Perioperative outcomes and phase-specific intraoperative glycemic management in simultaneous pancreas-kidney transplantation: A single-center case series

Abstract

BACKGROUND

Simultaneous pancreas-kidney transplantation (SPKT), an established treatment for patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) and end-stage renal disease (ESRD), provides metabolic stabilization and improved survival. Although perioperative glycemic control is crucial for graft viability; intraoperative management remains understudied, and standardized phase-specific protocols are lacking.

AIM

To explore the feasibility, safety, and immediate outcomes of a six-phase intraoperative glycemic control algorithm for SPKT.

METHODS

This retrospective case series included 11 patients with T1DM or T2DM and ESRD who underwent SPKT at a quaternary care center between January 2024 and May 2025. All patients were managed using a six-phase institutional glycemic control algorithm that maintains intraoperative blood glucose levels within predefined targets. Data on clinical, metabolic, surgical variables; complications; and early outcomes were collected.

RESULTS

In most cases, intraoperative blood glucose levels were maintained within target ranges; however variations were observed [range: 63-453 mg/dL (3.5-25.2 mmol/L)]. No severe hypoglycemia or ketoacidosis occurred. During the first 24 postoperative hours, seven patients (63.6%) achieved euglycemia without exogenous insulin, whereas two required transient insulin therapy. Six patients (54.5%) had postoperative complications, including thrombotic (n = 4), infectious (n = 2), and reperfusion syndrome (n = 1). One patient experienced more than one event. All events were successfully managed, without graft loss, acute rejection, or in-hospital mortality.

CONCLUSION

The phase-specific intraoperative glycemic protocol for SPKT is feasible and safe. However, prospective studies with larger cohorts are warranted to assess its long-term impact on graft survival and patient outcomes.

Key Words: Simultaneous pancreas-kidney transplantation; Intraoperative glycemic control; Perioperative management; Pancreatic graft function; Metabolic stability

Core Tip: This retrospective study introduces a structured six-phase intraoperative algorithm for metabolic control during simultaneous pancreas-kidney transplantation, defining phase-specific glycemic targets and key decision points from induction to reperfusion. Implemented in 11 consecutive cases, the algorithm proved feasible and safe, maintaining intraoperative glucose within target ranges and avoiding severe hypoglycemia. Most recipients achieved early postoperative euglycemia without exogenous insulin. Visual analysis suggested greater glycemic variability among patients with postoperative complications, underscoring the relevance of intraoperative metabolic stability for graft viability and early recovery.

INTRODUCTION

Simultaneous pancreas-kidney transplantation (SPKT) is an established treatment for patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), and end-stage renal disease (ESRD). Compared with other renal replacement strategies, it offers superior graft and patient survival related benefits, along with improved metabolic control and quality of life. Pancreatic grafts restore endogenous insulin production and promote metabolic stability[1,2]. However, perioperative glucose management remains a critical but understudied SPKT component.

Intraoperative anesthetic and metabolic management is essential for graft viability. A dynamic, multidisciplinary glycemic control strategy facilitates graft adaptation and minimizes the risks of hyperglycemia and hypoglycemia, both of which are associated with poor outcomes[3,4]. However, evidence on standardized intraoperative glycemic control protocols remains limited. Therefore, a structured, adaptable algorithm is warranted to optimize intraoperative glycemic control.

This study describes the implementation and early outcomes of a six-phase institutional algorithm for intraoperative glycemic control in patients undergoing SPKT. We aimed to evaluate the feasibility, safety, and short-term clinical impact of this institutional protocol.

MATERIALS AND METHODS

Study design and population

This retrospective observational case series included 11 patients diagnosed with T1DM, T2DM, and ESRD who underwent SPKT at a single quaternary referral center in Bogotá, Colombia, between January 2024 and May 2025. No exclusion criteria were applied.

The Institutional Ethics Committee approved the study. It adhered to the principles of the Declaration of Helsinki and the Declaration of Taipei on ethical considerations regarding health databases. Datasets were anonymized before analysis following institutional policies and guidelines, including the removal of direct identifiers, the assignment of a unique study code to each record, and the restriction of analysis to match the study’s objectives.

Perioperative management based on to the institutional intraoperative glycemic control protocol

All patients were managed using a standardized intraoperative glycemic control protocol implemented institutionally to facilitate pancreatic graft adaptation and prevent perioperative hypoglycemia and hyperglycemia. The protocol was structured into six distinct phases, each with defined glycemic targets and therapeutic actions; preoperative, induction, pre-clamping, clamping, reperfusion, and post-reperfusion (Supplementary material). The components of each phase are as follows:

Preoperative phase: A comprehensive metabolic evaluation, including blood glucose, amylase, and lipase levels, was performed at admission. The insulin pump was withdrawn, and basal and bolus insulin requirements were calculated based on the patient’s needs over the previous 24 hours using the “1800 rule”, which estimates the reduction in glucose levels (mg/dL) by one unit of rapid-acting insulin.

Induction phase: Initial monitoring included arterial blood gas and baseline glycemia. Immunosuppression and antibiotic prophylaxis were initiated following the transplant checklist. Hemodynamic management aimed to maintain a central venous pressure between 12 cmH₂O and 14 cmH₂O, preferably using albumin and mannitol, while minimizing the excessive use of crystalloids and colloids. Systolic blood pressure was maintained between 120 mmHg and 130 mmHg, with a mean arterial pressure of approximately 70 mmHg. To ensure a smooth transition to the new glycemic control protocol, an insulin infusion was prepared and initiated 1 hour before discontinuing the subcutaneous insulin pump.

Pre-clamping phase: A target glycemic range of 140-180 mg/dL (7.8-10 mmol/L) was established, with measurements taken every 15 minutes. If blood glucose dropped below 70 mg/dL (3.9 mmol/L) or hypoglycemia occurred, a bolus of 50-100 mL comprising 10% dextrose was administered, and glucose levels were monitored until the target range was achieved. For glucose levels > 180 mg/dL (10 mmol/L), an insulin infusion protocol was applied. Heparin (70 U/kg) was administered before vascular clamping to prevent thromboembolic events. The target of 140-180 mg/dL (7.8-10.0 mmol/L) was chosen based on perioperative guideline recommendations for major surgery and transplant settings, aiming to prevent hyperglycemia-induced endothelial dysfunction, oxidative stress, and microthrombotic risk, while minimizing hypoglycemia in the pre-reperfusion phase when graft perfusion is still adapting[5].

Clamping phase: During this phase, blood glucose was monitored every 15 minutes. The insulin infusion was paused for 20 minutes before declamping to prevent abrupt drops in glucose levels. A 10% dextrose infusion (30-50 mL/hour) was initiated to stabilize glucose concentrations. Following clamping, the glycemic target was set near 180 mg/dL (10 mmol/L) to mitigate hypoglycemia risk. This strategy maintains glucose availability in the ischemic graft, supporting ATP production and cellular metabolism while minimizing sudden hypoglycemia during the critical reperfusion phase[6].

Reperfusion phase: Blood glucose and arterial blood gas were measured 10 minutes after reperfusion. If glycemia decreased compared with pre-clamp levels, the 10% dextrose infusion was adjusted to maintain glucose between 80 mg/dL and 130 mg/dL (4.4 mmol/L and 7.2 mmol/L), with monitoring every 15 minutes until stabilization. If glucose remained stable or increased > 150 mg/dL (8.3 mmol/L), dextrose infusion was discontinued, and insulin was reintroduced. Amylase and lipase levels were measured to rule out early pancreatic complications. A target of 80-130 mg/dL (4.4-7.2 mmol/L) for tightness indicates return to near-normal blood sugar levels once the transplanted organ begins functioning properly, reducing damage caused by high blood sugar through oxidative and inflammatory processes, and limiting damage to small blood vessels in the vulnerable state that occurs after reperfusion[7].

Post-reperfusion phase: The aim was to maintain glycemia between 80 mg/dL and 130 mg/dL (4.4-7.2 mmol/L). Monitoring was performed every 15-30 minutes, with gradual adjustments to dextrose or insulin infusions to avoid fluctuations. If glucose levels remained stable, monitoring intervals were extended to every 30 minutes; otherwise, monitoring was intensified (every 15 minutes), with reduction in dextrose infusion and electrolyte monitoring. After graft insulin secretion stabilizes, near-physiologic glycemia maintains metabolic homeostasis, limits infection risk, promotes wound healing, and preserves graft β-cell function. However, sustained hypoglycemia defined as < 70 mg/dL (< 3.9 mmol/L) or persistent hyperglycemia [> 150 mg/dL (> 8.3 mmol/L)] may impair these outcomes[8,9].

Data collection and outcome variables

Clinical, metabolic, and intraoperative data were retrospectively collected from the institutional electronic medical records. The primary outcome was the achievement of intraoperative glycemic control within the target ranges. The secondary outcomes included insulin infusion requirements, intraoperative glycemic variability (minimum-maximum range), need for postoperative insulin, immediate graft function indicators, and postoperative complications.

Demographic (age, sex, and body mass index), clinical (history of hypertension, insulin pump use, chronic kidney disease stage, and dialysis modality), and metabolic (baseline blood glucose and C-peptide levels) variables were collected. Intraoperative variables included blood glucose levels during the induction and postreperfusion phases, intraoperative glycemic variability (minimum-maximum range), and warm ischemia time for both grafts.

Postoperative data included peak levels of amylase, lipase, and creatinine, glucose levels, and insulin requirements within 24 hours of intensive care unit admission. Complications, such as thrombotic events, infections, pancreatic reperfusion syndrome, and acute rejection, were recorded until hospital discharge.

Statistical analysis

Exploratory subgroup analyses were performed to compare T1DM and T2DM recipients. Owing to the small sample size, the categorical variables were compared using Fisher’s exact test, and the results are presented for exploratory purposes.

Intraoperative glycemic variability, defined as the difference between the highest and lowest intraoperative glucose levels, was associated with postoperative complications and was evaluated visually using box plot visualization. Given the limited sample size, the analysis was exploratory and was not powered for definitive conclusions.

RESULTS

During the study period, 11 patients underwent SPKT. Their demographic and clinical characteristics are summarized in Table 1. The mean age of the patients was 38 years (range: 25-48), and six of the patients (54.5%) were men. Nine individuals with T1DM and two with T2DM were involved. All patients had ESRD, six were on dialysis at the time of transplantation, and two patients were using preoperative insulin pumps.

Table 1 Demographic and preoperative clinical characteristics of patients undergoing simultaneous pancreas-kidney transplantation.

Variables	Age (years)	Sex	BMI (kg/m2)	Type of diabetes	Use of insulin pump	ESRD stage	Dialysis modality	C-peptide (ng/mL)
Case 1	42	M	20.13	T1DM	Yes	IV	Pre-D	3.16
Case 2	37	F	21.18	T1DM	Yes	V	PD	2.64
Case 3	25	F	19.74	T1DM	No	IV	Pre-D	< 0.03
Case 4	35	M	24.46	T1DM	No	V	PD	< 0.1
Case 5	36	F	20.7	T1DM	No	IV	Pre-D	4.06
Case 6	41	M	26.87	T1DM	No	V	Pre-D	NA
Case 7	38	M	25.64	T1DM	No	V	HD	NA
Case 8	43	M	25.06	T2DM	No	V	HD	NA
Case 9	48	F	26.73	T2DM	No	V	HD	NA
Case 10	40	F	23.64	T1DM	No	V	HD	15.4
Case 11	39	M	19.79	T1DM	No	V	HD	NA

All patients had a diagnosis of diabetes mellitus and chronic kidney disease in advanced stages (IV-V); six out of seven were receiving dialysis therapy at the time of transplantation. BMI: Body mass index; M: Male; F: Female; HD: Hemodialysis; PD: Peritoneal dialysis; Pre-D: Predialysis; NA: Not available; T1DM: Type 1 diabetes mellitus.

Cold ischemia time ranged from 6 hours 6 minutes to 9 hours 44 minutes for the pancreas and from 6 hours 11 minutes to 12 hours for the kidney. The warm ischemia time ranged from 29 minutes to 42 minutes for the pancreas and from 30 minutes to 48 minutes for the kidney (data available for 10 patients).

The intraoperative glycemic control protocol was systematically applied in all SPKT procedures. Although phase-specific targets were prespecified, intraoperative glucose ranges varied in several cases [case 5: 99-453 mg/dL (5.5-25.2 mmol/L)], underscoring the need to report time-in-range and variability metrics. The median glycemia during anesthetic induction was 124 mg/dL (6.9 mmol/L) [range: 88-254 mg/dL (4.9-14.1 mmol/L)], whereas the post- reperfusion median was 128 mg/dL (7.1 mmol/L) [range: 75-203 mg/dL (4.2-11.3 mmol/L)] as shown in Table 2.

Table 2 Intraoperative variables, n (%).

Variables	Induction glycemia mg/dL (mmol/L)	Pancreas cold ischemia time	Pancreas warm ischemia time	Renal cold ischemia time	Renal warm ischemia time	Intraoperative glycemic variability mg/dL (mmol/L)	Post reperfusion glycemia mg/dL (mmol/L)
Case 1	172 (9.6)	6 hours 56 minutes	42 minutes	8 hours	30 minutes	110-210 (6.1-6.7)	116 (6.4)
Case 2	143 (7.9)	8 hours 39 minutes	29 minutes	11 hours 40 minutes	30 minutes	68-274 (3.8-15.2)	203 (11.3)
Case 3	97 (5.4)	9 hours 19 minutes	29 minutes	11 hours 49 minutes	NA	63-275 (3.5-15.3)	75 (4.2)
Case 4	93 (5.2)	7 hours 55 minutes	NA	10 hours 50 minutes	45 minutes	93-198 (5.2-11)	99 (5.5)
Case 5	101 (5.6)	6 hours 16 minutes	40 minutes	8 hours 34 minutes	45 minutes	99-453 (5.5-25-2)	109 (6.1)
Case 6	100 (5.6)	8 hours 18 minutes	30 minutes	11 hours 5 minutes	40 minutes	88-290 (4.9-16.1)	120 (6.7)
Case 7	88 (4.9)	8 hours 11 minutes	35 minutes	11 hours 30 minutes	45 minutes	108-232 (6-12.9)	108 (6.0)
Case 8	112 (6.2)	9 hours 44 minutes	40 minutes	8 hours 18 minutes	40 minutes	73-201 (4.1-11.2)	146 (8.1)
Case 9	94 (5.2)	9 hours 30 minutes	30 minutes	6 hours 11 minutes	48 minutes	94-294 (5.2-16.3)	190 (10.6)
Case 10	114 (6.3)	6 hours 13 minutes	35 minutes	8 hours	35 minutes	166-332 (9.2-17.9)	83 (4.6)
Case 11	254 (14.1)	7 hours 14 minutes	40 minutes	10 hours 36 minutes	40 minutes	83-234 (4.6-13)	166 (9.2)

Cold and warm ischemia times for each graft are shown, expressed in hours and minutes. NA: Not available.

The intraoperative glycemic variability among the 11 cases ranged from 63 mg/dL to 453 mg/dL (3.5 mmol/L to 25.2 mmol/L). A box plot was generated to visualize the distribution of variability between patients with and without postoperative thrombotic or infectious complications (Figure 1).

Figure 1 Box plot illustrating intraoperative glycemic variability among simultaneous pancreas-kidney transplant recipients with and without postoperative thrombotic and infectious complications. A: Thrombotic complications; B: Infectious complications.

Seven patients (63.3%) maintained euglycemia during the first 24 postoperative hours without requiring exogenous insulin. Two patients (18.2%) required insulin therapy for transient hyperglycemia. Mild hypoglycemia, defined as < 70 mg/dL (< 3.9 mmol/L), was observed in two cases (18.2%), both of which resolved without complications, and severe hypoglycemia or ketoacidosis was absent (Table 3).

Table 3 Immediate postoperative metabolic evolution.

Variables	Peak POP glycemia (md/dL, first 24 hours)	Hypoglycemia	POP insulin requirement	Amylase (U/L)	Lipase (U/L)	Creatinine (mg/dL)
Case 1	140	Yes	No	174	94.7	0.8
Case 2	121	No	No	101	2163	2.5
Case 3	164	No	No	387	58	3.8
Case 4	449	No	Yes	95	16.8	11.3
Case 5	130	No	Yes	223	138.2	3.5
Case 6	134	Yes	No	135	35	1.4
Case 7	123	No	No	52	82.8	5.2
Case 8	300	No	Yes	422	22.5	11.4
Case 9	104	No	Yes	148	91.8	6.3
Case 10	64	No	No	184	502	3.9
Case 11	108	No	No	124	372	5.4

Postoperative glycemia: Peak of blood glucose values during the first 24 hours. Hypoglycemia: Any recorded value < 70 mg/dL (< 3.9 mmol/L). Amylase and lipase: Peak values during the first 24 hours postoperatively. Creatinine: Highest value during the first 24 hours postoperatively. POP: Postoperative.

Serum amylase and lipase levels remained within acceptable postoperative ranges in most patients. One case presented with an isolated lipase elevation of 2163 U/L and an amylase level of 101 U/L, which was interpreted as a transient manifestation of reperfusion syndrome without clinical evidence of acute pancreatitis. Regarding renal function, no patient developed acute rejection during hospitalization. However, 6 of 11 patients (54.5%) had serum creatinine values ≥ 5 mg/dL (442 μmol/L) within the first 24 hours, and only 3 (27.3%) achieved levels < 2 mg/dL (176.8 μmol/L).

Postoperative complications were observed in 6/11 patients (54.5%), with thrombotic events being common (n = 4). Infectious complications occurred in two patients: One with candidiasis and one with Klebsiella oxytoca-induced peritonitis. Additionally, two hypoglycemia cases and an isolated case of reperfusion syndrome were recorded. All complications were promptly identified and managed without graft loss or in-hospital mortality. No patient experienced acute graft rejection during hospitalization, and all were discharged with preserved graft viability.

The average length of hospital stay was 15.4 days (median: 12; range: 7-43). Most patients were discharged within 2 weeks, indicating adequate early recovery. Prolonged hospitalization occurred in two cases: One related to pancreatic reperfusion syndrome and the other due to pancreatitis complicated by a duodenojejunal anastomotic leak requiring reintervention.

At 30-day follow-up, all recipients maintained functioning pancreas and kidney grafts, with no early graft failure or major postoperative complications.

Exploratory subgroup analysis

Given the potential clinical and metabolic differences between diabetes phenotypes, an exploratory comparison was performed between T1DM (n = 9) and T2DM (n = 2). No differences were observed in postoperative infection (22.2% vs 0%) or thrombosis (33.3% vs 50%) between the two groups.

DISCUSSION

Intraoperative glucose management in SPKT is a critical determinant of early outcomes because metabolic control directly influences graft recovery, viability, and complications[10]. Evidence from liver and kidney transplantation shows that stricter glucose targets reduce infections and improve graft function, supporting the rationale for structured metabolic control in dual-organ procedures[11,12]. Although evidence in SPKT remains scarce, this series provides one of the first structured evaluations of intraoperative glycemic control in this context. Within this framework, the current series aligns with recent research addressing two key determinants of SPKT outcomes: (1) Perioperative blood glucose control; and (2) The immunothrombosis process, which plays a critical role in early graft thrombosis and recovery.

The clinical relevance of intraoperative glycemic patterns in SPKT is highlighted by increasingly available evidence. Lebedev et al[13] demonstrated that maintaining glucose within approximately 90-180 mg/dL (5-10 mmol/L) by the end of surgery was associated with improved graft function, reduced vascular and infectious complications, and shorter recovery in a cohort of 85 SPKT recipients. Although this series is substantially smaller and exploratory, our intraoperative management strategy achieved comparable target ranges in most cases, preserved early graft function and had zero mortality. These findings support the emerging premise that structured intraoperative glycemic control may play a key role in early outcomes, while recognizing that definitive evidence requires prospective comparative studies.

Finally, perioperative continuous glucose monitoring is an attractive tool for detecting and mitigating real-time dysglycemia and glucose variability. A recent scoping review showed high technical reliability but heterogeneous accuracy in the operating room, with limited clinical efficacy evidence[14,15]. Nevertheless, the potential to reduce rapid excursions is compelling and warrants evaluation for SPKT[14,15].

Emerging technologies, including fully automated insulin-dextrose closed-loop systems, offer the prospect of real-time glucose correction; however, remain largely experimental in SPKT[7,16]. In our practice, we rely on intermittent glucose measurements to guide clinical decision-making in the absence of these tools. Therefore, our six-phase manual algorithm provides a practical, physiologically grounded framework that ensures glycemic stability during critical intraoperative transitions, serving as a bridge toward future precision-medicine approaches.

Together, these findings contextualize the metabolic challenges unique to SPKT. In this 11-patient case series, a phase-specific intraoperative glycemic algorithm was feasible and safe, with no severe hypoglycemia or ketoacidosis. However, intraoperative glucose variability remained substantial, with ranges as wide as 99-453 mg/dL (5.5-25.2 mmol/L) in individual cases. Such variability may have contributed to early complications, as suggested in previous reports[8,9].

To further explore this relationship, a box plot was generated to visualize intraoperative glycemic variability in patients with and without postoperative thrombotic and infectious complications (Figure 1). Although exploratory, the visual comparison suggested a tendency toward wider glycemic fluctuations among recipients who experienced these events. This observation is consistent with recent reports emphasizing the association between glycemic instability and adverse outcomes in SPKT and other transplant settings[3,8]. These findings highlight the relevance of glycemic variability as an underrecognized marker of metabolic control and warrant confirmation in larger prospective studies.

In most patients, early postoperative euglycemia without exogenous insulin suggests early pancreatic graft function[14,15]. Although most published protocols do not specify phase-adapted glycemic targets, timing-specific interventions may have further supported graft adaptation during reperfusion[17-20].

Despite overall adequate glycemic control, two patients experienced hypoglycemic events. This may reflect the β-cell phenomenon, wherein sudden restoration of pancreatic endocrine activity after reperfusion leads to transient insulin hypersecretion[18-21]. Recognition of this mechanism underscores the need for continuous monitoring and adaptive protocols to prevent clinically significant hypoglycemia.

Six patients (54.5%) had postoperative complications, mainly thrombotic and infectious. Notably, both infection-related complications were observed in patients with significant dysglycemia, aligning with reports linking perioperative metabolic instability to a higher infectious risk[11,12,21,22]. One case of reperfusion syndrome resolved spontaneously, which is consistent with findings from previous studies on SPKT[23]. Renal recovery was delayed, consistent with expectation for this population[24,25], emphasizing the complexity of dual-organ adaptation. Early multidisciplinary management enabled the resolution of adverse events and the preservation of grafts, consistent with previous findings[25].

This study provides a detailed account of a structured intraoperative glycemic control protocol in SPKT, a field with limited standardized approaches. The main strengths of this case series include the implementation of a reproducible six-phase institutional algorithm and the systematic collection of perioperative variables, which enable comprehensive clinical characterization.

This study has some limitations. The small sample size (n = 11), the absence of a control group, the single-center design, and the restriction to in-hospital follow-up limit external validity and preclude the assessment of long-term outcomes. Nevertheless, it provides a valuable descriptive contribution by systematically reporting a reproducible intraoperative glycemic control algorithm for SPKT and may serve as a basis for prospective multicenter studies.

Another important limitation of this study is the small number of patients with T2DM. Although an exploratory subgroup analysis based on diabetes phenotype was performed, the comparison is substantially underpowered and should be interpreted with caution. Therefore, these results are hypothesis-generating rather than conclusive, warranting validation in larger cohorts, where phenotype-specific metabolic responses may be more accurately characterized.

We recommend implementing the following strategies: (1) Protocols that limit peaks above 150-180 mg/dL (> 8.3-10 mmol/L) and reduce glucose variability, such as insulin infusions with time-in-range goals; (2) Thromboprophylaxis and monitoring tailored to the donor characteristics, technical factors, and inflammation-complement markers; and (3) Targeted continuous glucose monitoring, with capillary or arterial verification for critical decisions, until reliable evidence on SPKT is available. These physiologically grounded adjustments have the potential to reduce technical failure and improve early graft outcomes.

CONCLUSION

The early adequate function of pancreatic and renal grafts observed in this series may support the value of targeted metabolic control strategies during the perioperative period of SPKT. Despite the postoperative complications, the absence of mortality and successful management of adverse events highlight the importance of a multidisciplinary approach. The observed thrombotic and infectious complications suggest that perioperative metabolic variability could contribute to adverse outcomes. This reinforces the need for strict intraoperative glucose control and a protocolized approach in such complex procedures. Consequently, future studies with larger cohorts are warranted to evaluate its impact on long-term graft survival and patient outcomes.