IBD, Coelic, cirhossis, chronic infection (HIV), some malignanciesEstablished risk factors
Consider:
20-year survival without RRT = 96% if no risk factors 36% with 3.
Histological methods
Useful for research but less useful for clinical decisions
MEST-C scoring - The Oxford Study
Mesangial hypercellularity, endocapillary hypercellularity, and crescent formation are histopathologic indicators of activity, while segmental sclerosis and tubular atrophy indicate chronicity. E is worst.
If you are C2, HRs for a (composite outcome of either ESRD or ≥50% reduction in eGFR; increased rate of eGFR decline) was of 3.26 (95% CI, 1.47 to 7.34; P=0.004) in untreated and and 2.43 (95% CI, 1.17 to 5.06) if treated with Immunosuppression. Not particularly different!
M, S crescents enhance ability to predict outcomes only in patients who had not received immunosupression. Nice NephJC
European validation of Oxford study
MST = predict loss of renal function
If eGFR <30, MT = predict loss of renal function
If Proteinuria <0.5/day, ME = predict rise in proteinuria to 1-2g/day
As with Oxford, MST enhance ability to predict outcomes only in patients who had not received immunosupression
International IgA Nephropathy Network Prediction models
Parameters:
Generalizability
Adult patients, no pediatric patients.
White, Chinese and Japanese patients only
Biopsy-proven IgA nephropathy only so the full models cannot be applied in patients who have not undergone biopsy.
Needs to be applied at the time of bx only
Not appropriate for Rx decisions
GWAS
Risk genes increase as you move West to East but ultimately only explain ~7% of overall risk.
Interesting implications for variable of “Race” in data and what it really is capturing – at times, these risk genes, but also captures range of diverse and ill-defined cultural/socioeconomic patterns.
Not entirely clear what relationship “race” has to IGAN, possibly worse outcomes in “Chinese” populations but unclear if that applies to Chinese Nationals of those with Chinese heritage in other countries. No evidence of differential treatment effects.
If proteinuria, optimise long term ACE-i/ARB to max tolerated
Threshold for starting per KDIGO >1g/d
BP <130/80
Heavy Immunosuppression for moderate IgA disease
Inclusion:
Bx confirmed IGAN, aged 18-70, proteinuria >0.75g/d & HTN, eGFR<90
Excluded:
Secondary IGAN, rapid progression/crescents, previous immunosuppression
Endpoint:
6 months run in to optimise | N= (337) ->177 randomised over 3 years
The immunosuppression
Results
Immunosuppression led to
Conclusion
Steroids in IgAN: the one that was reimagined half way through due to safety concerns
Inclusion:
Patients with IGAN >= 1g proteinuria/day, 12 week run in ACEi/ARB
Excluded:
Secondary IGAN, MCD, >50% crescents, infection, cancer
Endpoint:
40% decreased in eGFR/ESKD/death | ESKD | Death
The immunosuppression regime:
High dose: 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136
Low dose Regime: (0.4 mg/kg/day, maximum 32 mg/day) for 2 months, followed by weaning by 4 mg/day/month over 6-9 months, or matching placebo.
& PJP prophylaxis for 12 weeks (cotrim)
Results
Conclusion:
Probably low dose is reasonable in high risk of progression, single regime, I wouldn’t repeat if later “flare” or retreat unless they were exceptionally tolerant of initial regime and rebiopsy showed activity and minimal sclerosis
Notes:
E1, E0 both responded to treatment, despite previous suggestions from MEST 2009
Effect was not exclusive to Chinese (questions around Stop IgA suggested their European centres were the reason for lack of efficacy – this appears not to be the case)
By the end of trial, initial drop in proteinuria has returned to baseline
Oral, enteric coated Budesonide in IgA
Oral option, USA has enteric coated on patent (100k/9 months in US!)
Has less side effects due to first pass metabolism
Evidence that proteinuria reduction in phase 2, but ongoing phase 3 trials to correlate with longer term eGFR changes.
Sparsentan in IgA - prespecified interim analysis
Biopsy proven IGAN with >1g proteinuria /day.
Sparsentan 400mg vs Irbesartan 300mg
Primary Endpoint: Change from baseline to week 36 uPCR
At week 36, the geometric least squares mean percent change from baseline in urine protein–creatinine ratio was statistically significantly greater in the sparsentan group (–49·8%) than the irbesartan group (–15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51–0·69; p<0·0001)
The artist formally known as HSP
Diagnosis of IgA vasculitis is clinical, but in cases in which there is diagnostic uncertainty, it can be confirmed by biopsy of an affected organ.
International consensus guidelines require the presence of palpable purpura in addition to abdominal pain, arthritis or arthralgia, renal involvement, or compatible histopathologic evidence.
Elevated IgA levels are neither necessary nor sufficient for diagnosis
Type III immune complex diseases such as IgA vasculitis are complement-mediated, plasma complement levels are usually normal.
IgA vasculitis is primarily managed with supportive care and monitoring for complications. IgA vasculitis is generally self-limited, with complete resolution of symptoms and no long-term sequelae in the vast majority of cases.
Glucocorticoids are indicated for severe symptoms, especially those involving the gastrointestinal or musculoskeletal systems.
A systematic review including mostly retrospective studies and three randomized, placebo-controlled trials showed that glucocorticoids increased the odds of resolution of abdominal pain within 24 hours and suggested renal benefits.
However, the largest randomized trial involving patients with IgA vasculitis showed no evidence that glucocorticoids prevented the development of nephropathy.