Long-term survival of kidney transplant patients has always been a major concern for the transplant community. With the development and application of new immunosuppressive agents, kidney transplantation in China is now flourishing, the number of cases is expanding, and the 1-year survival rate of human and kidney is increasing year by year. However, if the long-term effect of kidney transplantation is predicted by the half-life period (the time when 50% of the grafts lose function after the first year of transplantation), the long-term survival rate of kidney transplantation has not been significantly improved in the past 20 years, and there are always 10%-15% of transplanted kidneys lose function within 1 year, and the survival rate is about 67% in 5 years and less than 38% in 10 years. The main obstacles to long-term survival of kidney transplantation are death with normal kidney function and chronic transplant kidney nephropathy (called chronic rejection or chronic transplant kidney function decline), the mechanism of chronic transplant kidney nephropathy is still unclear, it is generally believed that immune factors and non-immune factors are the main factors affecting chronic transplant kidney nephropathy, but also the main factors affecting the long-term survival of the transplanted kidney.
I. Immunological factors :
1, insufficient immunosuppression
As the survival time of kidney transplantation increases, how to choose the ideal immunosuppression program? How should the immunosuppression be adjusted? The dose of immunosuppressant should be taken and the trough concentration should be maintained, which is crucial for kidney transplant patients. Although there is a significant improvement in one-year transplant kidney survival rates. However, long-term use of these drugs can lead to renal impairment, produce dose-related and reversible nephrotoxicity, and increase the incidence of infection significantly. These toxic effects can promote chronic pathological changes in renal tissue and affect long-term survival of the transplanted kidney. Low doses of total immunosuppressive drugs in the “triple” or “double” immunosuppressive regimens of cyclosporine A + azathioprine + corticosteroids are the most common and major cause of late acute rejection. Unauthorized reduction/discontinuation of immunosuppression can directly lead to severe rejection of the transplanted kidney and affect the long-term survival of the transplanted kidney.
2. Acute rejection
Acute rejection is a powerful precipitating factor for chronic rejection, and is also the main factor leading to the failure of the transplanted kidney. Acute rejection, late acute rejection, frequent episodes of acute rejection and refractory acute rejection seriously affect the long-term survival of the transplanted kidney.
3. County reactive antibodies Population reactive antibodies are the most reliable indicators commonly used to determine the immune status of transplant recipients. It is believed that highly sensitized individuals are closely related to clinical hyperacute rejection,
There is also a significant correlation between the level of preoperative herd reactive antibodies and long-term survival of the transplanted kidney. The hypersensitivity status of kidney transplant recipients has always been an important issue in the progress of re-transplantation, and advance knowledge of the presence of hypersensitive immune status must rely on PRA analysis.
The survival rate of a second transplant is 10-15% lower than that of a first transplant. The long-term outcome of patients with multiple kidney transplants is even less satisfactory.
5. HLA Matching
The late 80s sparked a debate on the clinical value of mating, and it has been shown that there is a significant difference between mating and non-mating for both short-term and long-term survival. Data from China and Japan show that the effect of cadaveric kidney transplantation with HLA-A, B and DR matches is close to that of transplantation between siblings with the same HLA, with a 1-year kidney survival rate of 90%. This shows that matching of HLA-A, B, and DR loci, especially DR loci, can improve 1-year kidney transplant survival by 6-10% and 5-10-year kidney survival by 10-20%, with about 1-fold increase in predicted half-life. The selection of the donor with the closest histocompatibility antigen to the recipient minimizes the number and extent of acute rejection with the aim of improving transplantation outcomes. Obviously, inter-identical twin siblings are the best, followed by allogeneic twins, siblings, parents, and blood relatives in that order.
II. Non-immune factors
1, transplanted kidney ischemia time, acute tubular necrosis and delayed transplanted kidney function
Transplanted kidney heat ischemia time, cold ischemia time is longer, its function recovery will certainly be prolonged. The incidence of acute tubular necrosis in 3454 patients abroad is 37.5%, while in China it is mostly between 3.2 and 11.3%. The rate of recovery of renal function correlated with the time of cold ischemia. Acute tubular necrosis did not affect long-term survival. However, the coexistence of acute tubular necrosis with acute rejection results in a very high rate of transplanted kidney failure. Postoperative graft kidney survival rates at 1, 3, and 5 years in those with delayed graft function were 90%, 70%, and 57%, respectively. It was also found that the incidence of postoperative rejection increased in those with recent abnormal transplanted kidney function, which deserves our close attention.
2.Primary kidney disease
Most of the primary kidney diseases that were considered inappropriate for kidney transplantation in the past are no longer listed as contraindications so far. Due to advances in the treatment of these kidney diseases in internal medicine, most patients can obtain satisfactory results after transplantation. Of course, there are still some diseases where the failure rate of kidney transplantation is still very high, which obviously reduces the long-term survival rate.
3. Hypertension
The hypertensive state after kidney transplantation can be extremely harmful to the patient’s organism and the transplanted kidney. Long-term hypertension can lead to increased capillary pressure in the glomerulus, increased filtration pressure, and glomerular hyperfiltration, which can damage the basement membrane and lead to renal function damage. Long-term hypertension causes glomerular atherosclerosis, which can further aggravate hypertension. The occurrence of hypertension after transplantation often affects the long-term survival rate of the transplanted kidney.
4. Hyperlipidemia
The incidence of hypercholesterolemia is 30-67% and hyperlipidemia accounts for 20-33% due to long-term oral hormone and immunosuppressant administration. Hyperlipidemia is a risk factor for atherosclerosis in kidney transplant patients, and about 40% of kidney transplant patients die from cardiovascular disease and occlusive vascular disease.
5. Mismatch between donors and recipients
Mismatch between donors and recipients in terms of gender, age, weight and body surface area directly affects the long-term outcome of kidney transplantation. Female and elderly donors have poor outcomes after transplantation. In the U.S. transplant center, analysis of data over 10 years showed that the 3-year survival rate of transplanted kidney was >70% for those with donor kidney weight/recipient weight ratio >3.5g/Kg, and <2.0g/Kg for those with 3-year kidney survival rate.