Predictive Value of Hematologic Inflammatory Indices for Early Dialysis Requirement After Kidney Transplantation

Introduction

Kidney transplantation remains the gold standard treatment for patients with end-stage renal disease, providing superior long-term survival and quality of life, compared with dialysis therapy [1]. Despite advances in surgical techniques, immunosuppressive strategies, and donor selection, delayed graft function (DGF) – commonly defined as the need for dialysis within the first week after transplantation – continues to affect 20% to 50% of deceased-donor transplants and is strongly associated with graft loss and mortality [2,3].

Established risk factors for DGF include donor-related characteristics, such as age, type, and cold ischemia time, recipient comorbidities, such as diabetes and hypertension, and perioperative factors related to ischemia-reperfusion injury [3–5]. In recent years, attention has increasingly focused on systemic inflammatory markers derived from routine complete blood count (CBC) parameters, as these indices are inexpensive, readily available, and reproducible in clinical practice [6–8].

The systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and pan-immune inflammation value (PIV) have demonstrated prognostic utility in several clinical conditions characterized by immune activation and inflammatory burden [6,9]. Although inflammation plays a central role in transplantation biology, the relevance of these composite hematologic indices in kidney transplantation, and specifically in the prediction of DGF, has not been well established. Preliminary data suggest that heightened systemic inflammation may contribute to ischemia–reperfusion injury and early allograft dysfunction, whereas donor age and ischemia-related factors remain the most consistently validated predictors of DGF [10–13].

To date, evidence regarding the combined use of CBC-derived inflammatory indices for predicting early dialysis requirement after kidney transplantation remains limited. Therefore, this study was designed as a small-scale, retrospective, exploratory analysis to evaluate the association between SII, SIRI, and PIV and early dialysis requirement following kidney transplantation. The primary aim was to generate preliminary, hypothesis-forming evidence rather than to establish definitive predictive conclusions.

Material and Methods

STUDY POPULATION AND DATA COLLECTION:

The data of 33 adult recipients who underwent cadaveric kidney transplantation were retrospectively analyzed. Patients were classified into 2 groups based on the requirement for dialysis within the first postoperative week: dialysis group (n=14) and non-dialysis group (n=19). Donor-related variables, including age and sex, recipient demographic characteristics, and pretransplant laboratory parameters were extracted from institutional medical records.

All patients underwent the same postoperative laboratory monitoring. Daily CBC values and electrolyte, blood urea nitrogen, and creatinine levels were obtained during morning rounds. Arterial blood gas tests were ordered when clinically necessary. These evaluations are part of our routine postoperative protocol.

In our center, postoperative dialysis in kidney transplant recipients is not triggered by oliguria alone, as reduced urine output is common in the early period of DGF. Dialysis is initiated when patients develop clinically significant volume overload, refractory hyperkalemia (≥6.0 mmol/L or electrocardiogram changes), severe metabolic acidosis (pH <7.1–7.2), rapidly rising nitrogenous waste levels with clinical symptoms, or other uremic complications. These criteria reflect standard transplant nephrology practice and were applied consistently by the transplant nephrology team in our study population. Serum creatinine was measured daily during the first postoperative week. Recipient age and sex and donor age were recorded.

ETHICS APPROVAL:

The study was conducted in accordance with the Declaration of Helsinki and approved by the Health Sciences Research Ethics Committee of the university (approval code: 2025-04/150; date of approval: April 24, 2025). Patient consent was waived due to the retrospective design of the study and the use of fully anonymized data, as approved by the Ethics Committee.

HEMATOLOGIC INFLAMMATORY INDICES AND BIOLOGICAL RATIONALE:

Systemic inflammatory indices were calculated using pretransplant CBC parameters. These indices were selected because they reflect different components of the host inflammatory and immune response and have been investigated in various inflammatory and ischemia-related conditions, including transplantation-related outcomes.

In addition to composite indices, classical hematologic ratios, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR), were also evaluated. These ratios have been widely used as surrogate markers of systemic inflammation in clinical practice due to their simplicity and accessibility. However, they primarily represent isolated inflammatory pathways and may not fully capture the complexity of immune–inflammatory interactions in the transplant setting.

The SII integrates neutrophil, lymphocyte, and platelet counts, reflecting the balance between pro-inflammatory activation and immune regulation. The SIRI incorporates neutrophils, monocytes, and lymphocytes, capturing both innate immune activation and monocyte-mediated inflammatory signaling. The PIV combines neutrophil, monocyte, platelet, and lymphocyte counts to provide a broader representation of systemic inflammatory burden.

From a biological perspective, neutrophils and monocytes play central roles in ischemia–reperfusion injury and early inflammatory cascades following transplantation, whereas lymphocyte counts may reflect immune competence and regulatory balance. Platelets contribute to microvascular inflammation and endothelial dysfunction, processes implicated in early graft injury. Although these indices are not established predictors of DGF, they may offer insight into systemic inflammatory states that could influence early posttransplant outcomes.

INDEX CALCULATIONS:

Hematological inflammatory indices were calculated as follows:

STATISTICAL ANALYSIS:

Continuous variables were expressed as mean±standard deviation or median (interquartile range), as appropriate. Group comparisons were performed using the Mann-Whitney U test or t test for continuous variables and the chi-square or Fisher exact test for categorical variables.

Logistic regression analysis was performed solely as an exploratory association analysis, aiming to examine potential relationships between clinical variables, inflammatory indices, and early dialysis requirement. The regression analysis was not intended for predictive model development, risk stratification, or individual-level outcome prediction. To improve the robustness of estimates given the limited sample size, bootstrap resampling was applied.

Given the small cohort size and the exploratory nature of the study, formal predictive modeling techniques, including receiver operating characteristic curve analysis, were not performed, as such approaches require larger sample sizes to ensure model stability, discrimination accuracy, and avoidance of overfitting.

All statistical analyses were conducted using SPSS version 25.0 (IBM Corp, Armonk, NY, USA), and a P value <0.05 was considered statistically significant.

Results

In this study, a total of 33 recipients were included; 14 (42.4%) required dialysis while 19 (57.6%) did not. Demographic and baseline characteristics of the patients are shown in Table 1. Recipient age did not differ significantly (median 48.5 vs 51 years, P=0.927). Donor age was higher in the dialysis group, but the difference was not statistically significant (P=0.372).

Among the evaluated variables, monocyte count showed a preliminary signal in univariate analysis; however, this association did not persist in multivariable modeling and should therefore be interpreted as exploratory rather than predictive. In addition, hematological indices and postoperative creatinine are summarized in Table 2. Monocyte count was significantly lower among dialysis patients (P=0.032). Other indices (SII, SIRI, PIV) and postoperative creatinine levels did not differ significantly. The relationship between monocyte count and SII is shown in Figure 1, while associations with SIRI and PIV are presented in Figures 2 and 3, respectively. Logistic regression analysis showed no independent predictive value of SII, SIRI, or PIV for postoperative dialysis requirement (Table 3).

Early postoperative dialysis requirement was evaluated by effect size analysis comparing patients with and without the need for dialysis. As shown in Table 4, most clinical variables and classical inflammatory ratios, including NLR, PLR, and MLR, demonstrated very small effect sizes, indicating limited discriminative ability between the 2 groups. In contrast, monocyte count showed a moderate effect size, representing the most pronounced difference between groups, while SIRI and PIV exhibited small-to-moderate effect sizes. These findings suggest that, although conventional inflammatory ratios were largely uninformative, selected monocyte-based and composite inflammatory indices may provide exploratory signals in distinguishing early dialysis requirement.

Discussion

LIMITATIONS AND CLINICAL IMPLICATIONS:

Several limitations of this study should be acknowledged. First, the small sample size inherently limits statistical power and increases the risk of type II error, restricting the ability to detect modest associations between inflammatory indices and DGF. Second, the single-center, retrospective design may introduce selection bias and limits the external validity of the findings. In addition, key variables related to ischemia–reperfusion, including detailed warm and cold ischemia times, donor hemodynamic instability, and perioperative management factors, were not comprehensively available and therefore could not be incorporated into the analysis. These parameters are well-established modifiers of early graft outcomes and may have influenced inflammatory responses.

Given these constraints, the findings of the present study should not be considered generalizable to broader transplant populations or different clinical settings. The observed associations – particularly those related to monocyte counts – should be interpreted cautiously and viewed as hypothesis-generating rather than confirmatory.

Importantly, the results of this exploratory analysis should not influence or guide clinical decision-making regarding early dialysis initiation, graft monitoring, or immunosuppressive management. At present, established clinical predictors and standardized posttransplant surveillance strategies remain the cornerstone of patient care. The potential clinical relevance of hematologic inflammatory indices can only be clarified through larger, multicenter, prospectively designed studies incorporating standardized sampling windows and comprehensive ischemia–reperfusion and immunologic risk profiling.

Conclusıons

This study is the first investigation to collectively assess monocyte count, donor age, and composite hematologic inflammatory indices (SII, SIRI, and PIV) for predicting early dialysis requirement after kidney transplantation. Monocyte count appeared to show a potential signal, and this observation should be regarded as exploratory, while donor age demonstrated consistent trends. However, the SII, SIRI, and PIV were not independently predictive in this cohort.

In this small exploratory cohort, the SII, SIRI, and PIV did not demonstrate predictive value for early dialysis requirement after kidney transplantation. Although monocyte count showed an initial signal in univariate comparisons, it did not retain significance in multivariable analysis and should be interpreted as preliminary. These findings should be viewed as hypothesis-generating rather than conclusive, and larger multicenter studies are needed to determine whether specific hematologic parameters meaningfully contribute to early risk stratification in DGF.

These preliminary findings underscore the need for larger multicenter validation studies integrating CBC-derived markers with novel biomarkers to enhance early postoperative risk stratification in clinical practice.