Since the first transplant kidney biopsy was performed in 1994, routine pre- and post-transplant kidney biopsy has been widely performed in several transplant centers, and now routine kidney biopsy of transplanted kidneys has been proven to be safe and effective, and has led to a more in-depth understanding of the pathophysiological mechanisms of chronic transplant hypokalemia. Chronic transplant renal hypofunction is actually abnormal transplant kidney function with a slowly progressive increase in blood creatinine level, which makes many patients feel distressed and confused. Routine renal biopsy of the transplanted kidney confirms 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. Pre-transplant donor-associated injury (e.g., donor kidney derived from elderly and hypertensive patients) and perioperative-associated injury (e.g., brain-dead donors, cold and heat ischemia and ischemia-reperfusion injury of the donor kidney) are important causes of the long-term survival of the transplanted kidney. In contrast, multiple immune and non-immune injury factors that occur after transplantation promote the progression of chronic transplant kidney hypofunction, and the effects of this injury are often time-dependent. Routine renal biopsy of transplanted kidneys helps clinicians to adjust the application of immunosuppressive drugs to prevent and intervene in the onset and progression of chronic transplant renal hypoplasia. Although routine renal biopsy of the transplanted kidney has certain shortcomings and drawbacks, it has become an indispensable part of improving long-term survival of the transplanted kidney. The safety of routine transplantation biopsy is the most basic guarantee that it is widely performed in clinical practice. Compared with medical kidney biopsy, routine transplant kidney biopsy has certain characteristics: ① the location of the transplanted kidney is fixed and clearly demarcated from the surrounding tissues, which facilitates the positioning and operation of the operator; ② the location of the transplanted kidney is superficial, and the postoperative pressure to stop bleeding is good; ③ the condition of patients with routine transplanted kidney biopsy is relatively stable, and the possibility of other serious complications is small. Therefore, the possibility of serious postoperative complications is relatively low in patients undergoing routine kidney biopsy. In Western countries, outpatient transplant kidney biopsy is widely performed, and patients are kept in the clinic for four hours after puncture, and the stay can be ended after ultrasound of the transplanted kidney indicates no significant bleeding. Patients with severe complications or a diagnosis of acute rejection will be admitted to the hospital. The National Institute of Kidney Diseases National Center for Clinical Medical Research in Kidney Diseases performed 2944 transplanted kidney biopsies between January 1994 and November 2008 and found that the incidence of less serious complications such as simple hematuria and small perirenal hematoma was 1.7%, and all complications occurred within four hours postoperatively. The results of the study strongly confirm that routine biopsy of the transplanted kidney is safe for the majority of patients. However, clinicians still need to be careful in the operation of transplant kidney biopsy to avoid serious complications as much as possible: ① Conduct relevant preoperative education to ensure that patients cooperate with the physician; ② Position accurately to avoid accidental puncture of effusion and intestine; ③ Use appropriate length and inner diameter biopsy needles, using 18G biopsy needles, adequate tissue specimens can be obtained in about 98% of patients; ④ Postoperative compression of the puncture site for 30-60 60 minutes, with the patient lying in bed for 4-6 hours, to enhance postoperative care and observation, and early detection and management of related puncture complications. Preoperative routine renal biopsy of transplanted kidneys reveals that 30-40% of donor kidneys develop donor-associated kidney injury, and some donor kidneys even develop primary glomerulonephritis. These donor-associated kidney injuries are an independent risk factor for transplant kidney failure. All routine biopsies of transplanted kidneys suggest that new morphologic changes in kidney histology occur about three months after surgery and worsen with time, whether the kidney is transplanted cadaverically or in vivo. Usually, serologic indicators of transplant kidney function change later or less frequently than histopathologic changes in the transplanted kidney. Early routine renal biopsy of the transplanted kidney allows for early detection and early management. Therefore, routine kidney biopsy of transplanted kidneys as a means of responding to early transplanted kidney injury that has not yet caused changes in transplanted kidney function will provide an earlier and more definitive basis for further prevention or treatment of chronic transplanted kidney decompensation, which will also help to improve the long-term prognosis of the transplanted kidney. Routine biopsies of transplanted kidneys performed one year after transplantation revealed major pathologic changes in the transplanted kidney manifesting as persistent small arterial hyaline degeneration with mild to severe intimal thickening, progressive ischemic glomerulosclerosis, tubular atrophy and varying degrees of fibrosis, and persistent decline in transplanted kidney function. The incidence of severe chronic transplant renal hypofunction 10 years after surgery was 58.4%. The vast majority (92.3%) of patients with chronic transplantation hypokalemia showed pathological manifestations of non-specific tubulointerstitial injury. The nephrotoxic effects of calmodulin inhibitors (cyclosporine or tacrolimus) are particularly prominent in patients more than one year postoperatively, and patients who have used calmodulin inhibitors for about 10 years almost always develop corresponding histological changes, regardless of the dosage. Immunosuppression has an important role in halting the development of chronic transplant renal hypoperfusion, and routine biopsy of the transplanted kidney plays an irreplaceable role in guiding and adjusting the immunosuppression regimen. Although immunosuppressive agents can serve to reduce acute (subclinical) rejection and promote graft kidney repair, some of them (e.g., calmodulin inhibitors) have irreversible nephrotoxic effects. Although renal histopathology is the current gold standard for defining and quantifying transplanted kidney tissue damage, it still has limitations. Therefore we need more precise, reliable and reproducible definitional and quantitative criteria to respond to the corresponding histological alterations in the transplanted kidney. A more in-depth understanding of the different pathophysiologic processes of the transplanted kidney is needed. For example, if cellular infiltrates are observed in the transplanted kidney, we need to understand their origin, their prognostic impact, is it a host anti-graft response or a repair process of the kidney to ischemic or toxic injury? And whether these infiltrated cells will respond identically to the same immunosuppressive treatment. With the development of new molecular biology techniques, such as DNA microarray, reverse transcription PCR, and proteomics, if combined with traditional histological and clinical data, will allow us to further unravel the mystery of chronic transplant hyperalgesia.