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Kidney injury and disease in patients with haematological malignancies

Nature Reviews Nephrology volume 17, pages 386–401 (2021)Cite this article

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Abstract

Acute kidney injury (AKI) is common in patients with cancer, especially in those with haematological malignancies. Kidney injury might be a direct consequence of the underlying haematological condition. For example, in the case of lymphoma infiltration or extramedullary haematopoiesis, it might be caused by a tumour product; in the case of cast nephropathy it might be due to the presence of monoclonal immunoglobulin; or it might result from tumour complications, such as hypercalcaemia. Kidney injury might also be caused by cancer treatment, as many chemotherapeutic agents are nephrotoxic. High-intensity treatments, such as high-dose chemotherapy followed by haematopoietic stem cell transplantation, not only increase the risk of infection but can also cause AKI through various mechanisms, including viral nephropathies, engraftment syndrome and sinusoidal obstruction syndrome. Some conditions, such as thrombotic microangiopathy, might also result directly from the haematological condition or the treatment. Novel immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T cell therapy, can also be nephrotoxic. As new therapies for haematological malignancies with increased anti-tumour efficacy and reduced toxicity are developed, the number of patients receiving these treatments will increase. Clinicians must gain a good understanding of the different mechanisms of kidney injury associated with cancer to better care for these patients.

Key points

  • Kidney injury is common in patients with haematological malignancies and the onconephrology subspecialty has been created to better care for patients with cancer-associated kidney disease and direct research in this area.

  • Causes of kidney injury in patients with haematological malignancies include the presence of monoclonal proteins, direct tumour invasion of the kidney and adverse effects of cancer therapies, such as haematopoietic stem cell transplantation or chemotherapy.

  • Both the severity and rates of kidney injury in patients undergoing haematopoietic stem cell transplantation are related to the intensity of the conditioning regimen and the source of the haematopoietic stem cells (that is, autologous versus allogeneic).

  • Thrombotic microangiopathy is a common cause of acute kidney injury in patients with haematological malignancies, and can be caused by the malignancy itself or the anti-cancer treatment.

  • Tumour lysis syndrome is a substantial cause of acute kidney injury in patients with haematological malignancy; prevention and treatment are focused on reduction of serum uric acid, potassium and phosphorus concentrations.

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Fig. 1: Pathophysiology of light chain cast nephropathy.
Fig. 2: Pathophysiology of monoclonal immunoglobulin deposition diseases.
Fig. 3: Pathophysiology of Fanconi syndrome.
Fig. 4: Lymphomatous infiltration of the kidney.

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Acknowledgements

I.G. and V.G. are supported by NIH/NCI Cancer Center Support Grant P30 CA008748.

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Authors and Affiliations

  1. Department of Nephrology, and Centre d’Investigation Clinique (CIC INSERM 1402), Centre Hospitalier Universitaire et Université de Poitiers, Poitiers, France

    Frank Bridoux & Florent Joly

  2. CNRS, UMR7276, Limoges, France

    Frank Bridoux

  3. Centre de référence Amylose AL et autres maladies par dépôt d’immunoglobulines monoclonales, Poitiers, France

    Frank Bridoux

  4. Department of Nephrology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK

    Paul Cockwell

  5. Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK

    Paul Cockwell

  6. Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Ilya Glezerman & Victoria Gutgarts

  7. Weill Cornell Medical College, New York, NY, USA

    Ilya Glezerman & Victoria Gutgarts

  8. Renal, Electrolyte and Hypertension Division, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA

    Jonathan J. Hogan & Deirdre Sawinski

  9. Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Northwell Health, Great Neck, NY, USA

    Kenar D. Jhaveri

  10. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

    Samih H. Nasr

  11. Division of Nephrology and Hypertension, Division of Hematology, Mayo Clinic, Rochester, MN, USA

    Nelson Leung

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Contributions

All authors researched data for the article and wrote the manuscript. N.L., F.B., P.C., I.G., V.G., J.J.H., K.D.J., S.H.N. and D.S. made substantial contributions to discussions of the content. N.L., F.B., P.C., I.G., J.J.H., K.D.J., S.H.N. and D.S. reviewed and/or edited the manuscript before submission.

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Correspondence to Nelson Leung.

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Competing interests

N.L. is on the advisory board of AbbVie, Takeda, Aduro and BTG, has received grants from Omeros and Alnylam, and has stocks in Checkpoint Therapeutic Inc. I.G. has stocks in Pfizer Inc. K.D.J. is a consultant for Astex Pharmacueticals and Natera. The other authors declare no competing interests.

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Glossary

Involved immunoglobulin free light chain

The immunoglobulin light chain produced by the pathological clone.

Antigen excess

Occurs when the target antigen concentration is so high that it interferes with the antibody-antigen complex, resulting in false underestimation of the antigen concentration.

Plasma cell dyscrasia

A proliferative clonal plasma cell disorder.

Cryoglobulins

Immunoglobulins that precipitate at low temperatures.

Dysproteinaemia

A monoclonal gammopathy.

Paraneoplastic syndrome

A group of disorders triggered by an immune response to cancer antigens that result in off-target organ injury.

Evans syndrome

An autoimmune condition resulting in Coombs positive haemolytic anaemia and immune-mediated thrombocytopenia.

Conditioning regimens

Chemoradiation therapy used to prepare the patient for haematopoietic stem cell transplantation.

Engraftment syndrome

A condition that occurs around the time of leukocyte engraftment after haematopoietic stem cell transplantation that results from increased capillary permeability and is characterized by non-infectious fever, rash and non-cardiogenic pulmonary oedema.

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Bridoux, F., Cockwell, P., Glezerman, I. et al. Kidney injury and disease in patients with haematological malignancies. Nat Rev Nephrol 17, 386–401 (2021). https://doi.org/10.1038/s41581-021-00405-7

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