Kidney-shaped aquarium with protein streaming through cracked viewing glassKidney-shaped aquarium with protein streaming through cracked viewing glass

In IgA Nephropathy

Elevated Proteinuria Increases Risk of Disease Progression

Proteinuria is the single strongest modifiable prognostic indicator for disease progression in IgA nephropathy1-3

IgA nephropathy is characterized by the mesangial accumulation of immune complexes containing IgA.4

  • Proteinuria >1.0 g/d puts patients at higher risk of progression to CKD1,3
  • KDIGO guidelines recommend <1.0 g/d as a surrogate marker for improved kidney outcomes5

TARGET PROTEINURIA GOAL1,5

<1.0 g/d

Achieving this goal correlates with extended kidney survival

Lower proteinuria levels are associated with improved kidney survival in IgA nephropathy1

Graph depicts survival data from Reich 2005 study showing treatment effects of lowering proteinuria and improved probability of kidney survival

Each incremental gram per day above 1 is associated with a 10- to 25-fold more rapid rate of decline in renal function

Outcomes were in 542 patients with IgA nephropathy in the Toronto Glomerulonephritis Registry. In addition, it was found that the greater the rise in proteinuria, the worse the renal outcomes and rate of functional kidney decline in these patients.

Epidemiology of IgA nephropathy

  • The most prevalent primary glomerulonephritis worldwide. It is often progressive, and if uncontrolled is a major cause of kidney failure6,7
  • Can occur in susceptible individuals of any age, with a peak incidence in the third and fourth decades of life8
  • Highest prevalence is in patients with East Asian ancestry, followed by patients with European ancestry, and is rare in those with African ancestry9
  • A kidney biopsy is required to confirm diagnosis5

Endothelin-1 and angiotensin II are key drivers of disease progression in IgA nephropathy3,10-16

  • Working in tandem to amplify the inflammatory cytokine response
  • Increasing mesangial proliferation
  • Increasing proteinuria

Treatment options are limited

Patients with proteinuria >0.5 g/d, KDIGO guidelines recommend5:

  • Initiating ACEi/ARB; however, reversal of progressive disease or stabilization of kidney function are often difficult to achieve with these agents

Patients with >1.0 g/d at 3 months of maximal supportive care5:

  • May consider enrollment in clinical trials
  • Corticosteroids may be an option for some patients based on benefit-risk assessment

Research is ongoing into the urgent need for non-immunosuppressive treatment approaches for patients with IgA nephropathy who remain at high risk7

Accurate prognosis leads to optimized patient care

The International Risk-Prediction Tool in IgA Nephropathy18-21

This simple-to-use tool, based on a risk-prediction model, was developed to assess long-term prognosis in patients with IgA nephropathy18:

  • An at-biopsy version of the tool was designed for use at the time of biopsy-confirmed diagnosis18,19
  • A post-biopsy version was designed for reassessment of risk at 1 to 2 years after biopsy20,21
  • The tool predicts long-term risk of worsening kidney function, measured as a 50% reduction in eGFR or the development of ESKD13-16
  • The tool can be run with or without controls for ethnicity (Caucasian, Chinese, or Japanese)20,21
  • The tool cannot be used to determine the likely impact of any particular treatment regimen5
    • The tool incorporates clinical information at the time of biopsy and additional research is needed to determine if the output can be used at other time points in the progression of the disease18

2 ways to access the tool

Download the app:

Mobile device and calculator icons convey availability of IgA nephropathy risk-prediction tool as an app

Calculate by QxMD Mobile App

for iOS and Android devices

Go to the website:

Desktop screen and calculator icons convey availability of IgA nephropathy risk-prediction tool via Web browser

Calculate by QxMD Website

for desktop and mobile browsers

Applying research to clinical practice in FSGS

ACEi=angiotensin-converting enzyme inhibitor; ARB=angiotensin II receptor blocker; eGFR=estimated glomerular filtration rate; ESKD=end-stage kidney disease; FSGS=focal segmental glomerulosclerosis; IgA=immunoglobulin A; KDIGO=Kidney Disease Improving Global Outcomes.

References:

1. Reich HN, et al. J Am Soc Nephrol. 2007;18:3177-3183. 2. Inker LA, et al. Am J Kidney Dis. 2016;68:392-401. 3. Le WB, et al. Nephrol Dial Transplant. 2012;27:1479-1485. 4. Wyatt RJ, et al. New Engl J Med. 2013;368:2402-2414. 5. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. Kidney Int. 2021;100(4S):S1-S276. 6. McGrogan A, et al. Nephrol Dial Transplant. 2011; 26:414-430. 7. Nasri H, Mubarak M. J Nephropathol. 2015; 4:1-5. 8. Nair R, et al. Kidney Int. 2006; 69:1455-1458. 9. Yeo SC, et al. Nephrology. 2019; 24:885-895. 10. Lai KN, et al. Nat Rev Dis Primers. 2016;2:1-20. 11. Komers R, et al. Am J Physiol Regul Integr Comp Physiol. 2016:R877-R884. 12. Benigni A, et al. Pediatr Nephrol. 2021;36:763-775. 13. Kohan DE, et al. Kidney Int. 2014;86:896-904. 14. Raina R, et al. Kidney Dis. 2020;6:22-34. 15. Ebefors K, et al. Kidney Int. 2019;96:957-970. 16. Dhaun N, et al. Br J Pharmacol. 2012;167:720-731. 17. Zhang H. KDIGO. Accessed June 22, 2022. https://kdigo.org/wp-content/uploads/2020/01/Hong-Zhang.pdf. 18. Barbour SJ, et al. JAMA Intern Med. 2019;E1-E11. 19. QxMD IgAN prediction tool for adults at biopsy. Accessed June 16, 2022. https://qxmd.com/calculate/calculator_499/international-igan-prediction-tool-at-biopsy-adults. 20. Barbour SJ, et al. Kidney Int. 2022;102:160-172. 21. QxMD IgAN prediction tool for adults post-biopsy. Accessed June 16, 2022. https://qxmd.com/calculate/calculator_839/international-igan-prediction-toolpostbiopsy-adults.

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