Comorbid Conditions in Kidney Transplantation: Outcome Analysis at King Abdulaziz Medical City

Background: Kidney transplantation is most commonly performed for end-stage renal disease (ESRD) and provides the best chance for a cure. The surgery is shown to be beneficial to a patient’s quality of life after transplantation in multiple studies. But graft failure is a serious consequence that might happen. The term graft failure refers to the failure of a transplanted kidney to function properly. There are various reasons why this can happen, such as rejection, infection, or medication complications. Methods: A retrospective cohort study of comorbid conditions in patients who underwent renal transplantation at King Abdulaziz Medical City (KAMC) between 2016 and 2022. Data were collected by chart review using the BestCare system. The data collected included patients’ demographics, comorbidities, calculated Charlson Comorbidity Index (CCI), surgery-related data, laboratory data, and the outcome of transplantation. The categorical data were presented using percentages and frequencies, while the numerical data were presented as mean and standard deviation. The Chi-square test was used for inferential statistics to find the association between categorical variables. Results: A total of 669 patients were included in the current study. Of these, 422 (63.1%) were men, and the mean age was 44 years. The incidence of graft failure within one year at KAMC was found to be 1.2% (eight cases). Regarding the CCI and its association with graft failure within one year, 37 (5.5%) patients had a myocardial infarction (MI) and 17 (2.5%) had congestive heart failure; however, no patients with MI or congestive heart failure experienced graft failure, and no significant association was found between MI or congestive heart failure and graft failure (p-value = 1.000 for both). A total of 417 (62.3%) patients had no or diet-controlled diabetes, 122 (18.2%) had uncomplicated diabetes mellitus (DM), and 130 (19.4%) had end-organ damage. DM and graft failure were not significantly associated (p-value = 1.000). A total of 286 (42.8%) patients had ESRD of unknown etiology, 109 (16.3%) patients had ESRD caused by diabetic nephropathy, and 100 (14.9%) had ESRD resulting from hypertension, apart from other causes. Conclusion: Most patients were found to have ESRD of unknown etiology and the most frequently reported known risk factor for ESRD and subsequent transplantation was found to be diabetic nephropathy, followed by hypertension.


Introduction
Kidney transplantation is the definitive treatment for end-stage renal disease (ESRD) and is considered the best option for patients on dialysis [1][2][3]. There are two approaches to kidney transplant, namely laparoscopy and open surgery [1]. Multiple studies have reported the benefits of this surgery on patients' quality of life after transplantation [1,4]. However, comorbidities such as diabetes and heart failure can influence the outcome of the surgery. Researchers reported that an increased number of comorbidities both before and after transplantation increased the chance of death [5]. In another study, renal failure and hypertension (HTN) were found to be the most common etiologies of ESRD [6].
Patients who reach stage 4 of chronic kidney disease (CKD), defined as a glomerular filtration rate (GFR) of less than 30 mL/min/1.73 m 2 , should seek medical help and be informed regarding kidney failure and possible treatments, including transplantation [7]. Comorbidities affect perioperative and long-term outcomes as well [5].
Multiple indices are used to evaluate the effect of comorbidities on ESRD patients [8], including the Index of transplant patients [5]. A study found that CCI is the most sensitive in discriminating features, with a concordance C statistic of 0.71 [8]. Moreover, CCI is the most used score to measure comorbidity [12].
Even though many studies have reported the effect of multiple comorbidities on patients with ESRD, research on their impact on kidney transplant outcomes is insufficient. As the number of studies assessing the effects of comorbid conditions on kidney transplant patients is limited, we decided to evaluate the comorbidities in patients who underwent kidney transplant at King Abdulaziz Medical City (KAMC), Riyadh, Saudi Arabia.

Materials And Methods
This retrospective cohort study was conducted at KAMC, Riyadh, Saudi Arabia. We included all patients who underwent kidney transplantation between 2016 and 2022. The sampling technique utilized for the study was non-probability consecutive sampling, including all patients who met the inclusion criteria. Data were collected by the research team members by chart review using the BestCare system at KAMC. The data collected included patients' data, comorbidities, surgery details, donor characteristics, outcome variables, and grouping variables. Comorbidities include myocardial infarction (MI), congestive heart failure, peripheral vascular disease, cerebrovascular disease, dementia, chronic obstructive pulmonary disease (COPD), connective tissue disease, peptic ulcer disease (PUD), liver disease, diabetes mellitus (DM), solid tumor, depression, arthritis, asthma, and hypertension. We also collected HCV antibody results for patients. Also estimated GFR (eGFR) and creatinine were gathered to compare values before and after transplantation. After the transplant values were collected on day 0, day 1, day 7, day 30, day 60, day 90, and day 180.
The CCI was used to assess different comorbidities. CCI is a commonly used method for predicting mortality risk in those who have chronic health conditions [5]. The CCI has been used in a wide range of clinical settings. It has been shown to be helpful as a tool for predicting outcomes in a variety of patient populations, including those with cancer, heart disease, and CKD [9][10][11].
For data management and analysis, SPSS version 23 (IBM Corporation, Armonk, NY, USA) was used. Mean and standard deviation were used for quantitative variables, while qualitative variables were expressed as percentages and frequencies. The normality of the data was checked using the K-S test. The chi-square test, t-test, and nonparametric tests were used to compare qualitative and quantitative variables between groups. A p-value of 0.05 was considered significant.
Ethical approval was obtained from the Institutional Review Board to access the medical records. All the information was accessed only by the principal investigator and co-investigators of the study. The researchers ensured subjects' privacy and confidentiality by not collecting any identifiers such as medical record number (MRN), names, and identification. All data were securely stored within KAMC premises, and access to the research data was restricted to the research team members.

Results
A total of 669 patients were included in the current study. Their mean age was 44.4 ± 17 years (1-86 years). The mean age of those with graft failure was 43.6 ± 19.9 years. The mean body mass index (BMI) was 27.8 ± 5.7 (10.7-46). The mean BMI of the patients with graft failure was 27.0 ± 7.5, and that of patients with no graft failure was 27.8 ± 5.7. No statistically significant association was found between BMI and graft failure by Student's t-test. Four hundred and twenty-two (63.1%) patients were men and 247 (36.9%) were women. Six (75%) patients with graft failure were men and the remaining two (25%) were women. Half of the patients (335 (50.1%)) were married, 210 (31.4%) were single, 13 (1.9%) were widowed, 11 (1.6%) were divorced, and the status of 100 (14.9%) was unknown (  The incidence of graft failure within one year at KAMC was 1.2% (eight cases) ( Figure 1).

FIGURE 1: Incidence of graft failure within one year at King Abdulaziz Medical City
Regarding the CCI and its association with graft failure within one year, 37 (5.5%) patients had MI and 17 (2.5%) had congestive heart failure; no patients with MI or congestive heart failure had graft failure, and no significant association found between MI or congestive heart failure and graft failure (p-value = 1.000 for both). Peripheral vascular disease (PVD) was found in 16 (2.4%) patients, of whom one (12.5%) experienced graft failure; PVD and graft failure were not found to be significantly associated (p-value = 0.177). None of the patients with cerebrovascular accident (CVA; 11 (1.6%) patients), chronic obstructive pulmonary disease (COPD; four (0.6%) patients), connective tissue disease (18 (2.7%) patients), and peptic ulcer disease (PUD; seven (1%) patients) were found to have graft failure; thus, graft failure was not found to be significantly associated with CVA, COPD, connective tissue disease, and PUD (p-value = 1.000 for all parameters).   The mean serum creatinine level pre-transplantation was 799 ± 300 micromoles per liter (μmol/L), decreasing to 137 ±148 μmol/L at day 7 post-transplantation and reaching 104 ± 74 μmol/L at day 180 posttransplantation. Regarding eGFR, the mean eGFR was 7.3 ± 3.9 mL/min/1.73 m², reaching an average of 69.2 ± 30.2 mL/min/1.73 m² at day 7 post-transplantation and up to 74.9 ± 21.5 mL/min/1.73 m² at day 180 post-transplantation. The mean blood urea nitrogen (BUN) pre-transplantation was 20.5 ± 41.2 mg/dL; at day 7 post-transplantation, the average BUN was 9.2 ± 8.4 mg/dL, decreasing to 6.3 ± 4.6 mg/dL at day 180 post-transplantation ( Table 3).

Discussion
Comorbid conditions affect the outcome of kidney transplantation through a variety of factors. Analyzing comorbid conditions among patients undergoing kidney transplantation may result in a better understanding of etiology and consequences. It may also result in improvements in the treatment strategy, prognosis, and long-term outcomes of kidney transplantation [5,13]. This study aimed at identifying the patient-related risk factors of graft failure following kidney transplant at KAMC, Riyadh, Saudi Arabia.
The mean age of the patients was found to be 44.4 years. Nearly two-thirds (63.1%) of the patients were men. The incidence of graft failure within one year at KAMC was found to be 1.2% (eight cases). This incidence was lower than that reported in a congruent study by Hart et al., in which an incidence of at least 3% was mentioned [14].
Concerning the CCI and its association with graft failure within one year, about 5.5% of the patients had MI and 2.5% had congestive heart failure, but none of these patients had graft failure and no significant association was found between MI or congestive heart failure and graft failure. This result was contradictory to the findings of a study by Morales et al., who found an association between ischemic heart disease and graft failure among the study patients [15]. More than half (62.3%) of the patients had no or diet-controlled diabetes, less than one-fifth (18.2%) of the patients had uncomplicated DM, and 19.4% had end-organ damage. More than half (62%) of those with graft failure did not have DM, one-quarter (25%) had uncomplicated DM, and one (12.5%) had DM with end-organ damage. Thus, DM and graft failure were not significantly associated. However, this result was not in agreement with a parallel study conducted by Taber et al., in which pre-existing DM was found to be significantly associated with graft failure [16]. No significant association was found between cancer and graft failure, consistent with the findings of a study by Kim et al., in which no significant association was noted between cancer and graft failure [17]. More than two-thirds (77.9%) of the patients were hypertensive, and the majority (75%) of those with graft failure were hypertensive, but no significant association was noted between hypertension and graft failure. Similar results were obtained by Weir et al., who also reported a prevalence of hypertension of between 50% and 80% among kidney transplant recipients [18]. 9% of the patients, followed by IgA nephropathy (4.2%) and others. Analogous findings were noted in a study by Hashmi et al., in which diabetic nephropathy was the most frequently reported cause of ESRD [22]. Another study by Banaga et al. found that the most commonly reported etiological cause of ESRD was hypertension [23]. These minor differences could be attributed to different factors, including the study sample and the distribution of diseases.
The limitations of the current study were the fact that the data were gathered from one center, which limited the generalizability of the outcomes. This topic requires more exploration with a larger sample size and should include multiple centers in the region to reach an accurate estimate of the related comorbidities found in patients undergoing renal transplantation.

Conclusions
Most of the patients were found to have ESRD of unknown etiology and the most frequently reported known risk factor for ESRD and subsequent transplantation was found to be diabetic nephropathy, followed by hypertension. The incidence of graft failure within one year was about 1% lower than that reported in most parallel studies. All patients with graft failure were found to have multiple etiological risk factors.
More effort should be made toward the health education of the general population about the risk factors for ESRD, as knowledge of these etiological factors could result in a reduced incidence of ESRD and hence, the need for transplantation. This could be achieved by encouraging various educational programs, including community events and campaigns, and the distribution of knowledge through social media.