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Imaging features of immune checkpoint inhibitor-related nephritis with clinical correlation: a retrospective series of biopsy-proven cases

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Abstract

Objectives

Imaging appearances of immune checkpoint inhibitor-related nephritis have not yet been described. The primary objective of this study is to describe the appearances of immunotherapy-related nephritis on computerized tomography (CT) and positron emission tomography (PET). The secondary objectives are to investigate the association of radiologic features with clinical outcomes.

Methods

CT and PET-CT scans before the initiation of immunotherapy (baseline), at nephritis, and after resolution of pathology-proven nephritis cases were reviewed. Total kidney volume, renal parenchymal SUVmax, renal pelvis SUVmax, and blood pool SUVmean were obtained.

Results

Thirty-four patients were included. The total kidney volume was significantly higher at nephritis compared to baseline (464.7 ± 96.8 mL vs. 371.7 ± 187.7 mL; p < 0.001). Fifteen patients (44.1%) had > 30% increase in total kidney volume, which was associated with significantly higher renal toxicity grade (p = 0.007), higher peak creatinine level (p = 0.004), and more aggressive medical treatment (p = 0.011). New/increasing perinephric fat stranding was noted in 10 patients (29.4%) at nephritis. Among 8 patients with contrast-enhanced CT at nephritis, one (12.5%) developed bilateral wedge-shaped hypoenhancing cortical. On PET-CT, the renal parenchymal SUVmax-to-blood pool ratio was significantly higher at nephritis compared to baseline (2.13 vs. 1.68; p = 0.035). The renal pelvis SUVmax-to-blood pool SUVmean ratio was significantly lower at nephritis compared to baseline (3.47 vs. 8.22; p = 0.011).

Conclusions

Bilateral increase in kidney size, new/increasing perinephric stranding, and bilateral wedge-shaped hypoenhancing cortical foci can occur in immunotherapy-related nephritis. On PET-CT, a diffuse increase in radiotracer uptake throughout the renal cortex and a decrease in radiotracer activity in the renal pelvis can be seen.

Key Points

• CT features of immune checkpoint inhibitor-related nephritis include an increase in kidney volume, new/increasing perinephric stranding, and bilateral ill-defined wedge-shaped hypoenhancing cortical foci.

• FDG-PET features of immune checkpoint inhibitor-related nephritis include an increase in FDG uptake throughout the renal cortex and a decrease in FDG activity/excretion in the collecting system.

• > 30% increase in total kidney volume is associated with worse toxicity grade and more aggressive medical management.

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Abbreviations

CT:

Computerized tomography

eGFR:

Estimated glomerular filtration rate

FDG:

18F-flourodeoxyglucose

IFTA :

Interstitial fibrosis and tubular atrophy

irAE :

Immune-related adverse events

IV:

Intravenous

MRI:

Magnetic resonance imaging

PET-CT:

Positron emission tomography-computerized tomography

ROI :

Region of interest

References

  1. Ramos-Casals M, Brahmer JR, Callahan MK et al (2020) Immune-related adverse events of checkpoint inhibitors. Nat Rev Dis Primers 6:38

    Article  PubMed  PubMed Central  Google Scholar 

  2. Cortazar FB, Marrone KA, Troxell ML et al (2016) Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors. Kidney Int 90:638–647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Abdelrahim M, Mamlouk O, Lin H et al (2021) Incidence, predictors, and survival impact of acute kidney injury in patients with melanoma treated with immune checkpoint inhibitors: a 10-year single-institution analysis. Oncoimmunology 10:1927313

    Article  PubMed  PubMed Central  Google Scholar 

  4. Mamlouk O, Selamet U, Machado S et al (2019) Nephrotoxicity of immune checkpoint inhibitors beyond tubulointerstitial nephritis: single-center experience. J Immunother Cancer 7:2

    Article  PubMed  PubMed Central  Google Scholar 

  5. Puzanov I, Diab A, Abdallah K et al (2017) Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. J Immunother Cancer 5:95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Perazella MA, Shirali AC (2020) Immune checkpoint inhibitor nephrotoxicity: what do we know and what should we do? Kidney Int 97:62–74

    Article  CAS  PubMed  Google Scholar 

  7. Ala Abudayyeh AD, Garcia W, Lin JS et al (2021) Evaluation and management of suspected immune-mediated nephritis. Available via https://www.mdanderson.org/content/dam/mdanderson/documents/for-physicians/algorithms/clinical-management/clin-management-nephritis-web-algorithm.pdf. Accessed 01/24/2021 2022

  8. Anderson MA, Kurra V, Bradley W, Kilcoyne A, Mojtahed A, Lee SI (2021) Abdominal immune-related adverse events: detection on ultrasonography, CT, MRI and 18F-fluorodeoxyglucose positron emission tomography. Br J Radiol 94:20200663

    Article  PubMed  Google Scholar 

  9. Gandy N, Arshad MA, Wallitt KL, Dubash S, Khan S, Barwick TD (2020) Immunotherapy-related adverse effects on (18)F-FDG PET/CT imaging. Br J Radiol 93:20190832

    Article  PubMed  PubMed Central  Google Scholar 

  10. Bronstein Y, Ng CS, Hwu P, Hwu WJ (2011) Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy. AJR Am J Roentgenol 197:W992–W1000

    Article  PubMed  Google Scholar 

  11. Widmann G, Nguyen VA, Plaickner J, Jaschke W (2016) Imaging features of toxicities by immune checkpoint inhibitors in cancer therapy. Curr Radiol Rep 5:59

    Article  PubMed  Google Scholar 

  12. Kwak JJ, Tirumani SH, Van den Abbeele AD, Koo PJ, Jacene HA (2015) Cancer immunotherapy: imaging assessment of novel treatment response patterns and immune-related adverse events. Radiographics 35:424–437

  13. Kim HC, Yang DM, Jin W, Lee SH (2010) Relation between total renal volume and renal function: Usefulness of 3D sonographic measurements with a matrix array transducer. AJR Am J Roentgenol 194:W186–W192

    Article  PubMed  Google Scholar 

  14. Emamian SA, Nielsen MB, Pedersen JF, Ytte L (1993) Kidney dimensions at sonography: correlation with age, sex, and habitus in 665 adult volunteers. AJR Am J Roentgenol 160:83–86

    Article  CAS  PubMed  Google Scholar 

  15. Forde PM, Rock K, Wilson G, O'Byrne KJ (2012) Ipilimumab-induced immune-related renal failure--a case report. Anticancer Res 32:4607–4608

    PubMed  Google Scholar 

  16. Qualls D, Seethapathy H, Bates H et al (2019) Positron emission tomography as an adjuvant diagnostic test in the evaluation of checkpoint inhibitor-associated acute interstitial nephritis. J Immunother Cancer 7:356

    Article  PubMed  PubMed Central  Google Scholar 

  17. Vernuccio F, Patti D, Cannella R, Salvaggio G, Midiri M (2020) CT imaging of acute and chronic pyelonephritis: a practical guide for emergency radiologists. Emerg Radiol 27:561–567

    Article  PubMed  Google Scholar 

  18. Ishikawa I, Saito Y, Onouchi Z et al (1985) Delayed contrast enhancement in acute focal bacterial nephritis: CT features. J Comput Assist Tomogr 9:894–897

    Article  CAS  PubMed  Google Scholar 

  19. Maturen KE, Blane CE, Strouse PJ (2002) Computed tomographic diagnosis of unsuspected pyelonephritis in children. Can Assoc Radiol J 53:279–283

    PubMed  Google Scholar 

  20. Kuhlman JE, Browne D, Shermak M, Hamper UM, Zerhouni EA, Fishman EK (1991) Retroperitoneal and pelvic CT of patients with AIDS: primary and secondary involvement of the genitourinary tract. Radiographics 11:473–483

    Article  CAS  PubMed  Google Scholar 

  21. Craig WD, Wagner BJ, Travis MD (2008) Pyelonephritis: radiologic-pathologic review. Radiographics 28:255–277 quiz 327-258

    Article  PubMed  Google Scholar 

  22. Hartman DS, Davis CJ Jr, Lichtenstein JE, Goldman SM (1980) Renal parenchymal malacoplakia. Radiology 136:33–42

    Article  CAS  PubMed  Google Scholar 

  23. Zimina OG, Rezun S, Armao D, Braga L, Semelka RC (2002) Renal malacoplakia: demonstration by MR imaging. Magn Reson Imaging 20:611–614

    Article  PubMed  Google Scholar 

  24. Ranjan P, Chipde SS, Vashistha S, Kumari N, Kapoor R (2014) Reno-invasive fungal infection presenting as acute renal failure: importance of renal biopsy for early diagnosis. Saudi J Kidney Dis Transpl 25:1282–1284

    Article  PubMed  Google Scholar 

  25. Ronald Zagoria CB, Dyer R (2015) The kidney: diffuse parenchymal abnormalities. In: Dyer RZCBR (ed) Genitourinary imaging: the requisites. Elsevier, Philadelphia, PA, pp 107–145

    Google Scholar 

  26. Sherief LM, Azab SF, Zakaria MM et al (2015) Renal presentation in pediatric acute leukemia: report of 2 cases. Medicine (Baltimore) 94:e1461

    Article  PubMed  Google Scholar 

  27. Hilmes MA, Dillman JR, Mody RJ, Strouse PJ (2008) Pediatric renal leukemia: spectrum of CT imaging findings. Pediatr Radiol 38:424–430

    Article  PubMed  Google Scholar 

  28. Arora SK, Swarnim S, Hemal A, Bidhuri N (2019) Acute lymphoblastic leukemia presenting as nephromegaly in a child: a rare case report. Turk J Pediatr 61:97–101

    Article  PubMed  Google Scholar 

  29. Gibbins J, Pankhurst T, Murray J et al (2005) Extramedullary haematopoiesis in the kidney: a case report and review of literature. Clin Lab Haematol 27:391–394

    Article  CAS  PubMed  Google Scholar 

  30. Ganeshan D, Iyer R, Devine C, Bhosale P, Paulson E (2013) Imaging of primary and secondary renal lymphoma. AJR Am J Roentgenol 201:W712–W719

    Article  PubMed  Google Scholar 

  31. Nalcacioglu H, Yel S, Karadogan M, Mutlu FT, Bastug F, Altuner Torun Y (2018) Abdominal pain in a 5-year-old girl with bilateral nephromegaly: answers. Pediatr Nephrol 33:423–426

    Article  PubMed  Google Scholar 

  32. Lei W, Wang H, Di W, Feng M, Li L, Shiren S (2020) Bilateral primary renal lymphoma presented as homogenous renal enlargement and acute interstitial nephritis. Urol J 17:317–320

    PubMed  Google Scholar 

  33. Apter S, Zemer D, Terhakopian A et al (2001) Abdominal CT findings in nephropathic amyloidosis of familial Mediterranean fever. Amyloid 8:58–64

    Article  CAS  PubMed  Google Scholar 

  34. Tsukada H, Shimizu H, Kaname S (2017) Bilateral nephromegaly due to isolated renal sarcoidosis. Clin Exp Nephrol 21:169–170

    Article  PubMed  Google Scholar 

  35. Ling J, Wang H, Pan W et al (2020) Clinical and imaging features of IgG4-related kidney disease. Abdom Radiol (NY) 45:1915–1921

    Article  PubMed  Google Scholar 

  36. Kim B, Kim JH, Byun JH et al (2014) IgG4-related kidney disease: MRI findings with emphasis on the usefulness of diffusion-weighted imaging. Eur J Radiol 83:1057–1062

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank Erica Goodoff, Senior Scientific Editor in the Research Medical Library at The University of Texas MD Anderson Cancer Center, for editing this article. National Institute of Health K01 grant (N.A.: K01AI163412).

Funding

The authors state that this work has not received any funding.

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Authors and Affiliations

  1. Division of Diagnostic Imaging, Department of Abdominal Imaging, The University of Texas MD Anderson Cancer Center, Houston, 1515 Holcombe Blvd, Houston, TX, 77030, USA

    Muhammad O. Awiwi, Raghu Vikram & Khaled Elsayes

  2. Division of Internal Medicine, Section of Nephrology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Ala Abudayyeh

  3. Division of Internal Medicine, Section of Rheumatology and Clinical Immunology, Department of General Internal Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Noha Abdel-Wahab

  4. Department of Rheumatology and Rehabilitation, Faculty of Medicine, Assiut University Hospitals, Assiut, Egypt

    Noha Abdel-Wahab

  5. Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Adi Diab

  6. Department of Internal Medicine, Istanbul University-Cerrahpasa, Istanbul, Turkey

    Migena Gjoni

  7. Division of Diagnostic Imaging, Department of Nuclear Medicine and Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Guofan Xu

Authors
  1. Muhammad O. Awiwi
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  2. Ala Abudayyeh
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  3. Noha Abdel-Wahab
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  4. Adi Diab
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  5. Migena Gjoni
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  7. Raghu Vikram
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  8. Khaled Elsayes
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Corresponding author

Correspondence to Muhammad O. Awiwi.

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Guarantor

The scientific guarantor of this publication is Prof. Dr. Khaled Elsayes.

Conflicts of interest

N.A. has received honoraria for serving on a scientific advisory board as a consultant for ChemoCentryx. A.D. has received honoraria from Nektar and he has served as a consultant for Nektar, Memgen, and Pfizer.

Statistics and biometry

One of the authors has significant statistical expertise.

Informed consent

Written informed consent was waived in this retrospective study.

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Institutional Review Board approval was obtained.

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• Retrospective

• Observational study

• Single institution

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Awiwi, M.O., Abudayyeh, A., Abdel-Wahab, N. et al. Imaging features of immune checkpoint inhibitor-related nephritis with clinical correlation: a retrospective series of biopsy-proven cases. Eur Radiol 33, 2227–2238 (2023). https://doi.org/10.1007/s00330-022-09158-8

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  • DOI: https://doi.org/10.1007/s00330-022-09158-8

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