Validation of automatically measured T1 map cortico-medullary difference (ΔT1) for eGFR and fibrosis assessment in allograft kidneys.

MRI T1-mapping is an important non-invasive tool for renal diagnosis. Previous work shows that ΔT1 (cortex-medullary difference in T1) has significant correlation with interstitial fibrosis in chronic kidney disease (CKD) allograft patients. However, measuring cortico-medullary values by manually drawing ROIs over cortex and medulla (a gold standard method) is challenging, time-consuming, subjective and requires human training. Moreover, such subjective ROI placement may also affect the work reproducibility. This work proposes a deep learning-based 2D U-Net (RCM U-Net) to auto-segment the renal cortex and medulla of CKD allograft kidney T1 maps. Furthermore, this study presents a correlation of automatically measured ΔT1 values with eGFR and percentage fibrosis in allograft kidneys. Also, the RCM U-Net correlation results are compared with the manual ROI correlation analysis. The RCM U-Net has been trained and validated on T1 maps from 40 patients (n = 2400 augmented images) and tested on 10 patients (n = 600 augmented images). The RCM U-Net segmentation results are compared with the standard VGG16, VGG19, ResNet34 and ResNet50 networks with U-Net as backbone. For clinical validation of the RCM U-Net segmentation, another set of 114 allograft kidneys patient's cortex and medulla were automatically segmented to measure the ΔT1 values and correlated with eGFR and fibrosis. Overall, the RCM U-Net showed 50% less Mean Absolute Error (MAE), 16% better Dice Coefficient (DC) score and 12% improved results in terms of Sensitivity (SE) over conventional CNNs (i.e. VGG16, VGG19, ResNet34 and ResNet50) while the Specificity (SP) and Accuracy (ACC) did not show significant improvement (i.e. 0.5% improvement) for both cortex and medulla segmentation. For eGFR and fibrosis assessment, the proposed RCM U-Net correlation coefficient (r) and R-square (R2) was better correlated (r = -0.2, R2 = 0.041 with p = 0.039) to eGFR than manual ROI values (r = -0.19, R2 = 0.037 with p = 0.051). Similarly, the proposed RCM U-Net had noticeably better r and R2 values (r = 0.25, R2 = 0.065 with p = 0.007) for the correlation with the renal percentage fibrosis than the Manual ROI results (r = 0.3, R2 = 0.091 and p = 0.0013). Using a linear mixed model, T1 was significantly higher in the medulla than in the cortex (p<0.0001) and significantly lower in patients with cellular rejection when compared to both patients without rejection and those with humoral rejection (p<0.001). There was no significant difference in T1 between patients with and without humoral rejection (p = 0.43), nor between the types of T1 measurements (Gold standard manual versus automated RCM U-Net) (p = 0.7). The cortico-medullary area ratio measured by the RCM U-Net was significantly increased in case of cellular rejection by comparison to humoral rejection (1.6 +/- 0.39 versus 0.99 +/- 0.32, p = 0.019). In conclusion, the proposed RCM U-Net provides more robust auto-segmented cortex and medulla than the other standard CNNs allowing a good correlation of ΔT1 with eGFR and fibrosis as reported in literature as well as the differentiation of cellular and humoral transplant rejection. Therefore, the proposed approach is a promising alternative to the gold standard manual ROI method to measure T1 values without user interaction, which helps to reduce analysis time and improves reproducibility.

Shorter versus longer corticosteroid duration and recurrent immune checkpoint inhibitor-associated AKI.

BACKGROUND: Corticosteroids are the mainstay of treatment for immune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI), but the optimal duration of therapy has not been established. Prolonged use of corticosteroids can cause numerous adverse effects and may decrease progression-free survival among patients treated with ICPis. We sought to determine whether a shorter duration of corticosteroids was equally efficacious and safe as compared with a longer duration. METHODS: We used data from an international multicenter cohort study of patients diagnosed with ICPi-AKI from 29 centers across nine countries. We examined whether a shorter duration of corticosteroids (28 days or less) was associated with a higher rate of recurrent ICPi-AKI or death within 30 days following completion of corticosteroid treatment as compared with a longer duration (29-84 days). RESULTS: Of 165 patients treated with corticosteroids, 56 (34%) received a shorter duration of treatment and 109 (66%) received a longer duration. Patients in the shorter versus longer duration groups were similar with respect to baseline and ICPi-AKI characteristics. Five of 56 patients (8.9%) in the shorter duration group and 12 of 109 (11%) in the longer duration group developed recurrent ICPi-AKI or died (p=0.90). Nadir serum creatinine in the first 14, 28, and 90 days following completion of corticosteroid treatment was similar between groups (p=0.40, p=0.56, and p=0.89, respectively). CONCLUSION: A shorter duration of corticosteroids (28 days or less) may be safe for patients with ICPi-AKI. However, the findings may be susceptible to unmeasured confounding and further research from randomized clinical trials is needed.

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.