Tacrolimus Monotherapy after Intravenous Methylprednisolone in Adults with Minimal Change Nephrotic Syndrome
|
|
- Dorthy McCarthy
- 6 years ago
- Views:
Transcription
1 Tacrolimus Monotherapy after Intravenous Methylprednisolone in Adults with Minimal Change Nephrotic Syndrome Xiayu Li,* Zhangsuo Liu, Li Wang, Rong Wang, Guohua Ding, Wei Shi, Ping Fu,** Yani He, Genyang Cheng, Shukun Wu, Bing Chen, Juan Du, Zhiming Ye, Ye Tao,** Bengang Huo, Heng Li,* and Jianghua Chen* *Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China; Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; Department of Nephrology, Sichuan Academy of Medical Sciences, Sichuan Provincial People s Hospital, Chengdu, China; Department of Nephrology, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, China; Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China; Nephrology Division, Guangdong General Hospital, Guangzhou, China; **Division of Nephrology, West China Hospital of Sichuan University, Chengdu, China; and Department of Nephrology, Daping Hospital, Research Institute of Surgery, Third Military Medical University, Chongqing, China ABSTRACT Glucocorticoid treatment is the first choice therapy for adults with minimal change nephrotic syndrome; however, this therapy associates with many adverse effects. Tacrolimus may be an alternative to conventional glucocorticoid therapy. To investigate this possibility,we conducted a prospective, randomized, controlled trial (WHO International Clinical Trials Registry Platform: ChiCTR-TRC ) in eight renal units across China. We randomized enrolled patients with adult onset minimal change nephrotic syndrome (n=119) to receive glucocorticoid therapy or tacrolimus after intravenous methylprednisolone (0.8 mg/kg per day) for 10 days. Patients received a conventional glucocorticoid regimen or tacrolimus monotherapy, starting with 0.05 mg/kg per day (target trough whole blood level of 4 8 ng/ml)for weeks and subsequently tapering over approximately 18 weeks. Remission occurred in 51 of 53 (96.2%; all complete remission) glucocorticoid-treated patients and 55 of 56 (98.3%; 52 complete and three partial remission) tacrolimus-treated patients (P=0.61 for remission; P=0.68 forcompleteremission). Thegroups hadsimilarmeantime toremission(p=0.55). Relapse occurred in 49.0% and 45.5% of the glucocorticoid- and tacrolimus-treated patients, respectively (P=0.71), with similar time to relapse (P=0.86). Seven (13.7%) glucocorticoid-treated and four (7.3%) tacrolimus-treated patients suffered frequent relapse (P=0.28); five glucocorticoid-treated and two tacrolimus-treated patients became drug dependent (P=0.26). Adverse events occurred more frequently in the glucocorticoid group (128 versus 81 in the tacrolimus group). Seven adverse events in the glucocorticoid group and two adverse events in the tacrolimus group were serious. Consequently, tacrolimus monotherapy after short term intravenous methylprednisolone is noninferior to conventional glucocorticoid treatment for adult onset minimal change nephrotic syndrome in this cohort. J Am Soc Nephrol 28: ccc ccc, doi: /ASN Minimal change nephrotic syndrome (MCNS) accounts for 10% 25% of all nephrotic syndromes affecting adults. 1,2 Glucocorticoids (GCs) are the first-line therapy for adults with MCNS according to the Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines. 3 Their use has affected a remission in approximately 80% of patients with MCNS. 2 5 However, MCNS remains a Received March 22, Accepted September 15, Published online ahead of print. Publication date available at. Correspondence: Dr. Jianghua Chen, Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province, China. chenjianghua@zju.edu.cn Copyright 2016 by the American Society of Nephrology J Am Soc Nephrol 28: ccc ccc, 2016 ISSN : /2804-ccc 1
2 therapeutic challenge for physicians, because 48% 76% of initially steroid responsive patients with MCNS experience at least one relapse, whereas up to one third of patients frequently relapse or become steroid dependent, necessitating the use of a high cumulative dose of GCs. 2 6 The adverse effects of long term GC treatment include osteoporosis, infection, psychosis, cataract, hypertension, diabetes mellitus, gastrointestinal bleeding, and obesity, many of which are serious afflictions. 6 9 Second or third line immunosuppressive agents, such as cyclophosphamide, calcineurin inhibitors (CNIs), mycophenolate mofetil, and rituximab, have been used to reduce or alleviate the adverse effects of GCs in these patients. 2,3,8 11 Therefore, care must be taken to balance the risks and benefits of GCs for the treatment of adult MCNS. Ideal regimens in the treatment of adult MCNS should comprise rapid induction, longer term sustained remission, and fewer adverse effects. The theory that T and/or B cell mediated events result in the production of a yet to be identified circulating factor that harms glomerular cells, causing MCNS, is well documented. 12,13 In addition, the roles of two podocyte proteins (i.e., CD80 and angiopoietin-like protein 4) have been explored in MCNS Tacrolimus (TAC) is a stronger suppressor of the immune system, most notably of T cells, than cyclosporin and differs in the nature of its cytokine suppression. This may explain its differential effect on proteinuria in nephrotic syndromes, particularly MCNS. 16 Interestingly, recent findings showed that the additional effect of TAC on proteinuria was a result of the stabilization of the actin cytoskeleton or reduction of angiopoietin-like protein 4 levels in podocytes. 17,18 These results suggest that the antiproteinuric effect of TAC is independent of its immunosuppressive effect and instead, results from a direct effect on podocytes, indicating its potential application in the treatment of MCNS. Several previous studies have reported the use of TAC for the treatment of refractory MCNS in adult and pediatric patients. 10,19 22 A controlled trial suggested that TAC might be a promising alternative to cyclosporin because of its lower risk of relapse and lack of cosmetic adverse effects. 21 We have previously published a case series with TAC as the preferred CNI for the treatment of adults with steroid-dependent and steroid-resistant MCNS, showing that TAC was a more effective and safe treatment alternative for such patients. 19,20 In addition, our group recently found that TAC might be a potential rescue therapy of adult patients with MCNS irresponsive to a steroid (or a steroid combined with another immunosuppressive drug) treatment or who developed reversible acute renal failure. 23,24 Despite these promising results, further research is warranted to determine if TAC monotherapy has fewer adverse effects than observed for steroid therapy to successfully replace steroids as the primary course of therapy for patients with MCNS. This multicenter, randomized trial tested this hypothesis by comparing a new strategy of short term intravenous methylprednisolone followed by TAC monotherapy with conventional GC treatment in adult patients with MCNS. RESULTS Patients One hundred nineteen adult patients admitted between September 28, 2011 and May 10, 2013 at eight clinical centers were randomly enrolled into the trial (Figure 1). Fiftysix and sixty-three patients were assigned to the GC group and the TAC group, respectively. The baseline characteristics of the two groups were similar (Table 1). One hundred nine patients (53 in the GC group and 56 in the TAC group) completed at least 12 weeks of therapy and were included in the subsequent evaluation of efficacy. One hundred patients (47 in the GC group and 53 in the TAC group) completed at least 24 weeks of therapy. One patient from each group discontinued treatment due to serious adverse events (AEs) severe abdominal cavity infection in the GC group and reversible acute nephrotoxicity in the TAC group. A second renal biopsy was performed in some patients because of no remission, partial remission, or relapses (five and four in the GC and TAC groups, respectively), resulting in a modification of the initial histopathologic pattern in four patients (two each in the GC and TAC groups) from minimal change nephropathy to FSGS. The mean dose of TAC administered was mg/d (corresponding to mg/kg per day) during the first 20 weeks of treatment and mg/d (corresponding to mg/kg per day) during the following 16 weeks. Primary Outcomes Efficacy The treatment efficacy was evaluated on the basis of the outcome of patients who completed at least 12 weeks of therapy. The study was designed as a noninferiority trial to determine whether the difference in the remission (either complete or partial remission) rates between the GC and TAC groups was not.9.5%. The remission rates were 96.2% (51 of 53) and 98.3% (55 of 56) in the GC and TAC groups, respectively (P=0.61), and could be evaluated with a 95% confidence interval (95% CI) for difference (95% CI, 26% to 10%) in noninferiority of the TAC group. Complete remission was experienced by 51 of 53 patients (96.2%) in the GC group and 52 of 56 patients (92.9%) in the TAC group (P=0.68) (Figure 2). The mean time to remission was similar in the GC ( ; range = weeks) and TAC ( ; range = weeks) groups (P=0.55). Patients who showed no remission because of persistent severe proteinuria (two in the GC group and one in the TAC group) were recommended to receive the exchange protocol. One of these two patients in the GC group achieved complete remission after switching to the TAC protocol; the other patient exhibited resistance to both TAC and combinedtacandgctherapyandwasrediagnosedwithfsgs after repeat renal biopsy. The one patient with exhibiting resistance to TAC showed no response after switching to the GC protocol. 2 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc ccc, 2016
3 CLINICAL RESEARCH Figure 1. Flow chart of study populations, including the number of patients who were assessed for eligibility, underwent randomization, and completed the study treatment. Of 162 patients assessed for eligibility, 43 patients were withdrawn, 119 patients were randomly enrolled in GC group (n=56) or TAC group (n=63). One hundred patients (47 in the GC and 53 in the TAC group) completed at least 24 weeks of therapy. Changes in the Proteinuria and Serum Albumin Levels Figure 3 shows the proteinuria and serum albumin levels of the patients before the start and at the regular checkups after the start of GC and TAC treatments. No significant differences were observed in mean proteinuria during therapy between the two groups (P.0.05). The differences in the mean serum Table 1. Baseline characteristics of participants Characteristic Overall, n=119 GC Group, n=55 TAC Group, n=63 Women, n (%) 52 (43.7) 26 (46.4) 26 (41.3) Age at enrollment, yr Duration of disease, d Proteinuria, g/d Serum albumin, g/l SCr, mmol/l a egfr, ml/min per 1.73 m 2b BP, mmhg Systolic Diastolic Hypertension, n (%) 12 (10.5) 6 (11.5) 6 (9.7) Weight, kg Body mass index, kg/m Fasting blood sugar, mmol/l Serum cholesterol, mmol/l Serum triglyceride, mmol/l Serum LDL, mmol/l Serum uric acid, mmol/l Values are expressed as the mean6sd or number (percentage). a To convert creatinine values to milligrams per deciliter, multiply by b The GFR was estimated using the four variable Modification of Diet in Renal Disease Study equation: GFR=1863SCr (21.154) 3 age (20.203) (if black) (if woman). albumin levels between the two groups during the treatment period were not statistically significant (P.0.05). Secondary Outcomes Relapses The incidence of relapse in both treatment groups is presented in Table 2. Among those patients who experienced remission, 26 of 51 (51.0%; GC) and 30 of 55 (54.5%; TAC) patients who underwent remission sustained the remission successfully (P=0.71). The mean time to relapse was similar between the GC ( ; range = weeks) and the TAC ( ; range = weeks) groups (P=0.86). The Kaplan Meier curves show the probability of first relapse at different time points between the GC and TAC groups (P=0.81; log rank test) (Figure 4). Frequent relapses were observed in seven (13.7%; GC) and four (7.3%; TAC) patients (P=0.28), whereas five and two patients in the GC and TAC groups, respectively, became drug dependent (P=0.26). There were five late nonresponders (three in the GC group and two in the TAC group). Renal Function Four (7.1%) patients in the GC group and three (4.8%) in the TAC group suffered J Am Soc Nephrol 28: ccc ccc, 2016 Tacrolimus in Adult Minimal Change Disease 3
4 Figure 2. Percentage of patients who achieved complete remission (CR) and partial remission (PR) during the 36 weeks of therapy. The treatment efficacy was evaluated on the basis of the outcome of patients who completed at least 12 weeks of therapy. The remission rate was 96.2% (51 out of 53 patients) and 98.3% (55 out of 56 patients) in the GC and TAC group, respectively (P=0.61). Complete remission was experienced by 51 out of 53 patients (96.2%) in the GC group and 52 out of 56 patients (92.9%) in the TAC group (P=0.68). Three patients (2 in the GC group and 1 in the TAC group) showed no remission. G, GC group; T, TAC group. AKI. One patient in the TAC group developed exacerbated AKI, with an increase in serum creatinine (SCr) levels from 75 mmol/l before TAC therapy to 156 mmol/l after 1 week of therapy; the SCr decreased from 156 to 76 mmol/l after TAC treatment was discontinued for 1 week. The other patients in both groups suffered AKI because of a rapid decrease in the serum albumin levels during the relapse period. The changes in the SCr and egfr levels during the treatment period and the finalfollow-upperiodarepresentedinfigure5.thescr and egfr levels did not differ significantly between the GC and TAC groups (P.0.05). Repeat renal biopsies were performed in four patients after initiation of TAC. No evidence of TAC nephrotoxicity was observed in the sections obtained from patients. Changes in Metabolic Indices and Quality of Life The changes in metabolic indices during therapy with GC or TAC are presented in Supplemental Table 1. New onset overweight characteristics (body mass index of 25 to approximately 29.9 kg/m 2 ) were observed in six (10.7%; GC) and zero (TAC) patients (P=0.01). New onset glucose intolerance was observed in six (10.7%; GC) and four (6.4%; TAC) patients, and new onset diabetes mellitus was observed in three patients of the GC group. Dyslipidemia after the 12-week therapy was still observed in 11 (19.6%; GC) patients and three (4.8%; TAC) patients who required statin therapy. New-onset hyperuricemia was observed in six (10.7%; GC) patients and 11 (17.5%; TAC) patients, of whom nine showed reversal after cessation of TAC therapy. New-onset hypertension occurred in ten (17.9%; GC) patients versus four (6.4%; TAC) patients who required antihypertensive medication. Eight dimensions of the 36-item short form health survey (SF-36; physical functioning, mental health, physical role, bodily pain, general health, vitality, social functioning, and emotional role) were similar among the patients of the GC and TAC groups at all time points. AEs Two hundred nine AEs (128 and 81 in patients in the GC and TAC groups, respectively) were recorded in 92 patients (49, GC;43,TAC)(Table3);ofthese,nine (seven and two in the GC and TAC groups, respectively) were deemed as serious AEs that needed hospital treatment. The most common AEs observed in the two groups were infections, hepatotoxicity, gastrointestinal symptoms, and new-onset hypertension. The patients in the GC group had some additional AEs, including metabolic disorders, osteoporosis, Cushing syndrome, purple stripes, and acne; those in the TAC group also had reversible hyperuricemia. DISCUSSION This study suggests that TAC monotherapy after short term intravenous methylprednisolone is noninferior to conventional steroid therapy in inducing remission. A similar percentage of patients in the GC (96.2%) and TAC (98.3%) groups showed remission (complete or partial), with 96.2% (GC) and 92.9% (TAC) of the patients experiencing complete remission. Previous studies showed that GC therapy resulted in remission in approximately 80% of adults with MCNS, with 50% of the patients responding by 4 weeks, and 10% 25% of the patients requiring weeks of therapy. 2,4,5 However, the majority (over 90%) of the patients in this trial had attained remission by 4 weeks, and the mean time to remission was similar between the two groups. The optimal dose, trough level, and duration of TAC therapy remain unknown, because they are solely on the basis of case series reports In this trial, we found that a mean TAC dose of 0.05 mg/kg per day, with trough levels ranging from 4 to 8 ng/ml, was sufficient to induce remission in the majority of the patients with MCNS. 4 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc ccc, 2016
5 CLINICAL RESEARCH Figure 3. Changes in proteinuria and serum albumin levels at baseline and during the 36 weeks of therapy. (A) Proteinuria and (B) serum albumin before therapy (week 0) and during the 36 weeks of therapy. No significant differences between the two groups were observed in mean proteinuria and serum albumin levels before therapy and during the 36 weeks of therapy (P.0.05). Relapse rates in adults with MCNS are high. Case series data show that 48% 76% of the patients experience at least one relapse after steroid-induced remission, which is often accompanied by frequent relapses or steroid dependence. 4 6,25,26 Furthermore, in previous studies, the relapse group showed a significantly higher frequency of steroid AEs, such as cataract and osteoporosis, compared with the nonrelapse group. 6,7,26 Steroid-sparing agents, such as cyclophosphamide, CNIs, and mycophenolate mofetil, are recommended to avoid steroid dependence. 3 A recent trial indicated the efficacyof rituximab in childhood onset nephrotic syndrome, complicated frequent relapses, and steroid dependence. 11 In our previous study, we showed that steroid dependent/steroid resistant adult patients with MCNS undergoing TAC therapy experienced relapse rates of approximately 40% 50%. 20,21 This trial showed the occurrence of relapse in 49.0% and 45.5% of the patients treated with GC and TAC, respectively; frequent relapses also occurred at similar rates in both groups (13.7% versus 7.3%, respectively). Because of the high relapse rate observed using this particular treatment regimen, future research is warranted to evaluate whether extending the duration of TAC therapy would result in fewer patients with relapse. AKI in the presence of MCNS has been well documented and typically occurs in 25% 30%oftheadultpatients. 5,27 Waldman et al. 5 retrospectively examined 95 adults with MCNS, 25.2% of who met the criteria for AKI during initial presentation or relapse. In this trial, AKI was observed in 7.1% (GC) and 4.8% (TAC) of the patients, and the most common cause of AKI was relapse with a rapid decrease in serum albumin levels. Indeed, AKI in MCNS could be consistent with a sudden decreasing in serum albumin levels and severe plasma volume depletion. 5,24,27 Additionally, acute nephrotoxicity is a concern, because TAC is a CNI. 28 To reduce the risk of acute CNI nephrotoxicity in this study, a short term intravenous methylprednisolone infusion before TAC treatment was administered, and patients with SCr levels.133 mmol/l and/or AKI were excluded. Furthermore, long-term use of a CNI is associated with chronic nephrotoxicity. 28,29 The SCr and egfr levels remained stable in all patients of this study after TAC or GC therapy. These favorable results may be attributed to our use of a relatively low TAC dosage and short treatment course. There is no evidence of chronic CNI nephrotoxicity on the basis of repeat renal biopsies of TAC-treated patients. However, the repeat renal biopsies were acquired from only four patients who underwent short term follow-up periods. In this trial, changes in metabolic indices and disorders, such as dyslipidemia, glucose intolerance or diabetes mellitus, hyperuricemia, and being overweight, during the treatment J Am Soc Nephrol 28: ccc ccc, 2016 Tacrolimus in Adult Minimal Change Disease 5
6 Table 2. The incidence of relapses in GC and TAC groups n (%) Relapse Event GC Group, n=51 TAC Group, n=55 P Value Maintained sustained remission 26 (51.0) 30 (54.5) 0.71 Relapses 25 (49.0) 25 (45.5) 0.71 Relapses during therapy with tapering dose 19 (37.3) 18 (32.8.) 0.63 Relapses during therapy discontinuation 6 (11.8) 7 (12.7) 0.88 Frequent relapse 7 (13.7) 4 (7.3) 0.28 Drug dependence a 5(9.8) 2(3.6) 0.26 Late nonresponder 3 (5.9) 2 (3.6) 0.67 a Drug dependence included steroid dependence and TAC dependence. with GC and TAC were assessed. Interestingly, a greater number of patients in the GC group developed metabolic disorders (characteristics of being overweight, dyslipidemia, and glucose intolerance or new onset diabetes mellitus). Previous studies have reinforced the association between metabolic disorders and all-cause mortality TAC therapy has been reported to cause new onset diabetes mellitus and hyperuricemia more often in kidney transplant recipients. 34,35 Here, the number of patients with new-onset hyperuricemia was higher in the TAC group; however, in the majority of the patients, this was reversed after TAC discontinuation. The incidence of overall AEs tended to be more frequent in the GC group compared with that in the TAC group. No significant differences in the onset of infections, hepatotoxicity, and gastrointestinal symptoms were observed between the two groups. However, osteoporosis, new-onset hypertension, and symptoms affecting the skin, muscles, and joints occurred more frequently in patients who received GC therapy. There are some limitations to our study. First, the number of participants included was relatively small. However, this limitation does not diminish the importance of our findings, because the data used for the design of treatments for initial MCNS in adults are limited to case reports and case series. Second, the follow-up period was relatively short. We plan to follow these patients for a longer period of time to assess relapse occurrence, renal function, and AEs. In conclusion, the results of our trial suggest that TAC monotherapy after short term intravenous methylprednisolone is noninferior to conventional GC treatment for adultonset MCNS. This conclusion is on the basis of the similar remission and relapse rates observed in both treatment groups. Metabolic disorders occurred more frequently in the patients of the GC group. In addition, patients in the GC group had a higher number of AEs. Therefore, TAC monotherapy after short term intravenous methylprednisolone could be considered an alternative to conventional GC therapy for adult-onset MCNS. In future studies, it would be worthwhile to investigate if this novel treatment regimen could be used as the initial therapeutic course for MCNS in adults and children. CONCISE METHODS Study Design In this prospective, open label, multicenter, randomized, controlled trial, we compared a TAC monotherapy regimen after short term intravenous methylprednisolone with conventional GC treatment for adult-onset MCNS. The study protocol was registered at the Chinese Clinical Trial Registration of the World Health Organization International Clinical Trials Registry Platform (no. ChiCTR-TRC ). Detailed information is available at The trial was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the research ethics committees of all participating hospitals. All patients provided informed consent. Figure 4. The incidence of the first relapse in the GC and TAC groups. Kaplan-Meier curves show the probability of the event (first relapse) at different time points between the GC and TAC groups (P=0.81 by long rank test). Point 0 represents onset of remission. Participants In this trial, patients were recruited from eight nephrology centers across China. The inclusion criteria were as follows: age years old; 6 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc ccc, 2016
7 CLINICAL RESEARCH Figure 5. Changes in SCr and egfr levels at baseline, during the periods of therapy and follow-up. SCr (A) and egfr (B) before therapy (week 0), during the periods of therapy and follow-up. The SCr and egfr levels before therapy, during the periods of therapy and follow-up did not differ significantly between the GC and TAC groups (P.0.05). renal biopsy verified diagnosis of minimal change nephropathy (examined using light microscopy, immunofluorescence, and electron microscopy); new onset nephrotic syndrome (proteinuria.3.5 g/d and serum albumin,30 g/l); initial SCr level of,133 mmol/l; and urine volume of.600 ml/d (or.1000 ml/d after the use of diuretic drugs). Patients with the following conditions were excluded: secondary minimal changedisease,aki,hepatitisb or C infection, diabetes mellitus, a history of pancreatitis or gastrointestinal ulcer, a history of congenital or acquired immunodeficiency, or previous treatment with corticosteroids or other immunosuppressants (e.g., cyclophosphamide, CNIs, or mycophenolate mofetil). Randomization and Treatment Procedures After the confirmation of eligibility, the patients were randomly assigned (1:1) to one of two groups (according to a random number label): (1) GC group: short term intravenous methylprednisolone followed by a conventional tapering oral prednisone regimen or (2) TAC group: short term intravenous methylprednisolone followed by TAC monotherapy. The minimization method was applied using a computergenerated sequence. All patients received an intravenous methylprednisolone (0.8 mg/kg per day) infusion for 10 consecutive days at hospital admission. In the GC group, patients subsequently received oral prednisone at 1 mg/kg per day (maximum 80 mg/d) for 6 8 weeks according to the treatment response. This dose was subsequently reduced by 5 mg every week to 30 mg on alternate days and maintained for 8 weeks followed by tapering of the dose over approximately 12 weeks until complete withdrawal. In the TAC group, TAC therapy was initiated on the eighth day, with an initial oral dose of 0.05 mg/kg per day (that was divided into two doses administered over a 12- hour interval). The TAC dosage was adjusted to a target trough whole blood level of 4 8ng/ml and maintained for weeks according to the treatment response. Subsequently, the dose was tapered to achieve a target trough level of 2 5 ng/ml over approximately 18 weeks until complete withdrawal. The treatment course for both groups was 36 weeks. The treatment was prolonged by 8 weeks for patients who underwent partial remission after 12 weeks of therapy. Patients who showed no remission after 12 weeks of therapy with GC or TAC were recommended to withdraw from the trial and undertake the other treatment trial (TAC monotherapy or conventional GC therapy). Patients who relapsed during the therapy were treated with a second cycle of GC or TAC therapy. Patients who relapsed twice were recommended to withdraw from the study. The dose of angiotensin converting enzyme inhibitors or angiotensin II receptor blockers used by the respective patients was maintained for the duration of therapy. If required, additional antihypertensive drugs were administered to achieve adequate BP control. Statins were administered to those patients who still had dyslipidemia after 12 weeks of therapy. Definitions and Outcome Measures Complete remission was defined as a decrease in proteinuria to #0.3 g/d. Partial remission was defined as a decrease in proteinuria to,3.5 g/d but J Am Soc Nephrol 28: ccc ccc, 2016 Tacrolimus in Adult Minimal Change Disease 7
8 Table 3. AEs and serious AEs for GC and TAC therapy AEs GC Group (128 Reports, 49 Patients), n= g/d. The persistence of nephrotic proteinuria after 12 weeks of treatment with prednisone (1.0 mg/kg per day) or oral TAC (with a trough whole blood level of 4 8 ng/ml) was considered to be no remission (treatment resistance). The time to remission was defined as the time from the initiation of the therapy to the day when remission (complete or partial remission) was observed. Relapse was defined as an increase in proteinuria to $3.5 g/d in patients who underwent partial or complete remission. Time to relapse was defined as the time from initiation of remission to the day when the first relapse occurred. Frequent relapse was defined as two or more relapses within 6 months of the initial response or four or more relapses in any 12-month period, and patients with two consecutive relapses during steroid (or TAC) therapy or within 14 days of ceasing therapy were considered to be drug (steroid or TAC) dependent. Late nonresponder was defined as no response to the second period of steroid or TAC therapy after relapsing during tapering or discontinuation of steroid or TAC therapy. AKI was defined as an increase in SCr to.50% above baseline or.26.4 mmol/l during 48 hours according to KDIGO guidelines. The primary outcome measures were the cumulative numbers of patients who experienced complete remission or partial remission. Secondary outcome measures were determined using the following variables: relapse, time to remission, time to relapse, changes in the TAC Group (81 Reports, 43 Patients), n=63 Infection Urinary tract infection 3 4 Female genital tract infection 1 1 Upper respiratory infection Lower respiratory tract infection 2 (1 SAE) 2 Abdominal cavity infection 1 (1 SAE) Gastrointestinal symptoms 8 9 Hepatotoxicity 13 (1 SAE) 10 (1 SAE) AKI 4 (1 SAE) 3 (1 SAE) New-onset hypertension 10 4 Metabolic disorder New onset glucose intolerance 6 4 New onset diabetes mellitus 3 (2 SAE) New-onset hyperuricemia 6 11 Other 3 1 Osteoporosis 5 1 Electrolyte disorder 3 2 Arrhythmia 1 1 Menstrual disorders 4 Psychiatry/neurology 4 (1 SAE) 3 Cushing syndrome 20 Symptoms of skin, muscle, and joint Cramps 3 1 Arthralgia 2 2 Hypertrichosis 1 Cutaneous ulcer 1 Erythra 4 2 Alopecia 1 3 Purple stripes 5 Acne 6 SAE, serious adverse event. SCr and egfr levels, AKI, metabolic disorders (being overweight, glucose intolerance, diabetes mellitus, dyslipidemia, and hyperuricemia), AEs, and serious AEs. Follow-Up In this trial, the follow-up duration was 64 weeks after therapy. Follow-ups were performed weekly for the first 4 weeks, every 4 weeks for the subsequent 36 weeks, and every 8 weeks thereafter. During each visit, the patients underwent anthropometric measurements (body weight and standing height) and BP measurements. Complete blood count, proteinuria, blood glucose, SCr, serum uric acid, lipid profile, albumin, alanine aminotransferase, and aspartate aminotransferase levels were determined. The trough TAC level was measured every week until stable followed by measurements every 4 weeks. The body mass index (weight in kilograms divided by the square of the height in meters) was measured, and the questionnaire SF-36 and bone mineral density measurement (with dual energy x-ray absorptiometry)were performedatthe baseline andevery 12 weeks. Sample Size TAC therapy was hypothesized to be noninferior to GC therapy in achieving remission. On the basis of the results of previous studies and our observations that the remission rates of GC and TAC therapy in adult-onset MCNS were 80% and 90%, respectively, 2 5,19,20 a sample size of 54 patients in each group (total of 108 patients) was required to determine that TAC therapy was not.9.5% inferior to GC therapy with a type 1 error probability of 2.5% and a power of 80% according to the formulas by Gart and Nam. 36 Allowing for an expected dropout rate of 10%, we aimed at enrolling 120 patients. Statistical Analyses All efficacy analyses were on the basis of the intention-to-treat principle, comparing groups according to the randomly assigned treatment. For the primary efficacy analysis for noninferiority, we carried out a per-protocol analysis, which included patients who received protocol treatments as scheduled. Noninferiority was assessed by estimating the two sided 95% CI for the difference in remission rates between the GC and TAC groups using the method by Gart and Nam 36 and verifying that the lower limit of the 95% CI was not lower than 29.5%. The 9.5% margin was on the basis of clinical adjustment. All data were expressed as the mean6sd or median (interquartile range) for continuous variables and percentage for categorical variables. The differences in normally distributed continuous variables between two groups were compared using the two tailed independent sample paired t test. A paired t test was performed to compare 8 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc ccc, 2016
9 CLINICAL RESEARCH two means obtained at different times during the therapy. Nonparametric variables obtained at different times were compared using the Wilcoxon signed rank test, and categorical variables were compared by Fisher exact or chi-squared test. The probability of the first relapse between two groups was estimated by the Kaplan Meier method, and survival curves were compared with log rank tests. A P value,0.05 was considered statistically significant. All statistical analyses were performed using the SAS software, version 9.2. ACKNOWLEDGMENTS We thank Dr. Huiping Wang for reviewing the renal biopsies of the patients and Dr. Xiuyang Li (College of Medicine, Zhejiang University) for reviewing the statistical analyses. Dr. Rong Lv, Fei Han, Qun Li, Xuelin He, Rending Wang, and Wenhan Peng were in charge of patient care and follow-up. This trial was supported, in part, by National Nature Science Foundation of China grants 2011BAI10B07, 2012CR517603, and 2012AA02A512. The funding source had no role in the design of the study, data collection, data analysis, data interpretation, or writing of the manuscript. DISCLOSURES None. REFERENCES 1. Bargman JM: Management of minimal lesion glomerulonephritis: Evidence-based recommendations. Kidney Int Suppl 70: S3 S16, Hogan J, Radhakrishnan J: The treatment of minimal change disease in adults. J Am Soc Nephrol 24: , Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephrits Work Group: KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2: , Szeto CC, Lai FM, Chow KM, Kwan BC, Kwong VW, Leung CB, Li PK: Long-term outcome of biopsy-proven minimal change nephropathy in Chinese adults. Am J Kidney Dis 65: , Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G, D Agati V, Appel G: Adult minimal-change disease: Clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol 2: , Shinzawa M, Yamamoto R, Nagasawa Y, Oseto S, Mori D, Tomida K, Hayashi T, Izumi M, Fukunaga M, Yamauchi A, Tsubakihara Y, Isaka Y: Comparison of methylprednisolone plus prednisolone with prednisolone alone as initial treatment in adult-onset minimal change disease: A retrospective cohort study. Clin J Am Soc Nephrol 9: , Eguchi A, Takei T, Yoshida T, Tsuchiya K, Nitta K: Combined cyclosporine and prednisolone therapy in adult patients with the first relapse of minimal-change nephrotic syndrome. Nephrol Dial Transplant 25: , Bruchfeld A, Benedek S, Hilderman M, Medin C, Snaedal-Jonsdottir S, Korkeila M: Rituximab for minimal change disease in adults: Long-term follow-up. Nephrol Dial Transplant 29: , Fujiwara A, Hirawa N, Kobayashi Y, Yatsu K, Katsumata M, Ehara Y, Okuyama Y, Yutoh J, Kaneda T, Fujita M, Yamamoto Y, Saka S, Toya Y, YasudaG, Umemura S: Efficacy of cyclosporine combination therapy for new-onset minimal change nephrotic syndrome in adults. Clin Exp Nephrol 19: , Gulati A, Sinha A, Gupta A, Kanitkar M, Sreenivas V, Sharma J, Mantan M, Agarwal I, Dinda AK, Hari P, Bagga A: Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide as the initial therapy for children with steroid-resistant nephrotic syndrome. Kidney Int 82: , Iijima K, Sako M, Nozu K, Mori R, Tuchida N, Kamei K, Miura K, Aya K, Nakanishi K, Ohtomo Y, Takahashi S, Tanaka R, Kaito H, Nakamura H, Ishikura K, Ito S, Ohashi Y; Rituximab for Childhood-onset Refractory Nephrotic Syndrome (RCRNS) Study Group: Rituximab for childhoodonset, complicated, frequently relapsing nephrotic syndrome or steroiddependent nephrotic syndrome: A multicentre, double-blind, randomised, placebo-controlled trial. Lancet 384: , Araya C, Diaz L, Wasserfall C, Atkinson M, Mu W, Johnson R, Garin E: T regulatory cell function in idiopathic minimal lesion nephrotic syndrome. Pediatr Nephrol 24: , Wei C, Reiser J: Minimal change disease as a modifiable podocyte paracrine disorder. Nephrol Dial Transplant 26: , Clement LC, Avila-Casado C, Macé C, Soria E, Bakker WW, Kersten S, Chugh SS: Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med 17: , Macé C, Chugh SS: Nephrotic syndrome: Components, connections, and angiopoietin-like 4-related therapeutics. JAmSocNephrol25: , Budde K, Fritsche L, Neumayer HH: Differing proteinuria control with cyclosporin and tacrolimus. Lancet 349: 330, Li JS, Chen X, Peng L, Wei SY, Zhao SL, Diao TT, He YX, Liu F, Wei QJ, Zhang QF, Li B: Angiopoietin-Like-4, a potential target of tacrolimus, predicts earlier podocyte injury in minimal change disease. PLoS One 10: e , LiaoR,LiuQ,ZhengZ,FanJ,PengW,KongQ,HeH,YangS,ChenW, Tang X, Yu X: Tacrolimus protects podocytes from injury in lupus nephritis partly by stabilizing the cytoskeleton and inhibiting podocyte apoptosis. PLoS One 10: e , Li H, Shi X, Shen H, Li X, Wang H, Li H, Xu G, Chen J: Tacrolimus versus intravenous pulse cyclophosphamide therapy in Chinese adults with steroid-resistant idiopathic minimal change nephropathy: A multicenter, open-label, nonrandomized cohort trial. Clin Ther 34: , LiX,LiH,ChenJ,HeQ,LvR,LinW,LiQ,HeX,QuL,SuyaW: Tacrolimus as a steroid-sparing agent for adults with steroid-dependent minimal change nephrotic syndrome. Nephrol Dial Transplant 23: , Choudhry S, Bagga A, Hari P, Sharma S, Kalaivani M, Dinda A: Efficacy and safety of tacrolimus versus cyclosporine in children with steroidresistant nephrotic syndrome: A randomized controlled trial. Am J Kidney Dis 53: , Roberti I, Vyas S: Long-term outcome of children with steroid-resistant nephrotic syndrome treated with tacrolimus. Pediatr Nephrol 25: , LiX,LiH,YeH,LiQ,HeX,ZhangX,ChenY,HanF,HeQ,WangH,Chen J: Tacrolimus therapy in adults with steroid- and cyclophosphamideresistant nephrotic syndrome and normal or mildly reduced GFR. Am J Kidney Dis 54: 51 58, Li X, Xu N, Li H, Han F, Wang R, He Q, He X, Chen J: Tacrolimus as rescue therapy for adult-onset refractory minimal change nephrotic syndrome with reversible acute renal failure. Nephrol Dial Transplant 28: , TseKC,LamMF,YipPS,LiFK,ChoyBY,LaiKN,ChanTM:Idiopathic minimal change nephrotic syndrome in older adults: Steroid responsiveness and pattern of relapses. NephrolDialTransplant18: , Takei T, Koike M, Suzuki K, Shirota S, Itabashi M, Ohtsubo S, Sugiura H, Suzuki K, Kojima C, Takahashi M, Ino J, Ogawa T, Uchida K, Tsuchiya K, J Am Soc Nephrol 28: ccc ccc, 2016 Tacrolimus in Adult Minimal Change Disease 9
10 Yumura W, Nitta K: The characteristics of relapse in adult-onset minimalchange nephrotic syndrome. Clin Exp Nephrol 11: , Jennette JC, Falk RJ: Adult minimal change glomerulopathy with acute renal failure. AmJKidneyDis16: , Naesens M, Kuypers DR, Sarwal M: Calcineurin inhibitor nephrotoxicity. Clin J Am Soc Nephrol 4: , Morgan C, Sis B, Pinsk M, Yiu V: Renal interstitial fibrosis in children treated with FK506 for nephrotic syndrome. Nephrol Dial Transplant 26: , Kramer CK, Zinman B, Retnakaran R: Are metabolically healthy overweight and obesity benign conditions?: A systematic review and metaanalysis. Ann Intern Med 159: , Flegal KM, Kit BK, Orpana H, Graubard BI: Association of all-cause mortality with overweight and obesity using standard body mass index categories: A systematic review and meta-analysis. JAMA 309: 71 82, Wu CY, Chou YC, Huang N, Chou YJ, Hu HY, Li CP: Association of body mass index with all-cause and cardiovascular disease mortality in the elderly. PLoS One 9: e102589, Zhou B, Wu Y, Yang J, Li Y, Zhang H, Zhao L: Overweight is an independent risk factor for cardiovascular disease in Chinese populations. Obes Rev 3: , Batista F, Auyanet I, Torregrosa JV, Oppenheimer F: Long-term followup after conversion from tacrolimus to cyclosporin in renal transplant patients with new-onset diabetes mellitus after transplantation. Transplant Proc 44: , Kanbay M, Akcay A, Huddam B, Usluogullari CA, Arat Z, Ozdemir FN, Haberal M: Influence of cyclosporine and tacrolimus on serum uric acid levels in stable kidney transplant recipients. Transplant Proc 37: , Gart JJ, Nam JM: Approximate interval estimation of the difference in binomial parameters: Correction for skewness and extension to multiple tables. Biometrics 46: , 1990 This article contains supplemental material online at org/lookup/suppl/doi: /asn /-/dcsupplemental. 10 Journal of the American Society of Nephrology J Am Soc Nephrol 28: ccc ccc, 2016
Chapter 4: Steroid-resistant nephrotic syndrome in children Kidney International Supplements (2012) 2, ; doi: /kisup.2012.
http://www.kidney-international.org & 2012 KDIGO Chapter 4: Steroid-resistant nephrotic syndrome in children Kidney International Supplements (2012) 2, 172 176; doi:10.1038/kisup.2012.17 INTRODUCTION This
More informationMinimal change nephropathy: an update (for adults) Dr. CC Szeto Department of Medicine & Therapeutics The Chinese University of Hong Kong
Minimal change nephropathy: an update (for adults) Dr. CC Szeto Department of Medicine & Therapeutics The Chinese University of Hong Kong First, it is not uncommon Cameron JS. Am J Kidney Dis 10: 157 171,
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment. Membranous nephropathy role of steroids GUIDELINES
Membranous nephropathy role of steroids Date written: July 2005 Final submission: September 2005 Author: Merlin Thomas GUIDELINES There is currently no data to support the use of short-term courses of
More informationUse of mycophenolate mofetil in steroid-dependent and -resistant nephrotic syndrome
Pediatr Nephrol (2003) 18:833 837 DOI 10.1007/s00467-003-1175-4 BRIEF REPORT Gina-Marie Barletta William E. Smoyer Timothy E. Bunchman Joseph T. Flynn David B. Kershaw Use of mycophenolate mofetil in steroid-dependent
More informationQiu-Hong Li, Zi-Jun Yang, Li Li, Rong Gou, Yuan-Yuan Guo, Li-Li Yin, Lin Tang
Int J Clin Exp Med 2017;10(6):9764-9770 www.ijcem.com /ISSN:1940-5901/IJCEM0049488 Original Article Comparison of efficacy and safety between tacrolimus and cyclosporine combined with corticosteroids in
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment. Specific management of IgA nephropathy: role of steroid therapy GUIDELINES
Specific management of IgA nephropathy: role of steroid therapy Date written: July 2005 Final submission: September 2005 Author: Merlin Thomas GUIDELINES Steroid therapy may protect against progressive
More informationComparison of Efficacy of Tacrolimus Versus Cyclosporine in Childhood Steroid-Resistant Nephrotic Syndrome
ORIGINAL ARTICLE Comparison of Efficacy of Tacrolimus Versus Cyclosporine in Childhood Steroid-Resistant Nephrotic Syndrome Syed Sajid Hussain Shah and Farkhanda Hafeez ABSTRACT Objective: To compare the
More informationThe Value Of Tacrolimus Drug Levels In The Management Of Nephrotic Syndrome In Children
ISPUB.COM The Internet Journal of Nephrology Volume 6 Number 2 The Value Of Tacrolimus Drug Levels In The Management Of Nephrotic Syndrome In Children K Peyser, Y Steinberg, R Frank, S Vento, L Infante,
More informationAdditional file 2: Details of cohort studies and randomised trials
Reference Randomised trials Ye et al. 2001 Abstract 274 R=1 WD=0 Design, numbers, treatments, duration Randomised open comparison of: (45 patients) 1.5 g for 3, 1 g for 3, then 0.5 to 0.75 g IV cyclophosphamide
More informationRenal Biopsy Findings in Children Receiving Long-Term Treatment with Cyclosporine A Given as a Single Daily Dose
Tohoku J. Exp. Med., Posttreatment 2006, 209, 191-196 Renal Biopsy Following Once-daily CsA Treatment 191 Renal Biopsy Findings in Children Receiving Long-Term Treatment with Cyclosporine A Given as a
More informationOral mizoribine pulse therapy for patients with steroid-resistant and frequently relapsing steroid-dependent nephrotic syndrome
Nephrol Dial Transplant (2005) 20: 2243 2247 doi:10.1093/ndt/gfh996 Advance Access publication 19 July 2005 Brief Report Oral mizoribine pulse therapy for patients with steroid-resistant and frequently
More informationRecent advances in management of Pulmonary Vasculitis. Dr Nita MB
Recent advances in management of Pulmonary Vasculitis Dr Nita MB 23-01-2015 Overview of the seminar Recent classification of Vasculitis What is new in present classification? Trials on remission induction
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment. Idiopathic membranous nephropathy: use of other therapies GUIDELINES
Idiopathic membranous nephropathy: use of other therapies Date written: July 2005 Final submission: September 2005 Author: Merlin Thomas GUIDELINES No recommendations possible based on Level I or II evidence
More informationConsidering the early proactive switch from a CNI to an mtor-inhibitor (Case: Male, age 34) Josep M. Campistol
Considering the early proactive switch from a CNI to an mtor-inhibitor (Case: Male, age 34) Josep M. Campistol Patient details Name DOB ESRD Other history Mr. B.I.B. 12 January 1975 (34yo) Membranous GN
More informationAdult minimal-change disease: observational data from a UK centre on patient characteristics, therapies, and outcomes
Fenton et al. BMC Nephrology (2018) 19:207 https://doi.org/10.1186/s12882-018-0999-x RESEARCH ARTICLE Open Access Adult minimal-change disease: observational data from a UK centre on patient characteristics,
More informationMycophenolate Mofetil Following Rituximab in Children With Steroid-Resistant Nephrotic Syndrome
Mycophenolate Mofetil Following Rituximab in Children With Steroid-Resistant Nephrotic Syndrome Biswanath Basu, MD a, T.K.S. Mahapatra, MD b, Nirmal Mondal, MD c abstract BACKGROUND: Rituximab is being
More informationIdiopathic minimal change nephrotic syndrome in older adults: steroid responsiveness and pattern of relapses
Nephrol Dial Transplant (2003) 18: 1316 1320 DOI: 10.1093/ndt/gfg134 Original Article Idiopathic minimal change nephrotic syndrome in older adults: steroid responsiveness and pattern of relapses Kai-Chung
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Wanner C, Inzucchi SE, Lachin JM, et al. Empagliflozin and
More informationLi Wu, 1,2 Jianhua Mao, 1 Xia Jin, 1 Haidong Fu, 1 Huijun Shen, 1 Jingjing Wang, 1 Aimin Liu, 1 Qiang Shu, 1 and Lizhong Du 1. 1.
BioMed Research International Volume 2013, Article ID 292865, 5 pages http://dx.doi.org/10.1155/2013/292865 Clinical Study Efficacy of Triptolide for Children with Moderately Severe Henoch-Schönlein Purpura
More informationReducing proteinuria
Date written: May 2005 Final submission: October 2005 Author: Adrian Gillin Reducing proteinuria GUIDELINES a. The beneficial effect of treatment regimens that include angiotensinconverting enzyme inhibitors
More informationKDIGO GN Guideline update Evidence summary. Steroid-sensitive nephrotic syndrome. Corticosteroid therapy for nephrotic syndrome in children
KDIGO GN Guideline update Evidence summary Steroid-sensitive nephrotic syndrome Corticosteroid therapy for nephrotic syndrome in children PICO question In children (aged 3 to 18 years of age) with steroid-sensitive
More informationAdministration of low-dose cyclosporine alone for the treatment of elderly patients with membranous nephropathy
Administration of low-dose cyclosporine alone for the treatment of elderly patients with membranous nephropathy M.X. Li, Y.W. Yu, Z.Y. Zhang, H.D. Zhao and F.L. Xiao Department of Nephrology, The Navy
More informationNephrotic Syndrome NS
Nephrotic Syndrome NS By : Dr. Iman.M. Mudawi Pediatric Nephrology Unit Gaafar Ibn Auf Hospital Definitions: In children NS is applied to any condition with a triad of: Heavy proteinuria (UACR ratio >200
More informationIgA-Nephropathy: an update on treatment Jürgen Floege
IgA-Nephropathy: an update on treatment Jürgen Floege Division of Nephrology & Immunology juergen.floege@rwth-aachen.de Floege & Feehally, Nat Rev Nephrol 2013 Floege & Eitner, J Am Soc Nephrol. 2011 If
More informationOut of date SUGGESTIONS FOR CLINICAL CARE (Suggestions are based on level III and IV evidence)
Membranous nephropathy role of cyclosporine therapy Date written: July 2005 Final submission: September 2005 Author: Merlin Thomas GUIDELINES a. The use of cyclosporine therapy alone to prevent progressive
More informationChapter 6: Idiopathic focal segmental glomerulosclerosis in adults Kidney International Supplements (2012) 2, ; doi: /kisup.2012.
http://www.kidney-international.org chapter 6 & 2012 KDIGO Chapter 6: Idiopathic focal segmental glomerulosclerosis in adults Kidney International Supplements (2012) 2, 181 185; doi:10.1038/kisup.2012.19
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment
Specific management of IgA nephropathy: role of triple therapy and cytotoxic therapy Date written: July 2005 Final submission: September 2005 Author: Merlin Thomas GUIDELINES a. Triple therapy with cyclophosphamide,
More informationNephrotic syndrome minimal change disease vs. IgA nephropathy. Hadar Meringer Internal medicine B Sheba
Nephrotic syndrome minimal change disease vs. IgA nephropathy Hadar Meringer Internal medicine B Sheba The Case 29 year old man diagnosed with nephrotic syndrome 2 weeks ago and complaining now about Lt.flank
More informationDay Care Intravenous Cyclophosphamide Therapy in Steroid Dependent Nephrotic Syndrome
International Journal of advances in health sciences (IJHS) ISSN 2349-7033 Vol2, Issue2, 2015, pp161-166 http://www.ijhsonline.com Research Article Day Care Intravenous Cyclophosphamide Therapy in Steroid
More informationOUT OF DATE. Choice of calcineurin inhibitors in adult renal transplantation: Effects on transplant outcomes
nep_734.fm Page 88 Friday, January 26, 2007 6:47 PM Blackwell Publishing AsiaMelbourne, AustraliaNEPNephrology1320-5358 2006 The Author; Journal compilation 2006 Asian Pacific Society of Nephrology? 200712S18897MiscellaneousCalcineurin
More informationCharacteristics of Patients Initializing Peritoneal Dialysis Treatment From 2007 to 2014 Analysis From Henan Peritoneal Dialysis Registry data
DIALYSIS Characteristics of Patients Initializing Peritoneal Dialysis Treatment From 7 to 14 Analysis From Henan Peritoneal Dialysis Registry data Xiaoxue Zhang, 1 Ying Chen, 1,2 Yamei Cai, 1 Xing Tian,
More informationLow-dose cyclosporine in treatment of membranous nephropathy with nephrotic syndrome: effectiveness and renal safety
Renal Failure ISSN: 0886-022X (Print) 1525-6049 (Online) Journal homepage: http://www.tandfonline.com/loi/irnf20 Low-dose cyclosporine in treatment of membranous nephropathy with nephrotic syndrome: effectiveness
More informationLupus nephritis. Vladimir Tesar Department of Nephrology, General University Hospital, Prague, Czech Republic
Lupus nephritis Vladimir Tesar Department of Nephrology, General University Hospital, Prague, Czech Republic Disclosure of Interests Abbvie, Amgen, Baxter, Bayer, Boehringer-Ingelheim, Calliditas, Chemocentryx,
More informationUrinary CD80 as a Replacement for Renal Biopsy for Diagnosis of Pediatric Minimal Change Disease
KIDNEY DISEASES Urinary CD80 as a Replacement for Renal Biopsy for Diagnosis of Pediatric Minimal Change Disease Heba Mostafa Ahmed, 1 Dina Ahmed Ezzat, 1 Noha A Doudar, 2 Mai Adel 1 1 Departement of Pediatrics,
More informationSELECTED ABSTRACTS. All (n) % 3-year GS 88% 82% 86% 85% 88% 80% % 3-year DC-GS 95% 87% 94% 89% 96% 80%
SELECTED ABSTRACTS The following are summaries of selected posters presented at the American Transplant Congress on May 5 9, 2007, in San Humar A, Gillingham KJ, Payne WD, et al. Review of >1000 kidney
More informationEfficacy and Safety of Thymoglobulin and Basiliximab in Kidney Transplant Patients at High Risk for Acute Rejection and Delayed Graft Function
ArtIcle Efficacy and Safety of Thymoglobulin and Basiliximab in Kidney Transplant Patients at High Risk for Acute Rejection and Delayed Graft Function Guodong Chen, 1 Jingli Gu, 2 Jiang Qiu, 1 Changxi
More informationSteroid Minimization: Great Idea or Silly Move?
Steroid Minimization: Great Idea or Silly Move? Disclosures I have financial relationship(s) within the last 12 months relevant to my presentation with: Astellas Grants ** Bristol Myers Squibb Grants,
More informationA Randomized Controlled Trial of Intravenous Vs Oral Cyclophosphamide in Steroid Resistant Nephrotic Syndrome
Original article A Randomized Controlled Trial of Intravenous Vs Oral Cyclophosphamide in Steroid Resistant Nephrotic Syndrome Alpana Ohri 1, Kronal Shah 2, Uma Ali 3 1Associate Professor, 2 Jr. Registrar,
More informationoriginal article see commentary on page 1049
original article http://www.kidney-international.org & 2012 International Society of Nephrology see commentary on page 1049 Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide
More informationActhar Gel. H. P. Acthar Gel (corticotropin; ACTH) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.10 Subject: Acthar Gel Page: 1 of 7 Last Review Date: November 30, 2018 Acthar Gel Description H.
More informationRecurrent Idiopathic Membranous Glomerulonephritis After Kidney Transplantation and Successful Treatment With Rituximab
TRANSPLANTATION Recurrent Idiopathic Membranous Glomerulonephritis After Kidney Transplantation and Successful Treatment With Rituximab Khadijeh Makhdoomi, 1,2 Saeed Abkhiz, 1,2 Farahnaz Noroozinia, 1,3
More informationLong-term prognosis of BK virus-associated nephropathy in kidney transplant recipients
Original Article Kidney Res Clin Pract 37:167-173, 2018(2) pissn: 2211-9132 eissn: 2211-9140 https://doi.org/10.23876/j.krcp.2018.37.2.167 KIDNEY RESEARCH AND CLINICAL PRACTICE Long-term prognosis of BK
More informationREACH Risk Evaluation to Achieve Cardiovascular Health
Dyslipidemia and transplantation History: An 8-year-old boy presented with generalized edema and hypertension. A renal biopsy confirmed a diagnosis of focal segmental glomerulosclerosis (FSGS). After his
More informationClinical Commissioning Policy: Rituximab for the treatment of idiopathic membranous nephropathy in adults
Clinical Commissioning Policy: Rituximab for the treatment of idiopathic membranous nephropathy in adults Reference: NHS England: 16047/P NHS England INFORMATION READER BOX Directorate Medical Operations
More informationCHAPTER 14. Renal Transplantation
15th Report of the Malaysian RENAL TRANSPLANTATION CHAPTER 14 Renal Transplantation Editor: Dr. Goh Bak Leong Expert Panel: : Dato Dr. Dato Zaki Dr. Morad Zaik Morad Mohd (Chair) Zaher (Chair) Dr. Goh
More informationegfr > 50 (n = 13,916)
Saxagliptin and Cardiovascular Risk in Patients with Type 2 Diabetes Mellitus and Moderate or Severe Renal Impairment: Observations from the SAVOR-TIMI 53 Trial Supplementary Table 1. Characteristics according
More informationClinical trials in childhood steroid sensitive nephrotic syndrome: the PREDNOS studies
Clinical Research Facility Central Manchester University Hospitals NHS Foundation Trust Clinical trials in childhood steroid sensitive nephrotic syndrome: the PREDNOS studies Professor Nick Webb DM FRCP
More informationCan We Predict Relapses in Children with Idiopathic Steroid-Sensitive Nephrotic Syndrome?
JOURNAL OF TROPICAL PEDIATRICS, VOL. 59, NO. 5, 2013 Can We Predict Relapses in Children with Idiopathic Steroid-Sensitive Nephrotic Syndrome? by Om P. Mishra, 1 Abhishek Abhinay, 1 Rabindra N. Mishra,
More informationMINTAC. Tacrolimus vs prednisolone for the treatment of nephrotic syndrome secondary to minimal change disease: A Randomised Control Trial
MINTAC Tacrolimus vs prednisolone for the treatment of nephrotic syndrome secondary to minimal change disease: A Randomised Control Trial Version 4 01/07/2009 West London Renal and Transplant Unit EudraCT
More informationManagement and treatment of glomerular diseases KDIGO Controversies Conference Part 1
Management and treatment of glomerular diseases KDIGO Controversies Conference Part 1 Dr.M.Matinfar Assistant Professor of Internal Medicine & Nephrology IUMS -IKRC GENERAL PRINCIPLES IN THE MANAGEMENT
More informationEnhanced Steroid Therapy in Adult Minimal Change Nephrotic Syndrome: A Systematic Review and Meta-analysis
REVIEW ARTICLE Enhanced Steroid Therapy in Adult Minimal Change Nephrotic Syndrome: A Systematic Review and Meta-analysis Lingfei Zhao, Jun Cheng, Jingyi Zhou, Congcong Wu and Jianghua Chen Abstract The
More informationCHAPTER 5 RENAL TRANSPLANTATION. Editor: Dr Goh Bak Leong
CHAPTER 5 RENAL TRANSPLANTATION Editor: Dr Goh Bak Leong Expert Panel: Dr Goh Bak Leong (Chair) Dato Dr (Mr) Rohan Malek Dr Wong Hin Seng Dr Fan Kin Sing Dr Rosnawati Yahya Dr S Prasad Menon Dr Tan Si
More informationSYNOPSIS (PROTOCOL WX17796)
TITLE OF THE STUDY A prospective, randomized, double-blind, placebo-controlled, parallel group, multicenter, 52-week trial to assess the efficacy and safety of adjunct MMF to achieve remission with reduced
More informationHow I Treat Membranous Nephropathy
How I Treat Membranous Nephropathy Patrick H. Nachman, MD, FASN Marion Stedman Covington Professor May 20, 2017 Treating Membranous Nephropathy: after changes upon changes we are more or less the same
More informationCHAPTER 5 RENAL TRANSPLANTATION. Editor: Dr Goh Bak Leong
CHAPTER 5 RENAL TRANSPLANTATION Editor: Dr Goh Bak Leong Expert Panel: Dr Goh Bak Leong (Chair) Dato Dr Zaki Morad Mohd Zaher Dato Dr (Mr) Rohan Malek Dr Fan Kin Sing Dr Lily Mushahar Dr Lim Soo Kun Dr
More informationSteroid Resistant Nephrotic Syndrome. Sanjeev Gulati, Debashish Sengupta, Raj K. Sharma, Ajay Sharma, Ramesh K. Gupta*, Uttam Singh** and Amit Gupta
Steroid Resistant Nephrotic Syndrome Sanjeev Gulati, Debashish Sengupta, Raj K. Sharma, Ajay Sharma, Ramesh K. Gupta*, Uttam Singh** and Amit Gupta From the Departments of Nephrology, Pathology* and Biostatistics**,
More informationCurrent treatment recommendations in children with IgA nephropathy Selçuk Yüksel
Current treatment recommendations in children with IgA nephropathy Selçuk Yüksel Department of Pediatric Nephrology Pamukkale University School of Medicine IgA Nephropathy The most common cause of primary
More informationBK virus infection in renal transplant recipients: single centre experience. Dr Wong Lok Yan Ivy
BK virus infection in renal transplant recipients: single centre experience Dr Wong Lok Yan Ivy Background BK virus nephropathy (BKVN) has emerged as an important cause of renal graft dysfunction in recent
More informationGuidelines for the management of Nephrotic syndrome in children
Guidelines for the management of Nephrotic syndrome in children Children s Kidney Centre University Hospital of Wales Cardiff CF14 4XW DISCLAIMER: These guidelines were produced in good faith by the author(s)
More informationEfficacy of Tacrolimus in Treating Nephrotic Syndrome Children
British Journal of Medicine & Medical Research 12(6): 1-8, 2016, Article no.bjmmr.21806 ISSN: 2231-0614, NLM ID: 101570965 SCIENCEDOMAIN international www.sciencedomain.org Efficacy of Tacrolimus in Treating
More informationEmerging Drug List EVEROLIMUS
Generic (Trade Name): Manufacturer: Everolimus (Certican ) Novartis Pharmaceuticals NO. 57 MAY 2004 Indication: Current Regulatory Status: Description: Current Treatment: Cost: Evidence: For use with cyclosporine
More informationEditorial. Recent Concepts in Management of Nephrotic Syndrome
Editorial Recent Concepts in Management of Nephrotic Syndrome This is the third editorial on nephrotic syndrome in this journal in last 4 years. The previous 2 editorials were addressed to problems of
More informationIndividual Study Table Referring to Part of Dossier: Volume: Page:
Synopsis Abbott Laboratories Name of Study Drug: Paricalcitol Capsules (ABT-358) (Zemplar ) Name of Active Ingredient: Paricalcitol Individual Study Table Referring to Part of Dossier: Volume: Page: (For
More informationTreatment of Idiopathic Membranous Nephropathy
Treatment of Idiopathic Membranous Nephropathy Meryl Waldman and Howard A. Austin III Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health,
More informationEVIDENCE BASED TREATMENT OF IgA NEPHROPATHY. Jonathan Barratt
EVIDENCE BASED TREATMENT OF IgA NEPHROPATHY Jonathan Barratt EVIDENCE BASED TREATMENT OF IgA NEPHROPATHY We do not have much evidence EVIDENCE BASED TREATMENT OF IgA NEPHROPATHY We do not have much evidence.
More informationCase Report Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration Rate
Case Reports in Transplantation, Article ID 190516, 4 pages http://dx.doi.org/10.1155/2014/190516 Case Report Beneficial Effect of Conversion to Belatacept in Kidney-Transplant Patients with a Low Glomerular-Filtration
More informationCyclosporine versus Cyclophosphamide in Childhood Nephrotic Syndrome
ABSTRACT versus in Childhood Nephrotic Syndrome Sunita Khemani, Khemchand N Moorani Original Article OBJECTIVE: To determine the response of versus in childhood nephrotic syndrome. PLACE AND DURATION:
More informationRenal Protection Staying on Target
Update Staying on Target James Barton, MD, FRCPC As presented at the University of Saskatchewan's Management of Diabetes & Its Complications (May 2004) Gwen s case Gwen, 49, asks you to take on her primary
More informationCHAPTER 5 RENAL TRANSPLANTATION. Editor: Rosnawati Yahya. Expert Panels: Hooi Lai Seong Ng Kok Peng Suryati Binti Yakaob Wong Hin Seng.
CHAPTER 5 Editor: Roswati Yahya Expert Panels: Hooi Lai Seong Ng Kok Peng Suryati Binti Yakaob Wong Hin Seng Contents 5. Stock and Flow of Rel Transplantation Stock and Flow Transplant Rates 5.2 Recipients
More informationPractice Patterns and Outcomes of ACTHar use in Children with Nephrotic Syndrome
Page 1 of 16 Practice Patterns and Outcomes of ACTHar use in Children with Nephrotic Syndrome MANUAL OF OPERATIONS VERSION 1.0 March 10, 2016 Page 2 of 16 STUDY PERSONNEL CONTACT INFORMATION Principal
More informationREMISSION OF ACTIVE LUPUS NEPHRITIS WITH VOCLOSPORIN: RESULTS OF THE AURA-LV STUDY
REMISSION OF ACTIVE LUPUS NEPHRITIS WITH VOCLOSPORIN: RESULTS OF THE AURA-LV STUDY V. Dobronravov* 1, M. A. Dooley 2, S. A. Haq 3, I. Adzerikho 4, O. Bugrova 5, D. Isenberg 6, F. Houssiau 7, N. Solomons
More informationThe clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.
The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment. ACE Inhibitor and Angiotensin II Antagonist Combination Treatment GUIDELINES
ACE Inhibitor and Angiotensin II Antagonist Combination Treatment Date written: September 2004 Final submission: September 2005 Author: Kathy Nicholls GUIDELINES No recommendations possible based on Level
More informationEffect of Levamisole in Steroid-Dependent Nephrotic Syndrome
Kidney Diseases Effect of Levamisole in Steroid-Dependent Nephrotic Syndrome Abbas Madani, 1 Seyed-Taher Isfahani, 1 Nahid Rahimzadeh, 2 Seyed-Mohammad Fereshtehnejad, 3 Rozita Hoseini, 4 Mastaneh Moghtaderi,
More informationAurinia Pharmaceuticals Announces Voclosporin Meets Primary Endpoint in Phase IIB AURA-LV Study in Lupus Nephritis
August 15, 2016 Aurinia Pharmaceuticals Announces Voclosporin Meets Primary Endpoint in Phase IIB AURA-LV Study in Lupus Nephritis Conference call and webcast at 8am ET First therapeutic agent to meet
More informationFavorable Outcome of Low-dose Cyclosporine after Pulse Methylprednisolone in Japanese Adult Minimal-change Nephrotic Syndrome
ORIGINAL ARTICLE Favorable Outcome of Low-dose Cyclosporine after Pulse Methylprednisolone in Japanese Adult Minimal-change Nephrotic Syndrome Hiroshi MATSUMOTO, Toshiyuki NAKAO, Tomonari OKADA, Yume NAGAOKA,
More informationThe CARI Guidelines Caring for Australians with Renal Impairment. Membranous nephropathy Role of alkylating agents GUIDELINES
Membranous nephropathy Role of alkylating agents Date written: July 2005 Final submission: September 2005 Author: Merlin Thomas GUIDELINES a. Treatment with alkylating agents is associated with an increased
More informationClinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: medical therapy
Clin Exp Nephrol (2015) 19:6 33 DOI 10.1007/s10157-014-1030-x GUIDELINE Clinical practice guideline for pediatric idiopathic nephrotic syndrome 2013: medical therapy Kenji Ishikura Shinsuke Matsumoto Mayumi
More informationEvidence review: Rituximab for Membranous Glomerular Nephritis
NHS England Evidence review: Rituximab for Membranous Glomerular Nephritis 1 NHS England Evidence review: Rituximab for Membranous Glomerular Nephritis First published: March 2013 Updated: March 2016 Prepared
More informationRandom forest can accurately predict the development of end-stage renal disease in immunoglobulin a nephropathy patients
Original Article Page 1 of 8 Random forest can accurately predict the development of end-stage renal disease in immunoglobulin a nephropathy patients Xin Han 1#, Xiaonan Zheng 2#, Ying Wang 3, Xiaoru Sun
More informationTHE KIDNEY AND SLE LUPUS NEPHRITIS
THE KIDNEY AND SLE LUPUS NEPHRITIS JACK WATERMAN DO FACOI 2013 NEPHROLOGY SIR RICHARD BRIGHT TERMINOLOGY RENAL INSUFFICIENCY CKD (CHRONIC KIDNEY DISEASE) ESRD (ENDSTAGE RENAL DISEASE) GLOMERULONEPHRITIS
More informationControversies in Renal Transplantation. The Controversial Questions. Patrick M. Klem, PharmD, BCPS University of Colorado Hospital
Controversies in Renal Transplantation Patrick M. Klem, PharmD, BCPS University of Colorado Hospital The Controversial Questions Are newer immunosuppressants improving patient outcomes? Are corticosteroids
More informationNew Evidence reports on presentations given at EULAR Safety and Efficacy of Tocilizumab as Monotherapy and in Combination with Methotrexate
New Evidence reports on presentations given at EULAR 2009 Safety and Efficacy of Tocilizumab as Monotherapy and in Combination with Methotrexate Report on EULAR 2009 presentations Tocilizumab inhibits
More informationLONG-TERM OUTCOME OF PATIENTS WITH LUPUS NEPHRITIS: A SINGLE CENTER EXPERIENCE
& LONG-TERM OUTCOME OF PATIENTS WITH LUPUS NEPHRITIS: A SINGLE CENTER EXPERIENCE Senija Rašić 1 *, Amira Srna 1, Snežana Unčanin 1, Jasminka Džemidžić 1, Damir Rebić 1, Alma Muslimović 1, Maida Rakanović-Todić
More informationOverview of New Approaches to Immunosuppression in Renal Transplantation
Overview of New Approaches to Immunosuppression in Renal Transplantation Ron Shapiro, M.D. Professor of Surgery Surgical Director, Kidney/Pancreas Transplant Program Recanati/Miller Transplantation Institute
More informationCHAPTER 5 RENAL TRANSPLANTATION
CHAPTER 5 RENAL TRANSPLANTATION Editor: Dr. Goh Bak Leong Expert Panel: Dato Dr. Zaki Morad b Mohd Zaher (Chair) Dr. Goh Bak Leong (Co-Chair) Dr. Fan Kin Sing Dr. Lily Mushahar Mr. Rohan Malek Dr. S. Prasad
More informationDiltiazem use in tacrolimus-treated renal transplant recipients Kothari J, Nash M, Zaltzman J, Prasad G V R
Diltiazem use in tacrolimus-treated renal transplant recipients Kothari J, Nash M, Zaltzman J, Prasad G V R Record Status This is a critical abstract of an economic evaluation that meets the criteria for
More informationCancer Cell Research 14 (2017)
Available at http:// www.cancercellresearch.org ISSN 2161-2609 Efficacy and safety of bevacizumab for patients with advanced non-small cell lung cancer Ping Xu, Hongmei Li*, Xiaoyan Zhang Department of
More informationANCA-associated vasculitis. Vladimir Tesar Department of Nephrology, General University Hospital, Prague, Czech Republic
ANCA-associated vasculitis Vladimir Tesar Department of Nephrology, General University Hospital, Prague, Czech Republic Disclosure of Interests Abbvie, Amgen, Baxter, Bayer, Boehringer-Ingelheim, Calliditas,
More informationLupus Related Kidney Diseases. Jason Cobb MD Assistant Professor Renal Division Emory University School of Medicine October 14, 2017
Lupus Related Kidney Diseases Jason Cobb MD Assistant Professor Renal Division Emory University School of Medicine October 14, 2017 Financial Disclosures MedImmune Lupus Nephritis Kidney Biopsy Biomarkers
More informationSteroid-dependent nephrotic syndrome in children. Alexey Tsygin, MD, PhD NCZD Moscow, Russia
Steroid-dependent nephrotic syndrome in children Alexey Tsygin, MD, PhD NCZD Moscow, Russia Definition Nephrotic syndrome (NS) urinary albumin loss at the level of 3,5 g/1,73 m 2 /24h or 40 mg/м 2 /hour
More informationIncreased Early Rejection Rate after Conversion from Tacrolimus in Kidney and Pancreas Transplantation
Increased Early Rejection Rate after Conversion from Tacrolimus in Kidney and Pancreas Transplantation Gary W Barone 1, Beverley L Ketel 1, Sameh R Abul-Ezz 2, Meredith L Lightfoot 1 1 Department of Surgery
More informationNephrotic Syndrome. Sara Alsharhan PharmD candidate, KSU 2014
Nephrotic Syndrome Sara Alsharhan PharmD candidate, KSU 2014 Outline Introduction Nephrotic syndrome classifications Signs and symptoms Diagnoses Management Complications Monitoring Case presentation Introduction
More informationMulti-Drug Therapy Followed By Rituximab in Children with Refractory Nephrotic Syndrome Contributors
IOSR Journal of Dental and Medical Sciences (IOSR-JDMS) e-issn: 2279-0853, p-issn: 2279-0861.Volume 17, Issue 01 Ver. I (January. 2018), PP 05-09 www.iosrjournals.org Multi-Drug Therapy Followed By Rituximab
More informationHypertension targets: sorting out the confusion. Brian Rayner, Division of Nephrology and Hypertension, University of Cape Town
Hypertension targets: sorting out the confusion Brian Rayner, Division of Nephrology and Hypertension, University of Cape Town Historical Perspective The most famous casualty of this approach was the
More informationThe CARI Guidelines Caring for Australasians with Renal Impairment. Blood Pressure Control role of specific antihypertensives
Blood Pressure Control role of specific antihypertensives Date written: May 2005 Final submission: October 2005 Author: Adrian Gillian GUIDELINES a. Regimens that include angiotensin-converting enzyme
More informationActhar Gel. H. P. Acthar Gel (corticotropin; ACTH) Description
Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.30.10 Subject: Acthar Gel Page: 1 of 6 Last Review Date: December 8, 2017 Acthar Gel Description H. P.
More informationSupplementary Appendix
Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Serra AL, Poster D, Kistler AD, et al. Sirolimus and kidney
More informationManagement of Post-transplant hyperlipidemia
Management of Post-transplant hyperlipidemia B. Gisella Carranza Leon, MD Assistant Professor of Medicine Lipid Clinic - Vanderbilt Heart and Vascular Institute Division of Diabetes, Endocrinology and
More informationPRIMARY GLOMERULAR DISEASES
University of Sydney PRIMARY GLOMERULAR DISEASES David Harris 8/2015 Westmead Hospital KDIGO GUIDELINES Steroid-sensitive & resistant nephrotic syndrome in children Minimal-change disease and FSGS in children
More information