In recent years, with the relaxation of the indications for transplantation kidney biopsy, the clinical use of geriatric donor kidneys, and the widespread implementation of living relative donor kidney transplantation, the number of preoperative donor kidney biopsies has been increasing. The recent observation that pathological inflammatory changes can be seen in transplanted kidney puncture even when the kidney function is normal has led to further recognition of the importance and necessity of transplant kidney biopsy in clinical diagnosis and treatment. However, it is not clear which kidney transplant patients need kidney biopsy, this topic mainly introduces the indications for kidney transplant patients to perform transplant kidney biopsy for your reference. 1. bedside renal biopsy for patients with delayed recovery of transplanted kidney function The blood creatinine level after kidney transplantation generally returns to normal in 3-7 days after surgery. Once the blood creatinine level decreases slowly within a week after surgery, or even continues to rise, the transplanted kidney function cannot be restored and requires dialysis treatment for transition, clinically known as delayed recovery of transplanted kidney function. Early studies found that about 30% of patients with delayed recovery of transplanted kidney function after kidney transplantation had evidence of rejection on biopsy within the first week after surgery. The PLA Institute of Nephrology, Nanjing General Hospital, Nanjing Military Region, reported that the causes of delayed recovery of transplanted kidney function in 69 cases were: acute tubular necrosis in 69.7%, accelerated rejection in 23.2%, acute rejection in 7.3%, acute tubular necrosis plus acute rejection in 8.7%, acute cyclosporine nephrotoxicity in 1.4%, renal artery embolism in 1.4%, and urinary tract obstruction in 4.3%. Therefore, we believe that in patients with delayed recovery of transplanted kidney function, after excluding surgical complications, transplanted kidney biopsy must be performed in order to understand and clarify disease regression. In the absence of contraindications, renal biopsy is feasible at any time after surgery, and can be performed within 24 hours after surgery at the shortest. 2. Routine biopsy for patients with normal transplanted kidney function After kidney transplantation, patients with good recovery of transplanted kidney function should also routinely undergo transplanted kidney biopsy in January, June and December to facilitate early detection and management of various complications. Renal biopsies are routinely performed at the PLA Institute of Nephrology, Nanjing General Hospital, Nanjing Military Region, and reveal subclinical rejection, i.e., the patient may have normal blood creatinine levels, but pathologically shows mild rejection. This pathological change usually occurs within 6 months after surgery, and about 1/3 of the patients are found to have pathological mild rejection without clinical abnormalities of renal function, but with effective intensive treatment, the long-term survival of the transplanted kidney is significantly improved. Therefore, timely transplant kidney biopsy should be performed in the following clinical conditions: anuria and oliguria after kidney transplantation; acute transplant renal insufficiency; chronic transplant renal hypofunction; cyclosporine or tacrolimus nephrotoxicity, long-term proteinuria and rejection therapy failure. 3, repeat renal biopsy after treatment of acute rejection The results of two recent studies have changed the previous concept that once the blood creatinine value returns to normal, the acute rejection of the transplanted kidney has been eliminated. In fact, after successful clinical treatment of acute rejection, there is still evidence of rejection in 25-30% of patients with transplanted kidney pathology. Short-term follow-up studies show that some of these patients will have acute rejection again, or even change to chronic lesions, it is necessary to emphasize repeat renal biopsy in order to observe the response to treatment and changes in the condition. 4, chronic transplant hyperalgesia patients regular kidney biopsy after kidney transplantation blood creatinine level is slowly progressive increase, also known as “creeping creatinine” commonly known as chronic transplant hyperalgesia (including abnormal transplant kidney function or transplant kidney insufficiency, serious transplant kidney failure). Chronic transplant renal hypofunction is the main cause of transplant kidney loss in the late stage of kidney transplantation, its incidence accounts for 25% of the overall transplant kidney failure, accounting for 50% to 80% of the return to dialysis after kidney transplantation due to renal failure. The incidence of severe chronic transplant renal insufficiency 10 years after surgery is 58.4%. The vast majority (92.3%) of patients with chronic transplant renal insufficiency have non-specific tubulointerstitial injury as a pathological manifestation. Some patients cannot return to normal blood creatinine after surgery and keep on rising, or the transplanted kidney function recovered well at the beginning and then became abnormal again for some reasons, etc., which makes many patients feel very distressed and clinicians feel confused in the management. It is wrong to deal with it blindly, and only through kidney biopsy can the underlying cause be clarified. Regular renal biopsies of transplanted kidneys confirm that chronic transplant hypofunction is caused by the cumulative effect of the long-term presence of damage to the transplanted kidney, a process that was initiated before the transplanted kidney was offered to the recipient. It should be emphasized here that it is too late to perform a transplant kidney biopsy when chronic transplant kidney impairment has been clearly established, with a blood creatinine of 4 mg/dl for more than 3 months. Therefore, transplant kidney biopsy as a means of responding to early transplant kidney injury that has not yet caused changes in transplant kidney function will provide an earlier and more accurate basis for further prevention or treatment of chronic transplant kidney decompensation, which will also help to improve the long-term prognosis of the transplanted kidney. 5, proteinuria after kidney transplantation It is not uncommon to see proteinuria after kidney transplantation, many patients may have a plus of urine protein and do not care, as time progresses urine protein is getting worse, some reach the level of nephrotic syndrome proteinuria (>3g/24 hours), even accompanied by severe bilateral lower limbs and eyelid edema, pleural fluid or ascites. In fact, proteinuria can occur in kidney transplant recipients for a variety of reasons, and proteinuria itself can cause damage to the transplanted kidney or exacerbate the original lesion of the transplanted kidney, which is an important factor affecting the long-term survival of the kidney transplant recipient/kidney. The etiology of proteinuria in kidney transplant recipients is divided into immunologic and non-immunologic. Immunologic factors include various rejection reactions, new or recurrent glomerulonephritis; non-immunologic factors include hypertension, ischemia-reperfusion injury, cyclosporine nephrotoxicity, oral sirolimus, and renal unit deficiency phenomenon. Different components of proteinuria can mediate transplanted kidney injury by direct injury, activating cytokines, affecting vasoactive substance release, and are associated with chronic fibrosis in the transplanted kidney. The etiology of proteinuria can only be clarified through transplant kidney biopsy, and the treatment of proteinuria in transplant recipients can be individualized to address different etiologies, such as choosing a donor kidney with more ideal conditions, improving the mating type to reduce immune damage, targeting the treatment of new and recurrent kidney disease, and applying immunosuppressants in a rational and individualized manner. 6, cyclosporine / tacrolimus nephrotoxicity With the widespread use of new immunosuppressants, the incidence of acute rejection has decreased significantly, but the long-term survival of kidney transplantation has not achieved the desired results, and the rate of transplanted kidney loss after kidney transplantation is still increasing at a rate of about 5% per year. Some of the key factors affecting kidney survival in transplant recipients are related to immunosuppression, including hepatic and renal toxicity of immunosuppression, post-transplant diabetes, chronic transplant kidney nephropathy, and the development of malignancy after transplantation. Since the application of cyclosporine and tacrolimus, varying degrees of nephrotoxicity, such as generalized hair growth, gingival hyperplasia, hand and foot tremors, with or without hepatic and renal impairment, have been seen in almost all patients on this class of immunosuppressive agents. Renal transplant recipients need to apply these drugs to achieve rejection prevention at doses that reduce glomerular filtration rate (GFR) by approximately 15-25%, and long-term continuous application of cyclosporine can also lead to the progression of chronic transplant renal hypofunction and ultimately transplant renal failure. In addition, up to 25% of non-renal organ transplant recipients treated with cyclosporine develop renal insufficiency, with 1-1.5% of these patients leading to renal failure each year. Although cyclosporine may reduce acute (subclinical) rejection and promote repair of the transplanted kidney, long-term cyclosporine use has irreversible nephrotoxic effects. The nephrotoxic effects of cyclosporine are particularly prominent in patients more than one year postoperatively, and patients who have used cyclosporine for about 10 years almost always develop corresponding histological changes, regardless of the dosage. Typical cyclosporine-induced histologic changes in the transplanted kidney include primary or de novo microarterial hyaline degeneration, striated fibrosis and microcalcifications and tubular necrosis that cannot be explained by other causes. 7. Adjustment of immunosuppressive drugs Routine renal biopsy of transplanted kidneys helps clinicians to adjust the application of immunosuppressive drugs to prevent and intervene in the occurrence and development of chronic transplant renal hypoplasia. The blood creatinine level may fluctuate in some patients with chronic transplantation hypokalemia, as physicians and patients are mostly reluctant to repeat renal biopsy and prefer empirical treatment, but the treatment among different individuals should be integrated with clinical manifestations, ultrasound findings and histological changes. It should be noted here that patient compliance is quite important, and adherence to the appropriate immunosuppressive regimen and application of the right amount of immunosuppressive agents in compliance with medical advice can prevent many transplant kidney failure events. Repeated high-dose corticosteroid “shock” therapy should be avoided in patients with chronic transplant renal decompensation, and abrupt withdrawal of cyclosporine or discontinuation of cyclosporine is not advisable. Certain immunosuppressive regimens and their immunosuppressive agents have been found to be more effective in controlling the incidence of subclinical rejection in transplant kidney biopsies, for example, the incidence of subclinical rejection is lower in patients taking tacrolimus and primaquine than in patients using other immunosuppressive agents. The incidence of subclinical acute rejection in renal transplant patients treated with cyclosporine A-based immunosuppression was 23% at 3 months postoperatively and 28% at 2 months postoperatively. Thus, biopsy of the transplanted kidney provides a strong basis for adjusting and switching immunosuppressive regimens and is an indispensable part of improving long-term survival of the transplanted kidney.