Introduction

Chronic kidney disease (CKD) is a pathology that affects 10% of the global population with high impact and mortality¹. Living kidney transplant is the best therapeutic option for patients with CKD due to higher graft survival, lower cold ischemia time, and decreased risk of delayed graft function (DGF). The incidence of DGF in recipients with a cadaveric donor is 21.8% versus 3.5% in recipients with living donors².

Some of the general medical aspects of laparoscopic living donor nephrectomy (LDN) have been evaluated in different publications^3,5. For example, the use of mannitol during the living donor laparoscopic nephrectomy is associated with increasing the renal blood flow, decreasing endothelial swelling, and mitigation of free oxygen radicals^3,6

Mannitol (C₆H₈(OH)₆) is an alcohol that releases prostaglandins leading to renal vasodilatation and increased diuresis. The literature reported that these effects contribute to the protection of renal injury and the preservation of kidney function⁷. In kidney transplantation, the living donor kidney is susceptible to ischemic reperfusion insult while clamping the donor's renal artery and flushing it with a cooled preservation solution. The intraoperative mannitol in LDN results in the mitigation of this ischemic injury and the reduction of tubular cell swelling to prevent acute tubular necrosis (ATN) and DGF in kidney transplant recipients⁶. However, some studies assessing mannitol have contradictory findings^4,8.

DGF is determined as an indication for dialysis in the 1^st week after kidney transplantation and is associated with post-transplant oliguria, a higher risk of acute rejection, and lower graft survival⁹. The DFG increases the risk of acute rejection by 20-40%¹⁰. Some studies published that the administration of mannitol declined the incidence of acute rejection¹¹.

In Latin America, there are no studies with evidence that allow extrapolating data about the administration of mannitol during LDN and its benefits in kidney transplant. This research aimed to evaluate the administration of mannitol during the hand-assisted LDN (HALDN) and the incidence of DGF. Furthermore, this study aimed to achieve two specific objectives. First, the clinical and sociodemographic characteristics of donors and transplant recipients will be described within the timeframe of January 2015 to December 2019. Second, we will conduct a comparative analysis of post-operative outcomes, focusing on different follow-up times, specifically between recipients who received mannitol and those who did not receive mannitol. Our hypothesis was to examine the differences following the administration of mannitol since according to multiple scientific studies, the administration of mannitol has been demonstrated to reduce the occurrence of acute rejection. In addition, we are interested in determining whether these differences are statistically significant.

Methodology

Results

Demographics and baseline characteristics

A total of 367 recipients and their donors were evaluated during the study period. Among those, 129 (35%) had the administration of mannitol. The mean age of donors was 37.9 ± 11.1 years. Approximately half of donors were female (50.1°%). The recipients had a mean age of 36.6 ± 14.1 years old, and most of the patients were male compared to the gender proportion (58% versus 42%). There were no significant differences in the bivariate analysis corresponding to age or gender either in LKD or recipients with or without administration of mannitol. Table 1 depicted demographics and baseline characteristics of LKD and recipients with or with-out mannitol use.

Table 1 Demographics and baseline characteristics in LKD and recipients using or without mannitol 

SD: standard deviation; LKD: living kidney donors.

Clinical outcomes in recipients

The incidence of DGF was 5.9% in the group without mannitol compared to 6.2% with mannitol (p = 0.99). The urinary volume (diuresis) in the first 24 h after the kidney transplant was de 9740 ± 4720 ml without mannitol versus 9860 ± 5490 ml with mannitol. No significant differences were found in diuresis and mortality between both groups (p = 0.97 and p = 0.69, respectively). The incidence of acute rejection had a trend in the difference between the groups (without mannitol 12.2% versus mannitol 4.7%) but was still not significant in the bivariate analysis (p= 0.06) (Table 2).

Table 2 Clinical outcomes in the recipients without or with mannitol 

DGF: delayed graft function; ml: mililiters; SD: standard deviation.

Serum creatinine after kidney transplant

The serum creatinine mean was 1.59 ± 1.28 mg/dl without mannitol versus 1.54 ± 0.925 mg/dl with mannitol (p = 0.92) 1 month after kidney transplantation. At 3 months of follow-up, serum creatinine mean was 1.58 ± 1.61 mg/dl without mannitol compared to 1.35 ± 0.6 mg/dl with mannitol (p = 0.34) (Fig. 1).

Figure 1 Follow-up of serum creatinine in living kidney donor recipients without or with mannitol. A: 1-month post-transplant. B: 3 months post-transplant. 

Discussion

This is the first study in Colombia that sheds light on the role of mannitol administration, considering clinical and sociodemographic variables, as well as post-operative outcomes in our population. Mannitol is one of the main osmotic and diuretic medications used in kidney transplant¹⁵. The intraoperative administration of mannitol during the HALDN is associated with the prevention of DGF⁶ and acute kidney injury⁸ in LKD recipients. To the best of our knowledge, there are no publications about the assessment of the effect of mannitol in HALDN or kidney transplantation in Latin America. This study described the impact of intraoperative use of mannitol during HALDN in LKD and the incidence of DGF in kidney transplantation.

In our study, the demographic characteristics showed a gender distribution in LKD and recipients akin to the previous publications¹⁶.

At first glance, the main clinical outcomes analyzed for the recipients in this study without or with the use of mannitol were as follows: kidney function, the incidence of DGF, urinary volume after 24 h of a kidney transplant, the incidence of acute rejection, and mortality at 3 months of follow-up.

In the literature, the DGF is correlated with a higher risk of multiple post-transplant complications and less graft survival in kidney transplant recipients^9,17.

In our findings, the incidence of DGF did not have a significant difference within the comparison groups similar to a study of 413 LKD with laparoscopic nephrectomy¹⁸. Andrews et al.⁶ evaluated varying degrees of ATN by performing an optical coherence tomography in LKD comparing mannitol infusion for 15 min versus 30 min in the renal tubules. They found a higher incidence of ATN in the group with mannitol infusion for 30 min than with mannitol infusion for 15 min. In kidney transplantation, a meta-analysis that included two studies with 569 LKD recipients described that the use of intraoperative mannitol decreased the incidence of DGF from 30-55% to 14-21% in the mannitol groups (p = 0.02)⁸.

Esfahani et al.⁴ published a random clinical trial with 60 LKD with or without intraoperative mannitol evaluating the effect of mannitol on diuresis and serum creatinine concentration. The outcome did not show significant differences between mannitol and placebo in a way similar to our results. On the contrary, the meta-analysis mentioned above found in a study with kidney transplant patients that those who received mannitol had higher diuresis than the control group. In parallel, serum creatinine showed heterogeneous results in this meta-analysis⁸.

On the other hand, the reduction in the incidence of acute rejection at 1 year of follow-up in the Williams et al.¹⁸ results was not significant with the administration of mannitol in LKD equivalent to our findings. In addition, a total of 90 kidney recipients were evaluated to determine the incidence of acute rejection with or without mannitol in kidney transplantation. In this report, there was no significant association between a lower risk of acute rejection and the use of mannitol⁸. Finally, there were no publications that evaluated mortality and intraoperative mannitol use in LKD or kidney transplant recipients.

The study has several limitations that should be acknowledged. First, selection bias may exist due to the lack of standardized criteria for participant inclusion, potentially affecting the generalizability of the findings. Second, subgroup comparisons might be challenging due to the heterogeneity within the subgroups. Third, the use of retrospective measurement introduces the possibility of measurement bias and data quality issues. Inaccuracies or missing information may affect the reliability of the results. Finally, confounding bias could be present as unmeasured factors associated with both the exposure and outcome may influence the observed associations. Given that this study was conducted in a single healthcare center, the ability to extrapolate the findings is considered limited, and further studies are needed to gain a better understanding of the studied phenomenon. Consequently, the study exhibits low external validity and highlights the need for additional research.

The study has several strengths that enhance its value and credibility. First, despite its retrospective design, it provides valuable insights and allows for the examination of associations and trends over time. Second, the comprehensive data collection approach utilized in the study, including data retrieval from a reliable database, ensures a robust dataset for analysis. Third, the longitudinal analysis enables the assessment of outcomes and exposures over multiple time points, enhancing the understanding of temporal relationships. In addition, the inclusion of relevant variables, such as kidney function, provides valuable clinical information and allows for an in-depth analysis of relevant outcomes. Finally, the study's retrospective design reflects real-world clinical practices, offering the potential for real-world application and insights into the effectiveness of interventions in routine healthcare settings. These strengths collectively contribute to the study's overall significance and strengthen the validity and applicability of its findings.

Conclusión

The use of intraoperative mannitol in LKD during HALDN did not significantly impact the incidence of DGF in kidney transplant recipients. Lower episodes of acute rejection were documented in patients with mannitol administration but were not statistically significant.