scholarly journals Aliskiren and the dual complement inhibition concept

2019 ◽  
Vol 13 (1) ◽  
pp. 35-38 ◽  
Author(s):  
Maria Vanessa Perez-Gomez ◽  
Alberto Ortiz
Keyword(s):  
Kidney Disease ◽  
Haemolytic Uraemic Syndrome ◽  
Immunoglobulin A ◽  
High Dose ◽  
Complement Factor ◽  
C3 Glomerulopathy ◽  
Immunoglobulin A Nephropathy ◽  
Complement Inhibition ◽  
Direct Renin Inhibitor ◽  
Dense Deposit

Abstract In this issue of Clinical Kidney Journal, Plasse et al. report on the use of high-dose aliskiren as an adjunct therapy in a patient treated with eculizumab for haemolytic uraemic syndrome (HUS). This follows the recent description of the complement factor 3 (C3) activating activity of the enzyme renin and the successful therapeutic use of the direct renin inhibitor aliskiren in three cases of C3 glomerulopathy/dense deposit disease. We discuss the potential clinical and pathophysiological implications of these reports on nephropathies linked to complement, from HUS to C3 glomerulopathy to immunoglobulin A nephropathy as well as the concept of dual complement inhibition for kidney disease.

Molecular basis of complement-mediated renal disease

2015 ◽  
Author(s):  
Nicholas Medjeral-Thomas ◽  
Anna Richards ◽  
Matthew C. Pickering
Keyword(s):  
Haemolytic Uraemic Syndrome ◽  
Alternative Pathway ◽  
Protein Family ◽  
Factor H ◽  
Complement Factor ◽  
C3 Glomerulopathy ◽  
Ongoing Research ◽  
Dense Deposit ◽  
Atypical Haemolytic Uraemic Syndrome ◽  
Glomerular Lesions

Abnormal regulation of complement is intimately associated with C3 glomerulopathy and atypical haemolytic uraemic syndrome. Atypical haemolytic uraemic syndrome is characterized by renal thrombotic microangiopathy due to an inability to regulate complement activation along the renal endothelium. The development of thrombosis is critically dependent on the ability to activate C5. Eculizumab, a monoclonal anti-C5 antibody, is an effective therapy for this condition. C3 glomerulopathy refers to glomerular lesions characterized by accumulation of C3 in the absence of immunoglobulin. The prototypic example is dense deposit disease. This condition is associated with impaired regulation of the alternative pathway in plasma. In other subtypes of C3 glomerulopathy, familial studies have identified mutations within the complement factor H-related protein family. Polymorphic variation within this protein family also influences susceptibility to IgA nephropathy. The mechanism underlying these associations remains unknown and is the subject of ongoing research efforts.

Renal Outcomes of Pregnant Patients with Immunoglobulin A Nephropathy: A Systematic Review and Meta-Analysis

2019 ◽  
Vol 49 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Fan Wang ◽  
Jian-Da Lu ◽  
Ying Zhu ◽  
Ting-Ting Wang ◽  
Jun Xue
Keyword(s):  
Systematic Review ◽  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Lupus Nephritis ◽  
Pregnant Women ◽  
Pregnancy Outcomes ◽  
Meta Analysis ◽  
Immunoglobulin A ◽  
Immunoglobulin A Nephropathy ◽  
Renal Outcomes

Background: Is the prognosis of immunoglobulin A nephropathy (IgAN) influenced by pregnancy and delivery? The answer to this question still remains to be a controversial topic. Here, we undertook a systematic review and meta-analysis to obtain the overall estimate of potential effect of IgAN and pregnancy on each other. Methods: We systematically searched MEDLINE, EMBASE, Chinese Biological Medicine and Cochrane for cohort and case-control studies; a total of 1,378 articles were reviewed and 9 studies were included in the end. OR and mean difference (MD) were calculated with a random-effects model, kidney events and pregnancy outcomes were analyzed respectively. Results: The key finding of the meta-analysis of 145 renal events in 1,198 participants was that there was no difference in renal outcomes (defined as doubling of serum creatinine (SCr), 50% decline in glomerular filtration rate [GFR] and end-stage kidney disease) of pregnant women compared with non-pregnant women who had IgAN (OR 0.90; 95% CI 0.59–1.37; p = 0.63). Subgroup analysis indicated that there was no significant difference between the 2 groups according to sample size, follow-up year, age, level of SCr and proteinuria at baseline. There was no difference in the change of the eGFR/creatinine clearance rate (mL/min/1.73 m2 per year) in IgAN patients with pregnancy compared with non-pregnancy (MD –0.11 mL/min; 95% CI –0.50–0.27; p = 0.57) as well. Women with IgAN had a higher likelihood of pregnancy outcomes compared with the Chinese general population, while they had a lower risk of preterm delivery, preeclampsia and low birth weight compared with those who had lupus nephritis or diabetic nephropathy. Conclusions: Pregnancy did not accelerate kidney disease deterioration in women with IgAN in stages of chronic kidney disease 1–3. Moreover, patients with IgAN had a relatively low risk of adverse pregnancy events compared with those with lupus nephritis or diabetic nephropathy.

Specific renal conditions in pregnancy

2015 ◽  
Author(s):  
Kate Bramham ◽  
Catherine Nelson-Piercy
Keyword(s):  
Kidney Disease ◽  
Lupus Erythematosus ◽  
Immunoglobulin A ◽  
Reflux Nephropathy ◽  
Immunoglobulin A Nephropathy ◽  
Polycystic Kidney ◽  
Disease Exacerbation ◽  
Urological Disorders ◽  
Single Kidney ◽  
In Pregnancy

Pre-pregnancy glomerular filtration rate, proteinuria, and blood pressure are usually more important in determining the risk of pregnancy in patients with chronic kidney disease, but some diseases may be exacerbated in pregnancy, or appear more liable to complications. This chapter considers immunoglobulin A nephropathy, systemic lupus erythematosus (which may also be associated with some manifestations in the infant), diabetic nephropathy, polycystic kidney disease, reflux nephropathy, single kidney, urological disorders, and angiomyolipomata. Distinguishing underlying renal disease exacerbation from pre-eclampsia and other complications of pregnancy can be challenging. Renal biopsy is sometimes indicated.

scholarly journals A new complement factor B mutation associated with crescentic C3 glomerulopathy; a case report

2019 ◽  
Vol 8 (3) ◽  
pp. 30-30
Author(s):  
Sofia Semedo Coelho ◽  
Ana Raquel Fernandes ◽  
Elsa Soares ◽  
Patrícia Valério ◽  
Bruno Matos ◽  
...  
Keyword(s):  
Interstitial Fibrosis ◽  
Disease Patient ◽  
Dense Deposit Disease ◽  
Complement Factor ◽  
C3 Glomerulopathy ◽  
Glomerular Diseases ◽  
Factor B ◽  
Complement Factor B ◽  
Dense Deposit ◽  
Disease Case

Background: C3 glomerulopathy is a recently described entity classified as complementassociated glomerular disease. Case Presentation: We report a case of a 48-year-old man referred to the nephrology department for nephrotic syndrome with rapidly progressive kidney failure, acquired partial lipodystrophy and drusen in Bruch’s membrane of the retina. Blood tests showed low C3 and no evidence for autoimmune diseases, monoclonal gammopathy or infection. The renal biopsy revealed a proliferative endocapillary and crescentic glomerulonephritis with glomerular deposits exclusively of C3 and significant interstitial fibrosis. The electronic microscopy was consistent with dense deposit disease. The complement analysis revealed a pathogenic mutation of the complement factor B (CFB) gene not previously described in literature. Conclusions: The authors report a new mutation of CFB, in a dense deposit disease patient; this finding brings a new insight to the pathogenic pathway of C3 glomerulopathy and possibly to other complement dysregulation associated glomerular diseases. More clinical trials are needed to clarify both the pathogenicity and the optimal treatment for these entities.

Tildrakizumab Shows Significant Efficacy in Psoriasis Treatment With Comorbid Immunoglobulin A Nephropathy: A Case Report

2020 ◽  
Vol 5 (4) ◽  
pp. 160-163
Author(s):  
Eingun James Song
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Plaque Psoriasis ◽  
Global Assessment ◽  
Immunoglobulin A ◽  
Immunoglobulin A Nephropathy ◽  
Severe Plaque Psoriasis

Background: Chronic kidney disease is a relative contraindication for conventional systemic therapy in patients with psoriasis. Although biologic agents may be suitable in these patients due to their elimination via endogenous metabolism and protein degradation, no dedicated studies have evaluated the safety of biologics in patients with psoriasis and chronic kidney disease. Tildrakizumab—an anti-interleukin-23p19 monoclonal antibody—is approved for treatment of moderate-to-severe plaque psoriasis. Objective: To evaluate efficacy and safety of tildrakizumab in a 56-year-old woman with moderate-to-severe plaque psoriasis and comorbid immunoglobulin A nephropathy. Methods: Subcutaneous tildrakizumab 100 mg was administered at weeks 0, 4, 20, 33, and 48. Assessments included body surface area affected, physician’s global assessment score, and laboratory assessments. Results: At initial presentation, patient had predominantly plaque-type psoriasis involving 5% body surface area with a static physician’s global assessment score of 3. Patient failed an adequate trial of ultrapotent topical steroids. Baseline laboratory tests confirmed renal impairment with blood creatinine level of 2.0 mg/dL and an estimated glomerular filtration rate of 27.0 mL/min/1.73 m2. Administration of subcutaneous tildrakizumab 100 mg led to near-complete skin clearance by week 33, with a durable response to week 48. No treatment-related adverse events were reported through 48 weeks. Metabolic and hematological parameters remained grossly unchanged. Conclusion: Tildrakizumab was well tolerated and effective for treatment of moderate-to-severe plaque psoriasis in a patient with comorbid immunoglobulin A nephropathy.

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