Steroid-responsive nephrotic syndrome in a child with juvenile idiopathic arthritis

Renal disease is rare in children with juvenile idiopathic arthritis, although a number of associated nephropathies have been described, including mesangial glomerulonephritis. We report the presence of mesangial glomerulonephritis, revealed by a nephrotic syndrome, in a paediatric patient with juvenile idiopathic arthritis. Short-term steroid treatment induced a rapid remission of the nephrotic syndrome, but the presence of anti-nuclear antibodies, 1:320 in a homogeneous pattern, irregular deposits of C1q in a renal biopsy, and a mother with episodes of cutaneous lupus suggested an uncertain renal evolution for this infant.     

Long-term outcome of children treated with rituximab for idiopathic nephrotic syndrome

Background

Rituximab (RTX) has recently showed promising results in the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS).

Methods

This was a retrospective multicenter study of 18 children treated with RTX for SDNS, with a mean follow-up of 3.2 years. RTX was introduced because of side effects or relapses during therapy with immunosuppressive agents. The children received one to four infusions of RTX during the first course of treatment, and subsequent infusions were given due to CD19-cell recovery (CD19?>1 %; 54 % of children) or relapse (41 %), as well as systematically (5 %).

Results

Treatment with RTX maintained sustained remission without relapse in 22 % of patients and increased the duration of remission in all other patients. The time between two successive relapses was 9 months in the absence of re-treatment and 24.5 months when infusions were performed at the time of CD19-cell recovery. At the last follow-up, 44.5 % of patients were free of oral drug therapy. Of those still receiving oral drugs, all doses had been decreased. No serious adverse events occurred.

Conclusion

The results of this retrospective study confirm the efficacy and very good safety of RTX in the treatment of SDNS. The optimal therapeutic protocol seems to be a repeated single infusion at the time of CD19-cell recovery.     

Osteolysis syndrome mimicking juvenile idiopathic arthritis

Osteolysis syndromes include a group of heterogeneous disorders that can be mistakenly diagnosed as juvenile idiopathic arthritis (JIA) in early course of the disease. We report a case of 16-year-old girl who presented with severe joint deformities, subcutaneous nodules and linear skin indurations. She had been diagnosed as having JIA before and given immunosuppressive therapy. X-ray of the joints showed severe osteopenia and osteolysis of interphalangeal joints of the hands and feet. The patient was diagnosed as having Torg/nodulosis, arthropathy, osteolysis syndrome (NAO). Here, we briefly discuss osteolysis syndromes and the differential diagnosis between osteolysis syndromes and JIA.     

Long-term prognosis of idiopathic nephrotic syndrome in children

Abstract

Background: To investigate the demographic, clinical and laboratory data of the children with idiopathic nephrotic syndrome (INS), and to determine prognostic factors that affect the clinical outcome of the patients. Methods: Medical charts of 372 patients diagnosed to have INS and followed up at least 5 years between January 1990 and December 2008 were evaluated, respectively. After initial demographic, clinical and laboratory findings of the patients were documented, therapeutic protocols, prognosis and prognostic factors were investigated. Results: 299 of the patients (80.4%) were steroid responsive and 73 (19.6%) were not. Focal segmental glomerulosclerosis (FSGS) was observed in 57%, minimal change disease (MCD) in 20.6% and diffuse mesengial proliferation in 21.9% renal biopsy materials. Steroid sensitivity was higher in patients with MCD and under the age of five years. Resistance to steroids was higher in children with FSGS. Complete remission was achieved in 96% of patients who were sensitive to steroids and in 46.6% who were resistant. 15% of patients who were steroid resistant developed chronic kidney disease (CKD). Conclusion: Intercurrent infections and response to steroid therapy are the most important factors affecting the prognosis of the disease.     

Intermittent high-volume hemofiltration promotes remission in steroid-resistant idiopathic nephrotic syndrome

Abstract

Inflammation is a key part in the etiology and progression of idiopathic nephrotic syndrome (INS), we hypothesize that removing pro-inflammatory cytokines with intermittent high-volume hemofiltration (IHVHF) could improve the outcome in INS patients. The purpose of the current study is to examine whether IHVHF promotes remission in steroid-resistant INS. Fifty-one steroid-resistant INS patients were followed up on an open-label basis with prospective evaluations. Thirty-five patients received mycophenolate mofetil (SRD group) and 16 patients received drugs and IHVHF due to volume overload despite of diuretics (SRDF group). The rate of complete remission (CR) was analyzed. We also recruited 30 healthy individuals and 36 steroid-sensitive (SS) INS patients as controls to investigate the correlation of interleukin (IL)-8, IL-10, IL-6 and IL-17 with INS activity. Compared with the patients in the SRD group, the 6-month CR rate was higher (44% vs. 9%, p?<?0.001) and time to first CR was significantly shorter (7.3?±?3.6 vs. 11.1?±?5.3 months, p?=?0.02) in the SRDF group. Serum IL-8 was highest in the SRDF group and reduced by IHVHF clearance. Serum IL-8 was lower during remission than at onset or recurrence of INS, whereas no significant difference was seen in the other cytokines. Receiver operating characteristic curve analysis demonstrated that serum IL-8 predicted steroid sensitivity with moderate accuracy (area under the curve?=?0.79, 95% CI: 0.69–0.87). IHVHF promotes remission in patients with steroid-resistant INS and it may be partly due to serum IL-8 clearance.     

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome in children

Background

Several recent studies have shown improved short-term outcome of steroid-resistant nephrotic syndrome (SRNS) in children; however, only a few studies have evaluated the long-term outcome. The aims of our study were to obtain detailed data and analyze the long-term outcome of children with SRNS.

Methods

Sixty-nine children with idiopathic SRNS were enrolled and divided into two groups based on initial histopathological patterns: focal segmental glomerulosclerosis (FSGS) and minimal change (MC)/diffuse mesangial proliferation (DMP). The effects of initial treatment with the immunosuppressant of choice (cyclosporine or cyclophosphamide) on renal survival, remission, and incidence of complications were analyzed in both groups (4 subgroups).

Results

The renal survival rate was significantly different among the four different subgroups based on different combinations of initial histopathological pattern (FSGS vs. MC/DMP) and initial immunosuppressant used for treating SRNS (cyclosporine vs. cyclophosphamide) (P?=?0.013), with renal survival in the FSGS (cyclophosphamide) subgroup being especially low (54.6 %). Disease- and/or treatment-associated complications were relatively low; however, hypertension at last examination was observed in a considerable number of patients (31.9 %).

Conclusions

Our results suggest that a recently developed therapeutic regimen with cyclosporine considerably improves both the initial remission rate and the long-term renal survival rate of children with idiopathic SRNS.

     

Shoulder arthroplasty for patients with juvenile idiopathic arthritis

Between 1986 and 1997, 13 shoulders in adult patients who had severe polyarticular juvenile idiopathic arthritis were treated with primary arthroplasty. Eleven shoulders were evaluated retrospectively by an independent observer with a mean follow-up of 9 years. Patient evaluation included pain Visual Analogue Scale, range of motion, Disabilities of the Arm, Shoulder and Hand score, and Short-Form 36. Patients' pain decreased significantly after surgery (mean 6.7). Forward elevation improved on average by 41.1 degrees and external rotation by 39.1 degrees , without evidence of shoulder instability. Final Short-Form 36 scores and Disabilities of the Arm, Shoulder and Hand results (mean, 44.7) were poor, but all patients rated themselves satisfied with the procedure. Shoulder arthroplasty provided pain relief for end-stage shoulder involvement in adult juvenile idiopathic arthritis. Improvement in external rotation in this severely affected group appears to have a beneficial effect on functional outcome.     

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome: a multicenter study

Long-term outcome of idiopathic steroid-resistant nephrotic syndrome was retrospectively studied in 78 children in eight centers for the past 20 years. Median age at onset was 4.4 years (1.1–15.0 years) and the gender ratio was 1.4. Median follow-up period was 7.7 years (1.0–19.7 years). The disease in 45 patients (58%) was initially not steroid-responsive and in 33 (42%) it was later non-responsive. The main therapeutic strategies included administration of ciclosporine (CsA) alone (n = 29; 37%) and CsA + mycophenolate mofetil (n = 18; 23%). Actuarial patient survival rate after 15 years was 97%. Renal survival rate after 5 years, 10 years and 15 years was 75%, 58% and 53%, respectively. An age at onset of nephrotic syndrome (NS) > 10 years was the only independent predictor of end-stage renal disease (ESRD) in a multivariate analysis using a Cox regression model (P < 0.001). Twenty patients (26%) received transplants; ten showed recurrence of the NS: seven within 2 days, one within 2 weeks, and two within 3–5 months. Seven patients lost their grafts, four from recurrence. Owing to better management, kidney survival in idiopathic steroid-resistant nephrotic syndrome (SRNS) has improved during the past 20 years. Further prospective controlled trials will delineate the potential benefit of new immunosuppressive treatment.     

Current treatments for juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, most of which differ from the main adult-onset inflammatory joint diseases. Nonsystemic forms of JIA (oligoarthritis, polyarthritis with or without rheumatoid factors, and spondyloarthropathies) are managed similarly to adult-onset rheumatoid arthritis or spondylarthritis, with a few differences. More specifically, JIA-associated chronic uveitis may require the use of biotherapies that remain experimental in JIA, such as monoclonal antibodies to TNFα or abatacept. International networks have enabled therapeutic trials of medications targeting TNFα alpha, interleukin (IL)-1, IL-6, or T-cell co-stimulation (abatacept). Systemic-onset JIA (also called childhood-onset Still's disease) raises specific treatment challenges and may require treatment with IL-1 antagonists, tocilizumab, or even thalidomide; as a very last resort, intensive immunosuppressant therapy with autologous hematopoietic stem-cell transplantation may be considered. Close monitoring of growth velocity and bone mass accrual is in order, and some patients require additional medications such as growth hormone. Patients with JIA should be managed in specialized centers that have coordinated chains of care for the entire pediatric period and into adulthood. In addition, the use in pediatric patients of recently introduced treatments requires close monitoring for long-term side effects.     

Long-term effects of cyclosporine in children with idiopathic nephrotic syndrome: a single-centre experience

Background. Because of its potential nephrotoxicity, the long-termuse of cyclosporine (CsA) as treatment for nephrotic syndrome(NS) is controversial. The clinical outcome of the patientswith NS treated with CsA is unclear. Methods. This study reports the results of long-term CsA treatmentin 117 children with idiopathic NS, who received CsA therapyfor more than 2 years (median, 34 months). The mean age of childrenat initiation of CsA therapy was 11±4 years. The startingdose of CsA was 5 mg/kg/day, adjusted to maintain a trough levelof 100–150 ng/ml in the first 2 months, 50–100 ng/mlthereafter. Later, a level as low as 30 ng/ml was accepted solong as it maintained remission. All patients received CsA between1993 and 2003. Indications for treatment included steroid-dependentnephrotic syndrome (SDNS) in 74 patients and steroid-resistantnephrotic syndrome (SRNS) in 43 patients. Initial renal histologyshowed minimal change disease (MCD) in 38 patients and focalsegmental glomerulosclerosis (FSGS) in 79 patients. Most patientswere receiving moderate doses of prednisone. Sixty patientsreceived cyclophosphamide prior to CsA. The observation periodswere 5.8±3 years and 6.1±1.9 years before andafter CsA treatment, respectively. Results. Complete remission [proteinuria <4 mg/h/m²/bodysurface area (BSA)], partial remission (proteinuria between4.1 and 40 mg/h/m²/BSA) and resistance to CsA (proteinuria 45mg/h/m²/BSA) were observed in 82.1, 5.1 and 12.8%, respectively.Hypertension, renal impairment (>30% rise of serum creatinine),gingival hyperplasia and hypertrichosis occurred in 10.3, 6.0,32.5 and 70.1%, respectively. Steroids were stopped in 102 patients,of which 31 relapsed. Out of 29 patients for whom CsA was intentionallydiscontinued while in remission, 22 relapsed. Of these, sixpatients were resistant to a second course of CsA. Post-therapybiopsies, performed in 45 patients (33 with SDNS and 12 withSRNS), showed mild stripped interstitial fibrosis and tubularatrophy in two SDNS patients (4.4%). At the last follow-up,one child had developed end-stage renal failure and two hadchronic renal insufficiency. Conclusions. Long-term CsA therapy in low doses is effectivein the treatment of children with idiopathic NS, but the rateof relapse is high after drug withdrawal. Hypertension developedin 10% of patients and renal insufficiency in 6% (most patientswith FSGS).     

Dramatic remission of nephrotic syndrome after unusual complication of mucormycosis in idiopathic membranous nephropathy

Mucormycosis is a rare and fatal opportunistic infection occurring in severely immunocompromised patients. Here, we report, for the first time, on a 65-year-old man with idiopathic membranous nephropathy and moderate renal dysfunction who suffered from life-threatening pulmonary mucormycosis during immunosuppressive therapy. After amphotericin B (AmB) administration with a total accumulating dose of 1.5 g, not only has he recovered from this fatal infection, but also his nephrotic syndrome has entered complete and long-term remission without any continued corticosteroid and immunosuppressive therapy during the 6-year follow-up. Serum creatinine levels remained stable by adjusting the tolerable daily dose of AmB during the period of treatment.     

Predictors of remission and relapse in idiopathic nephrotic syndrome: a prospective cohort study

Background

Although most children with idiopathic nephrotic syndrome will respond to corticosteroid therapy, 80–90 % suffer one or more relapses.

Methods

Using Cox proportional hazard models, we analyzed predictors of remission and relapse in 1-year follow-up data on children aged below 15 years with new-onset nephrotic syndrome.

Results

Of 129 children, 107 achieved remission with corticosteroid therapy and 86 subsequently relapsed. Boys achieved remission more often than girls (adjusted hazard ratio [AHR] 1.52, 95 % confidence interval (CI) 1.02–2.3). Boys relapsed significantly more frequently than girls (AHR 1.77, 95 % CI 1.11–2.83) and were more likely to have frequently relapsing disease (AHR 3.3, 95 % CI 1.18–9.23). The risk of first relapse increased with the number of days to first remission (AHR 1.02, 95 % CI 1.01–1.04). The risk for a frequently relapsing course increased with a shorter time from remission to first relapse (AHR 0.92, 95 % CI 0.87–0.97).

Conclusions

In idiopathic nephrotic syndrome, boys are more likely to respond initially, more likely to relapse, and to be classified as having frequently relapsing nephrotic syndrome. A decrease in time from remission to first relapse predicts for a frequently relapsing course.     

The remission of nephrotic syndrome with cyclosporin treatment does not attenuate the progression of idiopathic membranous nephropathy

BACKGROUND: Idiopathic membranous nephropathy (IMN), a common cause of nephrotic syndrome in adults, is usually treated by combination of corticosteroids with cytotoxic drugs. In cases resistant to this regimen, the use of cyclosporin A (CsA) is followed by frequent remissions of the nephrotic syndrome. AIM: The purpose of this study was to estimate the effectiveness of prednisolone and small doses of CsA as first-line treatment of nephrotic patients with IMN, in relation to the progression of the disease, based on functional and histological changes. PATIENTS AND METHODS: Sixteen patients, with nephrotic syndrome due to IMN and well-preserved renal function, were treated with prednisolone (starting dose: 0.5 mg/kg bw/day) and CsA (starting dose: 3 mg/kg bw/day) for 24 months. A repeat renal biopsy was performed after 18 months of treatment in 10 patients with remission of nephrotic syndrome, to estimate the activity of the disease and to identify any features of CsA toxicity. RESULTS: Remission of the nephrotic syndrome was observed in 14 out of 16 patients after 5 +/- 2 months of treatment. Complete remission was observed in 8 and partial remission in 6 patients (urinary protein was reduced from 6.9 +/- 3.4-0.2 +/- 0.06 g/24 h and 1.2 +/- 1.0 g/24 h, respectively, p < 0.01). The renal function was well preserved in 13 out of 16 patients over a 24-month period of treatment. Deterioration of renal function was observed in 3 patients (creatinine clearance reduced from 86 +/- 21-37 +/- 17 ml/min, p < 0.05) who had either persistent nephrotic syndrome or frequent relapses. Relapses of the nephrotic syndrome were observed in 5 of 14 patients. Repeat renal biopsies showed that glomerular sclerosis, tubulointerstitial injury, vascular hyalinosis and stage of the disease were deteriorated in most patients. Isometric vacuolization of tubular epithelial cells was observed in 2 of 10 patients. CONCLUSION: IMN nephrotic patients treated with prednisolone and low doses of cyclosporin A showed a high remission rate of nephrotic syndrome. However, progression of chronic histological lesions was found in repeat renal biopsies. This suggests that cyclosporin can frequently induce remission of nephrotic syndrome in IMN patients, but even low doses of the drug are not free of potential renal toxicity.     

Antioxidant status of children with idiopathic nephrotic syndrome

The production of free radicals can cause renal injury and play an important role in the pathogenesis of idiopathic nephrotic syndrome. Markers of reactive oxygen species (ROS) were evaluated in 48 patients with active nephrotic syndrome (ANS) and 30 age- and gender-matched healthy children. Plasma malondialdehyde (MDA), protein carbonyl, nitrite, copper, zinc, selenium, ascorbic acid, and superoxide dismutase (SOD) levels were estimated in patients with ANS and controls. Measurements were repeated in 39 cases after achievement of remission, and in 10 other children who were in remission of >6 months’ duration. Plasma MDA and nitrite levels were significantly higher and selenium was lower in ANS patients compared with controls. Plasma protein carbonyl, copper ascorbic acid, zinc, and superoxide dismutase levels were comparable in ANS patients and controls. Plasma copper level was significantly higher in active cases than in the remission and long-term remission groups. Selenium value showed a rise and then normalized in long-term remission. Among different sub-groups of ANS, no significant differences were found in the levels of various parameters, except plasma selenium, which was significantly lower in first-attack nephrotic syndrome (FANS) in comparison to infrequently relapsing nephrotic syndrome (IRNS) and frequently relapsing nephrotic syndrome (FRNS) patients. Thus, we observed evidence of oxidative stress and impaired antioxidant defense during acute nephrotic syndrome. Antioxidant status recovered completely only during long-term remission.     

Longterm complete remission of AL-amyloid-related nephrotic syndrome

We describe a 59-year-old man with nephrotic syndrome that was diagnosed as suspected minimal change nephrotic syndrome by the routine examination of renal tissues at first biopsy, because renal histology showed segmental mild mesangial expansion with argyrophilic staining and partial foot process fusion without any deposition. Prednisolone therapy induced complete remission of nephrotic syndrome. Relapse occurred after 4 years of complete remission, and the second renal biopsy revealed amyloid light-chain (AL)-amyloidosis. Re-examination of the first biopsy tissues by Congo red staining confirmed a small amount of amyloid deposition in the mesangial areas although the mesangial areas showed argyrophilic staining, which is atypical for amyloid deposition. This case raises a caution that even when renal histology is not suggestive of amyloidosis and prednisolone therapy is very effective, when a renal histology diagnosis is not confirmed, the clinician should suspect amyloidosis and should, at least, undertake Congo red staining to definitively rule out amyloidosis.     

Shoulder hemiarthroplasty in patients with juvenile idiopathic arthritis

Replacement of the shoulder in juvenile idiopathic arthritis is not often performed and there have been no published series to date. We present nine glenohumeral hemiarthroplasties in eight patients with systemic or polyarticular juvenile idiopathic arthritis. The mean follow-up was six years (59 to 89 months). The mean age at the time of surgery was 32 years. Surgery took place at a mean of 27 years after diagnosis. The results indicated excellent relief from pain. There was restoration of useful function which deteriorated with time, in part because of progression of the systemic disease in this severely affected group. No patient has required revision to date and there has been no radiological evidence of loosening or osteolysis around the implants. We discuss the pathoanatomical challenges unique to this group. There was very little space for a prosthetic joint and, in some cases, bony deformity and the small size necessitated the use of custom-made implants.