Omega-3 fatty acids in the treatment of IgA nephropathy Eicosapentaenoic acid (EPA) and Docosahexaenoic ❖ Suppress in ammatory and/or acid (DHA) replace arachinodic acid as substrate for immunologic responses cyclooxygenase and lipoxygenase ❖ Inhibit cell proliferation ❖ Lowering blood pressure ❖ Reducing serum lipid levels ❖ Decreasing vascular resistance ❖ Preventing thrombosis Donadio JV, et al. Semin Nephrol. 2004; 24(3):225-43. fl
A Controlled Trial of Fish Oil in IgA Nephropathy Treatment 6% vs. control 33% ❖ 55 treatment (OMEGA3: 6 gm bid P = 0.002 (1.87 g EPA, 1.36 g DHA) and 51 placebo (Olive oil) ❖ Serum Cr < 3 mg/dL and proteinuria > 1 g/day ❖ Primary Outcome ( 50% in SCr at 2 years) Donadio JV Jr,et al. NEJM 1994: 331:1194 9.
Meta-analysis: Omega–3 ameliorate proteinuria in IgAN Chou, CC, et al. Nephron Clin Pract 2012;121:c30–c35
Dose of fish-oil treatment in randomized clinical trials ❖ Over-the-counter sh oil capsules in the US contain 0.18 g of EPA and 0.12 g of DHA per capsule. ❖ Each Omacor capsule provides 0.47 g of EPA and 0.37 g of DHA ❖ Patients with IgA nephropathy must consume 10 to 12 over-the-counter sh oil capsules compared with 4 Omacor capsules each day to achieve the current recommended dose of n-3 PUFA Donadio JV, et al. Semin Nephrol. 2004; 24(3):225-43. fifi
MMF therapies in IgAN ❖ Single RCT in China: MMF with low dose steroids ❖ Fewer steroid related side e ects KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES. Kidney Int 2021: 100, S1–S276 ff
HCQ therapies in IgAN ❖ Small, short-term RCT in China: HCQ reduced proteinuria by 48%at 6 months KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES. Kidney Int 2021: 100, S1–S276
Tonsillectomy in IgAN Tonsillectomy is suggested in someKDnIGaOtioCnLIaNlICgAuLidPeRlAinCeTsICfEoGrUtIhDeELtIrNeEaOtmN eGnLOt MofERreUcLAuRrrDeInStEAtoSnESs.ilKliitdinseiynInpta2t0i2e1n: 1ts00w, Si1th–SI2g7A6 N
Tonsillectomy in IgAN ❖ Tonsillectomy should not be performed as a treatment for IgAN in Caucasian patients ❖ Tonsillectomy is suggested in some national guidelines for the treatment of recurrent tonsillitis in patients with IgAN ❖ Multiple studies from Japan have reported improved kidney survival and partial or complete remission of hematuria and proteinuria following tonsillectomy alone or with pulsed glucocorticoids KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES. Kidney Int 2021: 100, S1–S276
❖ Novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy ❖ Randomised, double-blind, placebo-controlled phase 2b trial, comprised of 6-month run-in, 9-month treatment, and 3-month follow-up phases at 62 nephrology clinics across ten European countries (N=149) Fellström, Bengt C et al. Lancet 2017; 389: 2117–27 .
Change in UPCR and GFR from baseline Urine protein GFR TRF-budesonide 16 mg/day, added to optimised RAS eGFR remained stable in the TRF-budesonide groups but blockade, reduced proteinuria in patients with IgAN decreased in the placebo-treated group Fellström, Bengt C et al. Lancet 2017; 389: 2117–27 .
Changes over time in urinary albumin-to-creatinine ratio Wheeler DC, et al. Kidney Int. 2021; 100(1):215-224.
IgA nephropathy Number of participants with IgAN in clinical trials HR 0.29 (95%CI 0.12-0.73) Participants with IgA nephropathy, dapagli ozin reduced the risk of chronic kidney disease progression with a favorable safety pro le. Wheeler DC, Kidney Int. 2021: S0085-2538(21)00396-3. Heerspink HJL, et al. Nephrol Dial Transplant. 2020;35(2):274-282. fifl
Modified Kidney Disease Improving Global Outcomes algorithm Reich HN, Floege J. How I Treat IgA Nephropathy. Clin J Am Soc Nephrol. 2022 Jun 8:CJN.02710322.
Combining dapagli ozin with eplerenone resulted in a robust additive UACR-lowering e ect Provenzano M, et al. J Am Soc Nephrol. 2022 Apr 19:ASN.2022020207. fffl
Outline ❖ Pathogenesis of IgA nephropathy ❖ Clinical and Renal pathology classi cation ❖ Standard treatment in IgA nephropathy ❖ Optional treatment and other pharmacologic therapies evaluated in IgAN ❖ Special situations in IgA nephropathy or IgA variants fi
IgAN with nephrotic syndrome ❖ Mesangial IgA deposition can be associated with light and electron microscopy features otherwise consistent with a podocytopathy resembling MCD ❖ Treated in accordance with the guidelines for MCD ❖ Patients with nephrotic syndrome and MPGN should be managed in the same way as those patients at high risk of progressive CKD despite maximal supportive care ❖ Nephrotic-range proteinuria without nephrotic syndrome re ects coexistent secondary FSGS (obesity, uncontrolled hypertension) or development of extensive glomerulosclerosis and tubulointerstitial brosis KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES. Kidney Int 2021: 100, S1–S276 fifl
IgA nephropathy with AKI ❖ AKI can occur in patients with IgAN in the context of severe visible hematuria, commonly in association with an upper respiratory tract infection. Red blood cell extravasation in the interstitium and red blood cell cast in most tubules Interstitial hemosiderin, as determined by blue Perl staining ❖ A repeat kidney biopsy should be considered in patients who fail to show improvement in kidney function within two weeks following cessation of the hematuria. ❖ Immediate management of AKI with visible hematuria should focus on supportive care for AKI. Moreno JA, et al. Clin J Am Soc Nephrol 2012: 7: 175–184. KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES. Kidney Int 2021: 100, S1–S276
MEST classification increased risk of poor outcome based on crescents C0 (no crescents) C1 (<25% left panel) C2 (>25% right panel) Rodrigues JC, et al. Clin J Am Soc Nephrol; 2017 Zhang et al. Medicine (2017) 96:11
IgAN with RPGN ❖ A kidney biopsy demonstrate mesangial and endocapillary hypercellularity and a high proportion of glomeruli a ected by crescents with areas of focal necrosis. ❖ The presence of crescents in a kidney biopsy in the absence of a concomitant change in SCr does not constitute rapidly progressive IgAN. ❖ We suggest patients with rapidly progressive IgAN are treated with cyclophosphamide and corticosteroids in accordance with the guidelines for ANCA-associated vasculitis KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES. Kidney Int 2021: 100, S1–S276 ff
Clinical outcomes between adult-onset Henöch-Schönlein purpura nephritis and IgA nephropathy Clinical outcomes did not di er between HSPN and IgAN, suggesting the two forms of the same disease have a similar prognosis Oh HJ, et al. Kidney Int. 2012; 82(12):1304-12. ff
IgAN with vasculitis ❖ We recommend not using glucocorticoids to prevent nephritis in patients with isolated extrarenal IgAV (1B) ❖ Considerations for the treatment of all patients with IgAV-associated nephritis (IgAVN) who do not have an RPGN ❖ Considerations for the treatment of patients with IgAVN who are at high risk of progressive CKD despite maximal supportive care ❖ In those patients who wish to try immunosuppressive therapy, treatment with glucocorticoids is as described above for IgAN KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES. Kidney Int 2021: 100, S1–S276
IgAN and pregnancy planning ❖ Preconception counseling should include a discussion on cessation of RAS blockade. ❖ Blood pressure control should be optimized with alternative antihypertensive medications prior to conception. ❖ In those women at high risk of progressive CKD despite maximal supportive care, a trial of immunosuppression to optimize immunologic activity and reduce proteinuria prior to conception may be preferable to emergent initiation of immunosuppression during pregnancy KDIGO CLINICAL PRACTICE GUIDELINE ON GLOMERULAR DISEASES. Kidney Int 2021: 100, S1–S276
Outline ❖ Pathogenesis of IgA nephropathy ❖ Clinical and Renal pathology classi cation ❖ Standard treatment in IgA nephropathy ❖ Optional treatment and other pharmacologic therapies evaluated in IgAN ❖ Special situations in IgA nephropathy or IgA variants fi
Is IgA nephropathy different in different ethnic populations? Yeo SC, et al. Nephrology (Carlton). 2019; 24(9):885-895.
Risk of a 50% reduction in eGFR across the Pacific Asian origin (N=202) and other groups (N=467)\\ A large multiracial cohort of patients with IgAN, individuals of Paci c Asian origin have a higher risk of progression to ESRD Barbour SJ, et al. Kidney Int. 2013;84:1017–1024. fi
Poor prognosis in IgA nephropathy Clinical parameters Histopathologic parameters • Increasing age Light microscopy • Persistent microscopic hematuria • Mesangial and endocapillary proliferation • Severity of proteinuria • Extensive crescents • Hypertension • Focal and global glomerular sclerosis • Renal impairment • Tubule atrophy and interstitial brosis • Obesity • Vascular wall thickening • Increase serum uric acid Immuno uorescence • Capillary-loop IgA deposits Ultrastructure • Mesangiolysis, glomerular basement membrane abnormalities Satirapoj B. Essential Glomerular disease 2018. flfi
Intelligence Dialysis Center Nephrology Unit Phramongkutklao Hospital and College of Medicine
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