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Pediatric Nephrology (Berlin, Germany) Aug 2022Edema is one of the cardinal clinical features of nephrotic syndrome (NS). It may vary from mild periorbital edema to severe generalized edema (anasarca). In patients... (Review)
Review
BACKGROUND
Edema is one of the cardinal clinical features of nephrotic syndrome (NS). It may vary from mild periorbital edema to severe generalized edema (anasarca). In patients where edema does not improve with prednisone therapy, the most common supportive medications are diuretics and albumin. However, due to the complex pathophysiology of edema formation in NS patients resulting in intravascular normovolemia or hypovolemia, optimal therapy for edema is still debated. We conducted a systematic review with the objective of evaluating the change in urine volume and urine sodium excretion after treatment with furosemide only versus furosemide with albumin in edematous patients with NS.
OBJECTIVES
(1) To evaluate efficacy of furosemide alone versus furosemide with albumin in the treatment of nephrotic edema in adults and children. (2) To compare the harms and benefits of different doses of furosemide for treating nephrotic edema.
SEARCH METHODS
The search included all randomized or quasi-randomized controlled trials in English and French using MEDLINE, Embase, and CENTRAL Trials Registry of the Cochrane Collaboration using the Ovid interface.
CLINICALTRIALS
gov and the International Clinical Trials Registry Platform were also searched.
SELECTION CRITERIA
We included all RCTs and randomized cross-over studies in which furosemide and furosemide plus albumin are used in the treatment of children or adults with nephrotic edema. We excluded patients with hypoalbuminemia of non-renal origin and severe chronic kidney disease (CKD) with a glomerular filtration rate below 30 ml/min/1.74 m and patients with congenital NS.
DATA COLLECTION AND ANALYSIS
All abstracts were independently assessed by at least two authors to determine which studies met the inclusion criteria. Information on study design, methodology, and outcome data (urine volume, urine sodium excretion, adverse effects) from each identified study was entered into a separate data sheet. The differences in outcomes between the types of therapy were expressed as standardized mean difference (SMD) with 95% confidence intervals (CI).
RESULTS
The search yielded 525 records, and after screening, five studies were included in the systematic review and four of those studies in the meta-analysis. One study had high risk of bias and the remaining three studies were deemed to have some concerns. Urine excretion was greater after treatment with furosemide and albumin versus furosemide (SMD 0.85, 95% CI = 0.33 to 1.38). Results for sodium excretion were inconclusive (SMD 0.37, 95%CI = - 0.28 to 1.02).
AUTHORS' CONCLUSIONS
The current evidence is not sufficient to make definitive conclusions about the role of albumin in treating nephrotic edema. High-quality randomized studies with adequate samples sizes are needed. Including an assessment of intravascular volume status may be helpful.
TRIAL REGISTRATION
Prospero: CRD4201808979. https://www.crd.york.ac.uk/PROSPERO A higher resolution version of the Graphical abstract is available as Supplementary information.
Topics: Adult; Albumins; Child; Edema; Furosemide; Humans; Nephrotic Syndrome; Sodium
PubMed: 35239032
DOI: 10.1007/s00467-021-05358-4 -
Current Rheumatology Reports May 2023Undifferentiated connective tissue disease (UCTD) is characterized by the presence of clinical symptoms of a systemic autoimmune disease in addition to laboratory... (Review)
Review
PURPOSE OF REVIEW
Undifferentiated connective tissue disease (UCTD) is characterized by the presence of clinical symptoms of a systemic autoimmune disease in addition to laboratory evidence of autoimmunity with the patients not fulfilling any of the widely used classification criteria for classic autoimmune diseases. The presence of UCTD as a separate entity versus an early stage of such diseases as systemic lupus erythematosus (SLE) or scleroderma has long been debated. Given the uncertainty regarding this condition, we performed a systematic review on the topic.
RECENT FINDINGS
UCTD can be subcategorized as evolving (eUCTD) or stable UCTD (sUCTD) based on its evolution towards a definable autoimmune syndrome. Analyzing the data from six UCTD cohorts published in the literature, we found that 28% of patients have an evolving course with the majority developing SLE or rheumatoid arthritis within 5-6 years of the UCTD diagnosis. From the remaining patients, 18% do achieve remission. Published treatment regimens were similar to other mild autoimmune diseases with low-dose prednisone, hydroxychloroquine, and NSAID. One-third of patients did need immune suppressive medications. Importantly, the reported outcomes were excellent with survival rates of more than 90% over 10 years. It has to be noted though that as data on patient related outcomes are not available to date, the exact impact of this condition on quality of life is unclear. UCTD is a mild autoimmune condition with generally good outcomes. There is still great uncertainty though regarding diagnosis and management. Going forward, consistent classification criteria are needed to advance UCTD research and eventually provide authoritative guidance on the management of the condition.
Topics: Humans; Undifferentiated Connective Tissue Diseases; Quality of Life; Autoimmune Diseases; Lupus Erythematosus, Systemic; Arthritis, Rheumatoid; Connective Tissue Diseases
PubMed: 36884206
DOI: 10.1007/s11926-023-01099-5 -
Clinical and Experimental Rheumatology 2016Remitting seronegative symmetrical synovitis with pitting oedema (RS(3)PE) syndrome is a rare inflammatory arthritis, characterised by symmetrical distal synovitis,... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Remitting seronegative symmetrical synovitis with pitting oedema (RS(3)PE) syndrome is a rare inflammatory arthritis, characterised by symmetrical distal synovitis, pitting oedema of the hands and feet, absence of rheumatoid factor, and favourable response to glucocorticoids. The aim of our study is to further delineate the clinical and laboratory features, and response to treatment.
METHODS
We performed a systematic electronic search of Medline, PubMed, EMBASE, ACR and EULAR databases for case reports, case series, and related articles of RS(3)PE. Statistical analysis was done comparing categorical variables with Chi-square tests and frequencies of means via t-tests. Binary logistic regression analysis was performed to identify predictors of erosions, recurrence, malignancy and rheumatologic disorders.
RESULTS
331 cases of RS(3)PE were identified from 121 articles. RS(3)PE was found in older patients (71±10.42 years) predominantly in males (n= 211, 63.36%), was symmetrical (n=297/311, 95.50%) involved the hands (n=294/311, 94.53%) A concurrent rheumatologic condition was reported in 22 cases (6.65%), and malignancy in 54 cases (16.31%). Radiographic joint erosions were found in 5.5%. Most patients responded to medium-dose glucocorticoids (16.12±9.5 mg/day). Patients with concurrent malignancy requiring non-significantly higher doses of prednisone (18.12 vs. 15.76 mg, p 0.304) and higher likelihood of recurrence of disease (OR 4.04, 95% CI 1.10-14.88, p=0.03).
CONCLUSIONS
The symptoms and unique findings that make up RS(3)PE appear to represent a steroid-responsive disease that may be a harbinger of an underlying malignancy. More study is needed to understand the molecular origins of RS(3)PE in order to determine whether it is a separate disease process. Patients with concurrent cancer tend to have more severe presentations and higher rates of recurrence.
Topics: Disease Management; Edema; Foot; Glucocorticoids; Hand; Humans; Recurrence; Serologic Tests; Symptom Assessment; Syndrome; Synovitis
PubMed: 27050250
DOI: No ID Found -
Journal of Clinical Oncology : Official... Oct 2018To provide an updated joint ASCO/Infectious Diseases Society of America (IDSA) guideline on antimicrobial prophylaxis for adult patients with immunosuppression...
PURPOSE
To provide an updated joint ASCO/Infectious Diseases Society of America (IDSA) guideline on antimicrobial prophylaxis for adult patients with immunosuppression associated with cancer and its treatment.
METHODS
ASCO and IDSA convened an update Expert Panel and conducted a systematic review of relevant studies from May 2011 to November 2016. The guideline recommendations were based on the review of evidence by the Expert Panel.
RESULTS
Six new or updated meta-analyses and six new primary studies were added to the updated systematic review.
RECOMMENDATIONS
Antibacterial and antifungal prophylaxis is recommended for patients who are at high risk of infection, including patients who are expected to have profound, protracted neutropenia, which is defined as < 100 neutrophils/µL for > 7 days or other risk factors. Herpes simplex virus-seropositive patients undergoing allogeneic hematopoietic stem-cell transplantation or leukemia induction therapy should receive nucleoside analog-based antiviral prophylaxis, such as acyclovir. prophylaxis is recommended for patients receiving chemotherapy regimens that are associated with a > 3.5% risk for pneumonia as a result of this organism (eg, those with ≥ 20 mg prednisone equivalents daily for ≥ 1 month or on the basis of purine analog usage). Treatment with a nucleoside reverse transcription inhibitor (eg, entecavir or tenofovir) is recommended for patients at high risk of hepatitis B virus reactivation. Recommendations for vaccination and avoidance of prolonged contact with environments that have high concentrations of airborne fungal spores are also provided within the updated guideline. Additional information is available at .
Topics: Anti-Infective Agents; Humans; Immunocompromised Host; Infection Control; Infections; Neoplasms
PubMed: 30179565
DOI: 10.1200/JCO.18.00374 -
JAMA Jun 2016Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are related inflammatory disorders occurring in persons aged 50 years and older. Diagnostic and therapeutic... (Review)
Review
IMPORTANCE
Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are related inflammatory disorders occurring in persons aged 50 years and older. Diagnostic and therapeutic approaches are heterogeneous in clinical practice.
OBJECTIVE
To summarize current evidence regarding optimal methods for diagnosing and treating PMR and GCA.
EVIDENCE REVIEW
MEDLINE, EMBASE, and Cochrane databases were searched from their inception dates to March 30, 2016. Screening by 2 authors resulted in 6626 abstracts, of which 50 articles met the inclusion criteria. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool or American College of Cardiology Foundation/American Heart Association methodology.
FINDINGS
Twenty randomized clinical trials for therapy (n = 1016 participants) and 30 imaging studies for diagnosis and/or assessing response to therapy (n = 2080 participants) were included. The diagnosis of PMR is based on clinical features such as new-onset bilateral shoulder pain, including subdeltoid bursitis, muscle or joint stiffness, and functional impairment. Headache and visual disturbances including loss of vision are characteristic of GCA. Constitutional symptoms and elevated inflammatory markers (>90%) are common in both diseases. Ultrasound imaging enables detection of bilateral subdeltoid bursitis in 69% of PMR patients. In GCA, temporal artery biopsy remains the standard for definitive diagnosis. Ultrasound and magnetic resonance imaging (MRI) of large vessels revealing inflammation-induced wall thickening support the diagnosis of GCA (specificity 78%-100% for ultrasound and 73%-97% for MRI). Glucocorticoids remain the primary treatment, but the optimal initial dose and tapering treatment regimens are unknown. According to consensus-based recommendations, initial therapy for PMR is prednisone, 12.5 to 25 mg/day or equivalent, and 40 to 60 mg/day for GCA, followed by individualized tapering regimens in both diseases. Adjunctive methotrexate may reduce cumulative glucocorticoid dosage by 20% to 44% and relapses by 36% to 54% in both PMR and GCA. Use of tocilizumab as additional treatment with prednisone showed a 2- to 4-fold increase in remission rates of GCA in a randomized clinical trial (N = 30).
CONCLUSIONS AND RELEVANCE
Diagnosis of PMR/GCA is made by clinical features and elevated inflammatory markers. In PMR, ultrasound imaging may improve diagnostic accuracy. In GCA, temporal artery biopsy may not be required in patients with typical disease features accompanied by characteristic ultrasound or MRI findings. Consensus-based recommendations suggest glucocorticoids as the most effective therapy for PMR/GCA. Methotrexate may be added to glucocorticoids in patients at risk for relapse and in those with glucocorticoid-related adverse effects or need for prolonged glucocorticoid therapy.
Topics: Antibodies, Monoclonal, Humanized; Diagnostic Imaging; Drug Administration Schedule; Giant Cell Arteritis; Glucocorticoids; Humans; Methotrexate; Middle Aged; Polymyalgia Rheumatica; Prednisone; Randomized Controlled Trials as Topic
PubMed: 27299619
DOI: 10.1001/jama.2016.5444 -
The Lancet. Haematology Oct 2016Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review... (Comparative Study)
Comparative Study Review
BACKGROUND
Whether high-dose dexamethasone has long-term efficacy and safety in previously untreated patients with immune thrombocytopenia is unclear. We did a systematic review and a meta-analysis of randomised trials to establish the effect of high-dose dexamethasone compared with prednisone for long-term platelet count response.
METHODS
We searched MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature, and the Cochrane Library Database for papers published from 1970 to July, 2016, and abstracts from American Society of Hematology annual meetings published from 2004 to 2015 for randomised trials comparing different corticosteroid regimens for patients with previously untreated immune thrombocytopenia who achieved a platelet count response. Trials that compared corticosteroids exclusively with other interventions were excluded. The primary endpoint was overall (platelets >30 × 10/L) and complete (platelets >100 × 10/L) platelet count response at 6 months with high-dose dexamethasone compared with standard-dose prednisone. Children and adults were analysed separately. Estimates of effect were pooled with a random-effects model.
FINDINGS
Nine randomised trials (n=1138) were included. Of those, five (n=533) compared one to three cycles of dexamethasone (40 mg per day for 4 days) with prednisone (1 mg per kg) for 14-28 days followed by dose tapering in adults. We found no difference in overall platelet count response at 6 months (pooled proportions 54% vs 43%, relative risk [RR] 1·16, 95% CI 0·79-1·71; p=0·44). At 14 days, overall platelet count response was higher with dexamethasone (79% vs 59%, RR 1·22, 95% CI 1·00-1·49; p=0·048). The dexamethasone group had fewer reported toxicities. Long-term response rates were similar when the data were analysed by cumulative corticosteroid dose over the course of treatment. No difference in initial platelet count response was observed with different high-dose corticosteroid regimens in children.
INTERPRETATION
In adults with previously untreated immune thrombocytopenia, high-dose dexamethasone did not improve durable platelet count responses compared with standard-dose prednisone. High-dose dexamethasone might be preferred over prednisone for patients with severe immune thrombocytopenia who require a rapid rise in platelet count.
FUNDING
Canadian Institutes of Health Research, and Canadian Blood Services, and Health Canada.
Topics: Adult; Aged; Anti-Inflammatory Agents; Child; Dexamethasone; Dose-Response Relationship, Drug; Female; Humans; Male; Meta-Analysis as Topic; Middle Aged; Platelet Count; Prednisone; Purpura, Thrombocytopenic, Idiopathic; Randomized Controlled Trials as Topic; Young Adult
PubMed: 27658982
DOI: 10.1016/S2352-3026(16)30109-0 -
Skin Appendage Disorders Jan 2020Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In... (Review)
Review
Hair graying is a common sign of aging resulting from complex regulation of melanogenesis. Currently, there is no medical treatment available for hair repigmentation. In this article we review the literature on medication-induced hair repigmentation, discuss the potential mechanisms of action, and review the quality of the literary data. To date, there have been 27 studies discussing medication-induced gray hair repigmentation, including 6 articles on gray hair repigmentation as a primary objective, notably with psoralen treatment or vitamin supplementation, and 21 reports on medication-induced gray hair repigmentation as an incidental finding. Medications noted in the literature include anti-inflammatory medications (thalidomide, lenalidomide, adalimumab, acitretin, etretinate, prednisone, cyclosporin, cisplatinum, interferon-α, and psoralen), stimulators of melanogenesis (latanoprost, erlotinib, imatinib, tamoxifen, and levodopa), vitamins (calcium pantothenate and -amino benzoic acid), a medication that accumulates in tissues (clofazimine), and a medication with an undetermined mechanism (captopril). Diffuse repigmentation of gray hair can be induced by certain medications that inhibit inflammation or stimulate melanogenesis. There is also low-quality evidence that some vitamin B complex supplementation can promote gray hair darkening. While these compounds are not currently indicated for the treatment of gray hair, their mechanisms shed light on targets for future medications for hair repigmentation.
PubMed: 32021854
DOI: 10.1159/000504414 -
Chest Nov 2023Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the... (Meta-Analysis)
Meta-Analysis
Chronic obstructive pulmonary disease patient care must include confirming a diagnosis with postbronchodilator spirometry. Because of the clinical heterogeneity and the reality that airflow obstruction assessed by spirometry only partially reflects disease severity, a thorough clinical evaluation of the patient should include assessment of symptom burden and risk of exacerbations that permits the implementation of evidence-informed pharmacologic and nonpharmacologic interventions. This guideline provides recommendations from a comprehensive systematic review with a meta-analysis and expert-informed clinical remarks to optimize maintenance pharmacologic therapy for individuals with stable COPD, and a revised and practical treatment pathway based on new evidence since the 2019 update of the Canadian Thoracic Society (CTS) Guideline. The key clinical questions were developed using the Patients/Population (P), Intervention(s) (I), Comparison/Comparator (C), and Outcome (O) model for three questions that focuses on the outcomes of symptoms (dyspnea)/health status, acute exacerbations, and mortality. The evidence from this systematic review and meta-analysis leads to the recommendation that all symptomatic patients with spirometry-confirmed COPD should receive long-acting bronchodilator maintenance therapy. Those with moderate to severe dyspnea (modified Medical Research Council ≥ 2) and/or impaired health status (COPD Assessment Test ≥ 10) and a low risk of exacerbations should receive combination therapy with a long-acting muscarinic antagonist/long-acting ẞ2-agonist (LAMA/LABA). For those with a moderate/severe dyspnea and/or impaired health status and a high risk of exacerbations should be prescribed triple combination therapy (LAMA/LABA/inhaled corticosteroids) azithromycin, roflumilast or N-acetylcysteine is recommended for specific populations; a recommendation against the use of theophylline, maintenance systemic oral corticosteroids such as prednisone and inhaled corticosteroid monotherapy is made for all COPD patients.
Topics: Humans; Drug Therapy, Combination; Adrenergic beta-2 Receptor Agonists; Bronchodilator Agents; Canada; Pulmonary Disease, Chronic Obstructive; Muscarinic Antagonists; Administration, Inhalation; Dyspnea; Adrenal Cortex Hormones
PubMed: 37690008
DOI: 10.1016/j.chest.2023.08.014 -
The Cochrane Database of Systematic... May 2016Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood. Untreated, this incurable disease, which has an X-linked recessive inheritance, is... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood. Untreated, this incurable disease, which has an X-linked recessive inheritance, is characterised by muscle wasting and loss of walking ability, leading to complete wheelchair dependence by 13 years of age. Prolongation of walking is a major aim of treatment. Evidence from randomised controlled trials (RCTs) indicates that corticosteroids significantly improve muscle strength and function in boys with DMD in the short term (six months), and strength at two years (two-year data on function are very limited). Corticosteroids, now part of care recommendations for DMD, are largely in routine use, although questions remain over their ability to prolong walking, when to start treatment, longer-term balance of benefits versus harms, and choice of corticosteroid or regimen.We have extended the scope of this updated review to include comparisons of different corticosteroids and dosing regimens.
OBJECTIVES
To assess the effects of corticosteroids on prolongation of walking ability, muscle strength, functional ability, and quality of life in DMD; to address the question of whether benefit is maintained over the longer term (more than two years); to assess adverse events; and to compare efficacy and adverse effects of different corticosteroid preparations and regimens.
SEARCH METHODS
On 16 February 2016 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, EMBASE, CINAHL Plus, and LILACS. We wrote to authors of published studies and other experts. We checked references in identified trials, handsearched journal abstracts, and searched trials registries.
SELECTION CRITERIA
We considered RCTs or quasi-RCTs of corticosteroids (e.g. prednisone, prednisolone, and deflazacort) given for a minimum of three months to patients with a definite DMD diagnosis. We considered comparisons of different corticosteroids, regimens, and corticosteroids versus placebo.
DATA COLLECTION AND ANALYSIS
The review authors followed standard Cochrane methodology.
MAIN RESULTS
We identified 12 studies (667 participants) and two new ongoing studies for inclusion. Six RCTs were newly included at this update and important non-randomised cohort studies have also been published. Some important studies remain unpublished and not all published studies provide complete outcome data.
PRIMARY OUTCOME MEASURE
one two-year deflazacort RCT (n = 28) used prolongation of ambulation as an outcome measure but data were not adequate for drawing conclusions.
SECONDARY OUTCOME MEASURES
meta-analyses showed that corticosteroids (0.75 mg/kg/day prednisone or prednisolone) improved muscle strength and function versus placebo over six months (moderate quality evidence from up to four RCTs). Evidence from single trials showed 0.75 mg/kg/day superior to 0.3 mg/kg/day on most strength and function measures, with little evidence of further benefit at 1.5 mg/kg/day. Improvements were seen in time taken to rise from the floor (Gowers' time), timed walk, four-stair climbing time, ability to lift weights, leg function grade, and forced vital capacity. One new RCT (n = 66), reported better strength, function and quality of life with daily 0.75 mg/kg/day prednisone at 12 months. One RCT (n = 28) showed that deflazacort stabilised muscle strength versus placebo at two years, but timed function test results were too imprecise for conclusions to be drawn.One double-blind RCT (n = 64), largely at low risk of bias, compared daily prednisone (0.75 mg/kg/day) with weekend-only prednisone (5 mg/kg/weekend day), finding no overall difference in muscle strength and function over 12 months (moderate to low quality evidence). Two small RCTs (n = 52) compared daily prednisone 0.75 mg/kg/day with daily deflazacort 0.9 mg/kg/day, but study methods limited our ability to compare muscle strength or function.
ADVERSE EFFECTS
excessive weight gain, behavioural abnormalities, cushingoid appearance, and excessive hair growth were all previously shown to be more common with corticosteroids than placebo; we assessed the quality of evidence (for behavioural changes and weight gain) as moderate. Hair growth and cushingoid features were more frequent at 0.75 mg/kg/day than 0.3 mg/kg/day prednisone. Comparing daily versus weekend-only prednisone, both groups gained weight with no clear difference in body mass index (BMI) or in behavioural changes (low quality evidence for both outcomes, one study); the weekend-only group had a greater linear increase in height. Very low quality evidence suggested less weight gain with deflazacort than with prednisone at 12 months, and no difference in behavioural abnormalities. Data are insufficient to assess the risk of fractures or cataracts for any comparison.Non-randomised studies support RCT evidence in showing improved functional benefit from corticosteroids. These studies suggest sustained benefit for up to 66 months. Adverse effects were common, although generally manageable. According to a large comparative longitudinal study of daily or intermittent (10 days on, 10 days off) corticosteroid for a mean period of four years, a daily regimen prolongs ambulation and improves functional scores over the age of seven, but with a greater frequency of side effects than an intermittent regimen.
AUTHORS' CONCLUSIONS
Moderate quality evidence from RCTs indicates that corticosteroid therapy in DMD improves muscle strength and function in the short term (twelve months), and strength up to two years. On the basis of the evidence available for strength and function outcomes, our confidence in the effect estimate for the efficacy of a 0.75 mg/kg/day dose of prednisone or above is fairly secure. There is no evidence other than from non-randomised trials to establish the effect of corticosteroids on prolongation of walking. In the short term, adverse effects were significantly more common with corticosteroids than placebo, but not clinically severe. A weekend-only prednisone regimen is as effective as daily prednisone in the short term (12 months), according to low to moderate quality evidence from a single trial, with no clear difference in BMI (low quality evidence). Very low quality evidence indicates that deflazacort causes less weight gain than prednisone after a year's treatment. We cannot evaluate long-term benefits and hazards of corticosteroid treatment or intermittent regimens from published RCTs. Non-randomised studies support the conclusions of functional benefits, but also identify clinically significant adverse effects of long-term treatment, and a possible divergence of efficacy in daily and weekend-only regimens in the longer term. These benefits and adverse effects have implications for future research and clinical practice.
Topics: Adrenal Cortex Hormones; Glucocorticoids; Humans; Male; Muscle Strength; Muscular Dystrophy, Duchenne; Prednisolone; Prednisone; Pregnenediones; Quality of Life; Randomized Controlled Trials as Topic; Walking
PubMed: 27149418
DOI: 10.1002/14651858.CD003725.pub4 -
The Cochrane Database of Systematic... Feb 2022Focal segmental glomerulosclerosis (FSGS) can be separated into primary, genetic or secondary causes. Primary disease results in nephrotic syndrome while genetic and... (Review)
Review
BACKGROUND
Focal segmental glomerulosclerosis (FSGS) can be separated into primary, genetic or secondary causes. Primary disease results in nephrotic syndrome while genetic and secondary forms may be associated with asymptomatic proteinuria or with nephrotic syndrome. Overall only about 20% of patients with FSGS experience a partial or complete remission of nephrotic syndrome with treatment. FSGS progresses to kidney failure in about half of the cases. This is an update of a review first published in 2008.
OBJECTIVES
To assess the benefits and harms of immunosuppressive and non-immunosuppressive treatment regimens in adults with FSGS.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies to 21 June 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
Randomised controlled trials (RCTs) and quasi-RCTs of any intervention for FSGS in adults were included. Studies comparing different types, routes, frequencies, and duration of immunosuppressive agents and non-immunosuppressive agents were assessed.
DATA COLLECTION AND ANALYSIS
At least two authors independently assessed study quality and extracted data. Statistical analyses were performed using the random-effects model and results were expressed as a risk ratio (RR) for dichotomous outcomes, or mean difference (MD) for continuous data with 95% confidence intervals (CI). Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
Fifteen studies (560 participants) were included. No studies specifically evaluating corticosteroids compared with placebo or supportive therapy were identified. Studies evaluated participants with steroid-resistant FSGS. Five studies (240 participants) compared cyclosporin with or without prednisone with different comparators (no specific treatment, prednisone, methylprednisolone, mycophenolate mofetil (MMF), dexamethasone). Three small studies compared monoclonal antibodies (adalimumab, fresolimumab) with other agents or placebo. Six single small studies compared rituximab with tacrolimus, cyclosporin plus valsartan with cyclosporin alone, MMF with prednisone, chlorambucil plus methylprednisolone and prednisone with no specific treatment, different regimens of dexamethasone and CCX140-B (an antagonist of the chemokine receptor CCR2) with placebo. The final study (109 participants) compared sparsentan, a dual inhibitor of endothelin Type A receptor and of the angiotensin II Type 1 receptor, with irbesartan. In the risk of bias assessment, seven and five studies were at low risk of bias for sequence generation and allocation concealment, respectively. Four studies were at low risk of performance bias and 14 studies were at low risk of detection bias. Thirteen, six and five studies were at low risk of attrition bias, reporting bias and other bias, respectively. Of five studies evaluating cyclosporin, four could be included in our meta-analyses (231 participants). Cyclosporin with or without prednisone compared with different comparators may increase the likelihood of complete remission (RR 2.31, 95% CI 1.13 to 4.73; I² = 1%; low certainty evidence) and of complete or partial remission (RR 1.64, 95% CI 1.10 to 2.44; I² = 19%) but not of partial remission (RR 1.36, 95% CI 0.78 to 2.39, I² = 22%). In Individual studies, cyclosporin with prednisone versus prednisone may increase the likelihood of partial (49 participants: RR 7.96, 95% CI 1.09 to 58.15) or complete or partial remission (49 participants: RR 8.85, 95% CI 1.22 to 63.92) but not of complete remission. The remaining individual comparisons may make little or no difference to the likelihood of complete remission, partial remission or complete or partial remission compared with no treatment, methylprednisolone, MMF, or dexamethasone. Individual study data and combined data showed that cyclosporin may make little or no difference to the outcomes of chronic kidney disease or kidney failure. It is uncertain whether cyclosporin compared with these comparators in individual or combined analyses makes any difference to the outcomes of hypertension or infection. MMF compared with prednisone may make little or no difference to the likelihood of complete remission (33 participants: RR 1.05, 95% CI 0.58 to 1.88; low certainty evidence), partial remission, complete or partial remission, glomerular filtration rate, or infection. It is uncertain whether other interventions make any difference to outcomes as the certainty of the evidence is very low. It is uncertain whether sparsentan reduces proteinuria to a greater extent than irbesartan.
AUTHORS' CONCLUSIONS
No RCTs, which evaluated corticosteroids, were identified although the KDIGO guidelines recommend corticosteroids as the first treatment for adults with FSGS. The studies identified included participants with steroid-resistant FSGS. Treatment with cyclosporin for at least six months was more likely to achieve complete remission of proteinuria compared with other treatments but there was considerable imprecision due to few studies and small participant numbers. In future studies of existing or new interventions, the investigators must clearly define the populations included in the study to provide appropriate recommendations for patients with primary, genetic or secondary FSGS.
Topics: Adult; Cyclosporine; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Mycophenolic Acid; Prednisone; Randomized Controlled Trials as Topic
PubMed: 35224732
DOI: 10.1002/14651858.CD003233.pub3