Cyclosporine-A-induced nephrotoxicity in children with minimal-change nephrotic syndrome: long-term treatment up to 10 years.
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ABSTRACT:
SUBMITTER: Kranz B
PROVIDER: S-EPMC2259257 | biostudies-other | 2008 Apr
REPOSITORIES: biostudies-other
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Project description:BACKGROUND AND OBJECTIVES: Frequently relapsing and steroid-dependent minimal-change nephrotic syndrome (MCNS) that originates in childhood can persist after puberty in >20% of patients. These patients require immunosuppressive treatment during several decades of their life. We examined long-term adverse effects of persistent nephrotic syndrome and immunosuppressive medications, focusing on renal function, growth, obesity, osteoporosis, hypertension, ocular complications, and fertility in adult patients with biopsy-proven childhood-onset MCNS. Molecular analysis was performed to evaluate a possible association of a complicated course of MCNS with podocyte gene mutations. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed a prospective clinical examination of 15 adult patients that included serum and urine analysis; dual-energy x-ray absorptiometry; ophthalmologic examination; semen examination; and molecular analysis of NPHS1, NPHS2, CD2AP, and ACTN4 genes. RESULTS: All patients had normal GFR. Most frequent long-term complications were hypertension (in seven of 15 patients) and osteoporosis in one third of patients. Oligozoospermia was found in one patient, reduced sperm motility in four of eight patients, and teratozoospermia in six of eight patients. Ophthalmologic examination revealed myopia in 10 of 15 patients and cataract in three of 15 patients. CONCLUSIONS: Children with MCNS that persists after puberty are at risk for complications such as osteoporosis, hypertension, cataract, and sperm abnormalities. Our study underscores a need for more effective and less toxic therapies for relapsing MCNS.
| S-EPMC2758253 | biostudies-literature
Project description:Minimal change nephrotic syndrome (MCNS) is the most common cause of nephrotic syndrome in children and can also present in adults. Corticosteroids generally induce remission of MCNS, and relapses are common after reduction or discontinuation of corticosteroids. We experienced a rare case of steroid-sensitive MCNS where the patient relapsed after 52 years of remission. The patient was a 61-year-old Japanese male who visited our clinic for an edema of the lower extremities which had already persisted for a few days. Laboratory testing showed massive urinary protein and low serum total protein and albumin levels. Therefore, he was diagnosed with nephrotic syndrome. He had a history of nephrotic syndrome that initially developed when he was 5 years old. Although corticosteroids reduced the urinary protein level, frequent relapses occurred when their doses were reduced, or when they were discontinued. He had previously experienced a relapse when he was 9 years old. For his current condition, treatment with corticosteroids and diuretics for 1 week reduced his edema and proteinuria. We suspected that this is a case of MCNS and that the present event is a relapse. Thus, we concluded that this is a very rare case of steroid-sensitive nephrotic syndrome that relapsed after 52 years of remission.
| S-EPMC6167670 | biostudies-other
Project description:Minimal change disease (MCD) is characterized by edema and nephrotic range proteinuria (NS). However, the fate of MCD without nephrotic proteinuria requires elucidation. We retrospectively reviewed 79 adults diagnosed with primary MCD at their initial renal biopsy at a tertiary hospital between May 2003 and June 2017. Clinicopathologic features were compared between patients with and without NS. The frequency of flaring to nephrotic proteinuria and renal outcomes were assessed during follow-up. There were 20 and 59 patients in the Non-NS and NS groups, respectively. The Non-NS group had a lower frequency of acute kidney injury (AKI) during the follow-up period [5.0% vs. 59.3%, p <0.001]. The response rate to steroid treatment was 100% in the Non-NS group and 92.3% in the NS group (p = 1.000). Except for one patient, the Non-NS group was treated with steroids when their proteinuria increased to a nephrotic level. There were no differences in the frequency of the first relapse or the number of relapses among patients with initial remission from nephrotic range proteinuria. At the final visit, the complete remission rate was 73.4%. The estimated glomerular filtration rate during follow-up was significantly better in the NS group than the Non-NS group, given the higher rates of AKI at renal biopsy. The rates of renal events, end-stage renal disease, and mortality did not differ between the groups. Adult MCD patients with nephrotic and non-nephrotic range proteinuria showed similar outcomes. Accordingly, this population must be carefully managed, regardless of the amount of proteinuria at renal biopsy.
| S-EPMC10434851 | biostudies-literature
Project description: Not available
| S-EPMC10371375 | biostudies-literature
Project description: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-11001454) 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 16-20 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 for complete remission). The groups had similar mean time to remission (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.
| S-EPMC5373446 | biostudies-literature
Project description:BackgroundDNA methylation of gene promoters is associated with transcriptional inactivation. Changes in DNA methylation can lead to differences in gene expression levels and thereby influence disease development. We hypothesized that epigenetics underlies the pathogenesis of minimal change nephrotic syndrome (MCNS).MethodsGenome-wide DNA methylation changes between relapse and remission in monocytes (n = 6) and naive T helper cells (Th0s) (n = 4) isolated from patients with MCNS were investigated using the microarray-based integrated analysis of methylation by isochizomers (MIAMI) method. We confirmed the MIAMI results using bisulfite-pyrosequencing analysis. Expression analysis was performed using quantitative real-time PCR.ResultsThree gene loci (GATA2, PBX4, and NYX) were significantly less methylated in Th0s during relapse than in remission, compared to none in monocytes. In addition, the distance distribution from the regression line of all probes in MIAMI was significantly different between monocytes and Th0s. The mRNA levels of the three genes in Th0s were not significantly different between relapse and remission.ConclusionsOur results demonstrate that the change in DNA methylation patterns from remission to relapse in MCNS occurs predominantly in Th0s rather than in monocytes and suggest that epigenetic regulation in Th0s underlies the pathogenesis of MCNS.
| S-EPMC3491205 | biostudies-literature
Project description:Background: Minimal change nephrotic syndrome (MCNS) is considered to be associated with T cell dysfunction, via unknown mechanisms. Experimental observations suggest that some humoral factors alter the permeability of glomerular filtration barrier. However, the nature of such factors remains still uncertain. Methods: Using cDNA microarrays, we performed gene expression profiling of peripheral blood mononuclear cells (PBMC) from three patients with MCNS during nephrosis and remission phases. To confirm the cDNA microarray results, we performed quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses in nephrosis and remission samples from 20 MCNS patients and six patients with nephrotic syndrome due to membranous nephropathy. Results: Out of 24,446 genes screened, 33 genes were up-regulated (at least 1.5-fold) in PBMC from these MCNS patients during the nephrosis phase. Up-regulated genes mainly encoded proteins involved in signal transduction and cytokine response. For further examination, we selected two genes encoding provable secretary proteins, chemokine (C-C) ligand 13 (also known as monocyte chemotactic protein-4) (CCL13) and a novel galectin-related protein (HSPC159). The results of RT-PCR showed that expressions of CCL13 and HSPC159 mRNA in nephrosis PBMC samples are higher than those in remission PBMC samples from all 20 MCNS patients examined. On the other hand, these mRNA expression patterns were variable among six patients with membranous nephropathy. Conclusions: We conclude that CCL13 and HSPC159 mRNA expressions in PBMC is up-regulated in MCNS patients during the nephrosis phase. These expression changes in PBMC might be involved in the pathophysiologic processes of MCNS. Using cDNA microarrays, we performed gene expression profiling of peripheral blood mononuclear cells (PBMC) from three patients with MCNS during nephrosis and remission phases. To confirm the cDNA microarray results, we performed quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses in nephrosis and remission samples from 20 MCNS patients and six patients with nephrotic syndrome due to membranous nephropathy.
2010-05-25 | E-GEOD-7349 | biostudies-arrayexpress
Project description:Background: Minimal change nephrotic syndrome (MCNS) is considered to be associated with T cell dysfunction, via unknown mechanisms. Experimental observations suggest that some humoral factors alter the permeability of glomerular filtration barrier. However, the nature of such factors remains still uncertain. Methods: Using cDNA microarrays, we performed gene expression profiling of peripheral blood mononuclear cells (PBMC) from three patients with MCNS during nephrosis and remission phases. To confirm the cDNA microarray results, we performed quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) analyses in nephrosis and remission samples from 20 MCNS patients and six patients with nephrotic syndrome due to membranous nephropathy. Results: Out of 24,446 genes screened, 33 genes were up-regulated (at least 1.5-fold) in PBMC from these MCNS patients during the nephrosis phase. Up-regulated genes mainly encoded proteins involved in signal transduction and cytokine response. For further examination, we selected two genes encoding provable secretary proteins, chemokine (C-C) ligand 13 (also known as monocyte chemotactic protein-4) (CCL13) and a novel galectin-related protein (HSPC159). The results of RT-PCR showed that expressions of CCL13 and HSPC159 mRNA in nephrosis PBMC samples are higher than those in remission PBMC samples from all 20 MCNS patients examined. On the other hand, these mRNA expression patterns were variable among six patients with membranous nephropathy. Conclusions: We conclude that CCL13 and HSPC159 mRNA expressions in PBMC is up-regulated in MCNS patients during the nephrosis phase. These expression changes in PBMC might be involved in the pathophysiologic processes of MCNS. Keywords: CCL13 - cDNA microarray - gene expression profile - HSPC159 - minimal change nephrotic syndrome
2008-03-22 | GSE7349 | GEO
Project description:AimTo examine speech impairment severity classification over time in a longitudinal cohort of children with cerebral palsy (CP).MethodA total of 101 children (58 males, 43 females) between the ages of 4 and 10 years with CP participated in this longitudinal study. Speech severity was rated using the Viking Speech Scale (VSS), a four-level classification rating scale, at 4, 6, 8, and 10 years (age 4 years: mean = 52 months [3 SD]; age 6 years: mean = 75 months [2 SD]; age 8 years: mean = 100 months [4 SD]; age 10 years: mean = 125 months [5 SD]). We used Bayesian mixed-effects ordinal logistic regression to model (1) the extent to which speech severity changed over time and (2) patterns of change across age groups and classification rating group levels.ResultsVSS ratings decreased (speech severity became less severe) between 4 and 10 years of age. Children who were first classified in VSS levels I, II, or III at age 4 years had a high probability of staying at, or improving to, VSS level I by 10 years. Children who were first classified in VSS level IV at 4 years had a high probability of remaining in VSS level IV at 10 years.InterpretationEarly speech performance is highly predictive of later childhood speech abilities. Children with any level of speech impairment at age 4 years should be receiving speech therapy. Those with more severe speech impairments should be introduced to augmentative and alternative communication as soon as possible.What this paper addsChildren with early Viking Speech Scale (VSS) ratings below level IV have a good prognosis for speech improvement. Children with early VSS level IV ratings are likely to remain at VSS level IV over time. Children did not show worsening of VSS level between the ages of 4 and 10 years.
| S-EPMC9339470 | biostudies-literature
Project description:BackgroundCyclosporine is widely used for immunosuppressive treatment of various systematic and local autoimmune diseases. Breastfeeding is conventionally contraindicated when treating with cyclosporine due to its excretion into breast milk, which may cause immune suppression of exposed infants and affect infants` growth. A few cases have tested cyclosporine levels in random breast milk samples and concluded the infants exposed to safe cyclosporine levels during breastfeeding. Since infants do not maintain a fixed feeding schedule, we monitored cyclosporine levels in breast milk at different times of the day to assess the safety of breast milk for infants throughout the day.Case presentationA 32-year-old dichorionic twin-pregnancy woman had nephrotic syndrome with renal biopsy confirmed type V lupus nephritis for over five years. She was treated only with prednisone 10 mg a day before pregnancy and during early pregnancy. Cyclosporine was added in her regimen from 22 weeks gestation and was adjusted to 225 mg a day from 28 weeks gestation. After parturition, she partially breastfed her twin infants while being treated with cyclosporine 3 mg/kg a day as well as prednisone and hydroxychloroquine sulfate. The cyclosporine level in maternal blood was determined, and several breast milk samples were collected for consecutive 48 h beginning on the ninth day after parturition. The concentration of cyclosporine in breast milk was measured and ranged from 0.443 to 5.307 mcg/L. Both infants grew and developed normally at the three-month follow-up, with no adverse effects observed. The study was conducted at West China Second University Hospital of Sichuan University, started in September 2021, with the consent of the participant and the approval of the ethics committee.ConclusionIn this case, cyclosporine levels in breast milk were low at all times of the day. The growth and development of both infants were normal at three months postpartum. Thus, breastfeeding may still be an option for mothers with nephrotic syndrome who are treated with cyclosporine.
| S-EPMC9578242 | biostudies-literature