Immunosuppressant and anticancer drug-induced toxic nephropathy

　　One, the cause of the disease

　　The kidney is the main organ for the metabolism and excretion of drugs and toxins in the body. During the process of metabolism and excretion, toxic effects on the kidney can be produced in various ways, causing kidney damage and toxic nephropathy. In recent years, due to the widespread or excessive use of various drugs in clinical practice, the incidence of acute and chronic renal function failure caused by drugs has been increasing, especially in the elderly and patients with pre-existing kidney diseases. The reasons for kidney damage caused by immunosuppressants and anticancer drugs are:

　　1. Direct toxic effects on the kidney Normal kidney blood flow accounts for 25% of the total body, while the weight of the kidney is only 0.4% to 0.5% of the body weight, so the kidney is the organ with the highest blood flow in the body. A large number of drugs and their metabolites are transported to the kidney with blood flow, which is prone to produce direct toxic effects on the kidney.

　　2. Widespread contact between drugs and glomeruli and renal tubules The opportunity for toxic damage increases through widespread contact between drugs and the endothelial cells of glomerular capillaries and the epithelial cells of renal tubules.

　　3. The oxygen demand of the kidney is high due to the high metabolic activity of renal tissue, which requires sufficient blood flow and oxygen supply, with a large oxygen consumption. When ischemia and hypoxia occur, the kidney becomes more sensitive to drugs, and it is prone to produce toxic effects.

　　4. The retrograde doubling mechanism of renal tubules (concentration effect by convection) Due to the reabsorption of water by renal tubules, drugs are concentrated in the lumen of renal tubules, increasing the concentration of drugs in the tubular lumen, accumulating drugs and causing toxic nephropathy, especially in renal tubular lesions.

　　5. Hypoproteinemia and renal insufficiency Patients with pre-existing kidney disease or liver disease may have a decreased binding rate of drugs to plasma proteins due to hypoproteinemia, an increased free part of drugs, and thus an increased excretion of drugs from the kidneys, increasing the opportunity for renal damage. In cases of renal insufficiency, some drugs cannot be excreted normally through the kidneys, leading to an extended half-life and long-term accumulation of drugs in the body, which increases renal toxicity.

　　6. Age factor Elderly patients have a decreased renal reserve capacity and often have potential renal lesions (such as hypertension arteriosclerosis, diabetic microvascular lesions, etc.) and reduced body immunity, which are prone to infection. If medication is not careful, it is easy to cause renal toxic lesions. Common factors that can exacerbate bladder bleeding caused by cyclophosphamide (CTX) and ifosfamide (IFO) include excessive dosage, concurrent pelvic radiotherapy, accompanying other bladder lesions, oliguria, or co-administration with phenylalanine mustard, etc.

　　II. Pathogenesis

　　There may be several aspects: directly acting on renal blood vessels, causing a decrease in renal blood flow; blocking or inhibiting the production and release of prostacyclin stimulating factors, which is favorable for platelet aggregation and deposition, causing endothelial damage to blood vessels; directly damaging renal tubules, similar to other drug-induced toxic tubular lesions; activating calcium channels, leading to an increase in calcium ion-dependent nephrotoxicity.

　　The main extrarenal complications include bone marrow suppression, alopecia, liver damage, gonadal suppression, gastrointestinal reactions, secondary infections, and the induction of second tumors; the main intrarenal complications include acute renal failure, hemolytic uremic syndrome, and acute tubular necrosis.

　　The main clinical manifestations of renal damage caused by immunosuppressants and antineoplastic drugs vary with different drugs. The main clinical manifestations include hirsutism, gingival hyperplasia, increased blood pressure, liver damage, etc.; renal lesions are manifested as mild to moderate proteinuria, cast urine, oliguria, tubular acidosis, azotemia, electrolyte disturbance, hyperkalemia, hypertension, and acute and chronic renal failure. The following are the manifestations of renal damage caused by several common drugs.

　　Renal damage caused by cyclosporin

　　1. Acute tubular necrosis:Acute tubular necrosis caused by cyclosporin usually occurs in the early stage after transplantation. Research reports indicate that the incidence of anuria after cyclosporin treatment in transplant patients is high, and the duration of oliguria-anuria is long. Acute tubular necrosis in allogeneic renal transplant patients treated with cyclosporin has no specific morphological changes. In cases with prolonged oliguria-anuria, mild diffuse interstitial fibrosis can be seen. After renal function recovery, interstitial fibrosis in some cases can completely disappear, while in a few cases, focal or diffuse interstitial fibrosis can persist, accompanied by long-term renal dysfunction. There is still controversy about whether to discontinue cyclosporin for patients with prolonged anuria.

　　2, Tubular toxicity lesions:The tubular toxic lesions of cyclosporine refer to the tubular damage caused by short-term cyclosporine treatment, which is a different concept from cyclosporine-induced chronic kidney disease caused by long-term use. In the same kidney transplant patients treated with cyclosporine, both conventional and fine-needle biopsies can show several morphological changes in tubular cells, including giant mitochondria, vacuolation of tubular cells, and microcalcification. However, these lesions are not specific to cyclosporine toxicity. The clinical manifestations of cyclosporine tubular toxicity are similar to those of functional renal toxicity, but with a more significant decrease in glomerular filtration rate. Interestingly, there is no manifestation of proximal tubular dysfunction, and the excretion of lysosomes and N-acetylglucosaminidase in the urine is within the normal range, without reports of Fanconi syndrome. The occurrence of tubular toxicity is a manifestation of the overall toxicity of cyclosporine, and therefore, it can guide clinicians to adjust the dose of cyclosporine or discontinue other nephrotoxic drugs used concurrently with cyclosporine.

　　In clinical practice, it is of great importance to differentiate early diagnosis between acute cyclosporine toxicity and acute rejection, but it is sometimes difficult. Clinically, acute rejection is often accompanied by reduced urine output, fever, and ultrasound examination showing edema of the transplanted kidney. The increase in blood creatinine in patients with acute rejection is more rapid than that in cyclosporine toxicity. Although rare in acute rejection, reduced excretion of sodium and increased excretion of protein highly suggest rejection. Renal biopsy shows diffuse cell infiltration during acute rejection, while cyclosporine toxicity may sometimes be accompanied by arteriolar lesions. On the other hand, giant mitochondria, vacuolation of tubular cells, and microcalcification can also be seen in patients with rejection.

　　3, Cyclosporine-associated chronic nephropathy (CsA-associated chronic nephropathy):The most challenging complication of long-term cyclosporine treatment is the chronic progressive decline in renal function, which is referred to as cyclosporine-induced chronic kidney disease. The etiology is the chronic tubulo-interstitial toxicity of cyclosporine. It is difficult to distinguish its pathological and clinical manifestations from those of chronic rejection. The most characteristic pathological change of cyclosporine-induced chronic kidney disease is arteriole lesions and interstitial fibrosis, while the three main pathological changes of chronic rejection are intimal thickening of larger arteries within the kidney, interstitial infiltration and fibrosis, and glomerulosclerosis. The vascular lesions of cyclosporine-induced chronic kidney disease mainly occur in small arteries, including interlobular arteries and arcuate arteries. Recent reports indicate that cyclosporine-induced chronic kidney disease can also affect large arteries. Cyclosporine-induced arteriopathy occurs in two forms: one is the deposition of circulating proteins in the wall of small arteries, leading to stenosis or obstruction of the vascular lumen, and the other is intimal thickening, causing stenosis of the vascular lumen. These lesions further lead to scarring, secondary vasoconstriction, and ischemia, resulting in tubular collapse and interstitial fibrosis. Irregular focal or striped interstitial fibrosis and tubular atrophy lesions can be seen in the renal cortex.

　　The clinical characteristics of cyclosporine-induced chronic kidney disease are progressive renal function decline and arterial hypertension. Proteinuria can be mild or non-proteinuric. Although the clinical and pathological changes of cyclosporine-induced chronic kidney disease and chronic rejection are very similar, the vascular lesions of chronic rejection are mainly in larger arteries (Artery), and the lesions of smaller arteries (Arteriole) often correspond to the site of larger artery lesions. However, the vascular lesions of cyclosporine-induced chronic kidney disease are mainly in smaller arteries, which can be used to differentiate cyclosporine-induced chronic kidney disease from chronic rejection.

　　The natural course of cyclosporine-induced chronic kidney disease is not yet clear. In the past two years, the glomerular filtration rate has remained stable in recipients of heart transplantation receiving cyclosporine treatment. Myers et al. found severe renal tissue lesions and suggested that patients would experience progressive and irreversible renal function damage. Similar histological changes can also be seen in patients with normal renal function who have autoimmune uveitis and are treated with cyclosporine. These reports suggest that long-term cyclosporine treatment can cause irreversible renal failure. In clinical practice, most patients with chronic cyclosporine-induced kidney disease can maintain stable renal function after reducing the dose of cyclosporine. However, in a few cases, renal function does not improve after reducing the dose of cyclosporine. There is no consensus on whether to change cyclosporine to azathioprine in patients with cyclosporine-induced chronic kidney disease. Some reports have shown that after 5 years of follow-up, blood creatinine levels in patients continuing to use cyclosporine and those switching to azathioprine have slightly increased. On the other hand, patients switching to azathioprine are at risk of acute rejection. However, since cyclosporine cannot reduce the incidence of chronic rejection, both patients continuing to use cyclosporine and those switching to azathioprine are at risk of chronic rejection leading to organ failure of the transplanted organ.

　　4Renal damage caused by cyclophosphamide (CTX) and ifosfamide (IFO):CTX and IFO are metabolized by the kidneys into active cytotoxic forms, and the aldehydes and chloroacetic acids they produce can cause cystitis, manifesting as acute bladder hemorrhage and chronic fibrosis. Acute hemorrhagic cystitis is more common in children, presenting with hyperemia and ulcers of the bladder mucosa, with varying degrees of hematuria in clinical practice, 40% of cases have severe bleeding, and occasionally, bleeding may not stop and lead to death. The lesions are reversible, and most of them recover within 2 to 3 weeks after discontinuation of medication. Chronic lesions are bladder fibrosis, and some patients may develop bladder contraction, which may lead to urinary tract obstruction and slow progressive pyelonephrosis. This is more common in the later stages of chemotherapy or after chemotherapy stops. The bladder toxicity of IFO is greater than that of CTX. CTX can induce bladder cancer and renal pelvis cancer, and IFO can cause mild renal tubular lesions, resulting in transient proteinuria and increased urinary enzymes. Occasionally, Fanconi syndrome, severe hypokalemia, and renal insufficiency may occur. After discontinuation of medication, most renal tubular functions can recover. Extrarenal manifestations include bone marrow suppression, alopecia, liver damage, gonadal suppression, gastrointestinal reactions, secondary infections, and the induction of second tumors.

　　5. Streptozotocin:The kidney is the main excretion route of streptozocin. After administration, 73% of the drug and its metabolites are excreted in the urine. The pathological changes of nephrotoxicity mainly involve the proximal tubules, tubular atrophy, inflammatory cell infiltration, with varying clinical manifestations. Tubular dysfunction accompanied by phosphorus loss or presenting as Fanconi syndrome with glomerular dysfunction and progressing to renal insufficiency. If nephrotoxic symptoms appear, medication should be discontinued immediately. These changes can be reversed, otherwise the condition may progress. If medication is continued, irreversible renal damage may occur.

　　6. Fluorouracil (5-Fu):Its renal damage manifests clinically in two syndromes: hemolytic uremic syndrome and acute renal failure accompanied by microangiopathic hemolytic anemia and thrombocytopenia. Histologically, renal arterioles show fibrous infarction, interstitial fibrosis, tubular atrophy, and glomerular sclerosis. All of the above syndromes can be fatal. The course of the former is generally 3-4 weeks, and the latter 3-8 months.

　　7. 5-Azacytidine:It is a second-line drug for the treatment of non-lymphocytic leukemia. When used in combination with other antitumor drugs, it can cause defects in tubular transport function, such as defects in glucose, bicarbonate, phosphate, or sodium transport. The defects in tubular transport function can be reversed after stopping treatment, but the nephrotoxicity is extremely low when used alone.

　　8. Thioguanine (6-FG):Pyrimidine analogs can cause mild, reversible azotemia only at high doses, and have no nephrotoxic effects at standard oral doses.

　　9. Antitumor antibiotics

　　(1) Mitomycin C (self-induced doxorubicin C): Nephrotoxicity manifests as proteinuria, hematuria, azotemia, accompanied or not accompanied by microangiopathic hemolytic anemia and thrombocytopenia. Nephrotoxicity often appears after several courses of treatment, related to dosage, and cumulative dose less than 50mg/m2 or intermittent administration of 10-15mg/m2 per week for 6-8 weeks is still tolerable.

　　(2) Mithramycin: Nephrotoxicity manifests as proteinuria and decreased creatinine clearance, renal biopsy shows swelling of the proximal tubules, necrosis of the distal tubules, and occasionally hemolytic uremic syndrome.

　　(3) Doxorubicin: Nephrotoxicity manifests as prerenal azotemia and acute renal failure, occurring within 1-6 months after medication, usually within 2 months, and the drug dose should be preferably less than 20mg/m2 per week.

　　10. Biologics

　　(1) Interferon-induced nephrotoxicity mainly manifests as reversible acute renal insufficiency and nephrotic syndrome, with clinical and histological features of acute interstitial nephritis and minimal change nephropathy. Electron microscopy shows tubulointerstitial changes, diffuse foot process fusion of glomerular epithelial cells, no electron-dense deposits in the glomerular basement membrane, nephrotic proteinuria but negative for circulating immune complexes, suggesting that immune complexes are not the pathogenic mechanism of renal damage.

　　It has been reported that there may be nephrotic syndrome in patients treated with alpha-interferon for one year, which is membranoproliferative glomerulonephritis, and clinical manifestations include proteinuria from 1g/d to 2g/d. The proteinuria disappears 10 days after discontinuation of the drug.

　　(2) Interleukin-2 (Interleukin-2, IL-2): The nephrotoxicity manifests as pre-renal acute renal failure, which is caused by a decrease in intravascular volume due to the development of capillary leak syndrome after the application of IL-2, leading to a decrease in renal perfusion. Clinically, there is hypotension, oliguria, or a significant decrease in the filtration fraction of urine, and an increase in blood urea nitrogen and creatinine. In clinical observations, although fluid is supplemented to maintain a stable blood volume and pulmonary capillary wedge pressure at the same time, the incidence of acute renal failure is still high 5 days after the use of IL-2, some patients have developed acute tubular necrosis. For patients with nephrotoxicity, if the baseline serum creatinine is less than 132.6μmol/L (1.5mg/dl), the renal function can usually recover in the first week after discontinuation of the drug. Conversely, it may take a longer time to recover.

　　1, Strictly control the indications, drug dosage, and course of treatment. During the period of taking the drug, attention should be paid to closely monitor routine urine, urine enzymes, and renal function to discover nephrotoxic effects early and discontinue the drug in time.

　　2, The prevention and treatment of CsA nephrotoxicity should strictly control the indications, dosage, and course of treatment. The general dose is 4-6mg/(kg·d). When taking the drug, attention should be paid to monitoring the blood concentration of CsA. Blood concentration greater than 250ng/ml may produce nephrotoxicity, and when it is greater than 400ng/ml, the nephrotoxicity is very obvious. It can reduce nephrotoxicity when used in combination with calcium channel blockers.

　　2, When using the nephrotoxic prevention and treatment drugs for cyclophosphamide (CTX) and ifosfamide (IFO), attention should be paid to fluid replacement, maintaining urine output at 2-3L/24h, and alkalinizing the urine. Generally, diuretics are not added; the drug can be injected by adding it to normal saline. In recent years, there have been reports that calcium channel blockers and angiotensin-converting enzyme inhibitors can reduce their nephrotoxicity. For patients with hemorrhagic cystitis, timely cystoscopy should be performed, and the drug should be discontinued immediately when capillary dilation is found to prevent the progression of the lesion to bladder fibrosis and contraction.

　　One, Routine examination

　　1, Acute renal failure caused by drug poisoning usually presents as a non-oliguric type, with an average daily urine output of more than 600ml as isotonic urine. Blood creatinine and blood urea nitrogen can suddenly and rapidly increase, but they are lighter than those in the oliguric type, and the sodium content in the urine is also lower. Intracellular creatinine clearance decreases, urine osmolality and urine specific gravity decrease. In a few severe cases, complex conditions, and elderly patients, the disease may gradually develop into chronic renal insufficiency, leading to severe hypokalemia or hyperkalemia, increased urinary enzymes, and occasionally the clinical changes of Fanconi syndrome.

　　2, Acute interstitial nephritis caused by drugs is manifested in the laboratory as slight proteinuria, microscopic hematuria, sterile leukocyturia, and urine sediment showing eosinophils accounting for more than 1/3. There may be renal function impairment, manifested as increased blood urea nitrogen, creatinine, decreased intracellular creatinine clearance, and occasionally increased IgE in the blood and increased count of eosinophils in the blood.

　　3. In clinical practice, patients with nephritis syndrome or nephrotic syndrome often have proteinuria, hematuria. A few patients may present with nephrotic syndrome due to large amounts of proteinuria, hypoalbuminemia, and hyperlipidemia. Severe cases may be accompanied by renal function impairment, significantly elevated blood urea nitrogen, and creatinine.

　　4. Examination of acute obstructive nephropathy shows hematuria, significantly elevated blood urea nitrogen, and creatinine.

　　2. Renal biopsy pathological examination　　

　　1. The vascular lesions of chronic renal disease caused by cyclosporin mainly occur in small arteries, including interlobular arteries and arcuate arteries. Recently, it has been reported that chronic cyclosporin nephropathy can involve large arteries. The small artery disease caused by cyclosporin occurs in two forms: one is the deposition of circulating proteins in the small artery wall, leading to luminal stenosis or obstruction, and the other is intimal thickening, causing luminal stenosis. These lesions further lead to scarring, secondary vasoconstriction and ischemia, resulting in tubular collapse and interstitial fibrosis. Irregular focal or strip-like interstitial fibrosis and tubular atrophy lesions can be seen in the renal cortex.

　　2. The main manifestations of nephrotoxicity caused by alpha-interferon are reversible acute renal insufficiency and nephrotic syndrome. Histology shows fibrous infarction of renal arteries, interstitial fibrosis, tubular atrophy, and glomerular sclerosis. Clinically and histologically, it presents as acute interstitial nephritis and minimal change nephropathy. Electron microscopy shows changes in the tubular interstitium, diffuse podocyte fusion in the glomeruli, and no electron-dense deposits in the glomerular basement membrane, indicating a negative nephrotic circulation immune complex.

　　3. When there is acute tubular necrosis, pathological examination shows变性 and necrosis of the proximal renal tubular epithelial cells, basement membrane rupture, and interstitial edema. In severe cases, the distal renal tubules may also be involved, even affecting the glomeruli.

　　4. In patients with acute interstitial nephritis, light microscopy shows marked edema of the renal interstitium, with a large number of eosinophils, lymphocytes, and monocytes infiltrating the interstitium. There is also mild diffuse interstitial fibrosis, and in a few cases, focal or diffuse interstitial fibrosis can persist. At the same time, tubular epithelial cell degeneration and necrosis can be seen, and immunofluorescence shows linear deposition of IgG along the basement membrane of the renal tubules, accompanied by C3 deposition.

　　3. Other examinations

　　The radionuclide renal scan shows an obstructive pattern; ultrasound shows renal pelvis hydrops; for patients with hemorrhagic cystitis, cystoscopy can be performed to detect capillary dilation or progression to bladder fibrosis and contraction when the condition worsens.

　　1. It is recommended to eat light and easily digestible foods, and to avoid seafood, beef, mutton, spicy and刺激性 foods, alcohol, and all kinds of promoting foods such as five-spice powder, coffee, and cilantro; especially for patients with Yin deficiency, such as red tongue,洪大 pulse, night sweats, dry stools, hematuria, etc.; but for patients with Yang deficiency, such as pale tongue with white fur, deep pulse, cold body and limbs, loose stools, and can eat warm foods.

　　2. It is advisable to consume fresh vegetables and a moderate amount of fruit, and to drink water appropriately; it is prohibited to eat all kinds of tonics, supplements, and easily hot foods such as chili, litchi, chocolate, etc. Especially for patients with Yin deficiency and internal heat, such as purple tongue, slow pulse, chest stuffiness, abdominal distension, and other blood stasis symptoms.

　　3. All renal patients are prohibited from using neomycin, streptomycin, gentamicin, Rhizoma aristolochiae manshuriensis, and vaccines.

　　4. Uremic patients should maintain smooth defecation, aiming for 2-3 times a day, avoid staying up late, control sexual activity, pay attention to rest, and avoid catching a cold.

　　5. Those who have taken hormones should reduce the dosage and frequency of hormones according to specific circumstances under the guidance of a physician.

　　6. Those with severe edema should avoid salt, limit the intake of protein foods, and drink less water. Those with mild edema can consume low-sodium salt diet; those without edema should not limit the intake of water and protein foods; those with microscopic hematuria and those prone to fire should drink more water and eat more yin-nourishing and fire-reducing foods such as apples, white sugar, black sesame, and mushrooms.

　　7. Those with hyperkalemia due to uremia should avoid eating high-potassium foods such as bananas, oranges, potatoes, tomatoes, pumpkins, tea, soy sauce, and monosodium glutamate; while patients with low blood potassium should do the opposite.

　　7. Those with high blood uric acid should especially avoid eating animal internal organs, fish, shrimp, crab, clam, beer, mushrooms, beans, and spinach.

　　First, treatment

　　Currently, there is no special effective therapy for toxic nephropathy caused by immunosuppressants and anticancer drugs, and the treatment methods are the same as other related diseases.

　　1. Discontinue immunosuppressants and anticancer drugs:For mild cases, the nephrosis caused by the use of this class of drugs can be relatively relieved after discontinuation. If it is still necessary to use this class of drugs, then it should be reduced in dose or other drugs should be chosen to replace them.

　　2. Use adrenal cortical hormones:Hormonal therapy often achieves the effects of diuresis, improvement of renal function, and reduction of blood creatinine to normal levels. The general dosage is prednisone 30-60mg/d, and the treatment duration is about 1 month. The dose should not be too high, and the treatment course should not be too long. There are individual reports that high-dose methylprednisolone pulse therapy can alleviate acute renal failure. Since most drugs that cause acute interstitial nephritis do not require hormones, simple discontinuation of medication can quickly recover, therefore, the benefits and risks of hormone use should be weighed.

　　3. Strengthen symptomatic supportive treatment:General symptomatic treatment includes the active treatment of the primary disease, control of infection, supplementation of blood volume, anti-shock, correction of electrolyte and water balance, and close observation of blood pressure, urine output, changes in heart, lung, and renal function. When patients present with oliguria, timely diuretic therapy can be given, such as mannitol (25g) or 25% sorbitol 125-250ml intravenous rapid infusion. The combination of furosemide and mannitol can sometimes achieve better diuretic and natriuretic effects. For patients with poor response to furosemide in clinical practice, consideration can be given to small doses of dopamine or atropine to enhance diuretic effects.

　　The combination of atrial natriuretic peptide and mannitol in the ARF animal model has been proven to have a beneficial effect on renal function; usually, fluid replacement, mannitol, and furosemide are considered as the three-step曲 for the early prevention and treatment of ATN.

　　Angiotensin-converting enzyme inhibitors such as Captopril (thiopropyl aminopropionic acid), Enalapril, Benazepril, and Perindopril can inhibit the formation of angiotensin II, block the tubuloglomerular feedback, increase kallikrein, improve renal blood flow, and this measure can also be used in clinical practice.

　　In addition, the use of traditional Chinese medicine to activate blood circulation and remove blood stasis, such as Chuanxiong and Danshen. Studies have shown that Cordyceps sinensis can significantly promote the growth of renal tubular epithelial cells in vitro, and has a good protective effect on drug-induced nephrotoxicity in clinical practice, which may also have a certain therapeutic effect on interstitial nephritis.

　　4. Treatment for Concurrent Acute Renal Failure:Once ARF has formed, it should be treated strictly according to acute renal failure, and dialysis treatment should be performed immediately if necessary. The indications for acute renal failure dialysis are: anuria or oliguria for more than 2 days; serum creatinine (Scr) 442μmol/L; BUN > 21mmol/L; carbon dioxide combining power (CO2CP) < 13mmol/L; with signs of pulmonary edema or brain edema. Dialysis can maintain life, thereby winning treatment time. Since dialysis treatment can both replace the excretory function of the kidneys and remove some drugs accumulated in the plasma, it can help patients through the oliguria period, reduce mortality, and shorten the course of the disease. Therefore, most scholars advocate early dialysis. The methods of dialysis include hemodialysis and peritoneal dialysis. Hemodialysis is more commonly used. In addition, CAVH (Continuous Arteriovenous Hemofiltration), CAVHD (Continuous Arteriovenous Hemodialysis Filtration), CVVH (Continuous Venovenous Hemofiltration), and HDF (Hemodialysis Filtration) and other methods, due to their many advantages that cannot be replaced by simple hemodialysis, have been increasingly used in the treatment of ARF; but for some patients with low blood pressure, bleeding, and poor vascular conditions, peritoneal dialysis is more suitable. This therapy is simple, safe, and economical, and can be widely carried out.

　　II. Prognosis

　　Most lesions are reversible. When harmful drugs are discontinued, if timely treatment is provided, the prognosis is still good. Some clinical syndromes can spontaneously remit. Glomerular function (Scr and BUN) usually returns to normal first, while the complete recovery of tubular function (such as the distal tubular concentrating function) may require several months. However, if the causative drug is not identified in time and the drug is not discontinued promptly, delayed treatment can lead to the continuous deterioration of renal function, and some patients may suffer from permanent damage, ultimately progressing to end-stage renal failure.