Urine interleukin-9 and tumor necrosis factor-α for prognosis of human acute interstitial nephritis.

Abstract

BACKGROUND:

We previously demonstrated that urine interleukin (IL)-9 and tumor necrosis factor (TNF)-α can distinguish acute interstitial nephritis (AIN) from other causes of acute kidney injury. Here we evaluated the role of these biomarkers to prognosticate kidney function in patients with AIN.

METHODS:

In a cohort of participants with biopsy-proven, adjudicated AIN, we tested the association of histological features and urine biomarkers (IL-9 and TNF-α) with estimated glomerular filtration rate measured 6 months after diagnosis (6 m-eGFR) controlling for eGFR before AIN and albuminuria. We also evaluated subgroups in whom corticosteroid use was associated with 6 m-eGFR.

RESULTS:

In the 51 (93%) of the 55 participants with complete data, median (interquartile range) eGFR before and 6 m after AIN were 41 (27-69) and 28 (13-47) mL/min/1.73 m2, respectively. Patients with higher severity of interstitial fibrosis had lower 6 m-eGFR, whereas those with higher tubulointerstitial infiltrate had higher 6 m-eGFR. IL-9 levels were associated with lower 6 m-eGFR only in the subset of patients who did not receive corticosteroids [6m-eGFR per doubling of IL-9, -6.0 (-9.4 to -2.6) mL/min/1.73 m2]. Corticosteroid use was associated with higher 6 m-eGFR [20.9 (0.2, 41.6) mL/min/1.73 m2] only in those with urine IL-9 above the median (>0.66 ng/g) but not in others.

CONCLUSIONS:

Urine IL-9 was associated with lower 6 m-eGFR only in participants not treated with corticosteroids. Corticosteroid use was associated with higher 6 m-eGFR in those with high urine IL-9. These findings provide a framework for IL-9-guided clinical trials to test efficacy of immunosuppressive therapy in patients with AIN.

• Authors: Dennis G Moledina, F Perry Wilson, Lidiya Kukova, Wassim Obeid, Randy Luciano, Michael Kuperman, Gilbert W Moeckel, Michael Kashgarian, Mark A Perazella, Lloyd G Cantley, Chirag R Parikh
• Journal: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association (Nephrol Dial Transplant) Vol. 36 Issue 10 Pg. 1851-1858 (09 27 2021) ISSN: 1460-2385 [Electronic] England
• PMID: 33125471 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

Chemical References

• IL9 protein, human
• Interleukin-9
• Tumor Necrosis Factor-alpha

Topics

• Glomerular Filtration Rate
• Humans
• Interleukin-9 (urine)
• Nephritis, Interstitial (diagnosis, drug therapy)
• Prognosis
• Tumor Necrosis Factor-alpha (urine)