Thyroid hormone replacement for nephrotic syndrome patients with euthyroid sick syndrome: a meta-analysis

Objective: To assess the efficacy of thyroid hormone replacement therapy for nephrotic syndrome (NS) patients associated with euthyroid sick syndrome (ESS). Materials and methods: The Cochrane library, ISI, Ovid, PubMed, Chinese Biomedicine Database were searched, and reference list of relevant articles were selected. Randomized controlled trials (RCTs) or quasi-RCTs with thyroid hormone replacement on NS patients associated with ESS were included in this analysis. Results: Six trials (329 participants) were included. Meta-analysis showed that thyroid hormone replacement therapy can significantly increase the completely remission rate [OR?=?3.04, 95% confidence interval (CI): 3.04–1.88, p?p?Conclusions: Thyroid hormone replacement therapy significantly increases the remission of ESS in patients with NS.     

Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial

OBJECTIVE: To compare the efficacy (maintenance of remission), safety andtolerability of cyclosporin (CsA) with those of cyclophosphamidein patients with steroid-dependent or frequently relapsing nephroticsyndrome (NS). DESIGN: Open, prospective, randomized, multicentre, controlled studyfor parallel groups, stratified for adults and children. Thesetting was in nephrological departments in Italy. SUBJECTS AND INTERVENTIONS: Seventy-three patients with steroid-sensitive idiopathic NSadmitted to the study were randomly assigned to cyclophosphamide(2.5 mg/kg/day) for 8 weeks or CsA (5 mg/kg/day in adults, 6mg/kg/day in children) for 9 months, tapered off by 25% everymonth until complete discontinuation at month 12. Seven patientslost to follow up were not considered in the analysis. The remaining66 patients were followed up for 3–24 months after randomization. MAIN OUTCOME MEASURES: Relapse-free survival; number of N.S. relapses/patient/year;cumulative dose of prednisone/patient; laboratory investigations(kidney and liver functions, haematological parameters); incidenceof adverse events. RESULTS: At month 9, 26 of 35 CsA-treated patients were still in completeremission and a further five patients were in partial remission;18 of 28 cyclophos-phamide-treated patients were in completeremission, and one in partial remission (P=NS). No differencebetween adults and children was seen with either treatment.The risk of relapse was similar between frequent relapsers (19of 22) and steroid-dependent patients (8 of 14) given CsA, andthose given cyclophosphamide (5 of 15 and 6 of 15). The meannumber of relapses per year and the mean dose of prednisoneper year were significantly less (P<0.001) in both groupsfor the experimental year than for the year before randomization.At 2 years, 25% of the patients given CsA (50% adults and 20%children) and 63% of those given cyclophosphamide (40% adultsand 68% children) had not had any relapse of NS. Tolerance to the two drugs was generally good. The CsA-relatedside-effects were mild and disappeared after drug discontinuation. CONCLUSIONS: This study shows that both treatments are effective and welltolerated; more patients given cyclophosphamide had stable remissions.     

Serum selenium level and glutathione peroxidase activity in steroid-sensitive nephrotic syndrome

In our previous study the pattern of glutathione peroxidase (GPX) activity in the course of steroid–sensitive nephrotic syndrome (SSNS) in children suggested a defect in antioxidant defense. In the present report the serum selenium (Se) level, an essential component of GPX activity, was measured in a comparable group of children with SSNS at the same clinical stages at which GPX activity was determined in the previous study. Nephrotic children had normal serum Se levels during the edematous stage, at the end of prednisone treatment, and in remission. At the end of high-dose prednisone treatment, the serum Se level increased (P<0.01) simultaneously with enhanced activity of GPX. These results suggest that children with SSNS have a persistent defect in the antioxidant defense at the important stage of hydrogen peroxide and fatty acid hydroperoxide decomposition. This defect is transiently alleviated by high-dose prednisone treatment.     

Transient insulin-dependent diabetes mellitus in children with steroid-dependent idiopathic nephrotic syndrome during tacrolimus treatment

Despite the availability of immunosuppressive drugs such as prednisone, cyclophosphamide, cyclosporine A (CyA) and mycophenolate mofetil for the treatment of steroid-dependent idiopathic nephrotic syndrome (SDNS), medication-free remission is not achieved in a number of patients. To avoid excessive steroid toxicity, the use of tacrolimus (Tac) has been discussed. We report on five children diagnosed with SDNS on the histological basis of minimal change glomerulopathy or focal segmental glomerulosclerosis. Following the failure of other medications to achieve sustained remission, Tac was administered to these patients who varied in age from 10.5 to 13.5 years. Only one patient showed a substantial reduction in the number of relapses with the Tac treatment. Two boys, after 9 and 44 months on therapy, respectively, developed insulin-dependent diabetes mellitus (IDDM), necessitating the withdrawal of Tac and the daily use of insulin for 3 and 6 months. In both patients hyperglycemia had occurred during prednisone-based relapse therapy of SDNS. The patients had low serum protein concentrations, presumably increasing the free active Tac fraction, while trough levels of the drug remained unchanged. Both of the affected patients had additional risk factors for impaired glucose tolerance, such as morbid obesity (patient 1; BMI: 41.6 kg/m²) and African American origin (patient 2). Our case reports demonstrate that the use of Tac in patients with SDNS may be associated with an increased risk for IDDM, especially during relapse of NS, and particularly if additional risk factors are present. Moreover, Tac does not appear to substantially increase the success of treatment.     

Serum and urine soluble interleukin-2 receptor in idiopathic nephrotic syndrome

Although a cellular immune pathogenesis is suspected in idiopathic nephrotic syndrome of childhood (INS), there is scant direct evidence of in vivo immune activation. In order to investigate cytokine cascade activation in INS, soluble interleukin-2 receptor (sIL-2R) in plasma and urine was characterized and its levels measured in INS patients during relapse. Immunochemically detectable sIL-2R had a molecular mass of 35–46 kDa in both serum and urine and the molecule appears to be excreted intact; the pI was 5.05. INS patients had elevated serum sIL-2R levels compared with adult normal controls (845±97 vs. 373±47 U/ml,P=0.001) and were significantly higher than previously published age-matched controls. Urinary excretion of sIL-2R was 47.2±13 U/mg creatinine in patients. Both the sIL-2R excretion rate and the fractional excretion of sIL-2R were positively correlated with the excretion of albumin (P=0.02 and 0.002, respectively). These increased serum and urine levels occurred whether relapse was or was not associated with an intercurrent illness. We conclude that: (1) despite increased sIL-2R excretion during INS relapse, serum levels are significantly elevated; (2) while the elevated urinary levels could result from enhanced intrarenal production, they more likely reflect the increased serum levels; (3) the elevated sIL-2R levels support an immune pathogenesis in INS.     

Elevated urinary neopterin: A clue of activated macrophage and cellular immune response in the pathogenesis of idiopathic nephrotic syndrome

Summary: A study of cell mediated immunity (CMI) activation in patients with idiopathic nephrotic syndrome (INS) in the tropics was undertaken. Cell mediated immunity activation was investigated by measuring urinary neopterin excretion. All 31 patients with idiopathic nephrotic syndrome due to either minimal change nephrotic syndrome (MCNS), and focal and segmental glomerulosclerosis (FSGS) had significant elevation of neopterin excretion (mean values 451, 544 μmol neopterin/mol creatinine) when compared with 222 normal subjects (mean value 130, P < 0.001). However, in 25 patients with non-nephrotic IgA nephropathy and eight nephrotic membranous nephropathy the urinary neopterin was not raised (mean value 131 and 129). A further 10 patients with MCNS were restudied when in complete remission and their urinary neopterin was found to have decreased significantly (mean value 186); however, this level was still above the normal range. Our study suggests that CMI and macrophage activation takes place in the pathogenesis of idiopathic nephrosis.     

The long-term outlook to final outcome and steroid treatment results in children with idiopathic nephrotic syndrome

Abstract

Idiopathic Nephrotic Syndrome (INS) was defined as combination of a nephrotic syndrome and non-specific histological abnormalities of the kidney. Among these abnormalities, minimal change nephrotic syndrome (MCNS) is the most common. We report our experience with MCNS; its clinical course, treatments and outcomes. One-hundred twenty children (66 male, 54 female) with MCNS, admitted to Nephrology Department between 1987–2009 was assessed. Their clinical presentations, treatment and disease courses were reviewed. The mean duration of follow-up was 11.5?±?1.9 years. Initially, all patients given prednisone 2?mg/kg/ day single dose per four weeks a followed by eight weeks of the same daily dose given every other day. After week 12, prednisone was progressively tapered off at the rate of 0.5?mg/kg per 15 daily intervals until complete discontinuation had been achieved by week 16. Steroid resistance was accepted as no achievement of remission following four weeks of prednisone 2?mg/kg/day followed by three intravenous pulses of corticosteroids. At the end of the initial steroid treatment, 106 (88.3%) patients were determinate steroid responsive while 14 (11.7%) patients were steroid resistance. Thirty-eight patients underwent biopsy. At the end of study recovery rate was increased from 88.3% to 94.1%. In conclusion, most of patients entered remission by our therapy end of follow up time. With the support of our satisfactory results among the whole study group, long-term prednisolone treatment still remains valid.     

The efficacy and safety of tacrolimus monotherapy in adult-onset nephrotic syndrome caused by idiopathic membranous nephropathy

Introduction: The purpose of the study is to evaluate the efficiency and safety of tacrolimus (TAC) monotherapy in the treatment of nephrotic idiopathic membranous nephropathy (IMN) compared with the protocol of cyclophosphamide (CTX) combined with corticosteroids.

Methods: In total, 58 patients with nephrotic syndrome and biopsy-proven IMN were included in this study. 30 patients received TAC monotherapy with an initial dose of 0.05–0.1?mg/kg/day. 28 patients received transvenous CTX at a dose of 0.5–0.75?g/m² once in every month initially for 6?months and once in every 2 or 3?months for the later period, and the regimen was combined with corticosteroids (prednisone 1?mg/kg/d). All patients were observed for the treatment effects, recurrence and side effects.

Results: Twelve months after the initial treatment, a total of 24 (80%) patients in the TAC group and 23 (82.1%) patients in the CTX group achieved remission (either partial or complete remission). The survival curve of the probability of remission and complete remission were similar between the two groups (p?>?.05). Proteinuria (based on 24?h urinary protein excretion) was significantly decreased, and serum albumin was significantly increased after immunosuppressive treatment in both the groups. Estimated glomerular filtration rate (eGFR) was comparable between before and after treatment. The main adverse effects in TAC treatment were glucose intolerance, diabetes and abnormal aminotransferase.

Conclusions: TAC monotherapy is an alternative therapeutic regimen for patients with nephrotic IMN. Its short-term efficiency and patient tolerance are both acceptable.     

Comparison of immunosuppressive therapeutic regimens in patients with nephrotic syndrome due to idiopathic membranous nephropathy

In this prospective randomized trial, we compared the effects of cyclosporine- and cyclophosphamide-based treatment regimens in patients with idiopathic membranous nephropathy. Twenty-eight patients were randomized to receive treatment with one of the three therapeutic regimens: cyclosporine with methylprednisolone, cyclophosphamide with methylprednisolone or lisinopril (control). Renal function and nephrotic syndrome parameters were determined at baseline and during a 9-month treatment period. At the end of the study period, renal function improved significantly in the cyclophosphamide and deteriorated significantly in the cyclosporine group. Serum albumin levels increased significantly in the cyclosporine and cyclophosphamide group. Total cholesterol levels and proteinuria were significantly reduced in all groups. In the comparison between the groups, serum albumin levels were significantly lower in the control group and there were no differences in the rest of the studied parameters at the end of the study. Six patients from the cyclosporine group (1/10 complete and 5/10 partial), all cyclophosphamide-treated (4/8 complete and 4/8 partial) and all 10 lisinopril-treated patients (10/10 partial) were on remission at the end of the study. In conclusion, cyclosporine-based regimens are not inferior to cyclophosphamide-based regimens. Cyclophosphamide is associated with more complete remissions after 9 months of treatment. Lisinopril is associated with a significant proteinuria reduction and without inducing any complete remissions.     

Concomitant administration of cyclosporine and ketoconazole in idiopathic nephrotic syndrome.

BACKGROUND: The deliberate use of ketoconazole to reduce the need for cyclosporine (CsA) is not new, but it is particularly relevant because of the high cost of CsA. Many studies have documented this benefit in renal and cardiac transplants, but this co-administration has not been reported in patients with nephrotic syndrome. METHODS: This retrospective study included 207 nephrotic patients who were steroid resistant, dependent or frequent relapsers and received CsA therapy. Among these patients 153 received daily ketoconazole therapy in a dose of 50 mg with concomitant decrease of one-third of the CsA dose while 54 patients received CsA alone. The majority of our cases were children (179 were below 18 years) and male to female ratio was 1.7:1. RESULTS: The great majority of the study population received the drugs for 1-2 years. Patients who received CsA and ketoconazole were comparable with those who received CsA alone regarding age, sex, duration of renal disease, renal pathology, severity of nephrotic syndrome, renal function, hepatic function and steroid response. Co-administration of ketoconazole significantly reduced mean doses of CsA by 37% after 1 month and 47% at 1 year with overall net cost savings of 37%. Hepatic functions remained within the normal range in both groups. Additionally, co-administration of ketoconazole significantly improved the response to CsA therapy, successful steroid withdrawal and decreased the frequency of renal impairment. CONCLUSIONS: Co-administration of keto with CsA in idiopathic nephrotic patients significantly reduces CsA costs and may improve its response.     

家族性激素反应性肾病综合征一家系报告及文献复习

目的 报道家族性激素反应性肾病综合征，分析其临床病理特点及家族发病的特点，及其与NPHS2基因的关系。方法 分析患者临床及病理表现特点，并对其家族成员患病情况进行调查；与文献报告的家族性激素反应性肾病综合征对比。运用高效液相色谱(DHPLC)的方法检测该家系NPHS2基因突变。结果 该家族的患病情况符合文献报告的家族性激素反应性肾病综合征的定义，临床表现为肾病综合征，病理改变为肾小球微小病变，对足量的强的松治疗反应敏感，易复发，但发病年龄较国际上报道的中位年龄高。同国外同类报道一样，该家族中未发现NPHS2突变。结论 首次在国内报告家族激素反应性肾病综合征。该疾病在此家系中的发生与NPHS2无明显关系.     

Plasma total homocysteine concentration in nephrotic patients with idiopathic membranous nephropathy.

BACKGROUND: The atherothrombotic risk pattern of the nephrotic syndrome resembles that of hyperhomocysteinemia. However, the effect of nephrotic range proteinuria on homocysteine metabolism has never been studied. METHODS: The study included 11 male nephrotic patients with idiopathic membranous nephropathy who underwent a treatment trial with adrenocorticotrophic hormone and 11 male non-nephrotic, renal function-matched control subjects. The nephrotic patients were studied before and after the treatment, which induced a marked reduction in urinary protein excretion and a moderate improvement in renal function in all cases. RESULTS: Plasma total homocysteine (tHcy) concentration did not change significantly during treatment, whereas the nephrotic patients had significantly lower tHcy than the non-nephrotic patients (14.2 +/- 3.4 micromol/l vs 19.0 +/- 5.4 micromol/l). tHcy correlated significantly with serum concentrations of creatinine (r = 0.53, P < 0.05) and albumin (r = 0.43, P < 0.05), glomerular filtration rates (GFRs) (iohexol clearances) (r = -0.42, P < 0.05) and urinary albumin excretion (r = -0.47, P < 0.05). CONCLUSION: The expected tHcy-lowering effect of improved renal function may have masked a tHcy-elevating effect due to reduced proteinuria leading to no net change in tHcy during treatment. The notion of an increase in tHcy associated with remission of the nephrotic syndrome is in accordance with the significantly lower tHcy in the nephrotic renal patients compared with the non-nephrotic renal function-matched patients, and the relationships between tHcy and serum albumin concentrations as well as urinary albumin excretion. Thus, the results of this small study suggest that nephrotic range proteinuria directs homocysteine metabolism towards a decrease in tHcy. However, the findings need to be confirmed in larger patient populations and in different varieties of the nephrotic syndrome.     

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).     

Urotensin-II levels in children with minimal change nephrotic syndrome

Human urotensin-II (hU-II) is the most potent mammalian vasoconstrictor identified to date. Although it is expressed mainly in the brain and spinal cord, it is also detected in other tissues, such as the kidney. It has been speculated that U-II might be an important physiological mediator of vascular tone and blood pressure in humans. To our knowledge, no studies have investigated the level of U-II in children with minimal change nephrotic syndrome (MCNS). Considering the renal synthesis and vasoactive role of U-II, we aimed to measure the plasma and urinary levels of U-II in children with MCNS, and investigate the correlation with other clinical and laboratory findings. Twenty-six children with clinical MCNS, ranging in age from 2 to 7 years, were compared with 16 healthy age- and sex-matched controls. The median age of the children was 4.73±2.36 years. U-II level was measured by RIA. Plasma U-II concentrations (pg/ml) were decreased during relapse (20.11±14.43 in relapse, 38.94±23.86 in remission, P <0.05), whereas urinary U-II levels (pg/mg urinary creatinine) were significantly higher in relapse than in remission (37.31±28.43 in relapse, 31.09±21.10 in remission, P <0.05). We could not detect any relationship between U-II levels and other clinical and laboratory parameters. Our data indicate that the important changes in plasma and urinary U-II levels during relapse may be the result of heavy proteinuria rather than playing a role in mediating the clinical and laboratory manifestations of MCNS in children.     

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.     

Serum levels of immunoglobulins and IgG subclasses in steroid sensitive nephrotic syndrome

Alterations of serum immunoglobulins, especially hypogammaglobulinemia (HG), are a frequent finding in steroid sensitive nephrotic syndrome (SSNS). The exact mechanisms are unclear, especially the persistence of HG into remission. Therefore we studied serum immunoglobulins M, A and G including IgG subclasses 1–4 in 44 children with SSNS; 14 were studied during relapse (RL) and 30 in remission (RM). Data were compared with those of 23 healthy controls. In a subgroup of 23 patients (12 in RM and 11 in RL) we also studied IgG-1 specific antibodies to tetanus toxoid and IgG-2 specific antibodies to pneumococcus antigen. Increased serum concentrations of IgM in RL and reduction of serum IgG in RL and RM were confirmed. During relapse, HG was characterized to result from deficiency of IgG-1–3, whereas in early phases of relapse the reduction was due to low IgG-1 only. In RM the deficiency of IgG-2 persisted for 12 months and correlated strongly with the duration of remission (R=0.60, P<0.0001). IgG-4 levels were not altered in SSNS. In addition, IgG-2 specific antibodies to pneumococcus antigen were significantly reduced only in RL compared to RM (P<0.05). In conclusion, hypogammaglobulinemia of SSNS is characterized by a different constitution of IgG subclasses. In RL a reduction of serum levels of IgG-1–3 occurs, while low concentrations of IgG-2 might be the explanation for HG in remission of SSNS. Received: 3 October 2001 / Revised: 6 December 2001 / Accepted: 7 December 2001     

Atherosclerosis risk factors in young patients formerly treated for idiopathic nephrotic syndrome

A total of 30 patients (ten female/20 male), 9 years to 22 years old (mean age 17.3 years) and 30 healthy teenage controls (mean age 16.4 years) were included in our study. The patients had steroid-sensitive idiopathic nephrotic syndrome (INS) and had completed steroid therapy 4 years to 15 years ago. Height and weight, body mass index (BMI), body composition, and intima-media thickness (IMT) were determined, as were levels of total cholesterol (TCh), low-density lipoprotein cholesterol (LDL-Ch), high-density lipoprotein cholesterol (HDL-Ch), triacylglycerols (TAGs), homocysteine (HCY), and high-sensitivity C-reactive protein (hsCRP). We did not observe any differences between the study and control groups in IMT (0.47 ± 0.1 vs 0.46 ± 0.1 mm) and body composition (fat tissue and water content). Differences in HDL-Ch and hsCRP levels between groups were not significant. In the study group we found significantly higher TCh levels (187.6 ± 57.2 mg/dl vs 158.8 ± 25.7 mg/dl; P = 0.012), LDL-Ch (115.9 ± 63.7 mg/dl vs 79.4 ± 25.4 mg/dl; P = 0.005), HCY (12.3 ± 7.7 μmol/l vs 7.6 ± 1.6 μmol/dl; P < 0.001), apolipoprotein B (ApoB) (113.6 ± 30.0 mg/dl vs 78.7 ± 13.6 mg/dl; P < 0.001) and ApoA1 (203.5 ± 50.8 mg/dl vs 156.5 ± 12.4 mg/dl; P < 0.001) levels. Multi-factor analysis of the influence of independent factors (number of recurrences, duration of remission, age, gender, and BMI) on the parameters under investigation indicated a positive correlation between IMT and the number of recurrences. Conclusions: 1. Patients treated for idiopathic nephrotic syndrome in the past should undergo regular laboratory tests of atherosclerosis risk factors, including not only cholesterol and its fractions, but also ApoA1, ApoB and HCY. 2. It is necessary to continue systematic check-ups of the intima-media thickness of the carotid arteries among young patients with anamnesis of INS, especially among patients who suffered from numerous relapses of this disease.     

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.