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Kidney Failure Events, Cardiovascular Disease Events, and All–Cause Mortality in Patients with IgA Nephropathy in a Real–World Database

Journal article
Published on February 7, 2024

Topics: Nephrology IgAN RWE

Contributors:
Lerma E, Thakker K, Bensink M et al.
Name of Journal:
Kidney360


View Publication
DOI:
10.34067/KID.0000000000000379
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Home » Publications » Kidney Failure, Cardiovascular Disease and Mortality in IgAN

Summary

Proteinuria ≥1 g/day and progression to kidney failure (KF) due to IgA nephropathy are associated with cardiovascular disease (CVD) outcomes and mortality1

Background

IgA nephropathy is the most common primary glomerular disease.2 Defined by glomerular injury, patients experience proteinuria, hematuria, and progressive loss of estimated glomerular filtration rate (eGFR), ultimately leading to kidney failure (KF) due to IgA nephropathy.3,4

Advanced stages of chronic kidney disease (CKD) have been associated with cardiovascular disease (CVD) events and all-cause mortality.5 Proteinuria and lower eGFR have also been associated with a greater risk of CVD events.6 Changes in proteinuria have been associated with kidney failure.7,8 A registry-based study observed that almost all patients with IgA neuropathy progressed to kidney failure,9 indicating that patients are exposed to progressive CKD and thus likely an increased risk of CVD events.1

There is a need to assess the link between proteinuria reduction and slowing of eGFR decline with CVD events.1


Aim

The objective of this study was to assess the impact of proteinuria on CVD/all-cause mortality and KF/all-cause mortality outcomes.1


Approach

This observational, retrospective cohort study used Optum’s deidentified Market Clarity Data and proprietary Natural Language Processing (NLP) data.1

The study population included American adults with at least1:

  • Two signs, disease, and symptoms (SDS) NLP term entries 
  • 180 days of baseline activity

Patients were divided into cohorts1:

  • Proteinuria-CVD/mortality
  • Proteinuria-KF/mortality
  • KF-CKD/mortality
  • Exploratory (Event Rate, Incremental Cost)

Patients were excluded from the proteinuria-CVD/mortality cohort if there was1:

  • Evidence of KF or CVD at baseline
  • No proteinuria measurement during the baseline period

Patients were excluded from the proteinuria-KF/mortality cohort if there was1:

  • Evidence of KF at baseline
  • No proteinuria measurement during the baseline period

Patients were excluded from the KF-CKD/mortality cohort if there was1:

  • Evidence of CVD at baseline

Findings

Elevated proteinuria was significantly associated with CVD and KF all-cause mortality (P<0.001)1

Proteinuria-CVD/mortality cohort

Patients with <1 g/d and patients with ≥1 g/d of proteinuria experienced CKD/all-cause mortality events over a median follow-up of 39.3 and 24.9 months, respectively.1 Proteinuria ≥1 g/day was significantly associated with CVD/all-cause mortality events (P<0.001).1

Proteinuria-KF/mortality cohort

Patients with <1 g/d and patients with ≥1 g/d of proteinuria experienced KF/all-cause mortality events over a median follow-up of 37.0 and 23.9 months, respectively.1 Proteinuria ≥1 g/day was significantly associated with KF/all-cause mortality events (P <0.001).1

Post-KF at baseline was significantly associated with CVD/all-cause mortality (P<0.001)1

Patients with a pre-KF status at baseline experienced CVD/all-cause mortality over a median follow-up of 44.4 months; patients with a post-KF status at baseline experienced CVD/all-cause mortality over a median follow-up of 33.5 months.1 A post-KF status at baseline was significantly associated with a greater risk of CVD/all-cause mortality (P<0.001).1

CKD stage progression and CVD events were linked with substantial incremental costs1

Exploratory analyses found that although highly variable, progressing CKD stages were associated with CVD events with substantial incremental costs.1


Key takeaway

Elevated proteinuria and progression to KF due to IgA nephropathy were significantly associated with CVD/all-cause mortality.1 Additionally, pre-KF proteinuria was associated with KF/all-cause mortality.1

The authors hypothesize that reduction of proteinuria and slowing of progression to KF by novel IgA nephropathy therapies may reduce CVD risk and improve outcomes for patients.1






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Long-Term Outcomes in IgA Nephropathy

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Footnotes

CKD, chronic kidney disease; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; IgA, immunoglobulin A; KF, kidney failure; NLP, Natural Language Processing; SDS, signs, disease, and symptoms.

  1. Lerma EV et al. Kidney360. 2024;5(3):427-436.
  2. McGrogan A et al. Nephrol Dial Transplant. 2011;26:414-430.
  3. Wyatt RJ, Julian BA. N Engl J Med. 2013;368:2402-2414.
  4. Yeo SC et al. Pediatr Nephrol. 2018;33(5):763-777.
  5. Matsushita K et al. Lancet. 2010;375(9731):2073-2081
  6. Canney M et al. Am J Kidney Dis. 2022;80(6):740-750.
  7. Inker LA et al. Am J Kidney Dis. 2016;68(3):392-401.
  8. Thompson A et al. Clin J Am Soc Nephrol. 2019;14:469-481.
  9. Pitcher D et al. Clin J Am Soc Nephrol. 2023;18(6):727-738.

MA-DS-24-0028 | September 2024