Treatment Of Henoch-Schönlein Purpura Nephritis Research Articles

Efficacy and safety of mycophenolate mofetil versus cyclophosphamide therapy for Henoch schonlein purpura nephritis in children: A meta-analysis.

The objective of this meta-analysis was to compare the efficacy and safety between glucocorticoids combined with mycophenolate mofetil (MMF) versus glucocorticoids combined with cyclophosphamide (CTX) for henoch schonlein purpura nephritis (HSPN) in children. Databases including PubMed, EMbase, the Cochrane Library, China National Knowledge Infrastructure, and Wanfang database were searched from the inception to April 5th, 2024. Eligible studies comparing glucocorticoids combined with MMF versus glucocorticoids combined with CTX for HSPN in children were included. Data were analyzed using Review Manager Version 5.3. Ten studies were included in the meta-analysis. Six randomized controlled trials (RCTs) and 4 non-randomized studies involving 675 patients were identified. Compared with CTX therapeutic schedule, MMF therapeutic schedule had a higher complete remission (CR) within the 6 months (OR 1.61, 95%CI 1.16-2.22, P = .004) and CR within the 12 months (OR 1.73, 95%CI 1.00-2.97, P = .05). However, there was no significant difference between MMF and CTX therapeutic schedule concerning total remission (TR) within the 6 months (OR 1.54, 95%CI 0.82-2.92, P = .18) and TR within the 12 months (OR 2.08, 95%CI 0.86-5.01, P = .10). In addition, incidences of gastrointestinal discomfort (OR 0.33, 95%CI 0.19-0.56, P < .0001), liver function injury (OR 0.28, 95%CI 0.09-0.87, P = .03), myelosuppression (OR 0.15, 95%CI 0.06-0.41, P = .0001), alopecia (OR 0.25, 95%CI 0.07-0.91, P = .03) in MMF therapeutic schedule were all lower than CTX therapeutic schedule. There was no statistically significant difference between the 2 therapeutic schedules concerning infection (OR 0.90, 95%CI 0.50-1.61, P = .72), rash (OR 0.38, 95%CI 0.07-2.04, P = .26). Glucocorticoids combined with MMF had a higher CR and lower incidence of adverse effects compared with glucocorticoids combined with CTX in the treatment of HSPN in children.

Epidemiology of biopsy-proven Henoch-Schönlein purpura nephritis in children: A nationwide survey in Japan.

BackgroundLittle is known about the epidemiology of Henoch–Schönlein purpura nephritis (HSPN).MethodsWe conducted a nationwide epidemiological survey of Japanese children aged 1 to 15 years with HSPN. Children who were newly diagnosed with HSPN by biopsy between January 2013 and December 2015 were eligible for the survey to clarify the incidence of HSPN. We also conducted an institutional survey on kidney biopsy criteria and treatment protocols.ResultsA total of 353 of 412 institutions (85.7%) responded to the questionnaire. Of the 353 institutions, 174 reported to perform kidney biopsies at their institutions, and 563 children were diagnosed with HSPN. Considering the collection rate, the estimated incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year. The median age at biopsy was 7.0 years, and the male-to-female ratio was 1.2:1. The kidney biopsy criteria and treatment protocols for HSPN were as follows. Patients with acute kidney injury underwent biopsy at least one month after onset. For patients without kidney dysfunction, the timing for biopsy was determined by the amount of proteinuria. Regarding the treatment of HSPN, there were certain commonalities among the treatment protocols, they eventually differed depending on the institutions involved.ConclusionsThe incidence of biopsy-proven HSPN was 1.32 cases/100,000 children per year in Japan. The male-to-female ratio and date of diagnosis of HSPN were similar to those in previous studies. The kidney biopsy criteria and treatment protocols for HSPN varied among institutions. Further studies are warranted to establish an optimal treatment policy based on the prognosis.

The Efficacy of Tripterygium Glycosides Combined with LMWH in Treatment of HSPN in Children.

Objective This study aimed to explore the clinical efficacy and relevant mechanism of Tripterygium glycosides combined with low molecular weight heparin calcium (LMWH) in the treatment of Henoch–Schönlein purpura nephritis (HSPN) in children. Methods 64 cases of children patients with HSPN treated at Qilu Hospital (Qingdao) from January 2015 to May 2020 were selected and randomly divided into the control group and the observation group and 32 cases in each group. Conventional medical treatment was applied in the two groups, besides which the control group was given LMWH while the observation group was given Tripterygium glycosides based on the control group. The clinical efficacy and the indexes of clinical symptoms of the two groups were compared. Immune globulin level, fibrinogen content (FIB), prothrombin time (PT), platelet level (PLT), and activated partial thromboplastin time (APTT) level of the two groups were compared before and after the treatment. Results The total effective rate in the observation group was significantly higher than that of the control group, and the recurrence rate in the observation group was lower than that in the control group. After treatment, urine red blood cell count and 24 h urine protein were obviously better than those of the control group. There was no statistically significant difference in PT between the two groups of children before and after treatment. The levels of PLT and FIB in the two groups of patients after treatment were significantly lower than before treatment, and the PLT levels in the observation group were lower than those in the control group. Conclusion The combination of Tripterygium glycosides and LMWH had good clinical effects in the treatment of children with HSPN, and it could improve the clinical symptoms, the mechanism of which might be related to the increase of PT, a decrease of PLT, and the improvement of coagulation function.

Clinical effect and mechanism of total glucosides of paeony in the adjuvant therapy for children with Henoch-Schönlein purpura nephritis: a prospective randomized controlled study

OBJECTIVE To study the clinical effect and mechanism of total glucosides of paeony (TGP) in the adjuvant therapy for children with Henoch-Schonlein purpura nephritis (HSPN). METHODS Sixty-four HSPN children with moderate proteinuria were divided into a TGP treatment group (n=34) and a routine treatment group (n=30) using a random number table. Thirty healthy children who underwent physical examination were enrolled as the healthy control group. The children in the routine treatment group were given conventional treatment alone, and those in the observation group were given TGP in addition to the conventional treatment. The two groups were compared in the clinical outcome after 4 weeks of treatment. The proportion of follicular helper T (Tfh) cells in peripheral blood and the plasma levels of interleukin-21 (IL-21) and interleukin-4 (IL-4) were measured in the healthy control group and the two HSPN groups. The changes in serum cystatin C (CysC) level and urinary alpha 1-microglobulin (A1M) concentration were compared before and after treatment in the two HSPN groups. RESULTS Compared with the healthy children before treatment, the children with HSPN had higher proportion of Tfh cells and expression levels of IL-21 and IL-4 (P < 0.01). The TGP treatment group had a higher overall response rate to treatment than the routine treatment group (94% vs 67%, P < 0.05). After treatment, both groups had reductions in the proportion of Tfh cells in peripheral blood, the expression levels of IL-21, IL-4, serum CysC, and urinary A1M concentration. The TGP treatment group had greater reductions in these indices than the routine treatment group (P < 0.01). CONCLUSIONS TGP has a marked clinical effect in the treatment of HSPN and can reduce the inflammatory response of the kidney and exert a protective effect on the kidney by inhibiting the proliferation of Tfh cells and downregulating the expression of IL-21 and IL-4 in plasma.

Tripterygium glycosides in treatment of henoch-schonlein purpura nephritis: a systematic review of randomized controlled trials

To evaluate the clinical efficacy and safety of tripterygium glycosides (TG) in the treatment of henoch-schonlein purpura nephritis(HSPN). Seven English and Chinese databases (up to Nov. 9, 2017), were searched to collect the RCTs on TG for HSPN. Two researchers independently screened the literature according to inclusion criteria and exclusion criteria, extracted data, and evaluated the quality of the literature. After completion, cross-checking was performed and Meta-analysis was performed using RevMan 5.3 software. At the same time, different outcomes of the interventions were analyzed subgroupically. A total of 46 RCTs were included, with 1 659 in the experimental group and 1 596 in the control group. All the clinical studies showed a low quality. In terms of complete remission rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.82，95%CI[1.39，2.39];RR=2.03，95%CI[1.37，2.99]），the group with TG+GC performed better than the group with GC（RR=1.46，95%CI[1.32，1.60]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.35，95%CI[0.16，0.75]）. In terms of total effective rate, the group with TG performed better than the group with conventional therapy or GC（RR=1.44，95%CI[1.19,1.74];RR=1.30，95%CI[1.16，1.46]），the group with TG+GC performed better than the group with GC（RR=1.27，95%CI[1.21，1.34]），and the group with CTX+GC performed better than the group with TG+GC（RR=0.60，95%CI[0.43，0.85]）. No significant difference was found between the group with TG+GC and LEF+GC（RR=0.68，95%CI[0.30，1.53]）. In terms of urinary protein, urine occult blood negative time，the group with TG performed better than the group with conventional therapy（MD=-9.00，95% CI[-11.99，-6.01];MD=-12.00，95%CI[-16.13，-7.87]），the group with TG+GC performed better than the group with GC（MD=-8.86，95%CI[-10.08，-7.64];MD=-16.24，95%CI[-23.80，-8.67]）. In terms of recurrence rate, the group with TG+GC was lower than the group with GC（RR=0.13，95%CI[0.06，0.25]）, but there were no significant difference between the group with TG and conventional therapy（RR=0.43，95%CI[0.15，1.19]）. In adverse reactions, the common adverse effects of TG were gastrointestinal discomfort, liver damage and leucopenia. TG for the treatment of HSPN can improve clinical efficacy, reduce recurrence, and the adverse reactions are relatively safe. Due to the generally low methodological quality of the included studies, which affected the accuracy and reliability of the result. Therefore, more high-quality, large samples and multi-center randomized controlled trials are necessary for further evidence.

PP-47 Off-label use of tacrolimus in children with henoch-schonlein purpura nephritis: efficacy and safety

Background Tacrolimus was used off-label in the treat-ment of Henoch-Schonlein purpura nephritis (HSPN) in children. The objective of this pilot study was to assess its efficacy and safety. Methods Children with HSPN receiving tacrolimus and steroids as empirical treatment was included. Urine protein was assessed every 2 weeks during treatment. Pharmacogenetic analysis was performed on the CYP3A5 gene. Results A total of 25 patients with a mean age of 7.2 (range 3–12) years was included in this study. Pro-teinuria returned to negative in 21 patients with a mean treatment duration of 101 (SD 75) days. Patients with CYP3A5*1/*3 had longer duration of treatment achiev-ing negative proteinuria as compared with patients with CYP3A5*3/*3 (131±97 versus 80±39 days). No patients discontinued the tacrolimus treatment due to adverse events, and no drug-related adverse events were shown to have a causal association with tacrolimus therapy. Conclusion This preliminary study shows that tacrolim-us might be an effective, and well-tolerated drug for the treatment of HSPN in children.

Successful prednisolone therapy in elderly patients with severe forms of henoch-schönlein purpura nephritis.

INTRODUCTIONRecently, Henoch–Schönlein purpura (HSP) has been observed in elderly people, although it was believed to be uncommon in these subjects. The increased risks of developing end-stage renal disease (ESRD) in adults in comparison with children were highlighted by different studies; however, limited data are available on the treatment of HSP nephritis in adults.METHODSBetween 2002 and 2008, five elderly Japanese patients (>65 years old) (mean age, 68 years, ranging from 65 to 72) with severe forms of HSP nephritis were entered into a prospective study to evaluate prednisolone therapy on the outcome of nephropathy in terms of clinical symptoms and histopathological changes. The patients were considered at risk of developing chronic renal failure when they presented with a nephrotic syndrome and crescentic glomeruli.RESULTSAt the last follow-up, 4–10 years after initiation of the therapy, four patients had clinically recovered and one died of lung cancer. No patients developed ESRD. The clinical outcome seemed to be correlated with glomerular activity (massive proteinuria and crescent formation). In spite of a relatively large dose of prednisolone, a few adverse effects, such as insomnia and skin lesions, were observed.DISCUSSIONOur preliminary small study suggests that renal outcome as well as survival of elderly patients with severe forms of HSP might be altered by aggressive prednisolone therapy.

Roles of regulatory T cells and Th17 cells in pathogenesis of Henoch-Schonlein purpura nephritis in children

Henoch-schonlein purpura nephritis (HSPN)is the most common pediatric secondary renal glomerular disease.It could play an important role in the pathogenesis and progression of HSPN that regulatory T cells decline in the children and that the differentiation of Th17 cells are maybe not able to be effectively inhibited,leading to the insufficient immunosuppressive effect and the Th17 cells overexpression.We could further study the correlation among HPSN and the quantity and functional imbalance of Th17 cells and regulatory T cells to provide more theoretical basis for clinical treatment of HSPN. Key words: Henoch-Schonlein purpura nephritis; Children; Th17 ; Regulatory T cell

Pitfalls in recommending evidence-based guidelines for a protean disease like Henoch–Schönlein purpura nephritis

The long-term prognosis of Henoch–Schonlein purpura nephritis (HSPN) depends on the severity of initial clinical symptoms and histological features [1, 2]. The risk of evolution into a chronic kidney disease (CKD) may be as high as 50, 40 and 15 % for the combination of onset with nephrotic and nephritic syndrome, nephrotic syndrome, nephritic syndrome and/or heavy non-nephrotic proteinuria, respectively [1]. The International Study of Kidney Disease in Children (ISKDC) classified the risk of progression on the basis of the histology severity mainly according to the extent of crescent formations. Combining three studies with a follow-up of about 6 years [3–5], Haas [2] demonstrated that 25 % of children biopsied for HSPN had severe outcomes (persistently active renal disease and/or worsened stages of CKD, including endstage renal failure), in correlation with the ISKDC grades of renal pathology damage. These data indicate that children with HSPN have to be carefully followed, since some cases can have a catastrophic evolution. However, the therapeutic choice can be challenging because—apart from mild renal clinical symptoms and histological lesions that almost always are associated with good long-term outcome, and the association of nephrotic and nephritic syndrome with high histological grade [1–6] that most frequently leads to CKD—the long-term prognosis cannot predicted with certainty at disease onset. More importantly, there is a paucity of evidence-based (EB) data to guide treatment decisions for HSPN. Doctors are therefore confronted with the dilemma of undertreatment and increased risk of CKD or over-treatment and the risk of unnecessary side effects. Recently, the Kidney Disease Improving Global Outcome (KDIGO) initiative published guidelines on the treatment of HSPN [7]. In view of the lack of EB data for HSPN treatment and similarities between HSPN and primary immunoglobulin A nephropathy (IgAN), the KDIGO guidelines resorted to data regarding the treatment of the two diseases in similar clinical conditions. The aims of the present paper are:

HENOCH-SCH^|^Ouml;NLEIN PURPURA NEPHRITIS IN CHILDHOOD: PATHOGENESIS, PROGNOSTIC FACTORS AND TREATMENT

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. Thus, it is important to clarify the onset mechanism as well as the prognostic factors of Henoch-Schönlein purpura nephritis (HSPN) and to identify the most appropriate treatment. We herein review the pathogenesis, the prognostic factors and treatment of HSPN. As to the pathogenesis, several studies suggest that galactose-deficient IgA1 (Gd-IgA1) is recognized by anti-glycan antibodies, leading to the formation of circulating immune complexes and their mesangial deposition, thereby inducing renal injury. With regard to the prognostic factors, a number of factors have been suggested including nephrotic syndrome, decreased factor XIII activity, hypertension, severe renal injury, high renal accumulation of activated macrophage, alpha-smooth muscle actin, and high serum myeloid-related protein levels. For the treatment of severe HSPN, aggressive therapies including multiple drug combination therapy and plasmapheresis have been shown to be effective in ameliorating proteinuria and histological severity. Nevertheless, detailed investigation into the pathogenesis of HSPN and double-blind randomized control studies on children with HSPN are still necessary.

The Combination of Mycophenolate Mofetil with Corticosteroids Induces Remission of Henoch-Schönlein Purpura Nephritis

Background: Henoch-Schönlein purpura (HSP) is a form of systemic vasculitis that can progress to Henoch-Schönlein purpura nephritis (HSPN), and the most effective treatment remains controversial. Our aim was to compare the effects of oral mycophenolate mofetil (MMF) with low-dose prednisone and the full-dose corticosteroids (CS; prednisone) for the induction therapy of HSPN with large proteinuria. Methods: Fifty-three patients with biopsy-proved HSPN with large proteinuria (>2.0 g/24 h) were divided into two groups: the MMF group (n = 27) who received oral MMF 1.0 g/day (1.5 g/day for patients with a body weight >70 kg) combined with low-dose prednisone (0.4–0.5 mg/kg/day), and the CS group (n = 26) who received the full-dose prednisone (0.8–1.0 mg/kg/day). We compared the effects of inducing remission at 6-month follow-up and the overall remission rate at the end of the follow-up between the two groups. Results: At 6 months, the estimated glomerular filtration rate level remained stable, while the urine protein decreased significantly in both groups, and the remission rate was 76.9% in the CS group and 55.5% in the MMF group (p = 0.101). With a median follow-up of 28.8 months in the CS group and 28.2 months in the MMF group, the overall remission rate was 80.8% in the CS group and 77.8% in the MMF group (p = 0.788). The MMF group had less side effects than the CS group (48.1 vs. 76.9%, p = 0.031). The relapse was 4/21 (19.0%) in the CS group and 0/21 in the MMF group (p = 0.115). Conclusion: MMF is useful for inducing remission and maintaining remission in Chinese HSPN, and may be used as a steroid-sparing agent in the treatment of HSPN.

The pathogenesis and treatment of pediatric Henoch–Schönlein purpura nephritis

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. Thus, it is important to clarify the onset mechanism of Henoch-Schönlein purpura nephritis (HSPN) and to identify the most appropriate treatment. We herein review the pathogenesis and treatment of HSPN. As to the pathogenesis, several studies suggest that galactose-deficient IgA1 is recognized by anti-glycan antibodies, leading to the formation of circulating immune complexes and their mesangial deposition, thereby inducing renal injury. Aggressive therapies for the treatment of severe HSPN, including multiple drug combination therapy and plasmapheresis, have been shown to be effective in ameliorating proteinuria and histological severity. Nevertheless, detailed investigations of the pathogenesis of HSPN and double-blind randomized control studies on children with HSPN are still necessary.

Treatment of Henoch–Schönlein purpura: what evidence do we have?

The clinical features of Henoch–Schonlein purpura (HSP) are now well recognized; however, there remains uncertainty and a lack of consensus regarding treatment. Considerable concern has been expressed regarding the importance of identifying an improved, well-studied therapeutic protocol for use in the treatment of HSP. This article will focus on published studies, specifically randomized controlled trials, and aims to provide an evidence-based approach to the evaluation of therapy in children with HSP. We do have evidence that steroids do not protect against the development of kidney disease in patients with HSP. However, there is a clear lack of robust clinical trials for the treatment of moderate and severe HSP nephritis. At the present time, treatment of HSP nephritis is not guided by evidence from properly designed randomized controlled trials. We also lack consensus for the definition of outcome measures. Adequately powered, well-designed, multicenter, randomized controlled trials with follow-up peri...

Clinical remission of Henoch–Schönlein purpura nephritis after a monotherapeutic tonsillectomy

We herein describe an adult male patient who presented with tonsillitis, purpura, hematuria, and proteinuria. The serological analyses revealed elevated serum antistreptolysin, and the throat culture yielded Lancefield group A β-hemolytic streptococci. A renal biopsy revealed mild mesangial proliferation associated with granular mesangial depositions of IgA and C3, consistent with Henoch-Schönlein purpura nephritis (HSPN). Initially, the patient was treated with dipyridamole, which was followed by limited improvements in the proteinuria and hematuria. Nine months later, the tonsillitis relapsed due to GAS infection and deteriorated urinary abnormalities were noticed, which finally disappeared after monotherapeutic tonsillectomy. Although the impact of tonsillectomy on the treatment of HSPN remains to be characterized, our observations suggest that tonsillectomy in the present patient played a pivotal role in facilitating the recovery of the renal injuries. Because the arbitrary application of a tonsillectomy appears to be accompanied by ethical concerns, the evaluation of the clinical benefits of this procedure should be addressed more directly in the future.

Clinical practice:

Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. In this review, the main clinical features and complications are described. Although most features are self-limiting, renal disease is the most likely to result in long-term morbidity. Treatment of HSP nephritis is controversial, and the evidence for both prevention and treatment of established disease is reviewed. Follow-up for children presenting with HSP should be for at least 6 months and should include regular urine testing for proteinuria and haematuria and a blood pressure measurement. Women with a history of HSP during childhood are at increased risk of complications (such as proteinuria and hypertension) during pregnancy and should be monitored closely. This paper describes current practice with regard to investigation and management and proposes a practical care pathway of the management of a child with HSP.

Successful treatment of Henoch-Schonlein purpura nephritis with plasma exchange in an adult male.

Henoch-Schonlein purpura (HSP) frequently occurs in children under 15 years of age but is quite rare in adults. Most children who develop HSP nephritis completely recover from the illness, whereas up to 40% of adults have persistent hematuria and 10% develop chronic renal failure. Plasma exchange alone has been shown to be beneficial in children who have HSP nephritis. Adults have been treated using immunosuppressive drugs such as cyclophosphamide but effects are not certain. Here, we present a case of a 59-year-old white male who developed HSP nephritis while undergoing treatment with steroids. The patient developed acute renal failure with proteinuria and hematuria ∼2 weeks after being initially diagnosed with HSP by skin biopsy. Renal biopsy showed proliferative, exudative glomerulonephritis involving all 20 glomeruli; some with early crescent formation. Immunofluorescence staining showed 3+ IgA deposits in mesangium suggesting HSP-induced GN. The patient's serum creatinine rose to 2.5 mg/dl with ∼5 g of proteinuria by dipstick. Steroids were continued and the patient received plasma exchange treatments. Due to a very low leukocyte count, immunosuppressive agents were not given. Subsequently, renal function improved and the creatinine level came down to 1.3 mg/dl and proteinuria to <1 g/24 h. Since then, 1 year after this event, his serum creatinine has continued to stay at 1.2 mg/dl and he has trace proteinuria while taking a low-dose ACE inhibitor. This case illustrates the usefulness of plasma exchange in adult onset HSP nephritis, even without concomitant use of cytotoxic agents.

A Case of Henoch-Schönlein Purpura Nephritis in Pulmonary Tuberculosis

A 38-year-old man with pulmonary tuberculosis developed purpura over both lower extremities and renal disturbance after starting antituberculosis treatment. A renal biopsy and skin biopsy were performed to diagnose the new clinical manifestations, and leukocytoclastic vasculitis with IgA and C3 deposition were detected. Henoch-Schönlein purpura nephritis (HSPN) was diagnosed on the basis of the clinical and pathologic findings, and prednisolone therapy was added. The skin lesions disappeared in 7 days after starting steroid therapy, and renal function gradually improved. These results suggested that the pathogenesis of HSPN might be the consequence of the deposition of the circulating immune complexes. The treatment of HSPN has been not established yet. We should consider how to use steroid therapy for HSPN and call attention to the recurrences of renal disturbance and pulmonary tuberculosis. It is thus recommended to follow patients with HSPN in tuberculosis for long periods.