Cyclosporin A therapy for severe Henoch-Schönlein nephritis with nephrotic syndrome

To evaluate the efficacy of cyclosporin A (CyA) for treating severe Henoch-Schönlein nephritis (HSN), seven patients with nephrotic syndrome, aged 3.9–13.8 years (mean 6.5 years), were analyzed retrospectively. Mean follow-up times were 5.5 years (range 2–9 years). All underwent renal biopsy before treatment, and follow-up renal biopsy was performed in six of the seven patients. All patients improved, with 24-h protein declining from a mean of 9.2 g/m²/day (range 1.5–16 g/m²/day) to 0.3 g/m²/day (range 0.03–1.2 g/m²/day) (p=0.016) and serum albumin increasing from a mean of 2.1 g/dl (range 1.5–2.4 g/dl) to 4.6 g/dl (range 3.5–5.3 g/dl) (p=0.016) after CyA therapy. The activity index decreased significantly at the second renal biopsies obtained at a mean interval of 11.7 months after the first (6.4±3.3 vs 3.5±1.2, p=0.042, respectively), while the chronicity index and the tubulointerstitial scores did not change. On the immunofluorescent findings at the second biopsies, the degree of deposits of immunoglobulins such as IgA, IgM, C3, and fibrinogen decreased in five of the six patients. Although this case series is without controls, our study suggests that CyA may be beneficial to a subset of HSN patients with nephrotic syndrome.     

Henoch-Schönlein purpura nephritis with nephrotic state in children: predictors of poor outcomes

Nephritis develops in 18–81% of Henoch-Sch?nlein purpura patients, and the long-term outcomes of this nephritis show great variation. A nephrotic state at disease onset has been proposed as a predictor of poor renal outcomes. We studied 42 children with Henoch-Sch?nlein purpura nephritis (HSPN) who presented with a nephrotic state during the early phase of the disease. The median age of the patients at the time of diagnosis was 7.4 years. The median follow-up period was 6.2 years. Twenty-five children (60%) made a complete recovery; nine (21%) progressed to end-stage renal disease. Multivariate logistic regression analyses revealed that the nephrotic state lasting for more than 3 months had a significant effect on renal outcomes (odds ratio 11.6; 95% confidential interval, 1.16–348.4; p = 0.03), whereas initial renal insufficiency, renal pathological findings, age at onset, and types of treatment did not. These findings indicate that clinical presentation, particularly duration of the nephrotic state, is related to long-term outcomes in HSPN patients with nephrosis. Our results also indicate that the therapeutic options for HSPN patients with a nephrotic state should be based on the clinical presentation rather than on the initial pathological findings alone.     

Pathogenesis of Henoch-Schönlein purpura nephritis

The severity of renal involvement is the major factor determining the long-term outcome of children with Henoch-Schönlein purpura (HSP) nephritis (HSPN). Approximately 40% children with HSP develop nephritis, usually within 4 to 6 weeks after the initial onset of the typical purpuric rashes. Although the pathogenetic mechanisms are still not fully delineated, several studies suggest that galactose-deficient IgA1 (Gd-IgA1) is recognized by anti-glycan antibodies, leading to the formation of the circulating immune complexes and their mesangial deposition that induce renal injury in HSPN.     

Muscle involvement in a patient with Henoch-Schönlein purpura nephritis

Although Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis affecting multiple organ systems, muscle involvement has rarely been reported. This report describes muscle pain and weakness in a patient with HSP nephritis (HSPN). A 13-year-old boy suffered from purpura, abdominal pain, and symmetrical muscle pain and weakness of the extremities. He was diagnosed as having HSP with muscle involvement. His abdominal pain and muscle involvement improved 1 week after commencing oral prednisolone therapy. The patient subsequently developed biopsy proven HSPN. It should be noted that, although rare, muscle involvement might occur in HSP as in other systemic vasculitides. The precise pathogenic mechanism underlying its development is currently unclear.     

Autopsy case of Henoch-Schönlein purpura nephritis complicated with intestinal cytomegalovirus infection

A 55-year-old man was admitted to our hospital because of arthralgia, purpura, abdominal pain, melena and leg edema. Laboratory findings showed an increased serum creatinine level (2.4 mg/dL), hematuria and massive proteinuria (10.7 g/day). Renal biopsy revealed diffuse endocapillary proliferation and focal mesangial proliferation with IgA deposition predominantly in the glomerular capillary walls. Based on these findings, he was diagnosed as having Henoch-Sch?nlein purpura nephritis and steroid therapy was started. Following steroid therapy, his nephrotic state remained unchanged, although his renal function improved concomitantly with the disappearance of arthralgia, purpura and abdominal symptoms. Therefore, cyclosporine was added to the steroid therapy to enhance immunosuppression. However, melena recurred and anemia progressed. Endoscopy revealed multiple ulcers in the duodenum and jejunum, and clipping was performed at some bleeding sites. However, he died of hemorrhagic shock. The autopsy revealed that hemorrhagic lesions having cytomegalovirus infection spread widely in the stomach, duodenum and jejunum. Recurrence of gastrointestinal bleeding during the treatment of Henoch-Sch?nlein purpura nephritis is usually due to severe vasculitis or steroid ulcer. However, in patients receiving strong immunosuppressive therapy, cytomegalovirus infection needs to be considered as cause of gastrointestinal bleeding.     

Treatment of children with Henoch-Schönlein purpura nephritis with mycophenolate mofetil

Background

Henoch–Schönlein purpura (HSP) can progress to Henoch–Schönlein purpura nephritis (HSPN), and the most effective management remains unclear. Our aim was to evaluate the efficacy of mycophenolate mofetil (MMF) for treating pediatric patients with HSPN and nephrotic-range proteinuria.

Methods

Twelve children, seven boys and five girls, mean age 8.33 (range 6–12) years at the time of HSPN diagnosis with nephrotic-range proteinuria, were treated with MMF. All patients failed steroid treatment, and mean proteinuria at the time of MMF initiation was 5.6 g/d. MMF dosage ranged from 20 to 25 mg/kg per day. Patients also received an angiotensin-converting enzyme inhibitor (cliazapril) at MMF initiation. Mean follow-up was 3.9 (range 2.3–5.5) years.

Results

All patients responded to MMF at a mean of 2.5 (range 1–4 months). Among the 12 patients, MMF was administered for 10 months in five, 12 months in six, and 15 months in one. At last follow-up, all patients had negative proteinuria and normal renal function, and no relapses were noted. No serious adverse effects of MMF were noted in any patient.

Conclusion

MMF is useful for treating pediatric patients with HSPN and nephrotic-range proteinuria.

     

Outcome of Henoch-Schönlein purpura nephritis treated with long-term immunosuppression

This retrospective study investigated the outcome of 27 children (19 male) with Henoch-Schönlein purpura nephritis (HSN) of International Study of Kidney Disease in Children (ISKDC) grade 3b or higher treated with long-term immunosuppressive therapy in a single centre over a 10-year period. The mean age at presentation was 9.7 years. The median estimated glomerular filtration rate (eGFR) was 91.3 ml/min per 1.73 m², with the median urine protein creatinine ratio (UP:UC) 556 mg/mmol. The treatment protocol comprised daily steroids and cyclophosphamide for 8–12 weeks followed by azathioprine and a reducing regimen of alternate-day steroids for 8–12 months. After a mean follow-up period of 7 years following presentation, 37% made a complete recovery, 40.7% had persistent proteinuria, 7.4% had persistent proteinuria and were on antihypertensive therapy and 14.8% had progressed to end-stage kidney failure (ESKF). Children with poor outcome were older at presentation (p 0.005), had more crescents (p 0.015) and had heavier proteinuria 6 months post initial biopsy (p 0.023). All of the four children with ESKF had nephrotic range proteinuria and greater than 50% crescents on initial biopsy. Despite long-term immunosuppression, the majority of children with HSN grade 3b or higher will have persistent renal abnormalities on long-term follow-up.     

Polymorphism of the ACE gene in Henoch-Schönlein purpura nephritis

Individuals with IgA nephropathy (IgAN) who are homozygous for the deletion (D) polymorphism of the gene for angiotensin converting enzyme (ACE) are reported to be at increased risk of progressive renal damage. Since IgAN and Henoch-Schönlein purpura with associated nephritis (HSPN) share a common aetiology, we have investigated this influence in 31 children with HSPN. The distribution of genotypes was as follows: II: 4, ID: 17 and DD: 10 patients. Median length of follow-up was 4.5 years (range 0.5–15.75 years). Severe onset with nephrotic oedema and crescent formation on renal biopsy was seen in 10 of 17 patients with ID genotype and 5 of 10 patients with DD genotype. In the ID group, 2 patients have undergone renal transplantation and 4 have persistent proteinuria 4, 7, 9 and 10 years after presentation. One patient in the DD group has been transplanted and 1 patient has proteinuria and a reduced glomerular filtration rate 5 years after initial presentation. All other patients have either made a complete recovery or have microscopic haematuria alone. These results do not support an association between disease severity and DD genotype in children with HSPN; however larger studies are required to confirm this.     

Clinical outcome in children with Henoch-Schönlein nephritis

Henoch-Schönlein purpura (HSP) is the most common vasculitis in childhood. The long-term prognosis is variable and depends on renal involvement. The aim of this study was to evaluate both clinical features of the children with HSP and the prognoses of short- and long-term outcome of patients diagnosed as HSP nephritis (HSN). This is a retrospective data study of all children with HSP hospitalized from January 1991 to December 2005. The patients with HSN were classified according to their initial presentation, histologic findings, type of treatment and clinical outcome. All patients have been evaluated once every 2 months. Fifty-three of the patients had kidney biopsies. The patient population consisted of 141 children included 78 boys (55.3%) and 63 girls (44.7%) ranging in age at disease onset from 2 to 17 (8.9±3.29) years. Renal involvement was determined in 58.1%. Nephrotic and/or nephritic syndrome were found to be an unfavorable predictor both for short and long-term outcome (P<0.05). However, 35% of these patients and 62% of them showed complete remission after 6 months and long-term course. Overall prognosis of HSN is relatively good and long-term morbidity is predominantly associated with initial presentation and renal involvement.     

Early tubular proteinuria and the development of nephritis in Henoch-Schönlein purpura

The prognosis of Henoch-Schonlein purpura (HSP) is mainly determined by the involvement of the kidney, but prognostic markers have not been established. To study the extent of tubular involvement in HSP and its relationship to the development of HSP nephritis, we measured the urinary excretion of two tubular marker proteins in 36 children with HSP. After admission, urinary N-acetyl-beta-D-glucosaminidase (NAG) was determined in 20 children and alpha1-microglobulin (alpha1-MG) in 16 children respectively. These values were compared with the biochemical data on admission, 1 month, 6 months, and 12 months later. A total of 198 24-h urine samples from healthy children were used for the establishment of reference data for NAG and alpha1-MG (mean+/-2 SD). Twenty-one patients had elevated excretion of either NAG (>mean+2 SD, n=12) or alpha1-MG (>mean+2 SD, n=9). The highest values (>mean+4 SD) were found in patients with early kidney involvement. Normal values were accompanied by a benign further clinical course. Children with intermediate high values (>mean+2 SD, 相似文献   

Therapeutic strategy in children with Henoch-Schönlein purpura

Henoch-Sch?nlein Purpura (HSP) is the most frequent childhood primary immune vasculitis which affected skin, joints, gastro-intestinal tract and kidney. Renal involvement signs the future disease prognosis. The HSP don't have etiologic treatment but its immuno-histological aspects, leukocytoclastic vasculitis with immune complexes, imposed the including in the therapeutic equation, immunosuppressive and/or cytotoxic drugs, plasmapheresis, kidney transplant (severe renal deficiency resistant to medical treatment) and surgical treatment (in severe gastro-intestinal complications). Identifications of serum and/or urinary markers for the therapeutic answer contribute to appreciate long prognosis disease and precocious and individualized treatment.     

Clinical outcomes in children with Henoch-Schönlein purpura nephritis grade IIIa or IIIb

Henoch–Sch?nlein purpura (HSP) is one of the most common causes of systemic vasculitis in children. The incidence of HSP nephritis (HSPN) among HSP patients has been reported to be 15–62%. Even so, what constitutes severe HSPN is controversial. In the study reported here, we retrospectively reviewed the clinical features and prognosis of 101 children with HSPN, ISKDC grade IIIa/IIIb, from January 1992 to November 2008. Patients with isolated hematuria and/or proteinuria <50 mg/kg/day received triptolide alone, and those with nephrotic range proteinuria received a combination therapy of prednisone and triptolide. Nephrotic syndrome was the most common clinical manifestation (45.5%). There were no significant differences in the clinical features (χ² = 2.756, P = 0.252), the side effects related to treatment (χ² = 2.259, P = 0.894), prognosis between IIIa and IIIb (χ² = 3.013, P = 0.222), or prognosis in grade IIIa patients receiving triptolide alone or triptolide and prednisone (χ² = 1.207, P = 0.272) and grade IIIb patients (χ² = 1.158, P = 0.282). No significant difference in clinical manifestations and long-term prognosis of our HSPN patients with grade IIIa or grade IIIb were found, implying that our patients with International Study and Kidney Disease in Children (ISKDC) grade IIIb were not the most severe cases of HSPN. Our results may also suggest that treatment with steroid may not alter the clinical outcome of such grade IIIa or IIIb patients.     

A case of Henoch-Schönlein purpura in a patient on hemodialysis

Henoch-Sch?nlein purpura(HSP) is a systemic vasculitis and characterized by the tissue deposition of IgA-containing immune complexes. A 50-year-old man with end stage renal failure due to diabetic nephropathy on maintenance hemodialysis, presented purpura, hematuria, abdominal pain, and joint pain. He also presented a high fever with neutrophilia. Biopsy of skin lesions revealed inflammation of the small vessel accompanied by vascular IgA deposition. Based on the clinical symptoms and skin biopsy, we made the diagnosis of HSP. Oral prednisolone was administered resulting in an improvement of the clinical symptoms. A skin biopsy should be performed for histological and immunofluorescence studies in the case of clinical suspicion of HSP with end stage renal disease on hemodialysis.     

Henoch-Schönlein purpura associated with acetaminophen and codeine

We report a case of a relapse of Henoch-Sch?nlein Purpura (HSP) associated with intake of paracetamol (also known as acetaminophene) and codeine. A 69-year-old man presented with fever, gross hematuria, acute renal failure, palpable purpuric skin rash over the legs, feet and arms, arthralgias and abdominal discomfort. 1 week before he had started therapy with co-efferalgan (association of paracetamol and codeine) for cervical arthrosis. Blood test revealed increase in serum creatinine levels (2.6 mg/dl), CRP (375 mg/dl), with no thrombocytopenia or hypocomplementemia. Co-efferalgan was discontinued. Gross hematuria resolved in 2 days, purpuric rash disappeared in 10 days, renal function returned to normal after 2 weeks and abdominal pain and arthralgias improved on the following 2 - 3 weeks. An objective causality assessment in accordance with the Naranjo algorithm, revealed that the adverse drug reaction was probable between paracetamol/codeine and Henoch-Sch?nlein purpura. To our knowledge, and based on a medline search (up to 2005), we believe that this could be considered the first case of Henoch-Sch?nlein purpura, associated with intake of paracetamol and codein. Although this event could be considered rare, clinicians should to be aware of possible associations between HUS and the intake of paracetamol and/or codeine to provide an early therapeutic intervention and a close monitoring.     

Henoch-Schönlein purpura nephritis in a patient infected with the human immunodeficiency virus

There are various forms of renal lesions in patients with human immunodeficiency virus(HIV), however reported cases of immune-complex glomerulonephritis are scarce. Here we describe an HIV-positive patient with Henoch-Sch?nlein purpura nephritis(HSPN), which presented as nephrotic syndrome. In addition to therapy combined with glucocorticosteroid and inhibition of the renin-angiotesin system(RAS), plasmapheresis and antiretroviral therapy produced a favorable outcome. A 26-year-old HIV positive man was admitted for purpura on both lower limbs. Despite glucocorticosteroid treatment, purpura recurred and urinary protein increased to 5-10 g daily. HSPN was diagnosed based on the skin and renal biopsies. During 2 months of treatment with combined glucocorticosteroid and RAS inhibition, nephrotic syndrome persisted. He received double filtration plasmapheresis(DFPP). Soon after, urine protein decreased to 2-3 g daily and macrohematuria decreased. The second renal biopsy showed a decrease in IgA deposition and improvement of acute inflammatory changes. In addition, highly active antiretroviral therapy was started to reduce the high viral load. After 3 weeks, HIV-1-RNA rapidly decreased and urine protein decreased to 1 g daily. After a year, urinary protein was negative, but mild microhematuria persisted. We speculate that the refractory nephrotic syndrome in this patient might be associated with the abnormal immunological condition due to HIV infection.