Wednesday, December 26, 2018

In the NEWS: PD-1 inhibitors and ATN, not AIN

Check point inhibitors have been associated with kidney injury. The incidence of check point inhibitor associated renal injury varies widely in the literature. The most common kidney biopsy observed has been acute interstitial nephritis and in a few rare cases- podocytopathies

In a recent study from France, the authors report on the incidence of pembrolizumab associated kidney toxicity in a French single-center nephrology referral center and report that renal adverse events occur in 1.77% of patients. A renal biopsy was performed in all 12 patients and acute tubular injury was the most common lesion noted. The most common glomerular pathology in this case series was minimal change disease. In this study, surprisingly, acute tubular injury was the most commonly observed pattern of injury on histology. This is in contrast with other reports that identified acute tubulo-interstitial nephritis as the dominant form of renal injury associated with immunotherapy treatment. A possible explanation is the low threshold to perform a kidney biopsy in this study. 

About half of their patients had ATN. Those patients had more frequently cardiovascular risk factors and marked histological vascular lesions and are more frequently men than AIN patients. Two of them received platinum but at least 1 year before pembrolizumab was introduced. No known mechanism is postulated for the ATN related to pembrolizumab.

This is an important study as this highlights the varied degree of renal toxicities seen with these agents. AIN will respond to steroids and ATN won’t. A kidney biopsy will be important to distinguish that. Empiric steroid treatment by oncologist should not be the gold standard but should be based on kidney biopsies performed and or a nephrology consultation. 

Besides AIN and podocytopathies, it appears that PD-1 inhibitors also can cause ATN.

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