A specific immune transcriptomic profile discriminates chronic kidney disease patients in predialysis from hemodialyzed patients.

BACKGROUND:Chronic kidney disease (CKD) patients present a complex interaction between the innate and adaptive immune systems, in which immune activation (hypercytokinemia and acute-phase response) and immune suppression (impairment of response to infections and poor development of adaptive immunity) coexist. In this setting, circulating uremic toxins and microinflammation play a critical role. This condition, already present in the last stages of renal damage, seems to be enhanced by the contact of blood with bioincompatible extracorporeal hemodialysis (HD) devices. However, although largely described, the cellular machinery associated to the CKD- and HD-related immune-dysfunction is still poorly defined. Understanding the mechanisms behind this important complication may generate a perspective for improving patients outcome.METHODS:To better recognize the biological bases of the CKD-related immune dysfunction and to identify differences between CKD patients in conservative (CKD) from those in HD treatment, we used an high-throughput strategy (microarray) combined with classical bio-molecular approaches.RESULTS:Immune transcriptomic screening of peripheral blood mononuclear cells (1030 gene probe sets selected by Gene-Ontology) showed that 275 gene probe sets (corresponding to 213 genes) discriminated 9 CKD patients stage III-IV (mean +/- SD of eGFR: 32.27+/-14.7 ml/min) from 17 HD patients (p < 0.0001, FDR = 5%). Seventy-one genes were up- and 142 down-regulated in HD patients. Functional analysis revealed, then, close biological links among the selected genes with a pivotal role of PTX3, IL-15 (up-regulated in HD) and HLA-G (down-regulated in HD). ELISA, performed on an independent testing-group [11 CKD stage III-IV (mean +/- SD of eGFR: 30.26+/-14.89 ml/min) and 13 HD] confirmed that HLA-G, a protein with inhibition effects on several immunological cell lines including natural killers (NK), was down-expressed in HD (p = 0.04). Additionally, in the testing-group, protein levels of CX3CR1, an highly selective chemokine receptor and surface marker for cytotoxic effector lymphocytes, resulted higher expressed in HD compared to CKD (p < 0.01).CONCLUSION:Taken together our results show, for the first time, that HD patients present a different immune-pattern compared to the un-dialyzed CKD patients. Among the selected genes, some of them encode for important biological elements involved in proliferation/activation of cytotoxic effector lymphocytes and in the immune-inflammatory cellular machinery. Additionally, this study reveals new potential diagnostic bio-markers and therapeutic targets

Head to Head Impact of Margin, Ischemia, Complications, Score Versus a Novel Trifecta Score on Oncologic and Functional Outcomes After Robotic-assisted Partial Nephrectomy: Results of a Multicenter Series

BACKGROUND: There is a paucity of data describing the ability of margin, ischemia, complications, score (MIC) and trifecta in predicting long-term outcomes of robotic-assisted partial nephrectomy (RAPN).OBJECTIVE: To compare a novel trifecta (negative margins, no significant complications, and perioperative estimated glomerular filtration rate [eGFR] decrease 6430%) versus standard MIC as predictors of oncologic and functional results in a large series of RAPNs.DESIGN, SETTING, AND PARTICIPANTS: Between 2009 and 2019, a multicenter dataset was queried for patients with nonmetastatic renal masses who underwent RAPN at eight participating institutions.INTERVENTION: RAPN.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: MIC and trifecta achievement were determined for the overall cohort and a subgroup undergoing off-clamp RAPN (ocRAPN), respectively. The overall survival (OS), recurrence-free survival (RFS), and new onset of end-stage renal disease (ESRD; defined as eGFR &lt;30 ml/min) probabilities were assessed by the Kaplan-Meier method. Cox regression analyses were used to identify predictors of OS, RFS, and ESRD. For all analyses, two-sided p &lt; 0.05 was considered significant.RESULTS AND LIMITATIONS: Out of 1807 patients, MIC and trifecta were achieved in 71.1% (n = 1285) and 82.6% (n = 1492), respectively, and once restricted to the ocRAPN cohort, in 95.6% (n = 625) and 81.6% (n = 534), respectively. On Kaplan-Meier analysis, both MIC and trifecta achievement predicted higher OS and lower ESRD probabilities (all p &lt; 0.014), while only trifecta achievement was a predictor of RFS probabilities (p = 0.009). On multivariable Cox regression, MIC did not predict any of the endpoints independently, while trifecta achievement was an independent predictor of higher OS (hazard ratio [HR] 0.4, 95% confidence interval [CI] 0.18-0.86; p = 0.019) and lower ESRD development probabilities (HR 0.32, 95% CI 0.15-0.72; p = 0.005).CONCLUSIONS: Trifecta, initially described as comprehensive measures of perioperative outcomes, needs to stand the test of time. Compared with MIC, the recent trifecta was an independent predictor of clinically significant endpoints, namely, survival and ESRD development probabilities.PATIENT SUMMARY: Our novel trifecta represents a reliable method for estimating survival and development of end-stage renal disease after robotic-assisted partial nephrectomy

Surgical quality, cancer control and functional preservation: Introducing a novel trifecta for robot-assisted partial nephrectomy

BACKGROUND: In order to improve standard reporting of outcomes after partial nephrectomy, different "trifecta" systems have been conceived. The subjective assessment of the included parameters and the unreliability for off-clamp procedures limited their reproducibility; their role in predicting functional and oncologic outcomes has never been assessed. We propose a new trifecta, based on standardized parameters, that summarizes PN outcomes regardless the clamping technique used and predicts main clinical outcomes.METHODS: A retrospective analysis of a multicenter, multi-national dataset of patients with non-metastatic cT1-2 renal masses undergoing Robot-assisted partial nephrectomy was performed. Baseline demographic, clinical, pathologic and perioperative data were collected. Trifecta was defined as the coexistence of negative margins, no Clavien-Dindo &gt;= 3 complications and &lt;= 30% postoperative estimated glomerular filtration rate reduction. Univariable and multivariable regression analyses identified predictors of trifecta achievement. Kaplan-Meier method assessed differences in oncological outcomes between patients achieving trifecta or not. Univariable and multivariable Cox regression analysis identified predictors of newly onset chronic kidney disease stage &gt;= IIIa, recurrence-free and overall survival.RESULTS: Overall, 1492 patients achieved trifecta. This cohort displayed significantly lower incidence of newly onset IIIa-V chronic kidney disease stages (all P&lt;0.001), higher recurrence-free (P=0.009) and overall (P=0.014) survival probabilities. Patients achieving trifecta had a 65% reduced risk of developing newly onset stage IIIb-V Chronic Kidney Disease and a 55% reduced risk of overall mortality. Heterogeneity of surgical technique is a limitation.CONCLUSIONS: This novel reproducible trifecta is based on standardized parameters and is an independent predictor of severe chronic kidney disease development and mortality

Comprehensive long-term assessment of outcomes following robot-assisted partial nephrectomy for renal cell carcinoma: The ROMe?s achievement and its predicting nomogram

BACKGROUND: We proposed a new tool (named ROMe's) to summarize long-term outcomes after partial nephrectomy (PN), identified its predictors and generated a predicting nomogram.METHODS: A retrospective analysis of a multicenter dataset of patients with non-metastatic pT1-3a renal cell carcinoma was performed. Baseline demographic, clinical, pathologic and perioperative data were collected. ROMe's was defined as the concomitant lack of cancer-recurrences, death and newly onset Chronic Kidney Disease (CKD), at long term follow-up. Kaplan-Meier method investigated the predictive role of Trifecta on ROMe's achievement. Univariable and multivariable Cox regression analyses identified its predictors. A nomogram was generated and its accuracy was quantified using concordance index (CI). A calibration plot was obtained with 200 bootstraps resampling to explore nomogram performance at 5 years and decision curve analyses (DCA) assessed the net benefit of the model at 12, 36 and 60 months.RESULTS: We included 927 patients. The rates of ROAfe 's were 82%, 72% and 56% at 1, 3 and 5 years follow-up. At Kaplan-Meier analysis, patients who achieved Trifecta displayed a significantly higher probability of Ratie:s (log rank P&lt;0.001). Young age (OR-0.982; P=0.001). low RENAL score (OR=0.86; P=0.037). high preoperative filtration rate (OR=1.02; P&lt;0.001) and Trifecta achievement (OR=2.03; P).015), were independent predictors of ROMe 's. The nomogram showed a CI of 0.76 at 60 months. The 5-years calibration plot confirmed a good discrimination accuracy (0.74); on DCA, the net benefit of using the model was evident for probabilities &gt;30%.CONCLUSIONS: We conceived a triad to summarize the main long-term oncologic and functional outcomes after PN and generated a predicting nomogram

Robotic partial nephrectomy versus radical nephrectomy in elderly patients with large renal masses

BACKGROUND: Recent evidence suggests that the "oldest old" patients might benefit of partial nephrectomy (PN), but decision-making for this subset of patients is still controversial. Aim of this study is to compare outcomes of robotic partial (RPN) or radical nephrectomy (RRN) for large renal masses in patients older than 65 years.METHODS: We identified 417 &gt;= 65 years old patients who underwent RRN or RPN for cT1b or &gt;= cT2 renal mass at 17 high volume centers. Propensity score match analysis was performed adjusting for age, ASA &gt;= 3, pre-operative eGFR, and clinical tumor size. Predictors of complications, functional and oncological outcomes were evaluated in multivariable logistic and Cox regression models.RESULTS: After propensity score analysis, 73 patients in the RPN group were matched with 74 in the RRN group. R.E.N.A.L. Score (9.6 +/- 1.7 vs. 8.6 +/- 1.7; P&lt;0.001), and high complexity (56 vs. 15%; P=0.001) were higher in the RRN. Estimated blood loss was higher in the RPN group (200 vs. 100 mL; P&lt;0.001). RPN showed higher rate of overall complications (38 vs. 23%; P=0.05), but not major complications (P=0.678). At last follow-up, RPN group showed better functional outcomes both in eGFR (55.4 +/- 22.6 vs. 45.7 +/- 15.7 mL/min; P=0.016) and lower eGFR variation (9.7 vs. 23.0 mL/min; P&lt;0.001). The procedure type was not associated with recurrence free survival (RFS) (HR: 0.47; P=0.152) and overall mortality (OM) (0.22; P=0.084).CONCLUSIONS: RPN in elderly patients with large renal masses provides acceptable surgical, and oncological outcomes allowing better functional preservation relative to RRN. The decision to undergo RPN in this subset of patients should be tailored on a case by case basis