Background Reservoir‐wave approach is an alternative model of arterial hemodynamics based on the assumption that measured arterial pressure is composed of volume‐related (reservoir pressure) and wave‐related components (excess pressure). However, the clinical utility of reservoir‐wave approach remains debatable. Methods and Results In a single‐center cohort of 260 dialysis patients, we examined whether carotid and radial reservoir‐wave parameters were associated with all‐cause and cardiovascular mortality. Central pulse pressure and augmentation index at 75 beats per minute were determined by radial arterial tonometry through generalized transfer function. Carotid and radial reservoir‐wave analysis were performed to determine reservoir pressure and excess pressure integral. After a median follow‐up of 32 months, 171 (66%) deaths and 88 (34%) cardiovascular deaths occurred. In Cox regression analysis, carotid excess pressure integral was associated with a hazard ratio of 1.33 (95% CI , 1.14–1.54; P <0.001 per 1 SD) for all‐cause and 1.45 (95% CI : 1.18–1.75; P <0.001 per 1 SD) for cardiovascular mortality. After adjustments for age, heart rate, sex, clinical characteristics and carotid‐femoral pulse wave velocity, carotid excess pressure integral was consistently associated with increased risk of all‐cause (hazard ratio per 1 SD, 1.30; 95% CI : 1.08–1.54; P =0.004) and cardiovascular mortality (hazard ratio per 1 SD, 1.31; 95% CI : 1.04–1.63; P =0.019). Conversely, there were no significant associations between radial reservoir‐wave parameters, central pulse pressure, augmentation index at 75 beats per minute, pressure forward, pressure backward and reflection magnitude, and all‐cause or cardiovascular mortality after adjustment for comorbidities. Conclusions These observations support the clinical value of reservoir‐wave approach parameters of large central elastic vessels in end‐stage renal disease.

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Immune checkpoint inhibitors (ICI) are now widely used in the treatment of many cancers, and currently represent the standard of care for multiple malignancies. These agents enhance the T cell immune response to target cancer tissues, and have demonstrated considerable benefits for cancer outcomes. However, despite these improved outcomes, there are important kidney immune-related adverse events (iRAEs) associated with ICI. Acute tubulo-interstitial nephritis, remains the most frequent kidney iRAE, however glomerular lesions and electrolytes disturbances are increasingly being recognized and reported. In this review, we summarize clinical features and identified risk factors for kidney iRAEs, and discuss current understanding of pathophysiologic mechanisms. We highlight the evidence basis for guideline-recommended management of ICI-related kidney injury as well as gaps in current knowledge. We advocate for judicious use of kidney biopsy to identify ICI-associated kidney injury, and early use of corticosteroid treatment where appropriate. Selected patients may also be candidates for re-challenge with ICI therapy after a kidney iRAE, in view of current data on recurrent rates of kidney injury. Risk of benefits of re-challenge must be considered on an individual considering patient preferences and prognosis. Lastly, we review current knowledge of ICI use in the setting of patients with end-stage kidney disease (ESKD), including kidney transplant recipients and those receiving dialysis, which suggest that these patients should not be summarily excluded from the potential benefits of these cancer therapies.

Background: Cisplatin-based chemotherapy regimens remain the optimal first-line treatment for patients with metastatic urothelial carcinoma (mUC). However, many patients are deemed cisplatin-ineligible, predominantly due to reduced kidney function. Other treatment options include split-dose cisplatin, carboplatin and non-platinum-based regimens. We compared the incidence of acute kidney injury (AKI) and cancer outcomes within 3 chemotherapy regimens. Methods: We conducted a single-center retrospective study of mUC patients who received first-line chemotherapy from 2005-2019. We compared standard gemcitabine-cisplatin (gem-cis) to two alternative regimens: 1) gemcitabine-cisplatin split dose regimen (split) with cisplatin divided over days 1 and 8; and 2) combination of gemcitabine-carboplatin or single-agent gemcitabine (gem/gem-carbo). The primary outcome was KDIGO-defined AKI. Secondary outcomes included overall survival (OS) and progression free survival (PFS). Results: We identified 183 patients (98 gem-cis, 32 split and 53 gem/gem-carbo). Median baseline eGFR in the gem/cis group was 78 mL/min/1.73m2 (IQR: 66-91); in the split group 64 (48-77); and in the gem/gem-carbo 45 (33-57). There was no significant association between regimen type and incidence of AKI when adjusted for age, ECOG, baseline eGFR, hypertension, diabetes and visceral disease. The adjusted hazard ratios (aHR) were 1.31 (95%CI: 0.61-2.78; p=0.49) and 0.98 (95%CI:0.46-2.07; p=0.95) for split and gem/gem-carbo groups respectively versus gem-cis. Split and gem/gem-carbo regimens were associated with higher mortality and progressive disease relative to gem-cis with an aHR of 1.54 (95%CI: 1.02-2.33; p=0.04) and 1.96 (95%CI: 1.31-2.95; p<0.01) respectively. Median PFS was 8.1 (IQR: 4.6-14.8), 6.1 (4.1-9.3) and 4.4 (2.3-8.6) months in the gem-cis, split and gem/gem-carbo groups. Conclusion s: There was no significant difference in the incidence of AKI between the three regimens studied. However, standard gem-cis was associated with improved cancer outcomes. Novel regimens and kidney protective strategies are needed for mUC patients with kidney disease.