Minor Urinary Abnormalities Research Articles

ANCA-associated nephritis without crescent formation has atypical clinicopathological features: a multicenter retrospective study

Although crescentic glomerulonephritis is a hallmark of ANCA-associated nephritis, the clinicopathological features of ANCA-associated nephritis without crescent formation remain to be elucidated. We enrolled 146 Japanese ANCA-associated vasculitis (AAV) patients subjected to renal biopsy in 16 hospitals from 2001 to 2018, and compared those with and without crescent formation (C + and C- groups). The primary endpoint was end-stage renal disease (ESRD) and/or death. C- group comprised 25 (17.1%) subjects. They had better renal function at the time of renal biopsy [estimated glomerular filtration rate (eGFR); median 41.7 vs 27.5ml/min/1.73m2, p < 0.01] with minor urinary abnormalities but had a higher serum C-reactive protein level (8.8 vs 5.4mg/dl, p = 0.01) and frequency of extra-renal lesions of AAV (76.0% vs 48.8%, p = 0.02) than C + group. Pathologically, C- group had a higher frequency of arteritis (40.0% vs 16.5%, p < 0.01). Kaplan-Meier method with log-rank tests showed no significant difference in renal and life prognosis combined, regardless of crescent formation. Multivariate Cox regression analysis revealed baseline eGFR, sclerotic class, and extra-renal lesions to be risk factors of ESRD and death combined. Competing risk analysis showed baseline eGFR and sclerotic class to be associated with ESRD, whereas baseline eGFR and extra-renal lesions were associated with death. ANCA-associated nephritis without crescent formation had different clinicopathological features from those with crescent formation, suggesting an atypical subtype of ANCA-associated nephritis. Despite the better renal function at the time of renal biopsy, these results suggest that this subtype requires especially careful attention, especially in the presence of extra-renal involvement.

Complement activation is associated with crescent formation in IgA nephropathy.

IgA nephropathy (IgAN) is common chronic glomerulonephritis with variable prognosis, ranging from minor urinary abnormalities to end-stage renal disease. The revised Oxford classification of IgAN explains that cellular/fibrocellular crescents are associated with poor renal prognosis, proposing an extension to the MEST-C score. C3 immunofluorescent staining follows a distribution similar to IgA staining. Therefore, complement activation was reported to play a pivotal role in IgAN pathogenesis. This study included 132 IgAN patients diagnosed by renal biopsies. The clinical parameters at the time of the biopsies were obtained from patient data records. We classified the patients into C ≥ 1 and C0 groups, and compared clinical, light microscopic, and immunofluorescent features. In the C ≥ 1 group, 2 (1.5%) and 31 (23.5%) patients were assigned to C2 and C1, respectively. The remaining 99 patients (75%) were classified as C0. The C ≥ 1 group had lower average age and rate of hypertension, and higher score of urinary occult blood and E score. The C ≥ 1 group had significantly higher average immunofluorescence scores for IgA, C5b-9, mannose-associated serine protease (MASP) 1/3, MASP2, properdin, factor B, and kappa. The steroid use rate was significantly higher in the C ≥ 1 group. During the follow-up period of 2.90years on average, the rate of renal dysfunction was not significantly different between groups. Crescent formation in IgAN was associated with activation of the lectin and alternative pathways. The C ≥ 1 group had significantly increased use of steroids, which probably caused comparable renal function during the follow-up period.

Patient Outcomes of Henoch–Schönlein Purpura Nephritis According to the New Semiquantitative Classification

Background: A new semiquantitative classification (SQC) for pediatric Henoch–Schönlein nephritis (HSN) was defined recently. The outcomes of pediatric HSN patients are reevaluated according to the new classification. Methods: Primary kidney biopsies from 80 HSN patients were scored using the new SQC. The International Study of Kidney Disease in Children (ISKDC) and SQC classifications were compared in terms of the patient outcomes. Outcomes were defined as: Outcome A (n = 44) patients with no sign of renal disease, Outcome B (n = 32) patients with minor urinary abnormalities, and Outcome C (n = 4) patients with active renal disease. Results: The patients with outcome C had significantly higher biopsy scores and chronicity indices than patients in group A. There was no significant difference in areas under the curve between total biopsy SQC scores and ISKDC findings. Conclusions: Our results suggest that the modified SQC is not more sensitive than ISKDC classification for predicting the outcome in HSN cases.

Clinical and pathological features of anti-neutrophil cytoplasmic antibody-associated vasculitis in patients with minor urinary abnormalities.

Kidney biopsy is the gold standard for diagnosis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but it is unknown whether vasculitis can be detected from AAV patients with minor urinary abnormalities. Ninety ANCA-positive patients undergoing kidney biopsy were evaluated retrospectively after being divided into two groups, which were group A (minor urinary abnormalities with both proteinuria <0.5 g/day and red blood cells ≤5/high power field) and group B (major urinary abnormalities except group A). Thirteen patients were included in group A and 77 patients were in group B. Crescentic glomeruli were detected less frequently in group A than in group B (61.5% vs. 92.2%, P < 0.01). The percentage of crescentic glomeruli relative to total glomeruli was significantly lower in group A than in group B (median [interquartile range]; 2.7% [0-5.2%] vs. 27.3% [8.1-56.1%], P < 0.01). Vasculitis of the small renal arteries was detected more frequently in group A than in group B without significant difference (30.8% vs. 19.5%, P = 0.46). Overall renal vasculitis (crescentic glomeruli and/or small renal artery vasculitis) was detected less frequently in group A than in group B (69.2% vs. 92.2%, P = 0.03). These findings indicate that renal biopsy can be a useful tool for histological diagnosis of ANCA-associated vasculitis in ANCA-positive patients with minor urinary abnormalities, even though the rate of renal vasculitis to the total number of glomeruli sampled is lower in patients with minor urinary abnormalities than patients with major abnormalities.

Urinary sediment miRNAs reflect tubulointerstitial damage and therapeutic response in IgA nephropathy

BackgroundImmunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide. The clinical spectrum of IgAN varies from minor urinary abnormalities to rapidly progressive renal failure. Evaluation of the disease by repeated renal biopsy is not practical due to its invasive procedure. Urinary sediment miRNAs promise to serve as non-invasive biomarkers to assess kidney injury of IgAN.MethodsFifty two biopsy-proven IgAN patients and twenty five healthy controls were enrolled in the study. Urinary sediment miRNAs were extracted. Expressions of miR-34a, miR-205, miR-21, miR-146a and miR-155 were quantified by real-time quantitative polymerase chain reaction (RT-QPCR). The receiver operating characteristic (ROC) curve was used to investigate the value of the miRNAs for predicting diagnosis of IgAN and evaluating histopathological injury. The patients were treated according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines and followed up. The roles of miRNAs in reflecting therapeutic efficacy and disease progression were analyzed.Results1. The IgAN group had significantly lower urinary miR-34a, miR-205, and miR-155, but higher miR-21 levels than controls. The ROC revealed that urinary miR-34a ≤ 0.047, miR-205 ≤ 0.209, miR-21 ≥ 0.461 and miR-155 ≤ 0.002 could distinguish patients with IgAN from healthy ones. In addition, miR-205 ≤ 0.125 and miR-21 ≥ 0.891 can distinguish IgAN patients with severe tubular atrophy/interstitial fibrosis from those with mild tubular atrophy/interstitial fibrosis. 2. After a mean 15.19 months follow-up, the reduction of proteinuria (g/24 h/year) was positively correlated with baseline urinary miR-21 and inversely correlated with miR-205. The levels of baseline eGFR and miR-205 in the complete remission group were significantly higher than non-complete remission group (p < 0.001; p = 0.018), while proteinuria, miR-21 and miR-146a were lower than non-complete remission group (p = 0.002; p = 0.021; p = 0.009). But multivariate analysis revealed that only baseline eGFR correlated with the remission of IgAN (p = 0.001, OR = 1.042).ConclusionsThe levels of some urinary sediment miRNAs, especially baseline miR-21 and miR-205, may be used as potential prognostic markers for evaluating the tubulointerstitial damage of IgAN. Furthermore, baseline levels of urinary miRNAs may be predictors of therapeutic efficacy and disease progression.

Long-term follow up of pediatric immunoglobulin A nephropathy treated with tonsillectomy plus methylprednisolone pulse therapy.

The aim of this study was to clarify the long-term efficacy of tonsillectomy plus methylprednisolone pulse therapy (tonsillectomy pulse therapy [TMP]) for pediatric immunoglobulin A nephropathy (IgAN). The clinical and laboratory findings as well as the prognosis for IgAN treated with TMP at long-term follow up were evaluated. We collected data on 33 IgAN children treated with TMP. The children were retrospectively divided into two groups. Group 1 consisted of 18 children treated with TMP as the initial therapy, and group 2 consisted of 15 children treated with TMP as rescue therapy for IgAN relapse. The clinical features, and laboratory and pathological findings, including those at first and second renal biopsy as well as at the latest follow up, were analyzed for both groups. Mean urinary protein excretion, incidence of hematuria, and serum creatinine in groups 1 and 2 were all decreased significantly after TMP compared with beforehand. The percentage of glomeruli showing crescents after TMP in groups 1 and 2 was significantly lower than before TMP. At the most recent follow up, 94% of patients in group 1 and 87% in group 2 had normal urine, 6% in group 1 and 13% in group 2 had minor urinary abnormalities, and no patients in either group had active renal disease or renal insufficiency. TMP is effective in ameliorating urinary abnormalities and improving the long-term outcome of pediatric IgAN both as an initial and as a rescue treatment.

Long-term prognosis of IgA nephropathy presenting with minimal or no proteinuria: A single center experience.

The long-term prognosis of patients with IgA nephropathy (IgAN) who present with preserved renal function and minimal proteinuria is not well described. We investigated the long-term outcomes of IgAN patients with an apparently benign presentation and evaluated prognostic factors for renal survival and clinical remission. We studied Japanese patients with biopsy-proven IgAN who had an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and proteinuria <0.5 g/day at the time of renal biopsy. The renal biopsies were reviewed using the Oxford classification. Twenty patients met the inclusion criteria. At diagnosis, the median eGFR (interquartile range) was 76.8 (65.2–91.1) mL/min/1.73 m2, and the median proteinuria level was 0.31 (0.16–0.39) g/day. Only one patient had an increase in serum creatinine of over 50% and no patient progressed to end-stage renal disease. The 15-year renal survival rate was 93.8%. Clinical remission was observed in 9 (45%) patients. Baseline proteinuria was the only factor significantly associated with the absence of clinical remission. The long-term prognosis of Japanese patients with IgAN who presents with minor urinary abnormalities and preserved renal function is excellent.

Resistance factors for the treatment of immunoglobulin A nephropathy with diffuse mesangial proliferation

Some patients with severe immunoglobulin A nephropathy (IgAN) are resistant to multi-drug combination therapy; however, there have been few reports on the risk factors for non-responsiveness to treatment for severe IgAN. We, therefore, evaluated the risk factors for non-responsiveness to treatment in cases of severe IgAN. We collected data on 44 children who had been diagnosed with IgAN with diffuse mesangial proliferation and treated with multi-drug combination therapy. The children were divided into two groups based on the prognosis at the latest follow-up. Group 1 consisted of 30 children with normal urine and nine children with minor urinary abnormalities and Group 2 consisted of four children with persistent nephropathy and one child with renal insufficiency. The clinical, laboratory, and pathological findings for both groups were analyzed. The age at the onset in Group 2 was higher than that in Group 1. C3 deposits and high chronicity index values at the first renal biopsy were more frequently found in Group 2 than in Group 1 patients. IgA deposits, serum IgA and myeloid-related protein (MRP) 8/14 levels, and glomerular and interstitial MRP8+CD68+ scores at the second biopsy were all higher in Group 2 than in Group 1 patients. Our results, although based on only a small number of patients in a retrospective study, suggest that age, presence of C3 deposits and interstitial changes at the onset, and persistent renal inflammatory activation may be risk factors for non-responsiveness to treatment for IgAN with diffuse mesangial proliferation.

Long-Term Outcomes of IgA Nephropathy Presenting with Minimal or No Proteinuria

The long-term outcome of patients with IgA nephropathy who present with normal renal function, microscopic hematuria, and minimal or no proteinuria is not well described. Here, we studied 141 Caucasian patients with biopsy-proven IgA nephropathy who had minor abnormalities at presentation and a median follow-up of 108 months. None of the patients received corticosteroids or immunosuppressants. We reviewed renal biopsies using the Oxford classification criteria. In this sample, 46 (32%) patients had mesangial proliferation, whereas endocapillary proliferation, focal glomerulosclerosis, and tubulointerstitial abnormalities were uncommon. Serum creatinine increases >50% and >100% were observed in five (3.5%) patients and one (0.7%) patient, respectively; no patients developed ESRD. After 10, 15, and 20 years, 96.7%, 91.9%, and 91.9% of patients maintained serum creatinine values less than a 50% increase, respectively. Using Cox proportional hazards regression, the presence of segmental glomerulosclerosis was the only factor that significantly associated with a >50% increase in serum creatinine. Clinical remission occurred in 53 (37.5%) patients after a median of 48 months. Proteinuria>0.5 and >1.0 g/24 h developed in 21 (14.9%) and 6 (4.2%) patients, respectively. Median proteinuria at the end of follow-up was 0.1 g/24 h, with 41 (29.1%) patients having no proteinuria. At presentation, 23 (16.3%) patients were hypertensive compared with 30 (21.3%) patients at the end of follow-up; 59 (41.8%) patients were treated with renin-angiotensin blockers because of hypertension or increasing proteinuria. In summary, the long-term prognosis for Caucasian patients with IgA nephropathy who present with minor urinary abnormalities and normal renal function is excellent.

Outcome results in children with IgA nephropathy: a single center experience

BackgroundImmunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Patients manifest variable clinical symptoms (eg, microhematuria) with preserved or progressive deterioration of renal function resulting in end-stage renal disease. The aim of this study was to evaluate patients from a single center to describe the clinical features, treatments, and follow-up results of those with the disease.MethodsThis is a retrospective data study of all children with IgAN. Patients who had a histopathologically proven diagnosis of IgAN and were followed up for at least 5 years were included in the study. Renal biopsy, graded as Hass classification, was performed on all patients. A total of 39 patients were included in the study.ResultsThe mean follow-up time (± standard deviation) was 10.4 ± 3.51 (range 5–16) years. Twenty-nine patients (74.4%) were male and ten (25.6%) were female. Nineteen (48.7%) patients presented with recurrent macroscopic hematuria, ten (25.6%) with microscopic hematuria ± proteinuria, six (15.4%) with nephritic syndrome, and four (10.3%) with nephrotic syndrome. All patients underwent a renal biopsy, which was graded according to the Hass classification. At the end of follow-up time, 18 (46.1%) patients were normal, 15 (38.5%) had minor urinary abnormalities, three (7.7%) had active renal disease, and three (7.7%) developed renal failure.ConclusionThe results of the present study are better than those from most other series. The majority of children with IgAN in this study were admitted with recurrent macroscopic hematuria and found to have a good prognosis. We suggest that children with IgAN have a good prognosis in the first 5-year follow-up period.

Treatment of IgA nephropathy

IgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum covers a wide range of features from minor urinary abnormalities (asymptomatic hematuria and mild proteinuria with normal renal function) to acute and chronic renal insufficiency. Ideally, the goal of treatment would be to correct any defects in IgA1 glycosylation and to modify mesangial deposition or removal of IgA1 deposits. There are only a few randomized controlled trials in IgA nephropathy; for this reason most treatment options are largely based on expert opinion. Authors discuss therapeutic options of different clinical pictures and the optimized renoprotective treatment of all IgA nephropathy patients. Orv. Hetil., 2011, 152, 2039–2046.

Current Therapy for IgA Nephropathy

IgA nephropathy (IgAN) is a very common glomerulonephritis worldwide. In this review, we discuss therapeutic options in four clinical scenarios encountered in patients with IgAN: first is the patient with minor urinary abnormalities where the mainstay of treatment is long-term, regular follow-up to detect renal progression and hypertension. Second is the typical patient presenting with microhematuria, significant but non-nephrotic proteinuria, hypertension, and variable degrees of renal failure. Here the mainstay of treatment is optimized supportive care. If this does not lower proteinuria below 1 g/d, corticosteroid monotherapy may be effective, as long as the GFR is above 50 ml/min. There is insufficient data to advocate the use of other immunosuppressive drugs or even combination therapy in such patients. Third is the atypical patient with overt nephrotic syndrome, or acute or rapidly progressive kidney injury where a possible vasculitic form of IgAN should be sought and, if present, treated with immunosuppression. In other atypical patients with secondary IgAN, treatment should target the underlying primary disease. And fourth is the transplanted patient with recurrent IgAN where the mainstay of treatment is optimized supportive care.

Methylprednisolone pulse plus mizoribine in children with Henoch–Schoenlein purpura nephritis

We evaluated whether methylprednisolone and urokinase pulse therapy combined with mizoribine (MUPM) was effective in children with severe Henoch-Schoenlein purpura nephritis (HSPN). We studied 12 patients who had been diagnosed with HSPN of at least ISKDC type III. All patients were treated with MUPM. Clinical features, pathological findings, and prognosis were prospectively investigated. Ten patients (responders; nine with ISKDC grade IIIb and one with grade IVb) were treated with MUPM, whereas MUPM was discontinued due to the lack of response in two patients (non-responders; two with grade IVb). Among responders, urinary protein excretion had decreased significantly from 99.7 ± 37.8 to 25.9 ± 33.4mg/m(2) per hour after 3months of therapy. The acute index and tubulointerstitial scores decreased significantly from 5.8 ± 1.5 and 3.8 ± 0.6 at the first biopsy to 2.3 ± 1.3 and 1.0 ± 0.8 at the second biopsy, respectively. At the most recent follow-up, eight of the responders had normal urine, and two had minor urinary abnormalities. Non-responders demonstrated continued high levels of urinary protein excretion after 3months of therapy, and MUPM was discontinued. Our study suggests that MUPM is effective in ameliorating the proteinuria and the histological severity of HSPN in patients with <50% crescents but is not so effective for HSPN in patients with >50% crescents.

GLOMERULONEPHRITIS AND THE NEPHROTIC SYNDROME IN PREGNANCY

Glomerulonephritis (GN) may be manifest clinically in several ways. It may be asymptomatic and associated with only minor urinary dipstick abnormalities, GN may present with one of the classic renal nephritic or nephrotic syndromes, or may be associated with progressive chronic kidney disease with hypertension and the gradual development of uraemia, or it may present with fulminating life threatening illness with severe acute kidney injury. The development of GN may indicate a primary renal limited disease, or may be secondary in association with systemic diseases such as systemic lupus erythematosus (SLE), myeloma, infections or diabetes. Although immunological abnormalities underlie the development of many forms of GN, precise pathogenic mechanisms remain unclear and diagnostic labels may simply reflect a description of the glomerular histological changes observed (Table 1).

Clinical effectiveness of steroid pulse therapy combined with tonsillectomy in patients with immunoglobulin A nephropathy presenting glomerular haematuria and minimal proteinuria

The effectiveness of steroid pulse therapy combined with tonsillectomy (ST) has been shown in immunoglobulin A nephropathy (IgAN) patients with moderate or severe urinary abnormalities. The present study aimed to clarify whether the effectiveness may be extrapolated to IgAN with minor urinary abnormalities, and whether the effectiveness may depend on the histological severity with minor urinary abnormalities. Data on 388 IgAN patients diagnosed by renal biopsies between 1987 and 2000 in Sendai Shakaihoken Hospital, who presented glomerular haematuria and minimal proteinuria (<or=0.5 g/day) at baseline, were analyzed. Cox regression was used to examine associations between baseline use of ST and subsequent clinical remission (CR), defined as negative proteinuria by dipstick and urinary erythrocytes of less than 1/high-power field. The instrumental variable method was also used to overcome confounding by treatment indication. During a median follow up of 24 months, we observed 170 CR cases. Patients receiving ST were younger and showed a better case-mix profile. Patients with ST had a significantly higher rate of CR than patients without tonsillectomy or steroid pulse in an unadjusted (hazard ratio (HR) = 5.51, 95% confidence interval (CI) = 3.33-9.12, P < 0.001) or adjusted Cox model (HR = 4.65, 95% CI = 2.43-8.88, P < 0.001). Less severe histological findings were substantially associated with higher CR rate in ST group. Adjusting for confounding by treatment indication showed an attenuated but still significant effect of ST (HR = 3.10, 95% CI = 2.02-4.77, P < 0.001). ST significantly increased the probability of CR in IgAN patients with glomerular haematuria and minimal proteinuria, and it was more effective in those with less severe histological findings.

Accumulation of Macrophages Expressing Myeloid-Related Protein 8 Associated with the Progression of Sclerotic Changes in Children with IgA Nephropathy

Myeloid-related protein (MRP) 8 is a calcium-binding protein of the S100 family. The renal accumulation of macrophages expressing MRP8 is associated with the inflammatory activity of glomerulonephritis. We evaluated the renal accumulation of macrophages expressing MRP8 in children with IgA nephropathy (IgAN). We collected data on 25 IgAN children who had been treated with prednisolone and divided these patients into two groups: Favorable group, consisting of 11 patients with normal urine and 6 with minor urinary abnormalities at 4.3 +/- 1.3 years after initial treatment; and Unfavorable group, consisting of 8 patients with persistent nephropathy. The pathological renal findings were compared between both groups. The second biopsy was performed at two years after first biopsy at 5.5 +/- 4.9 months from onset. In Favorable group, the glomerular accumulation of macrophages expressing MRP8, and mesangial cells expressing alpha-smooth muscle actin (alpha-SMA) were lower in the second biopsy specimens than those of the first biopsy specimens. In Unfavorable group, the glomerular accumulation of macrophages expressing MRP8 detected in the second biopsy specimens was similar to that of the first biopsy, while the number of mesangial cells expressing alpha-SMA and the index of renal sclerosis were higher in the second biopsy than in the first biopsy. The indexes of renal sclerosis were higher in children with more macrophages expressing MRP8 than in children with less macrophages expressing MRP8. Our results suggest that renal macrophages expressing MRP8 may be involved in the progression of sclerotic changes in children with IgAN.

Tonsillectomy with Methylprednisolone Pulse Therapy as Rescue Treatment for Steroid-Resistant IgA Nephropathy in Children

Primary immunoglobulin A (IgA) nephropathy is characterized by microhematuria and proteinuria and by the deposition of IgA in the glomerular mesangium. Steroid was a main drug for treatment of IgA nephropathy. However, some of children with IgA nephropathy are resistance to steroid treatment, but the therapy for steroid-resistant IgA nephropathy was not established. There have been reports on the efficacy of tonsillectomy as an initial treatment for IgA nephropathy in adults and children. We examined whether tonsillectomy with methylprednisolone pulse therapy (tonsillectomy pulse therapy) was effective as rescue treatment for steroid-resistant pediatric IgA nephropathy. We studied 11 patients (age at onset and duration of follow-up, 11.7 +/- 2.0 and 6.2 +/- 1.1 years) who had been diagnosed with steroid-resistant IgA nephropathy. Clinical features, laboratory data, and pathological findings were retrospectively compared between before and after tonsillectomy pulse therapy. Urinary protein excretion was significantly decreased at 24.7 +/- 7.3 months after tonsillectomy pulse therapy. On renal pathologic examination of 6 patients who underwent renal biopsy at 17.1 +/- 6.9 months after tonsillectomy pulse therapy, the activity index, an index of inflammation, was lower compared to the index evaluated before the therapy, but the chronic index, an index of renal sclerosis, remained unchanged. At 24.7 +/- 7.3 months after tonsillectomy pulse therapy, seven patients had normal urine and four had minor urinary abnormalities; namely, none had active renal disease or renal insufficiency. Our findings suggest that tonsillectomy pulse therapy may be effective as rescue treatment for steroid-resistant IgA nephropathy in childhood.

Goodpasture's syndrome with positive C-ANCA and normal renal function: A case report

IntroductionGoodpasture's syndrome consists of a triad of pulmonary hemorrhage, rapidly progressive glomerulonephritis and anti-glomerular basement membrane (anti-GBM) antibodies, either in circulation or fixed to the kidney. The absence of renal manifestations is uncommon. We present a case of biopsy proven anti-GBM antibody disease with normal renal function, mild urinary abnormalities and positive C-antineutrophil cytoplasmic antibody (C-ANCA) serology.Case presentationA 44-year-old female was treated for repeated episodes of hemoptysis and one episode of respiratory failure requiring ventilatory support. She had minor urinary abnormalities in the form of microscopic hematuria and non-nephrotic proteinuria. She also had positive C-ANCA. Her lung biopsy showed evidence of intra-alveolar hemorrhage with linear IgG deposits in the basement membrane of the alveolar capillaries. Owing to these lung biopsy findings, a kidney biopsy was carried out, which showed minimal thickening of the glomerular basement membrane and linear IgG and C3 deposits along the capillary walls. Her renal function remained persistently normal.ConclusionGoodpasture's syndrome is a rare disease. Even though the classical presentation is that of rapidly progressive glomerulonephritis pulmonary hemorrhage and anti-GBM antibodies in the circulation and kidneys, in rare cases it can present with repeated pulmonary hemorrhage and minor urinary abnormalities. In all cases of repeated pulmonary hemorrhage, the possibility of Goodpasture's syndrome should be considered and investigated further.

Can azathioprine and steroids alter the progression of severe Henoch-Schönlein nephritis in children?

To evaluate the effect of azathioprine with steroids on the clinical course and histologic parameters of severe Henoch-Schönlein nephritis (HSN), 20 patients with a median age of 9.3 years (range 4.4-17 years) and a follow-up period of 4.8 years (range 1-14 years) were included in this study. The patients were divided into two groups. Ten patients received azathioprine with steroids for 8 months (group A), and the other ten received steroids alone (group B). All patients underwent renal biopsy at presentation, and ten of them who were treated with azathioprine underwent follow-up biopsy after therapy. Six patients in group A achieved clinical remission, and the remaining four showed minor urinary abnormalities at the latest observation. The histological grades of the International Study of Kidney Disease in Children (ISKDC) improved in four of the ten patients, and the activity index decreased significantly from 6.8+/-2.0 to 4.3+/-2.3 (p=0.016). In group B, however, four patients had normal urine and renal function; two had minor urinary abnormalities; one had active renal disease, and three had chronic renal insufficiency, at the latest observation. The combination treatment of azathioprine and steroids may be beneficial in ameliorating histopathological features and improving the clinical course of severe HSN.

Myeloid-related protein 8 expression on macrophages is a useful prognostic marker for renal dysfunction in children with MPGN type 1

To clarify the role of subclasses of macrophages in chronic glomerulonephritis, we evaluated the relationship between myeloid-related protein 8 (MRP8) and MRP14 expression on macrophages and the progression of membranoproliferative glomerulonephritis (MPGN). We enrolled 35 patients with MPGN type 1 who had a normal creatinine clearance at the time of their first renal biopsy and divided them into 2 groups based on clinical status at the time of their most recent examination: 12 patients with normal urine test results and 12 patients with minor urinary abnormalities at the latest observation (group 1) and 7 patients with persistent nephropathy and 4 patients with renal insufficiency (group 2). The first and second renal biopsy findings and MRP8 and MRP14 expression on macrophages were investigated in both groups. Mean scores for positive glomerular and interstitial MRP8 and CD68 staining at the time of the first and second biopsies were significantly higher in group 2 than group 1. At the time of the second biopsy, mean scores for interstitial CD68-positive (CD68 +) staining were higher in group 2 than group 1. Mean scores for glomerular and interstitial MRP8 + and CD68 + staining at the time of the first biopsy correlated with the chronicity index at the time of second biopsy in both groups. Results suggest that MRP8 expression on macrophages in glomeruli and interstitial lesions at the first biopsy can be a useful prognostic marker for renal dysfunction in children with MPGN type 1.