The Systemic Immune-Inflammation Index Predicts Clinical Outcomes in Kidney Transplant Recipients

Abstract

Background: Outcomes after kidney transplantation (KTx) remain limited by delayed graft function (DGF) and acute rejection. Non-invasive biomarkers may help identify patients at increased risk for these events. We examined the association between the systemic immune-inflammation index (SII), a novel inflammatory biomarker, and outcomes after KTx and evaluated its ability to predict post-transplant prognosis. Patients and Methods: Adult patients who underwent primary KTx at our institution between 2016-2019 were included. SII was calculated from pre-transplant complete blood counts as the ratio of the neutrophil count to the lymphocyte count multiplied by the platelet count. The cutoff between high and low SII was determined by maximizing the area under the curve. Multivariable logistic and Cox regression were used to identify factors associated with DGF and patient, rejectionfree, and graft survival respectively. Results: Overall, 378 KTx recipients were included; 224 (59.3%) had high SII. On unadjusted analysis, high SII was associated with reduced odds of DGF, and improved patient and rejection-free survival. After adjustment, high SII was independently associated with improved patient survival alone. Multivariable models incorporating SII performed well for the prediction of DGF (c-statistic=0.755) and patient survival (c-statistic=0.786), though rejection-free survival was more difficult to predict (c-statistic=0.635). Conclusion: SII demonstrated limited utility as an independent predictor of outcomes after KTx. However, in combination with other clinically relevant parameters, SII is a useful predictor of post-KTx prognosis. Validation of this novel inflammatory biomarker in a multi-institutional study is needed to further elucidate its practical applications in transplantation.Kidney transplantation is the standard of care for patients with end-stage renal disease (ESRD), offering significant health and quality of life benefits compared to remaining on dialysis (1). Despite a steady increase in the number of kidney transplants performed in the US, delayed graft function (DGF) and acute rejection (AR) remain prevalent, hindering optimization of patient and allograft survival (2, 3). In the past decade, research on the transplant community has given increasing attention to the development and identification of novel biomarkers that allow for rapid, safe, non-invasive, and accurate detection of immunological injury to the kidney allograft (4, 5). Of particular interest are prognostic and predictive biomarkers that can identify patients at increased risk for allograft injury, including DGF and AR (6, 7).The neutrophil-to-lymphocyte ratio (NLR) and platelet-tolymphocyte ratio (PLR) are two biomarkers that provide an indication of inflammatory status and have been shown to be strong predictors of negative prognosis in a variety of conditions including cancer (8, 9), cardiovascular disease (10, 11), ESRD (12), and, more recently, kidney and liver transplantation (13)(14)(15)(16)(17)(18). Despite a growing body o...

Systemic Immune-Inflammation Index Is Associated With Increased Urinary Albumin Excretion: A Population-Based Study

“…Another retrospective study found the association between SII and increased TNM stage and poor prognosis of renal cell carcinoma patients undergoing radical nephrectomy ( 34 ). However, there have also been several studies that revealed the limitations of SII ( 35 , 36 ). A study that enrolled 378 patients who underwent primary kidney transplantation (KTx) in America reported that SII demonstrated limited utility as an independent predictor of outcomes after KTx, while in combination with other clinically relevant parameters, SII could be a useful predictor of prognosis after KTx ( 35 ).…”

“…However, there have also been several studies that revealed the limitations of SII ( 35 , 36 ). A study that enrolled 378 patients who underwent primary kidney transplantation (KTx) in America reported that SII demonstrated limited utility as an independent predictor of outcomes after KTx, while in combination with other clinically relevant parameters, SII could be a useful predictor of prognosis after KTx ( 35 ). Another meta-analysis with 2,693 subjects included suggested that elevated SII indicated poor prognosis in patients with urinary system cancers.…”

Prognostic role of CRP‐independent inflammatory patterns in patients undergoing primary percutaneous interventions

“…[1][2][3][4][5] SII index is the most tested and validated inflammation-based index since it provides an integrative evaluation of both immune and inflammatory activation, and its prognostic role has been documented in several groups of patients. [15][16][17][18][19][20] The role of SII in atherosclerotic disease and ischemic cardiomyopathy has been assessed by previous studies, [6][7][8] and a single SII Index determination appeared to significantly improve risk stratification of major cardiovascular events than traditional risk factors in CAD patients requiring PCI. 6 Off note, according to our analysis, patients with a higher SII at admission have a more severe CAD compared to those admitted with a low SII.…”

“…Atherosclerotic plaque formation involves a large number of cells, such as macrophages, T cells and several mediators of inflammation, 28 defining complex crosstalk between adaptive and innate immunity from the earliest stage of lesion development to ultimate clinical complications 1–5 . SII index is the most tested and validated inflammation‐based index since it provides an integrative evaluation of both immune and inflammatory activation, and its prognostic role has been documented in several groups of patients 15–20 . The role of SII in atherosclerotic disease and ischemic cardiomyopathy has been assessed by previous studies, 6–8 and a single SII Index determination appeared to significantly improve risk stratification of major cardiovascular events than traditional risk factors in CAD patients requiring PCI 6 .…”

“…At the present time, the most robust and studied index of inflammation is the systemic immune‐inflammatory index (SII), which is an inexpensive, routinely available, scientifically endorsed index, which considers patients' inflammatory and immune status simultaneously. The prognostic value of a single SII determination has been documented in various medical scenarios, including CAD 15–20 . To our knowledge, no previous study assessed potential changes over time of SII and the prognostic impact of in‐hospital SII patterns in ST‐segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (pPCI).…”