**3. Indications for pancreas transplantation**

important topics regarding pancreas transplantation, including indication and patient evalu-

Diabetes is a spectrum of diseases characterized by a disorder in glucose metabolism leading to persistent hyperglycemia, with clinical manifestations varying according to disease etiol-

Type 1 diabetes mellitus (DM) is an autoimmune disorder characterized by the generation of autoantibodies against β cells and the development of a localized inflammatory response with consequent islet destruction. Current models suggest that the disease progresses as a relapsing-remitting disease, with a nonlinear β cell mass loss at each relapse as a result of the imbalance between β cell proliferation and destruction, eventually leading to persistent hyperglycemia. At diagnosis, these patients may present with nearly normal serum concentrations of insulin and C-peptide but with a rapid decrease in the following 8–12 weeks.

Several autoantibodies have been described in patients with type 1 diabetes—antibodies to insulin (IAA), glutamic acid decarboxylase (GAD), Zinc transporter 8 antibodies (ZnT8A), and protein tyrosine phosphatase-like protein IA2 (IA2 or ICA512). The risk for overt diabetes better correlates with the number of autoantibodies present rather than the titter of a single antibody [1]. Type 1 diabetes usually presents at a young age (6 months to 25 years old), and there is a geographical variation, with a tendency toward an increased incidence in developed countries—, as

**Etiology Prevalence** 

Autoimmune (some genetic associations); β cell mass loss; Insulin deficiency

Insulin resistence; β cell exaustion

Reduced insulin production or secretion; higher glucose sensor threashold

**(of total diabetes)** **Obesity**

5–10% Uncommon

80–90% Common

2% Incidence similar to

general population

ation, surgical techniques, immunosuppression protocols, and outcomes.

**2. Epidemiology and pathophysiology of diabetes**

260 Organ Donation and Transplantation - Current Status and Future Challenges

ogy (**Table 1**).

**Diabetes Age presentation Clinical** 

young adulthood

Type 2 Adulthood Variable; from

pubertal except glucokinase and neonatal diabetes

**Table 1.** Etiology and clinical presentation of diabetes.

Type 1 6 months to

Monogenic Often post

**presentation**

rapid

Most often acute,

slow, mild (often insidious) to severe

Variable (may be incidental in glucokinase)

Transplant of β cells is a treatment alternative to insulin-dependent diabetic patients with the objective of reestablishing glucose homeostasis without the need for exogenous insulin.

Both pancreas and islet transplantation are currently used in clinical practice as β cell mass transplant techniques. Islet transplantation is still limited to nearly experimental protocols, though a few centers have introduced them into their clinical practice. According to the Collaborative Islet Transplant Registry (CITR), 1927 procedures have been performed worldwide from 2004 to 2013 [5]. Though conceptually attractive, its high cost of isolation and the sub-optimal insulin-independency results (when compared to whole-organ transplantation) have halted its clinical application.

Pancreas transplantation is indicated in patients with insulin deficiency and end-stage renal disease (ESRD) in those or with brittle diabetes and normal renal function. Indications should take into account disease-related characteristics:

**a.** Type of DM: pancreas transplantation is indicated in patients with type 1 DM, selected patients with type 2 DM, as well as to those with diabetes secondary other etiologies(acute and chronic pancreatitis, cystic fibrosis, and trauma). According to data obtained from the last US Pancreas Transplant Registry (OPTN/SRTR), pancreas transplantation in type 2 diabetes is increasing worldwide [6], representing up to 8% of all transplants performed in the US [7]. The most recent report demonstrates a 3-year graft survival of 83.3%. Indication in these patients is not consensual. At our center, we indicate in patients <50 years, body mass index (BMI) <30, at least 5 years of insulin therapy, C-Peptide <3.0 ng/mL, and daily insulin at <0.5 U/kg/day. Larger cohorts, standardized inclusion criteria, and long-term results are warranted.


and a kidney transplant followed by a pancreas transplant alone should be considered. Similarly, centers with long pancreas waiting lists (>2 years) should evaluate the risk of maintaining the patient on dialysis or use a pancrease after kidney transplantation (PAK) approach, since mortality on the waiting list can be up to 42% at 4 years in this popula-

**Figure 1.** Hospital Clinic's flowchart for performing pancreas graft biopsy. Ultrasound-guided survaillance biopsies are performed at 3 weeks and 12 months post-transplant. Biopsies are also performed if clinicaly indicated, and are followed

Pancreas Transplantation

263

http://dx.doi.org/10.5772/intechopen.76667

This type of transplant is considered for those patients who are candidates for a kidney and pancreas transplant and who have an available living kidney donor or where waiting-list vintage is significantly shorter to kidney when compared to pancreas transplant. The major benefit of PAK is reducing, or avoiding, time on dialysis while waiting for pancreas transplantation. Restoration of kidney function may reduce uremia-induced anticoagulation and possibly reduce bleeding during surgical complications. This approach implies, nonetheless, two different surgical procedures. Moreover, up-to-date results are somewhat poorer for patients who have undergone PAK transplant, with an inferior pancreas graft survival and higher acute rejection incidence [10]. The decision to perform a PAK (live donor kidney) or an SPK will depend fundamentally on the characteristics of the living donor (age, HLA compatibility), the possibility of performing a preventive transplant, the expected time on the waiting list, as well as the patient's expectations

tion (**Figure 1**) [9].

(**Table 2**).

*3.1.2. Pancreas after kidney transplantation (PAK)*

by a survaillance biopsy 4 weeks after the treatment of rejection.

#### **3.1. Indications according to transplant modality**

Pancreas transplantation can be performed individually or simultaneously with kidney transplantation in patients with ESRD. Each type of transplant has certain characteristics that must be highlighted.

#### *3.1.1. Simultaneous transplantation of pancreas and kidney (SPK)*

Simultaneous kidney-pancreas transplantation (SPK) is the most common type of pancreas transplant, representing over 98% of all pancreas transplants performed in the US [7]. It is currently the best treatment alternative to patients with ESRD who are candidates to a kidney transplant. In addition to the demographic and clinical parameters previously described, immunological and waiting-list vintage should be considered when proposing a patient to an SPK. The presence of HLA alloantibodies reduces the probability of finding a suitable donor and increases waiting-list vintage. In moderate (cPRA > 50%) and highly sensitized (cPRA > 90%) patients, an individual approach is advised

**Figure 1.** Hospital Clinic's flowchart for performing pancreas graft biopsy. Ultrasound-guided survaillance biopsies are performed at 3 weeks and 12 months post-transplant. Biopsies are also performed if clinicaly indicated, and are followed by a survaillance biopsy 4 weeks after the treatment of rejection.

and a kidney transplant followed by a pancreas transplant alone should be considered. Similarly, centers with long pancreas waiting lists (>2 years) should evaluate the risk of maintaining the patient on dialysis or use a pancrease after kidney transplantation (PAK) approach, since mortality on the waiting list can be up to 42% at 4 years in this population (**Figure 1**) [9].
