Abstract

Abstract Background and Aims Onconephrology is a recently developed discipline aimed at diagnosing and managing renal disease in cancer patients. Few data are available regarding clinical and histological aspects concerning the whole population referred to an onconephrology clinic. Our study aimed to describe the clinical and histopathological characteristics of these patients and to evaluate indices of renal function recovery, renal damage progression, and mortality; a specific aim was to determine in our cohort the prevalence of acute kidney injury (AKI), chronic kidney disease (CKD) and acute kidney disease (AKD) which included all patients meeting KDIGO criteria for AKD but not for AKI. Secondary aims were the analysis of the immunotherapy subgroup and to determine the rate of immune-related adverse events (IRAEs). Method In this prospective observational study, we consecutively enrolled 84 patients for the clinical analysis and 10 patients in two centres for the histopathological study. Clinical assessment in the former group were performed at the first visit (T0), 1 month (T1), 3 months (T2) and 1 year (T3) and compared with a pre-determined baseline. Complete oncological and nephrological assessments were performed. For kidney biopsies, histopathological findings were expressed with quantitative and semi-quantitative parameters. Outcomes were: AKI or AKD complete or partial recovery of renal function (respectively defined as: return to baseline; sCr reduction ≥ 0.3 mg/dl or ≥ 25% or improvement to a lower stage of AKI); a composite of events (MAKE) based on CKD development or progression or death (only at T3). Results Our population was predominantly elderly, hypertensive, in metastatic phase (64.2%), M>F; other factors associated with increased cardiovascular risk were: previous AKI (18.8%), diagnosis of type 2 diabetes (25.9%), history of former/current smoker (55.4% and 19.6%), hyperuricemia (mean uric acid 7 mg/dl), previous/current cisplatin treatment (15.5% and 3.6%). The estimated prevalence in our cohort was: AKI 30.1%; CKD 27.7%; AKI on CKD 25.7%; AKD 9.6%. Regarding AKI, 68.4% were stage 1; for CKD, most patients were stage 3A and 3B (28.2% and 46.2%). More than 1/3 of the patients presented with suspended anticancer treatment; complete therapy resume rates were modest. Complete and partial AKI recovery rates at T2 were both ∼33%. Renal function was fully recovered in 50% of the AKD patients. During the follow-up, a new episode of AKI was observed in 15.5% of the patients, more frequently in the first 3 months. Patients receiving immunotherapy showed worse renal function (sCr 2.02 vs 1.51 mg/dl at T0, p<.001) and higher mortality (4 vs 0, p<.05); patients with IRAEs (25.8%) presented more frequently with discontinued therapy (Table 1). Of 36 patients with data available at 1 year, 21 (58.3%) presented the outcome MAKE; 11 patients died, 4 in the first three months. No nephrological conditions were found to predict MAKEs; presence of metastasis and female sex were the only predictors with Cox regression. Patients who underwent renal biopsy showed marked heterogeneity in the diagnoses (4 Membranous nephropathy, 1 drug-induced podocyte damage, 1 extracapillary GN after SARSCoV2 vaccination, 1 Light/Heavy Chain Deposition Disease, 1 Chronic Tubulointerstitial Nephritis, 1 sclerohyalinosis, 1 nonspecific); histopathological data was unremarkable. Conclusion AKI and CKD occur frequently in the onconephrological population. These patients are susceptible to new AKI episodes. The absence of AKI recovery and anticancer therapy withdrawal are common, potentially holding negative prognostic value. Particular attention should be paid to patients undergoing immunotherapy, especially when associated with IRAE. A larger number of patients is needed to estimate the impact of nephrological factors in the extended follow-up.

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