onset and start of treatment was a prognostic factor for outcome. Fibrous crescents were associated with a worse outcome than fibrocellular crescents (P<0.05). Outcome was not, however, related to the percentage of glomeruli affected (P>0.05). Although the effectiveness of the individual components of the treatment regimens used was difficult to assess, one-third of patients at the latest follow-up had a GFR of more than 30 ml/min per 1.73 m².     

Acute post-streptococcal glomerulonephritis in an 8-month-old girl

We describe a middle class Sicilian girl who at 8 months of age suffered from acute post-streptococcal glomerulonephritis documented by clinical history, a positive type 12 -haemolytic streptococcus throat culture, a raised anti-sterptolysin O titre and a low C3 rising to normal after 8 weeks.     

HLA-DRB1* alleles in Egyptian children with post-streptococcal acute glomerulonephritis

To investigate the association between HLA-DRB1* alleles and post-streptococcal acute glomerulonephritis (PSAGN) in Egyptian children, 32 unrelated patients with PSAGN and 380 healthy individuals from the same locality were typed for DRB1* alleles using the polymerase chain-reverse hybridization technique. Patients with PSAGN had significantly increased frequency of both DRB1* 03011 (46.9 vs. 19.2% in controls, P  = 0.00025) and DRB1* 1105 (31.1 vs. 15.6% in controls, P = 0.0097) alleles. However, after correction of P values, only the difference for DRB1* 03011 allele remained significant (Pc = 0.025). Their relative risks were significantly high (3.71, confidence interval [CI] = 1.8–7.8, and 3.57, CI = 1.4–8.9 respectively). No significant differences in the frequency of the two alleles were observed among patients with different grades of hypertension or proteinuria. In conclusion, DRB1* 03011, and possibly 1105, alleles confer susceptibility to PSAGN. However, the severity of the disease is not determined by these two alleles.     

Cerebral vasculitis in acute post-streptococcal glomerulonephritis

Neurological complications in acute post-streptococcal glomerulonephritis (APSGN) have been traditionally attributed to hypertensive encephalopathy. A 9-year-old girl with biopsy-documented APSGN developed seizures at a time she was normotensive and biochemically well balanced. Computed tomography of her brain was consistent with vasculitis, a finding which was also clinically supported by apparent vasculitic involvement of other organ systems. All clinical, laboratory and radiological abnormalities resolved with recovery from the APSGN. We suggest that on rare occasions neurological complications in APSGN may result from involvement of the central nervous system in multiorgan transient vasculitis.     

Impact of clinical and histopathological factors on outcome of egyptian patients with crescentic glomerulonephritis

This study included 128 patients with crescentic glomerulonephritis (CGN) having sufficient clinical and histopathological data and were followed up in our institute for a mean period of 34 +/- 28 months. There were 49 males and 79 females with mean age 22.7 +/- 14 years. We studied the effect of clinical, laboratory and histopathological parameters on kidney function and patient survival at the end point of the study. The multivariate analysis revealed that serum creatinine at presentation, nephrotic range proteinuria during the follow up period, percentage of glomeruli affected by crescents, percentage of fibrous crescents and absence of cellular infiltration were significant risk factors affecting the kidney function at termination of the study. The only risk factor which correlated significantly with the patient mortality was the serum creatinine at last follows up.     

Glomerular deposits and hypoalbuminemia in acute post-streptococcal glomerulonephritis

In a search for correlations between glomerular morphology and clinical manifestations in acute post-streptococcal glomerulonephritis, data for 40 biopsied patients were reviewed. A major correlation was observed between severe hypoalbuminemia and the absence of deposits on the paramesangial portion of the glomerular basement membrane. Subepithelial deposits were present on both the capillary loop and paramesangial segments of the basement membrane in 29 patients, whereas in 11 the deposits were present only on the capillary loop. Patients with paramesangial segments devoid of deposits had a mean (±1 SD) nadir serum albumin level of 1.90 (±0.40) g/dl, whereas the mean nadir level in those with deposits in both locations was 2.83 (±0.64) g/dl (P<0.001). Also significant was the difference in paramesangial deposit scores in patients with nadir serum albumin levels ≤2.5 g/dl versus those with levels >2.5 g/dl. The amount of subepithelial deposit on the capillary loop was not significantly different in the two groups, and no correlation was found between loop deposits and serum albumin levels. Except for greater edema and significantly less-frequent gross hematuria in those with absent paramesangial deposits, clinical and laboratory findings for the two groups did not differ. Received September 18, 1997; received in revised form December 8, 1997; accepted January 27, 1998     

Acute glomerulonephritis—changing patterns in Singapore children

This study compared the pattern of acute glomerulonephritis (AGN), a disease known to be influenced by socioeconomic and environmental factors, in children 12 years and under, for the years 1971 and 1985. All children admitted to the four major paediatric departments with haematuria and at least two of the following (oedema, hypertension or oliguria) had an initial diagnosis of AGN. A sample population from one unit from 1980 to 1984 showed that over 70% of these children had evidence of a post-streptococcal aetiology. In 1971, 411 children were admitted with AGN, as compared with only 58 in 1985. The age-sex-race standardized rates for 1971 and 1985 were 0.632 and 0.023/1,000 children 12 years and under, respectively (P<0.001). The mean age of presentation was lower in 1971. Over this period, Singapore saw a threefold rise in the gross national product, accompanied by rapid urbanization. On analysis of the housing pattern, only 31% of the children lived in high-rise apartments in 1971, in contrast with 86% in 1985 (P<0.001). The majority of non-apartment dwellers had homes in runal districts. From an epidemiological perspective, factors which could have led to the highly significant decline in prevalence of AGN in Singapore children included improvement in the socioeconomic status and health care system, and urbanization of the country.     

Complement profiles in acute post-streptococcal glomerulonephritis

It is well known that the hypocomplementemia of acute post-streptococcal glomerulonephritis (APSGN) is characterized by markedly reduced serum concentrations of C3 and moderately reduced levels of C5 and properdin (P). However, the extent of the activation of the classical pathway is not well defined and only limited data are available concerning serum concentrations of terminal components other than C5. In serial serum specimens from 14 children with APSGN, the presence and extent of C4 activation was directly assessed by measurement by rocket immunoelectrophoresis for C4 and C4 (C4d/C4 ratio). Elevated values for this ratio, indicating C4 activation, were found in 8 of 14 of the initial serum specimens, and in some patients the ratio remained elevated for several weeks. In contrast, the serum C4 level was low in only 1 specimen (the specimen with the highest C4d/C4 ratio). However, in 10 patients C4 concentrations within the normal range rose in serial serum specimens. Serum C2 concentrations were depressed in the initial specimens from 5 patients. The concentrations of 13 other complement component and control proteins were also measured in these specimens. Levels of terminal components, other than C5, in the initial serum specimens were normal except for depressed C8 in 3 of 13 patients and depressed C6 in 1 of 14. Of these 4 individuals, 3 had the lowest C3 levels in the study. It is concluded that the classical complement pathway is frequently activated in patients with APSGN early in the condition and that subtle abnormalities in C6 and C8 levels occasionally occur.Supported by National Institutes of Health Grants AM 00777, AI 10386 and RR 05374.     

Expression of Ki-67 antigen using monoclonal antibody MIB-1 in children with post-streptococcal glomerulonephritis

We investigated the expression of Ki-67 antigen using monoclonal antibody MIB-1 in glomeruli and renal tubules of 21 children (18 males, 3 females) with post-streptococcal glomerulonephritis (PSGN). Patients were divided into two groups of active and convalescent phases. The active group (n=13) comprised those patients with clinical manifestations of the acute nephritic syndrome consisting of edema, hypertension, hematuria, and oliguria or those in whom percutaneous renal biopsy was performed within 4 weeks of onset of the symptoms of PSGN and those with serum C3 levels below 55 mg/dl at the time of biopsy. MIB-1 expression was considered positive when staining of endocapillary cells was observed. Of the 21 biopsies, expression of MIB-1 in glomeruli and renal tubules was observed in 14 cases (63.6%) and 20 cases (95.7%), respectively. The expression of MIB-1 in glomeruli of patients with active disease (11/13, 84.6%) was significantly higher than that of the convalescent group (2/8, 25%) (P=0.018). The cellularity in the glomeruli was more severe in the active group than the convalescent group (P=0.0475). There was a significant difference of neutrophilic infiltration in glomeruli between the active group and the convalescent group (P=0.0117). However, glomerular MIB-1 expression did not correlate with the degree of immunofluorescence, the number of neutrophils in the glomeruli on light microscopy, and the presence of subepithelial dense deposits on electron microscopy. There was no significant correlation between MIB-1 and serum C3 level. There was no significant correlation between glomerular MIB-1 expression and creatinine clearance (r=–0.180, P=0.556) or 24-h urinary protein excretion (r=0.434, P=0.137). Our results suggest that the expression of MIB-1 in glomeruli in the active phase in PSGN was higher than in the convalescent phase and expression of glomerular MIB-1 appears to be related to glomerular endocapillary proliferation with exudative lesions in children with PSGN. Received: 20 October 1998 / Revised: 27 July 1999 / Accepted: 30 July 1999     

Acute post-streptococcal glomerulonephritis in a renal allograft

We report a 12-year-old male with acute post-streptococcal glomerulonephritis (APSGN) occurring 1 year after a cadaveric renal transplant. Although recurrent and de novo renal transplant glomerulonephritides have been well described in large series of adult and pediatric renal transplant recipients, post-infectious glomerulonephritis has been rarely reported, and APSGN has never been reported in either adult or pediatric transplant series. We speculate on the reasons for the lack of occurrence of APSGN in renal transplant recipients.     

Changing epidemiology of acute post-streptococcal glomerulonephritis in Northeast Florida: a comparative study

The objective of this study was to review the epidemiological patterns of acute post-streptococcal glomerulonephritis (APSGN) in a pediatric population. We compared incidence, pathogenesis, clinical presentation and outcomes in two APSGN pediatric patient cohorts in northeastern Florida. Retrospective medical records were reviewed of children who were admitted to our institution with a diagnosis of APSGN. Patients admitted between 1999 and 2006 (recent cohort) were compared with a previously reported cohort of patients admitted between 1957 and 1973 (earlier cohort). The recent cohort comprised 45 children with APSGN of whom 87% were male and 13% were female; the median age was 7 years, and there was an average incidence of 6.4 patients per year. The earlier cohort comprised 153 children with APSGN of whom 62% were male and 38% were female; the median age 4.25 years, and there was an average incidence of 10.9 patients per year. The recent cohort was predominantly White-American (62%) and the earlier cohort predominately African American (87%). In the recent cohort, 64% of patients had antecedent pharyngitis, and in the earlier cohort, 66% of patients had antecedent pyoderma. In the recent cohort, 11% of APSGN cases occurred between August to October, and in the earlier cohort, 50% occurred during these months. In the recent cohort, symptoms of APSGN at presentation were milder and all cases recovered, but in the earlier cohort two deaths (1.3% mortality) were reported. In conclusion, there has been a decline in the incidence and severity of APSGN at our institute in recent decades. Pharyngitis has replaced impetigo as the predominant cause of APSGN. The etiological agent for impetigo has changed over the last decade, which has impacted the incidence, racial distribution, seasonal variation and severity of APSGN.     

Histologically confirmed superimposition of post-streptococcal acute glomerulonephritis during IgA nephropathy

We describe a 39-year-old Japanese man with post-streptococcal acute glomerulonephritis (PSAGN) super-imposed on long-term immunoglobulin A nephropathy (IgA-N). The histological findings of the first renal biopsy, done at 21 years of age, revealed mild mesangial proliferative glomerulonephritis with mesangial IgA deposition. Nineteen years later, acute nephritic syndrome with hypocomplementemia and an increasing anti-streptolysin O (ASO) titer developed 2 weeks after the onset of an upper respiratory infection. A second renal biopsy revealed severe segmental endocapillary proliferative and exudative glomerulonephritis, with fibrocellular crescents in about 40% of the glomeruli. Immunofluorescence showed that more C3 than IgA was deposited in the mesangium and that the IgA deposits had decreased. Electron microscopy revealed hump electron-dense deposits on the epithelial side of the glomerular basement membrane. These features were consistent with PSAGN superimposed on IgA-N. After 2 weeks of observation, blood pressure, C3 level, and ASO titer had returned to normal, although the persisting nephritic syndrome necessitated steroid therapy. Six months after the onset of the acute nephritic syndrome, the patient remained asymptomatic, except for microhematuria.     

Anti-neutrophil cytoplasmic antibody-associated glomerulonephritis in children

Two cases of anti-neutrophil cytoplasmic antibody (ANCA)-associated necrotizing and crescentic glomerulonephritis are reported. A 12-year-old girl and a 10-year-old boy presented with polyarthritis, anaemia, haematuria, proteinuria, impaired renal function, anorexia, nausea, marked loss of weight and lethargy. The boy also had a vasculitic rash and anterior uveitis. Both children had diffuse cytoplasmic ANCA identified by indirect immunofluorescence and confirmed by specific enzyme-linked immunosorbent assay. Renal biopsies showed severe focal and segmental necrotizing glomerulonephritis with 100% crescents. They were treated with plasma exchange, prednisolone, cyclophosphamide and heparin. Within 1 month of commencing treatment, both had normal serum creatinine concentrations and ANCA was not detectable. Renal biopsies 6 weeks following commencement of treatment revealed quiescent disease, although up to 40% of glomeruli were sclerosed or had fibrous crescents. Following cessation of cyclophosphamide and heparin after 7 months and reduction in steroid dose, a biopsy at 10 months in the boy revealed quiescent disease, but the girl had recurrent disease associated with reappearance of a low titre of ANCA and small cellular crescents in 20% of the glomeruli. These cases reflect the potential usefulnes of ANCA determination for categorizing paediatric patients, helping in the selection of therapy and as a possible marker of disease activity, similar to the experience in adults.     

Vasculitis associated with septicemia: case report and review of the literature

We report an unusual case in which infectious endocarditis presented systemic vasculitis and glomerulonephritis as the initial manifestation of the disease. The patient was a 16-year-old girl with congenital cyanotic heart disease who presented with skin purpura, proteinuria, and hematuria. She had hypergammaglobulinemia, cryoglobulinemia, and positive circulating immune complexes. Renal biopsy revealed crescentic glomerulonephritis. Her serum C3 level, which was initially normal, became decreased, and prednisolone and azathioprine were administered with a tentative diagnosis of systemic lupus erythematosus (SLE). Soon after, she developed fever and renal failure. Blood culture grew Streptococcus pyogenes, and the diagnosis of infectious endocarditis was made. Eight cases of systemic vasculitis and glomerulonephritis associated with infectious endocarditis have been described in the literature. Infectious endocarditis should be included in the differential diagnosis of systemic vasculitis and glomerulonephritis. Received: 19 March 2001 / Revised: 14 August 2001 / Accepted: 21 August 2001     

Serum complement levels before and after the onset of acute post-streptococcal glomerulonephritis. A case report

Low serum C3, properdin, and C5 levels found in the acute stage of acute post-streptococcal glomerulonephritis (APSGN) indicate the presence of aggressive complement activation. We followed serum complement component levels in a child hospitalized with erysipelas who developed APSGN on the 2nd hospital day. Her initial serum sample, obtained prior to the clinical onset of nephritis, had a low properdin level and normal C3 and C5 levels despite the presence of C3 splitting activity. Two days later she developed gross hematuria and subsequent sera contained low C3, properdin, and C5 levels, as is usual in APSGN. These observations suggest that complement activation, predominantly through the alternative pathway, precedes the clinical onset of APSGN.     

Clinical spectrum and outcome of crescentic glomerulonephritis in children in developing countries

Crescentic glomerulonephritis (CsGN) is an uncommon entity in children. This prospective study was conducted to evaluate the aetiology, clinical spectrum and outcome in children with crescentic glomerulonephritis. The single-centre prospective study comprised of 22 children with biopsy proven CsGN who had been referred to our institute over the period January 2000 to December 2005. These patients were subjected to detailed clinical and biochemical examinations. The diagnosis of underlying renal disease was based on various criteria, including the clinical picture, serology and histopathology. The patients received intravenous methyl prednisolone, oral steroid treatment, and oral cyclophosphamide with or without plasmapheresis. All patients received supportive care, including control of hypertension and oedema and supportive management of renal insufficiency. During this 5-year period, CsGN accounted for 5.1% of all biopsies done in children. The mean age was 12.27 years (range 4 years to 18 years). There were eight girls and 14 boys. The mean duration of symptoms prior to referral was 2.47 months (range 5 days to 21 months). Aetiology was immune complex in 19 cases, anti-glomerular basement membrane (anti-GBM) antibody disease in two cases and pauci-immune (Wegener’s granulomatosis) in one case. The percentage of crescents ranged from 50% to 100% (mean 70.6%). Twenty-one out of 22 (95.5%) children in our series had hypertension at presentation that required treatment with antihypertensive medications. The serum creatinine level at presentation ranged from 1.5 mg/dl to 11.4 mg/dl (mean 5.5 mg/dl). Of the 22 children, two were lost to follow-up, while the mean follow-up period of the rest of the 20 children was 8.13 months (range 1 month to 43 months). At the last follow-up of the 22 children, ten had stage 5 chronic kidney disease (CKD) and three had stage 4 CKD, while seven children had a calculated glomerular filtration rate (GFR) of >60 ml/min per 1.73 m² body surface area. Persistent proteinuria was seen on follow-up in the majority [13/20 (65%)] of patients. The outcome of CsGN in children continues to be poor, in our experience, due to delayed referral and delayed diagnosis. This was correlated histologically by the presence of fibrocellular crescents in the majority of our patient. Thus CsGN should be treated as a renal emergency. A greater awareness of this disease needs to be created amongst the referring paediatricians in developing countries to facilitate early diagnosis and prompt treatment.     

Increased chymase-positive mast cells in children with crescentic glomerulonephritis

Mast cell-derived chymase is an angiotensin II-forming enzyme that appears to be involved in tubulointerstitial fibrosis in the kidneys. Previous studies have shown that the level of chymase increases in grafted kidneys after rejection and in adult patients with diabetic nephropathy. However, the significance of chymase in children with renal diseases has not been investigated. Using immunohistochemistry, we have investigated chymase expression in biopsy samples of renal tissue from 104 children with kidney diseases, including rapidly progressive crescentic glomerulonephritis (n?=?3), diabetic nephropathy (n?=?2), allografted kidney (n?=?3), membranoproliferative glomerulonephritis (n?=?6), immunoglobulin A nephropathy (n?=?33) and Henoch–Schönlein purpura nephritis (n?=?23). Increased numbers of chymase-positive mast cells were observed in the renal cortex of all three patients with crescentic glomerulonephritis (mean 26.0/mm²; range 19.3–36.8/mm²). Chymase-positive cells were also observed in the renal biopsy of an allografted kidney and in those from children with diabetic nephropathy. The mean number of chymase-positive cells in renal tissue samples characterized by each renal disease was significantly correlated with the mean intensity of the interstitial fibrosis in that same tissue sample (Spearman’s rank correlation test p?=?0.0013; rank correlation coefficient ?0.84). These findings suggest that mast cell-derived chymase plays an important role in juvenile crescentic glomerulonephritis.     

骨调素对巨噬细胞在新月体肾炎肾脏组织局部浸润的影响

目的观察骨调素（ＯＰＮ）在大鼠实验性新月体肾炎肾脏组织中的表达及功能性抑制ＯＰＮ的活性对巨噬细胞在肾脏局部浸润的影响。方法ＯＰＮ在肾脏组织蛋白和基因水平的表达分别应用免疫组化双标记及原位杂交技术。结果在实验性新月体肾炎肾脏组织内ＯＰＮ的表达明显升高，并与肾脏局部巨噬细胞的浸润、肾脏病理损害程度及肾功能的下降明显相关。应用抗ＯＰＮ抗体治疗以后可显著抑制ＯＰＮ在肾脏组织的表达，同时巨噬细胞在肾脏组织局部的浸润也明显减少，肾脏病理损害减轻、肾功能明显改善。结论ＯＰＮ的高表达是实验性新月体肾炎发病过程中巨噬细胞在肾脏组织局部浸润的重要介导因子，抑制ＯＰＮ的表达和功能可显著抑制肾脏局部巨噬细胞的聚集及改善肾功能。     

Clinicopathological features and prognosis of Chinese patients with acute post-streptococcal glomerulonephritis

Aim: To investigate clinicopathological and prognostic differences between adults and children with acute post‐streptococcal glomerulonephritis (APSGN). Methods: A retrospective case series of 112 patients with APSGN was undertaken. Patients were divided into two groups according to age: adults aged more than 17 years and children aged less than 15 years. Results: The incidence of APSGN, especially in adults, has decreased in the past three decades. Children have had a higher incidence of macroscopic haematuria than adults (58.3% vs 32.7%, P < 0.05). Laboratory test showed that red blood cell count of urine sediment in children was more significant. On light microscopy, adults had more global glomerulosclerosis, tubular basement membrane thickening, tubular atrophy and interstitial fibrosis, while children had more glomerular infiltrating neutrophils and monocytes and cellular casts. Immunofluorescence microscopy showed that classical staining was seen more in children. The short‐term prognoses were good in both children and adults. But the recovery rate of proteinuria in children was faster than that in adults. Conclusion: Adults with APSGN had similar clinical features as children except that children had more significant haematuria. On pathology, adults had more outstanding chronic changes by light microscopy and more untypical staining by immunofluorescence.