New stage, new concept, new pattern——Professor Fu Yingxin talks in detail about the current situation of combined pancreas-kidney transplantation and builds a new blueprint for transplantation

Type 2 diabetes (T2DM) accounts for approximately 90% of global diabetes and is the main cause of end-stage renal disease (ESKD)1,2
.

90%-95% of diabetes patients in the United States have type 2 diabetes3
.

In recent years, the incidence of diabetes in China has risen sharply.
The latest global diabetes map released by the International Diabetes Federation (IDF) in 2019 shows that China has become the country with the most diabetes patients in the world, ranking first in the list of adult (20-79 years old) diabetes patients.
One 1,4
.

For ESKD patients with T2DM, kidney transplantation (KTA) alone or simultaneous pancreas transplantation (SPK) can be performed 5
.

In clinical situations, there is still a lack of consensus on whether to recommend KTA or SPK for T2DM patients with ESKD
.

On June 11, 2021, World Organ Donation Day, Yimaitong had the honor to interview Professor Fu Yingxin, a member of the Organ Transplantation Branch of the Chinese Medical Association, and Professor Fu Yingxin, Department of Kidney Transplantation, Tianjin First Central Hospital Organ Transplantation Center, on kidney transplantation and pancreas-kidney The current status, research results, treatment concepts, and future development of joint transplantation are interpreted in detail for readers
.

New stage-Promoting new development of combined pancreas-kidney transplantation The medical development in the field of kidney transplantation is changing with each passing day.
Kidney transplantation technology has become a more mature medical technology, but compared with the overall medical development history, transplantation medicine is still at a relatively young frontier stage
.

However, the level of pancreatic transplantation is quite different at home and abroad.
"The number of pancreatic transplants performed in the United States each year ranges from 800 to 1,000.
There has been a downward trend in recent years, but the overall level is about 800
.

Compared with European and American countries, the development of pancreatic transplantation in China started late.
Since the start of solid organ transplantation, the number of all pancreatic transplants has been less than 700, and pancreatic transplantation alone has accounted for less than 10%
.

"Professor Fu introduced
.

Pancreatic transplantation can be divided into three categories.
The first category is combined pancreas-kidney transplantation, mainly for patients with T2DM/T1DM combined with ESKD, accounting for more than 90% of the overall pancreatic transplantation; the second category is pancreatic transplantation after kidney transplantation.
, Mainly for patients whose uremia has been improved after kidney transplantation and who need further treatment of diabetes; the third category is pure pancreas transplantation, mainly for patients with type 1 diabetes
.

"Pancreas-kidney transplantation also has a large scale at home and abroad.
Difference
.

First, the indications and options are different.
Most patients receiving combined pancreas-kidney transplantation in European and American countries have type I diabetes with ESKD, accounting for about 80%
.

In China, 80% of the recipients of combined pancreas-kidney transplantation are T2DM (approximately more than 90% of the diabetic population)
.

Second, the pathogenesis is different.
Diabetes patients in Europe and the United States are more obese.
They are different from China in terms of insulin resistance, so they choose different surgical procedures
.

This all reflects a certain relationship with the type and characteristics of diabetes in the country
.

The development of combined pancreas-kidney transplantation will be a focus of clinical and scientific research in the future
.

"Professor Fu said
.

New concept-new practice of assisting pancreas-kidney transplantation.
At present, there are few comparative studies on the metabolic outcome and renal function of KTA and SPK in T2DM patients, especially in the Chinese population with the heaviest burden of T2DM
.

On April 25, 2021, the Metabolic Outcomes and Renal Function after Simultaneous Kidney/Pancreas Transplantationcompared with Kidney Transplantation Alone for Type 2 Diabetes Mellituspatients led by Professor Fu Yingxin was published in Transplant International 6
.

The purpose of this study is to describe the clinical efficacy of KTA and SPK in a single transplant center in China in patients with T2DM, and to provide evidence for comparing KTA and SPK treatment of ESKD patients with T2DM in terms of metabolism, renal function, and survival prognosis
.

This retrospective study included ESKD and T2DM patients who were treated with KTA (n=85) or SPK (n=71) at the transplant center, with a median follow-up period of 1.
8 years
.

The patient's metabolism, renal function and survival results were repeatedly evaluated at different follow-up time points
.

The mixed model repeated measurement method was used to detect and analyze the renal and metabolic outcome levels between KTA and SPK over time
.

Professor Fu explained this important research result in detail
.

"We found that compared with KTA, SPK has more advantages
.

First, it has good metabolism.
After SPK, the blood glucose and blood lipids of patients are effectively controlled, and glycosylated hemoglobin (HbAlc), fasting blood glucose, triglycerides, cholesterol, low-density lipoprotein The level is low (all P<0.
05)
.
The
second is to protect the function of the transplanted kidney.
The glomerular filtration rate (eGFR) of patients after SPK is relatively high (P<0.
001)
.

"Professor Fu said that in clinical practice, combined pancreas-kidney transplantation highlights its advantages
.

Due to the current difficulties in blood glucose control after transplantation and the diabetes-related complications that cause new challenges to doctors, there are often such doubts in clinical practice.
After combined pancreas-kidney transplantation, can insulin resistance in T2DM patients be relieved to a certain extent? To what extent can diabetes and its complications be controlled? Professor Fu answered one by one
.

"After combined pancreas-kidney transplantation, 90% The above patients can stop using hypoglycemic drugs and insulin, and can use immunosuppressive agents like kidney transplant patients to maintain organ rejection
.

From the many monitoring results, the degree of insulin resistance in patients after surgery has been relieved
.

In addition, patients with diabetes-related complications can also be well controlled
.

"In addition to the clinical efficacy of concern, postoperative adverse reactions should not be ignored
.
The
study reported that the infection rate in the SPK group was significantly higher than that in the KTA group (44.
7% vs.
15.
8%, P=0.
006)
.

Professor Fu also commented on this.
a detailed interpretation
.

"kidney transplants where the SPK different from that, one way operation, SPK more complex, the incidence of postoperative complications related will be higher, possibly based on medical conditions different transplant centers Different from surgical experience, each has its own advantages and disadvantages
.

Second, the immunosuppressant regimen is different.
Most (more than 80%) pancreas-kidney transplantation immune induction regimens choose polyclonal antibodies.
Such immunosuppressive agents will increase the risk of infection in patients
.

The third is the postoperative recovery time.
Because the combined pancreas-kidney transplantation is more complicated, the patient's recovery time (days of hospitalization) will increase correspondingly, and the incidence of infection will also increase
.

"Because of this, there has been clinical controversy over whether combined pancreas-kidney transplantation is suitable for T2DM
.

Because the mechanism of T2DM is not simply a lack of insulin, but also insulin resistance
.

If giving excess insulin does not improve the problem of insulin resistance, it may instead.
Turning a simple insulin injection into a complicated operation
.

Professor Fu also expressed his unique view on this
.

"The statement that'T2DM is an indication for combined pancreas-kidney transplantation' is not absolute.
It depends on the patient's age and body mass index (BMI).
), pancreatic islet function, C peptide level, cardiopulmonary function, cardiovascular and cerebrovascular assessment, basic comorbidities and other comprehensive factors
.

In general, if the age is less than 60 years old, BMI is less than 30kg/m2, C-peptide level is less than 10ng/ml, cardiopulmonary function assessment is good, there are no other complications, and the patient can tolerate this operation, then the postoperative effect will be better.
In order to achieve the purpose of alleviating insulin resistance in the treatment of T2DM
.

Of course, any number is not an absolute indicator, but more caution and strictness must be exercised when evaluating patients who exceed the standard
.

If the patient has elderly type 1 diabetes with ESRD, good physical fitness, good cardiovascular and cerebrovascular function, and no clear contraindications such as malignant tumor, severe infection, arteriosclerosis, etc.
, he can also choose pancreas-kidney transplantation
.

"New pattern-leading the new trend of combined pancreas-kidney transplantation.
In the history of pancreatic transplantation, the development of surgical technology is of great significance.
There are various surgical methods for pancreatic transplantation, including the choice of different vascular sites and the choice of different intestinal anastomosis methods.
and the like
.

in the intestinal anastomosis, for example, into the outer drainage secretion (including intestinal and bladder drainage drainage) and endocrine reflux (including portal venous drainage and circulation reflux)
.

In the early stages of the development of combined pancreas-kidney transplantation, bladder drainage was often selected clinically.
With the development of surgical technology, more than 95% of them now choose intestinal drainage
.

The surgical procedures of endocrine reflux also have their own advantages and disadvantages.
Portal vein reflux mimics the entry vein of normal insulin reflux, which is more in line with the physiological metabolism of normal insulin
.

The surgical method of systemic reflux is simpler, and it is also the most commonly used surgical method in clinical practice
.

In addition, the pancreas and kidneys can be placed in different ways, including bilateral placement and ipsilateral placement
.

The internationally mainstream surgical methods are intestinal drainage and vena cava reflux, and the pancreas and kidneys are placed on the same side
.

In addition to the selection of surgical options, the proposed combined pancreas-kidney transplantation should also pay attention to the prevention and treatment of complications during the perioperative period, including thrombosis, intestinal and pancreatic fistula, abdominal infection, etc.
, especially rejection, which is also a pancreatic transplant One of the difficulties
.

Professor Fu pointed out, “The incidence of acute rejection in kidney transplantation is about 7-10%, while the incidence of rejection in pancreatic transplantation is higher, about 15-20%
.

In addition, unlike simple kidney biopsy, pancreatic transplantation Needle biopsy may be difficult in the clinical operation.
Therefore, the diagnosis of pancreatic transplant rejection depends on clinical judgments, including the evaluation of the patient’s blood glucose, the detection of amylase, and the monitoring of pancreatic B-ultrasound blood flow.
, Both need to be used as the main means to evaluate whether a patient’s pancreas rejection occurs, and it is also a project that requires follow-up monitoring in the long-term pancreas transplantation
.

“It can be seen that the prevention and treatment of rejection is very important
.

Immunosuppressive agents have played an important role in this.
At present, most transplant centers at home and abroad use calcineurin inhibitor (CNI)-based triple immunosuppressive medication regimen, namely cyclosporine A or tacrolimus plus auxiliary One of the drugs such as: mycophenolate mofetil (Xiaxi®), azathioprine, rapamycin, mizolabin plus glucocorticoid
.

Once a patient has a rejection, the type of rejection first needs to be judged, and different anti-rejection treatment options are selected accordingly.
For example, for cell-mediated rejection, shock therapy with hormones or polyclonal antibodies can be selected
.

For antibody-mediated rejection, plasma exchange or monoclonal antibody therapy can be selected
.

Although combined pancreas-kidney transplantation started late, it starts with a single step against the current.
Doctors in the field strive to make breakthroughs in development and persist in the difficult situation.
Combined pancreas-kidney transplantation has entered a benign development stage
.

More and more clinical studies have shown that combined pancreas-kidney transplantation can reduce the dependence of ESKD patients with T2DM on insulin injections, improve patient metabolism and renal outcomes, and improve the quality of life of patients
.

At present, the main limitation of combined pancreas-kidney transplantation is the inevitable surgical complications after the operation
.

With aspirations, research and thinking, and perfection, with the ever-changing technical methods and sincere collaboration in scientific research, I believe that the future pancreas-kidney transplantation will be able to meet the international standards, with lower surgical risks, better patient prognosis, and brighter application prospects ! Keeping pace with the times and gaining momentum, more Chinese voices of joint pancreas-kidney transplantation will appear on the international transplant stage! The Organ Transplant Center of Tianjin First Central Hospital was established in 1998.
Under the leadership of Professor Shen Zhongyang, an expert in the field of organ transplantation in the National 863 Program, it has been approved by the Ministry of Health to carry out liver, kidney, heart, pancreas, small intestine, lung, and cornea at the same time.
As well as the islet cell transplant center, there are liver transplantation, kidney transplantation, heart transplantation, pediatric liver transplantation, hepatobiliary surgery, cell transplantation, transplantation care unit, hemodialysis center, transplantation laboratory and other disciplines.
It is currently Asia One of the large-scale organ transplantation centers is also the organ transplantation center in Mainland China included in Clinical Transplants.
The number and quality of transplant operations have been leading the country for many consecutive years
.

The steady development of the transplant field is inseparable from the training of technical talents.
This is a transplant-related training center.
Doctors who apply for transplant qualifications can receive professional training here
.

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Saran R, Robinson B, Abbott KC, et al.
US RenalData System 2019 Annual Data Report: Epidemiology of Kidney Disease in the United States.
Am J Kidney Dis.
2020;75:A6-A7.
USCDC, National Diabetes Statistics Report,2020.
Atlanta, GA: Centers for Disease Control and Prevention, US Dept ofHealth and Human Services, 2020.
Hu C, Jia W.
Diabetes in China: Epidemiology andGenetic Risk Factors and Their Clinical Utility in Personalized Medication.
Diabetes.
2018; 67:3-11.
Gruessner AC, Gruessner R.
Pancreas Transplantation for Patients with Type 1 and Type 2 Diabetes Mellitus in the United States:A Registry Report.
Gastroenterol Clin North Am.
2018;47:417-441.
Fu Y, Cao Y, Wang H, et al.
Metabolic Outcomes and Renal Function after Simultaneous Kidney/Pancreas Transplantation compared with Kidney Transplantation Alone for Type 2 Diabetes Mellitus patients.
Transpl Int.
2021 Apr 25.
doi: 10.
1111/tri.
13892.
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