Immune related nephritis - Immune Checkpoint Inhibitor Therapy- Toxicity Management

Publication: 02/06/2021  
Next review: 02/06/2024  
Clinical Guideline
ID: 7031 
Approved By: Trust Clinical Guidelines Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2021  


This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Immune Checkpoint Inhibitor Therapy-Toxicity Management

Immune related nephritis

Summary of Guideline

Patients presenting with renal dysfunction whilst receiving treatment with ICPI therapies are usually asymptomatic or have non-specific symptoms such as fatigue, nausea, reduced appetite. Patients may present with these symptoms within primary care and it is important to recognize the potential toxicities of immune checkpoint inhibitor therapy and consider sending routine blood work to screen for potential toxicities. This includes full blood count, urea and electrolytes, liver function tests, thyroid function and 9am cortisol as a baseline. If you are concerned about a patient presenting in primary care this can be discussed with oncology at Leeds Teaching Hospitals trust by calling switchboard and asking for the ‘oncology bleep holder’. It is therefore common that renal toxicities of treatment are detected only at the time of blood test monitoring as the patient progresses through treatment. History, examination and investigations should aim to exclude other causes of renal dysfunction and the mnemonic ‘STOP AK’I can be helpful to frame these. Management of immune-mediated nephritis involves pausing or complete cessation of the ICPI therapy and there is a graded mechanism for the considering other therapies e.g. corticosteroids.

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Renal toxicity from ICPIs is rare but the frequency increases with combination therapies and this renal toxicity can progress to cause dialysis-dependent renal failure. The most common immune mediated toxicity is acute interstitial nephritis however lupus nephritis, thrombotic microangiopathies, focal segmental glomerulosclerosis, minimal change disease, membranous nephropathy, pauci-ummune glomerulonephritis (both ANCA negative and positive) and minimal change disease have all been associated with treatment with ICPIs.

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The diagnosis of immune-related nephritis involves the exclusion of any other cause of renal dysfunction. Therefore, the history and examination should focus on the consideration of pre-renal, renal, and post-renal causes of acute kidney injury. It is also important to remember that patients can suffer from more than one ICPI toxicity at once and these can have a complex interplay on diagnosis; for example does the patient with severe diarrhea and AKI have an AKI due to dehydration or immune-mediated renal dysfunction? History and examination should include a thorough assessment of hydration status, review of medications, assessment for potential infection, and a useful way to remember the assessment required is the “STOP” AKI mnemonic (Sepsis, Toxins, Optimise hydration status/blood pressure, Prevent harm).

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Investigations should again be targeted towards looking for other causes of renal dysfunction and assessment for evidence of end-organ damage. In the first instance a urine dipstick is a very helpful way of screen for evidence of nephritis, assessing for haematuria and proteinuria and if there is evidence of this, further quantifying this is helpful. It is also important in a patient with a known cancer to assess for evidence of renal tract obstruction and a targeted renal ultrasound scan can help to answer this question. Auto-antibody screening can also be helpful to assess for other potential causes if the patient has a nephritic picture. If other causes of AKI have therefore been excluded referral to a nephrologist and consideration of renal biopsy is therefore indicated to guide further management. Finally, as suggested above, it is helpful to assess for other potential immune-related toxicities and therefore assessment of thyroid function, cortisol and liver function are also important.

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Record: 7031

Immune checkpoint inhibitor therapies (ICPIs: anti-CTLA4, anti-PD-1, anti-PD-L1 therapies) have been in routine use in the management of cancers for almost a decade. It is well recognised that patients receiving this class of systemic anti-cancer therapies are at risk of multiple and wide ranging toxicities from these treatments owing to immune activation against self-antigens outside of the therapeutic indication of the drug(s).Immune-related nephritis is documented as a potential toxicity in the case of these patients and this document aims to provide the clinician with an initial plan for investigation and management of patients who present with deranged renal function on these agents.

Clinical condition: Immune-related nephritis; Immune-mediated renal dysfunction; Immunotherapy toxicitiy; Pembrolizumab, Nivolumab, Ipilimumab, Atezolizumab, Avelumb, Durvalumab
Target patient group: Those patients currently receiving or who have previously received treatment with immune checkpoint inhibitor therapies.
Target professional group(s): Pharmacists
Primary Care Doctors
Secondary Care Doctors
Primary Care Nurses
Secondary Care Nurses
Adapted from:

Evidence base

Not supplied

Approved By

Trust Clinical Guidelines Group

Document history

LHP version 1.0

Related information

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