pulmicort and Proteinuria

The use of corticosteroids to treat IgA nephropathy (IgAN) has been limited by many controversies related to uncertain benefit and safety concerns. Recent trials have tried to address these limitations.. After being paused because of an excess of adverse events in the full-dose steroid arm, the TESTING trial compared a reduced dose of methylprednisolone to placebo in patients with IgAN after optimization of supportive therapy. Steroid treatment was associated with a significant reduction in the risk of a 40% decline in estimated glomerular filtration rate (eGFR), kidney failure and kidney death as well as a sustained decrease in proteinuria compared with placebo. Serious adverse events were more frequent with the full dose regimen but less common in the reduced dose regimen. A phase III trial evaluating a new formulation of targeted-release budesonide showed a significant reduction in short-term proteinuria and has resulted in accelerated FDA approval for use in the United States. In a subgroup analysis of DAPA-CKD trial, sodium-glucose transport protein 2 inhibitors reduced the risk of kidney function decline in patients who have completed or are not eligible for immunosuppression.. Both reduced-dose corticosteroids and targeted-release budesonide are new therapeutic options that can be used in patients with high-risk disease. More novel-targeted therapies with a better safety profile are currently under investigations.

Topics: Adrenal Cortex Hormones; Budesonide; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Immunosuppressive Agents; Proteinuria; Steroids

The connection between a dysregulated gut-associated lymphoid tissue and IgA nephropathy (IgAN) was supposed decades ago after the observation of increased association of IgAN with celiac disease. Pivotal studies have shown a role for alimentary antigens, particularly gliadin in developing IgAN in BALB/c mice, and a reduction in IgA antigliadin antibodies and proteinuria was reported after gluten free-diet in patients with IgAN. Recently a genome-wide association study showed that most loci associated with IgAN also are associated with immune-mediated inflammatory bowel diseases, maintenance of the intestinal barrier, and response to gut pathogens. Transgenic mice that overexpress the B-cell activating factor develop hyper-IgA with IgAN modulated by alimentary components and intestinal microbiota. Mice expressing human IgA1 and a soluble form of the IgA receptor (sCD89) develop IgAN, which is regulated by dietary gluten. Recent observations have confirmed gut-associated lymphoid tissue hyper-reactivity in IgAN patients with IgA against alimentary components. Interesting results were provided by the NEFIGAN randomized controlled trial, which adopted an enteric controlled-release formulation of the corticosteroid budesonide targeted to Peyer's patches. After 9 months of treatment, a reduction in proteinuria was observed with stabilized renal function and limited adverse events. The gut-renal connection is an area of promising new treatment approaches for patients with IgAN.

Topics: Animals; Antibodies; Budesonide; Celiac Disease; Comorbidity; Gastrointestinal Microbiome; Gliadin; Glomerulonephritis, IGA; Glucocorticoids; Glutens; Humans; Immunoglobulin A; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines; Lymphoid Tissue; Mice; Mice, Inbred BALB C; Mice, Transgenic; Peyer's Patches; Proteinuria; Receptors, Fc

Topics: Budesonide; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Prospective Studies; Proteinuria

The benefits and risks of systemic corticosteroids in the treatment of IgA nephropathy are still controversial. Part A results of the Efficacy and Safety of Nefecon in Patients With Primary IgA Nephropathy (NefIgArd) trial provide significant effects on decrease in proteinuria and protection from estimated glomerular filtration rate decline after 9 months of treatment with budesonide (Nefecon). Targeting the initiating pathogenetic event in the gut-associated lymphoid tissue would offer a disease-modifying approach to IgA nephropathy. Results, adverse events, and possible multiple effects of this treatment are critically discussed.

Topics: Budesonide; Glomerular Filtration Rate; Glomerulonephritis, IGA; Glucocorticoids; Humans; Immunoglobulin A; Proteinuria

The best treatment for IgAN is still debated. The trials NEFIGAN and NEFIGARD have demonstrated that TRF-budesonide (Nefecon) efficiently and safely reduced proteinuria in adults, leading to FDA approval of Nefecon for adult IgAN. In pediatric IgAN, an etiological treatment does not yet exist, and the main therapies remain RAAS inhibitors and oral steroids. To our knowledge, this is one of the few pediatric reports of TRF-budesonide therapy.. A 13-year-old boy underwent a kidney biopsy for recurrent macrohematuria and proteinuria, resulting in an IgAN diagnosis (MEST-C score M1-E1-S0-T0-C1). At admission, serum creatinine and UPCR were slightly increased. Three methylprednisolone pulses were performed, followed by prednisone and RAAS inhibitors therapy. However, after 10 months, macrohematuria became constant, and UPCR increased. A new kidney biopsy was performed, showing an increase in sclerotic lesions. Prednisone was discontinued, and a trial with IBD TRF-budesonide 9 mg/day started. One month later, macrohematuria episodes disappeared and UPCR decreased, with a stable kidney function. After 5 months, due to a reduction in morning cortisol levels and difficulty in drug provisioning, we started to wean TRF-budesonide by 3 mg every 3 months, with complete withdrawal after 1 year. During this period, episodes of macrohematuria dramatically decreased, and UPCR and kidney function were maintained stable.. Our case demonstrates that TRF-budesonide could be considered an effective second-line treatment in pediatric IgAN, particularly when a long course of steroids is necessary to control active inflammation. However, pediatric clinical trials to identify the correct dosage and tolerability of TRF-budesonide are urgently needed.

Topics: Adolescent; Adult; Budesonide; Child; Glomerulonephritis, IGA; Hematuria; Humans; Male; Prednisone; Proteinuria

Budesonide (Tarpeyo) has received accelerated approval to reduce proteinuria in adults with primary immunoglobulin A nephropathy, also known as Berger's disease.Nurses should assess if any coprescribed drugs could induce a drug-drug interaction via the cytochrome P-450 isoenzyme system. Because budesonide causes immunosuppression, patients are at high risk for developing infections and should be told to avoid anyone who is known to have an infection.

Topics: Adult; Budesonide; Glomerulonephritis, IGA; Humans; Proteinuria

Topics: Budesonide; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Proteinuria; Transplants

Primary immunoglobulin A (IgA) nephropathy is associated with a dysfunctional mucosal immune system, leading to renal deposition of IgA and injury. Fifty patients with biopsy-proven IgA nephropathy were included. All patients were initiated on renin-angiotensin-aldosterone system (RAAS) inhibitors, polyunsaturated fatty acids, and a controlled release formulation (CRF) of budesonide. All drugs were started together, as isolated RAAS inhibitors will not prevent the immunological damage caused by the ongoing deposition of IgA. Depending on the histology (mesangial hypercellularity, endocapillary proliferation, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and crescents score), the patients received 9 mg or 12 mg of budesonide. All patients were followed up every 4 weeks to monitor renal function, 24-h urinary protein, and adverse effects. Our primary outcome was a mean change in the estimated glomerular filtration rate (eGFR) and 24-h urinary protein from the baseline to the end of 6 months. The percentage of decline in mean 24-h protein at 6 months from the baseline was 33%. The mean decrease in serum creatinine from the baseline was 0.73 mg/dL. The mean gain in eGFR from the baseline was an increase of 9 mL/min/1.73 m2. Of 50 patients, 11 (22%) achieved complete remission, 20 (40%) achieved partial remission, and 16 (32%) were non-responders. Three patients (6%) were lost to follow-up. The early initiation of CRF budesonide with optimized supportive care led to reductions in proteinuria and improvements in eGFR at 6 months in patients with IgA nephropathy. Early lesions with minimal chronicity showed an excellent response to budesonide.

Topics: Biopsy; Budesonide; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Immunoglobulin A; Proteinuria; Retrospective Studies; Steroids

IgA Nephropathy (IgAN) is characterized by mesangial deposition of dominant, polymeric, galactose-deficient IgA1 molecules of gut-associated lymphoid tissue origin. We sought to evaluate the efficacy of targeting the mucosal immune system dysregulation underlying IgAN pathogenesis with a pH-modified formulation of budesonide with a maximum release of active compound in the distal ileum and proximal colon.We did a retrospective study evaluating the efficacy of budesonide (Budenofalk) in the treatment of IgAN. From a retrospective cohort of 143 patients with IgAN followed in our department we identified 21 patients that received treatment with budesonide. These patients received budesonide at a dose of 9 mg/d in the first 12 months, followed by a dose reduction to 3 mg/d for the subsequent period. Only patients that received a 24-month treatment with budesonide were included in the analysis (n = 18). We matched the budesonide-treated cohort to 18 patients with IgAN treated with systemic steroids from the same retrospective cohort. Efficacy was measured as change in proteinuria, hematuria and estimated glomerular filtration rate over a 24-month period.Treatment with budesonide was associated with a 24-month renal function decline of -0.22 (95%CI, -8.2 to 7.8) ml/min/1.73m, compared to -5.89 (95%CI, -12.2 to 0.4) ml/min/1.73m in the corticosteroid treatment group (p = 0.44, for between group difference). The median reduction in proteinuria at 24-month was 45% (interquartile range [IQR]: -79%; -22%) in the budesonide group and 11% (IQR: -39%; 43%) in the corticosteroid group, respectively (P = .009, for between group difference). The median reduction in hematuria at 24-month was 72% (IQR: -90%; -45%) in the budesonide group and 73% (IQR: -85%; 18%) in the corticosteroid group, respectively (P = .22, for between group difference). Treatment with budesonide was well tolerated with minimal side effects.Budesonide (Budenofalk) was effective in the treatment of patients with IgAN at high-risk of progression in terms of reducing proteinuria, hematuria and preserving renal function over 24 months of therapy.

Topics: Adrenal Cortex Hormones; Adult; Budesonide; Female; Glomerular Filtration Rate; Glomerulonephritis, IGA; Hematuria; Humans; Male; Middle Aged; Propensity Score; Proteinuria; Retrospective Studies

IgA nephropathy is an immune-mediated chronic glomerulonephritis with a great variability in clinical presentation and outcome. The disease can progress to end-stage renal failure in 25% of patients. For this reason we should identify patients with potential to progress. Most important risk factors for progression are persistent proteinuria, hypertension, decreased renal function and some histological lesions. The actually suggested treatment is summarized in KDIGO Clinical Practice Guideline from 2012. They suggest to give firstly non-specific supportive treatment (especially renin-angiotensin system blocking agents). Recommendation about steroid/immunosuppression treatment is based on low level of evidence. Recently three studies were organised concerning benefits and risk of steroid/immunosuppressive treatment added together with specific supportive treatment. In the STOP-IgAN study, systemic steroid/immunosuppressive treatment significantly decreased proteinuria but did not stop progression. In the TESTING study, systemic steroid treatment significantly decreased proteinuria and progression. However, the study was recently discontinued due to several severe side effects of steroid treatment. Involvement of intestinal mucosal immunity in the pathogenesis of IgA nephropathy suggested the NEFIGAN study with budesonide treatment. Budesonide releases corticosteroid in distal small intestine and colon. Proteinuria was significantly decreased and renal function remained stabile. High number of withdrawals owing to adverse effects is a major concern implying a substantial systemic effect of budesonide. We need further information on the characteristics of patients who most likely benefit from steroid/immunosuppressive treatment given after or together with specific supportive treatment. Orv Hetil. 2017; 158(49): 1946-1952.

Topics: Budesonide; Critical Pathways; Glomerular Filtration Rate; Glomerulonephritis, IGA; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Failure, Chronic; Proteinuria; Risk Assessment; Steroids; Treatment Outcome