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Nephrology (Carlton, Vic.) Oct 2018Focal segmental glomerulosclerosis (FSGS) is a glomerulonephritis with podocyte injury. The renal prognosis of FSGS is relative poor. The overall remission rate of the...
Focal segmental glomerulosclerosis (FSGS) is a glomerulonephritis with podocyte injury. The renal prognosis of FSGS is relative poor. The overall remission rate of the FSGS patients with nephrotic syndrome to immunosuppressive treatments was reported as 47-66%, highlighting its therapeutic challenge-lacking in sufficient evidence-based interventions. In first-line treatment of nephrotic syndrome, daily oral prednisolone is a commonly used drug, whereas optimal treatment strategies, like indications and duration, remain controversial. Calcineurin inhibitor and cyclophosphamide are recommended in steroid-dependent/steroid-resistant patients. However, the high unmet need in effective immunosuppressive treatments calls for the development of new therapy methods. Rituximab, a monoclonal antibody targeting CD20 B-cells, could increase the complete or partial remission rate, and decrease the relapse rate based on several previous studies on FSGS. In addition, the using of rituximab could potentially help the FSGS patients to stop the concomitant therapy include steroid and immunosuppressive agents. Other treatment options like adalimumab or abatacept also showed potential therapeutic effect, but still required larger Randomized Controlled Trial study to determine its efficiency and safety. Besides, expanding understanding of the genetic basis of FSGS is necessary to investigate new therapeutic agents. With the unsatisfied patients' outcome under the current treatments, innovation should be encouraged on the treatment strategy based on Kidney Disease: Improving Global Outcomes guideline and international collaborations are required for the potential novel immunosuppressive or immunomodulatory therapies.
Topics: Adrenal Cortex Hormones; Biological Products; Clinical Decision-Making; Glomerulosclerosis, Focal Segmental; Humans; Immunosuppressive Agents; Kidney Glomerulus; Recurrence; Remission Induction; Risk Factors; Treatment Outcome
PubMed: 30298667
DOI: 10.1111/nep.13463 -
Pregnancy Hypertension Oct 2018Early detection of pre-eclampsia remains one of the major focuses of antenatal obstetric care. There is often a delay in the diagnosis, mainly due to the non-specific... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Early detection of pre-eclampsia remains one of the major focuses of antenatal obstetric care. There is often a delay in the diagnosis, mainly due to the non-specific nature of the condition. Podocytes which play a pivotal role in glomerular function become injured in pre-eclampsia leading to subsequent proteinuria. Our aim was to review available studies to determine the clinical utility of biomarkers of podocyte injury in pre-eclampsia.
METHODS
We used QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria to perform a systematic review of the literature to determine the clinical utility of podocyte injury biomarkers in predicting pre-eclampsia.
RESULTS
This study identified five potential renal biomarkers including podocytes, nephrin, synaptopodin, podocin and podocalyxin. The pooled sensitivity of all biomarkers was 0.78 (95% CI 0.74-0.82) with a specificity of 0.82 (95% CI 0.79-0.85). The area under the Summary of Receiver Operating Characteristics Curve (SROC) was 0.926 (SE 0.30). Urinary nephrin achieved the highest diagnostic values with a sensitivity of 0.81 (95% CI 0.72-0.88) and specificity of 0.84 (95% CI 0.79-0.84).
CONCLUSION
Biomarkers of glomerular injury show promise as diagnostic aids in pre-eclampsia. A large-scale prospective cohort study is warranted before these biomarkers can be recommended for routine clinical care.
Topics: Biomarkers; Case-Control Studies; Female; Glomerular Filtration Barrier; Humans; Kidney Glomerulus; Membrane Proteins; Podocytes; Pre-Eclampsia; Pregnancy; Proteinuria; ROC Curve; Sensitivity and Specificity; Sialoglycoproteins
PubMed: 29567337
DOI: 10.1016/j.preghy.2018.03.002 -
Clinical Rheumatology May 2019Podocytic infolding glomerulopathy (PIG) is a newly proposed disease entity, and only 29 cases have been reported worldwide so far, characterized by microspheres or...
Podocytic infolding glomerulopathy (PIG) is a newly proposed disease entity, and only 29 cases have been reported worldwide so far, characterized by microspheres or microtubular structures or both associated with podocytic infolding into the glomerular basement membrane (GBM) on electron microscopy. We present two new cases of PIG with connective tissue disease (CTD), one with primary Sjögren's syndrome and the other with systemic lupus erythematosus (SLE), and make a systemic review of the literature. In the entire 31 patients of PIG, 24 (77.42%) were women and seven (22.58%) were men, with an average age of 41.2 ± 15.2 (ranging from 14 to 79) years old. Almost two-thirds of patients (67.74%) were diagnosed with CTD, in which 76.19% were SLE. All patients presented with proteinuria and six (19.35%) patients were accompanied with hematuria. Serum creatinine was elevated in six (19.35%) patients. Pathological findings of all patients were consistent with PIG characteristics, and four patients with repeated renal biopsies further provided profound insights.
Topics: Adult; Creatinine; Female; Glomerular Basement Membrane; Hematuria; Humans; Kidney Diseases; Lupus Erythematosus, Systemic; Podocytes; Proteinuria; Sjogren's Syndrome; Young Adult
PubMed: 30879204
DOI: 10.1007/s10067-019-04504-6 -
Molecular Genetics and Metabolism Mar 2019Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can...
BACKGROUND
Fabry disease is caused by a deficiency of the lysosomal enzyme α-galactosidase, resulting in progressive accumulation of globotriaosylceramide (GL-3). The disease can manifest early during childhood and adolescence. Enzyme replacement therapy (ERT) with recombinant human α-galactosidase is the first specific treatment for Fabry disease and has been available in Europe since 2001. This paper presents the findings of a systematic literature review of clinical outcomes with ERT in paediatric patients with Fabry disease.
METHODS
A comprehensive systematic review of published literature on ERT in Fabry disease was conducted in January 2017. The literature analysis included all original articles reporting outcomes of ERT in paediatric patients.
RESULTS
Treatment-related outcomes in the paediatric population were reported in six publications derived from open-label clinical trials and in 10 publications derived from observational or registry-based studies. ERT was shown to significantly reduce plasma and urine GL-3 levels in paediatric patients with Fabry disease. The effect of ERT on GL-3 clearance from renal podocytes appeared to be agalsidase dose-dependent. ERT relieved pain and improved gastrointestinal symptoms and quality of life.
CONCLUSIONS
Based on the published literature, the use of ERT in paediatric patients can significantly clear GL-3 accumulation, ameliorate the early symptoms of Fabry disease, and improve quality of life. Treatment with ERT in paediatric patients with Fabry disease may be important to prevent further disease progression and overt organ damage.
Topics: Child; Enzyme Replacement Therapy; Europe; Fabry Disease; Female; Humans; Isoenzymes; Male; Observational Studies as Topic; Pain; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Treatment Outcome; Trihexosylceramides; alpha-Galactosidase
PubMed: 29785937
DOI: 10.1016/j.ymgme.2018.04.007