Cyclosporin A in adult patients with Henoch-Schönlein purpura nephritis and nephrotic syndrome; 5 case reports

Henoch-Sch?nlein purpura (HSP) is usually followed by mild renal involvement, but heavy proteinuria may also occur. Limited experience with cyclosporin A in children shows reduction of proteinuria. In this report, the use of cyclosporin A in 5 adult HSP patients with nephrotic-range proteinuria is described. Cyclosporin A in combination with prednisolone was given in 3 patients with HSP nephritis and nephrotic syndrome after a course of other immunosuppressive drugs and in 2 patients as initial treatment. All patients showed complete or partial remission of nephrotic syndrome with cyclosporin A and preserved stable renal function over a follow-up period of 5 years. We conclude that the combination of cyclosporin A with corticosteroids is effective in inducing remission of nephrotic syndrome in adult patients with HSP nephritis.     

Cyclosporin A for the treatment of severe Henoch-Schönlein glomerulonephritis

We evaluated the efficacy of cyclosporin A (CyA) for treating pediatric patients with severe Henoch-Schönlein glomerulonephritis (HSP-GN) and nephrotic-range proteinuria. Seven pediatric HSP-GN patients (5 boys, 2 girls) were treated with CyA, with a mean age of 10.6 years at diagnosis (range 7.2–15.2 years) and mean follow-up times of 6.0 years (range 4.4–8.9 years) from diagnosis and 5.2 years (range 3.4–7.7 years) from the beginning of the CyA treatment. All had developed nephrotic-range proteinuria within 1–3 months of the HSP diagnosis. A renal biopsy was performed on all the patients, and two showed rapidly progressive glomerulonephritis. They all received additional angiotensin converting enzyme inhibitor medication and one to three types of immunosuppressive treatment had been tried in five of the seven patients before CyA was initiated at a mean interval of 0.7 years after diagnosis (range 0.1–2.0 years). All the patients responded to the CyA treatment within a mean of 1.4 months (range 1 week to 4 months). Four patients achieved a stable remission and had been without CyA treatment for a mean of 3.7 years (range 2.9–5.3 years) by the end of the follow-up. Three patients seemed to become CyA dependent, since they developed proteinuria when the treatment was stopped. CyA treatment had been started significantly earlier (P=0.045) in the former group (mean 0.2 years, range 0.1–0.3 years) than in the latter (mean 1.5 years, range 1.2–2.0 years). Renal function was preserved in all patients, the glomerular filtration rate, plasma cystatin C, serum albumin, and serum creatinine being within normal limits at the end of the follow-up. We conclude that CyA treatment for severe treatment-resistant HSP-GN is promising, since four of the seven patients enjoy stable remission and all have retained their renal function after a mean follow-up of 6.0 years. However, some patients seem to develop CyA-dependent nephritis.The results were presented as a poster at the 36th meeting of the European Society for Pediatric Nephrology in Bilbao     

Plasmapheresis therapy for rapidly progressive Henoch-Schönlein nephritis

Six Japanese children with rapidly progressive Henoch-Schönlein purpura nephritis (HSPN) received multiple drug therapy combined with plasmapheresis (PP). After five courses of PP, multiple drug therapy, including methylprednisolone and urokinase pulse therapy, oral prednisolone, cyclophophamide, dipyridamole, and warfarin was given. At presentation, urine protein excretion and histological indices of the mean activity and chronicity were 245±101 mg/m² per hour, 6.6±1.2, and 1.5±1.3, respectively. After 6 months of therapy, urinary protein excretion had decreased significantly (P<0.001). The activity index decreased significantly at the second renal biopsy performed at a mean interval of 4.3 months after the first (2.8±1.4, P<0.05), while the chronicity index did not change. At the most recent observation, all showed clinical improvement. Two patients had normal urine, three had proteinuria of <20 mg/m² per hour, one had proteinuria of >20 mg/m² per hour, and none had renal insufficiency. Although this case series is without controls, our treatment protocol may be of benefit to children with rapidly progressive HSPN.     

Successful therapy with tonsillectomy for severe ISKDC grade VI Henoch–Schönlein purpura nephritis and persistent nephrotic syndrome

Henoch–Schönlein purpura (HSP) is a systemic disorder characterized by leukocytoclastic vasculitis involving the capillaries and the deposition of IgA immune complexes. Renal involvement is the principal cause of morbidity and mortality in children with HSP. We report here a 13-year-old girl with Henoch–Schönlein purpura nephritis (HSPN) of International Study of Kidney Disease in Children (ISKDC) grade VI and persistent nephrotic syndrome despite receiving conventional therapy, such as prednisolone, methylprednisolone and urokinase pulse therapy and plasmapheresis (PP). The patient was treated with tonsillectomy, which subsequently decreased proteinuria, induced the disappearance of microscopic hematuria, and improved renal pathological findings. A regimen of methylprednisolone and urokinase pulse therapy plus PP with tonsillectomy may be an effective and useful therapy for some children with severe HSPN children of ISKDC grade VI and persistent nephrotic syndrome.     

Treating severe Henoch-Schönlein and IgA nephritis with plasmapheresis alone

The aim of our study was to determine the outcome of children with severe Henoch-Schönlein nephritis (HSN) and immunoglobulin A (IgA) nephritis (IgAN) treated with early plasmapheresis alone. Children with acute renal impairment, heavy proteinuria or both and histology greater than grade 3 were treated with early plasmapheresis alone. Glomerular filtration rate (GFR) estimated from plasma creatinine (eGFR), urine albumin:creatinine ratio (UA/UC) and blood pressure 2 weeks after treatment and were measured at the last follow-up. Sixteen children (14 HSN, 2 IgAN) had a mean eGFR of 56 (17–136) ml/min per 1.73 m² and UA/UC of 590 (12–1,379) mg/mmol. Fifteen were referred at presentation and one after 2 months, and all commenced plasmapheresis within 6 (2–13) days. All had at least nine exchanges of 90 ml/kg over 2 weeks. At 2 weeks, the eGFR had increased by 51 (95% CI 34–68; P?=?0.002), and the UA/UC fell by 457 (95% CI 241–673; P?=?0.0001). At last review after 4 (1–7.5) years, the late-referred child had required a renal transplant but the other 15 had normal eGFRs (98–142), did not require hypotensive medication, and had normal or minimally elevated UA/UC (maximum 42). Children with severe HSN and IgAN recover well if treated with plasmapheresis alone without the need for immunosuppressive therapy. A randomised trial is needed.     

Cyclosporin A therapy for Henoch�CSch?nlein nephritis with nephrotic-range proteinuria

To evaluate the therapeutic role of cyclosporin A (CyA) for the treatment of Henoch–Sch?nlein nephritis (HSN), 29 patients (18 boys, 11 girls) with nephrotic-range proteinuria were analyzed retrospectively. Mean age was 8.6 years (range 2.0–15.5 years) at diagnosis of Henoch–Sch?nlein purpura (HSP). All patients had developed the nephrotic-range proteinuria at a mean interval of 4.4 months (range 0–50.7 months) after the diagnosis of HSP. Mean duration of CyA treatment was 12.3 months (range 2.6–55.0 months). Mean follow-up times were 3.7 years (range 1.2–12.9 years) from the beginning of the CyA treatment. Steroids were tapered off and stopped gradually after initiation of CyA. All patients responded to the CyA treatment within a mean of 1.8 months (range 1 week to 3.5 months). Twenty-three patients achieved stable remission with mean follow-up duration of 3.2 years and 6 patients seemed to become CyA-dependent, since they developed proteinuria when the treatment was stopped. Renal function was preserved in all patients but one who developed end-stage renal disease after poor compliance with CyA. We concluded that CyA treatment for HSN showing nephrotic-range proteinuria is very effective and a safe method, although some patients become CyA-dependent.     

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.     

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.     

Effect of early corticosteroid therapy on development of Henoch-Schönlein nephritis

BACKGROUND: Henoch-Sch?nlein purpura (HSP) is a systemic, small vessel vasculitis, which is very common among pediatric population. Findings of previous reports addressing the preventive effect of corticosteroid treatment in HSP nephritis have been inconsistent. The aim of this study was to determine whether corticosteroid therapy was effective in preventing Henoch-Sch?nlein nephritis. METHODS: The medical records of 216 children with HSP, seen in 2 tertiary care pediatric nephrology centers, were reviewed retrospectively. The effect of corticosteroid therapy on preventing nephritis was assessed in 157 patients who had no evidence of nephritis at the initial urinalysis. The treatment group (n=61) had received oral corticosteroids for gastrointestinal symptoms and/or arthritis. The dosage of prednisone was 1 mg/kg per day for 1-2 weeks, with weaning over a week. We compared the rate of renal involvement during follow-up between the groups who were treated with corticosteroids and not. RESULTS: Nephritis developed in 17 of the 61 (27.8%) corticosteroid-treated patients and 18 of the 96 (18.7%) untreated patients during follow-up. CONCLUSION: There was no evidence that corticosteroids reduced the risk of renal involvement in HSP, and these results do not support the use of corticosteroids in early HSP to prevent renal injury.     

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.

     

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.     

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.     

Henoch-Schönlein nephritis complicated with pulmonary hemorrhage but treated successfully

Henoch-Sch?nlein purpura (HSP) is a common vasculitic syndrome in children who, in most cases, achieve complete recovery. Occasionally, however, patients develop nephritis or nephrotic syndrome with renal failure, or develop significant gastrointestinal bleeding. Pulmonary hemorrhage, found mostly in adolescents and adults, and with a high mortality rate, has been reported only in a few prepubertal children, with a slightly better outcome. A 9-year-old-girl with HSP, renal failure, and nephrotic syndrome developed severe bilateral pulmonary hemorrhage. After an unsuccessful trial of glucocorticoid therapy, she showed an excellent response to cytotoxic therapy.     

Mycophenolate mofetil treatment of crescentic Henoch-Schönlein nephritis with IgA depositions

Mycophenolate mofetil (MMF) is considered to be a promising therapeutic agent in primary glomerulonephritis but there are no data on the use of MMF in Henoch-Sch?nlein nephritis (HSN). Herein we report the first adult crescentic HSN patient in whom long-term complete remission was achieved after MMF therapy.