Acute kidney injury in patients treated with immune checkpoint inhibitors

BACKGROUND: Immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer. METHODS: We collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI. RESULTS: ICPi-AKI occurred at a median of 16 weeks (IQR 8-32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3-10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI. CONCLUSIONS: Patients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery

Paediatric HIV - trends & challenges

With the availability of antiretroviral therapy (ART), HIV infection, which was once considered a progressively fatal illness, has now become a chronic treatable condition in children, as in adults. However, the challenges these children are forced to face are far more daunting. The most significant shortcoming in the response to paediatric HIV remains the woefully inadequate prevention of mother-to-child transmission (PMTCT), allowing a large number of children to be born with HIV in the first place, in spite of it being largely preventable. In the west, mother-to-child transmission has been virtually eliminated; however, in resource-limited settings where >95 per cent of all vertical transmissions take place, still an infected infants continue to be born. There are several barriers to efficient management: delayed infant diagnosis, lack of appropriate paediatric formulations, lack of skilled health personnel, etc. Poorly developed immunity allows greater dissemination throughout various organs. There is an increased frequency of malnutrition and infections that may be more persistent, severe and less responsive to treatment. In addition, these growing children are left with inescapable challenges of facing not only lifelong adherence with complex treatment regimens, but also enormous psychosocial, mental and neuro-cognitive issues. These unique challenges must be recognized and understood in order to provide appropriate holistic management enabling them to become productive citizens of tomorrow. To address these multi-factorial issues, there is an urgent need for a concerted, sustainable and multi-pronged national and global response