白血病肾损害

　　一、发病原因

　　白血病细胞肾损害的发生可能与胚胎期肾脏亦属造血组织有关。急性白血病引起肾脏浸润为最常见，其中急性单核细胞型白血病及急性淋巴细胞型白血病更易浸润肾脏。白血病细胞常直接浸润肾脏，其可浸润肾实质、肾间质、肾血管、肾周围组织及泌尿道。

　　Second, pathogenesis

　　1. Leukemic cell infiltration Leukemic cells often directly infiltrate the kidneys, which can infiltrate renal parenchyma, interstitium, renal vessels, perirenal tissue, and urinary tract. The high incidence of renal infiltration may be related to the fact that the kidneys also belong to hematopoietic tissue during embryonic development. Acute leukemia causing renal infiltration is the most common, with acute monocytic and acute lymphoblastic leukemia being more prone to renal infiltration.

　　2. Immune response Chronic lymphocytic leukemia can complicate immune complex nephritis, and fibrous submicroscopic structures can be found under the electron microscope. These fibrous deposits are immune complexes composed of IgG and anti-IgG antibodies. In addition, cellular immune pathogenicity is also possible.

　　3. Metabolic abnormalities The nuclear protein metabolism of leukemic cells accelerates, leading to an increase in blood uric acid production. Acute lymphoblastic leukemia has the highest level, followed by acute granulocytic and acute monocytic leukemia. Thirty percent of chronic leukemias develop uric acid nephropathy. The blood uric acid level often reaches 893-2975μmol/L, and the degree of uric acid increase is related to the metabolism and destruction speed of tumor cells. Acute leukemia often manifests as acute uric acid nephropathy; chronic leukemia, especially chronic granulocytic leukemia, often causes urinary tract stones, but the increase in blood uric acid is not as obvious as in acute leukemia. During chemotherapy, especially strong chemotherapy, tumor cells rapidly disintegrate, leading to a significant increase in uric acid production. Dehydration or acidic urine pH value makes it easier for uric acid to deposit in renal tissue and urinary tract, leading to urinary system stones or acute uric acid nephropathy, and even acute renal failure.

　　4. Electrolyte disorders and those with hypercalcemia account for 2.5%, mostly acute lymphoblastic leukemia patients, followed by stem cell and chronic lymphocytic leukemia, due to bone destruction caused by leukemic cell infiltration, releasing an excessive amount of calcium into the blood. Persistent long-term hypercalcemia can lead to hypercalcemic nephropathy. Low blood potassium may occur during the course of leukemia, which can also lead to renal tubular damage.

　　Monocytic and granulomonocytic leukemia can produce a large amount of lysozyme, which can damage the proximal renal tubules, manifested as hypokalemia, acidosis, and renal glycosuria. Methotrexate, commonly used in treatment, has a water solubility 4 times lower than methotrexate in its urinary metabolite 7-hydroxymethotrexate, forming yellow precipitates in an acidic environment, even forming large crystals, which deposit in the renal tubules, causing tubular dilation and damage, leading to urinary tract obstruction and renal insufficiency.

　　1. Urolithiasis is a general term for kidney, ureter, bladder, and urethra stones. However, kidney and ureter stones are more common. The clinical manifestations vary depending on the location of the stones. The main clinical manifestations include sudden onset of severe lumbar pain, radiation to the lower abdomen, frequent urination, urgency, dysuria, cloudy urine, and even blood or sand stones in the urine. Abdominal X-ray films may show shadows of stones, or B-ultrasound examination may show stone-like light spots. The TCM literature refers to it as shilin, shalin, and xuelin (urine with obvious blood). Urolithiasis can cause urinary tract injury, obstruction, and concurrent infection, leading to renal function damage.

　　2. Uremia actually refers to the inability of the human body to produce urine through the kidneys to excrete waste products and excessive water from the body, causing toxicity. Modern medicine believes that uremia is a complex syndrome produced by a series of complex metabolic disorders after the loss of renal function, rather than an independent disease, known as renal failure syndrome or abbreviated as renal failure.

　　3. Chronic renal failure (chronic renal failure, CRF) refers to the slow progressive renal function damage caused by various kidney diseases, which eventually leads to uremia and complete loss of renal function, causing a series of clinical symptoms and metabolic disorders in biochemistry, endocrinology, and other metabolic systems. The interval from the onset of the primary disease to the onset of renal insufficiency can be several years to more than ten years. Chronic renal failure is a serious stage of renal insufficiency.

　　Clinical manifestations of renal damage caused by leukemia include:

　　1. Obstructive nephropathy:Obstructive nephropathy is the main manifestation of renal damage caused by leukemia, mostly caused by uric acid crystals or stones, a few caused by methotrexate treatment. Uric acid nephropathy often presents with unilateral flank pain, sometimes manifested as renal colic, with red blood cells in urine microscopy, sometimes presenting as gross hematuria. A large amount of uric acid crystals can be detected in the urine, and sometimes uric acid stones can be excreted. In acute renal failure, oliguria or anuria is often present.

　　According to the different deposition sites of uric acid, obstructive nephropathy is divided into intrarenal obstruction and extrarenal obstructive uric acid nephropathy. Intrarenal obstructive nephropathy is mainly caused by acute leukemia, especially lymphoblastic leukemia, with significantly increased blood uric acid, rapid deposition of uric acid in renal tubules, causing acute intrarenal obstructive uric acid nephropathy, presenting as acute oliguria or anuria type acute renal failure. In chronic leukemia, blood uric acid increases slightly and slowly, uric acid gradually deposits in the urinary tract, forming stones and causing extrarenal obstruction, which can lead to extrarenal obstructive nephropathy in the long term. The two types may coexist.

　　2. Glomerulonephritis syndrome:Leukemic cell infiltration of renal parenchyma or immune reaction may cause hematuria, proteinuria, hypertension, and even present as rapidly progressive glomerulonephritis syndrome, causing oliguria or anuria and renal failure in a short period of time.

　　3. Nephrotic syndrome:Some patients may suffer from glomerular damage due to immune dysfunction, resulting in a large amount of proteinuria (greater than 3.5g/24h), low plasma albumin (less than 30g/L), high blood lipids, and edema.

　　4. Renal tubular-interstitial lesions:Clinical manifestations include polyuria, diabetes, alkaline urine, and in severe cases, acute renal failure may occur. Occasionally, it may present as nephrogenic diabetes insipidus. The cause is due to infiltration of leukemic cells into renal tubules and interstitium, electrolyte disturbance, the generation of a large amount of lysozyme, or chemotherapy drugs.

　　5. Uremia:With the progress of chemotherapy drug treatment, the survival time of leukemia patients has significantly increased, and the complications of leukemia have also increased, especially renal involvement, leading to chronic renal insufficiency, increased blood creatinine, decreased creatinine clearance, acidosis, shrinkage of both kidneys, and eventually uremia.

　　Since renal damage in leukemia is often asymptomatic, close observation is required in the diagnosis and treatment of leukemia. Once abnormalities in urine, hypertension, pain or masses in the renal area are observed, further examination should be conducted to determine the diagnosis. Check blood uric acid, urine uric acid, urine volume, urine routine, and renal function before and during chemotherapy for leukemia, and pay attention to early detection of uric acid nephropathy. Through renal B-ultrasound and X-ray examination, extrarenal obstruction and urinary tract stones can be detected.

　　The 21st century is an era that focuses on the quality of life, and leukemia patients are no exception. Chronic myeloid leukemia patients, due to poor body resistance and immunity, should pay more attention to self-care and nursing in addition to adhering to drug treatment. Maintain an optimistic mood and actively cooperate with treatment. Before the 1970s, leukemia was always considered incurable and once became synonymous with death. However, today, people no longer fear or feel helpless about leukemia because they have mastered the weapons to control or even defeat it. A good mood can improve the body's resistance to cancer cells, which cannot be replaced by any medicine. Maintaining an optimistic mood, a good mental state, and actively cooperating with treatment are crucial for self-recovery.

　　1. Blood examination:In addition to the clinical and laboratory examination results of leukemia, renal damage can cause plasma albumin to be low (less than 30g/L), blood lipids to rise, blood creatinine to increase, creatinine clearance to decrease, and blood uric acid to be higher than 773.24μmol/L (13mg％) and above. Acidosis can lead to uremia and other changes.

　　2. Urine examination:Urinalysis shows a large number of red blood cells (sometimes visible to the naked eye as hematuria), and a large number of uric acid crystals can be detected in the urine (sometimes uric acid stones can be excreted). In addition to hematuria, proteinuria can be seen, and in nephrotic syndrome, a large amount of proteinuria (greater than 3.5g/24h) can occur. There are also diabetes, alkaline urine, and severe cases may appear with acute renal failure changes, occasionally with the symptoms of nephrogenic diabetes insipidus.

　　3. Bone marrow examination:It has a significant diagnostic value. In the early stage of the disease, changes in the bone marrow can help diagnose leukemia.

　　4. X-ray examination:Common uric acid deposits form stones in the urinary tract, with extrarenal obstruction symptoms.

　　5. Ultrasound examination:Ultrasound examination of the kidney can detect extrarenal obstruction, urinary tract stones, and changes in kidney morphology.

　　6. Pathological examination:The weight of the kidneys significantly increases, mainly related to infiltration of leukemic cells, hemorrhage, and other non-specific changes in the kidneys. There is calcification in the renal tubules, and sometimes calcification can also be found in the glomeruli. When leukemic cell infiltration is the main lesion, the pathological changes in the affected kidneys can be divided into two types: diffuse infiltration and nodular types.

　　(1) Diffuse infiltration type: kidney enlargement, color change, medullary streaks are unclear on the section, and the renal units are infiltrated by leukemia cells, seen in acute and chronic leukemia renal damage.

　　(2) Nodular type: nodules of different sizes from several millimeters to several centimeters can be seen, usually distributed in the cortex, more common in acute leukemia, leukemia cell infiltration of the kidney, with acute lymphoblastic leukemia being the most serious, mononuclear cell leukemia being the next, and granulocytic leukemia being the least serious.

　　Clinical manifestations of nephrotic syndrome, renal glomerular pathology can be minimal change nephritis, may also be membranous nephritis and mesangiocapillary lesion, some patients with renal tubules, renal calyces, renal pelvis have uric acid crystal deposition, even forming uric acid stones, at the same time, renal tubular dilation and damage and other obstructive nephropathy histological changes, renal interstitium呈 interstitial nephritis pathological changes, but minimal change is the most common.

　　In the case of hyperuricemia, uric acid deposits can be seen in the interstitium and renal tubules, and renal interstitial fibrosis in the late stage.

　　Patients should pay attention to food hygiene in their daily lives, avoid eating raw and cold, leftover or deteriorated food; fresh fruits must be washed and peeled before eating; some fried or hard foods should also be avoided; for those with habitual constipation before the disease, attention should be paid to supplementing fiber-rich foods, and spicy and刺激性 foods should be eaten less; it is also necessary to maintain smooth defecation every day as much as possible to prevent constipation from aggravating hemorrhoids or causing anal fissure, increasing the opportunity for local infection. Choose high-quality, easily digestible animal protein and soybean protein, such as poultry eggs, milk, fish and shrimp, lean meat, tofu, soy milk, etc., to meet the body's protein needs. Eat foods rich in vitamins, such as tomatoes, kiwi, lemons rich in vitamin C; carrots, pumpkins, yolks, fish liver oil rich in vitamin A, which can enhance the body's local resistance and systemic immune function. In addition, more iron-containing foods should be eaten.

　　One, Traditional Chinese medicine treatment for leukemia renal damage

　　1, Danggui, Danshen, Chishao each 20 grams, Chuanxiong 10 grams, Shashen 20 grams, Maidong 15 grams, Banlangen 50 grams, Shandoushen 30 grams, Shanchiguzhi 50 grams. Decocted in water for oral administration, one dose per day.

　　2, Maqianzi 0.9 grams, Dahuang, Zhuangyang, Banlian, Shehexie, Baihua she舌头 grass each 30 grams. Decocted in water for oral administration, one dose per day.

　　3, Dog tongue grass, Zhuangyang, Baihua she舌头 grass, Longkui, Xianhecao, Beishashen each 30 grams, Jinyinhua, Danshen each 18 grams, Baizhu 15 grams, Zhizhi Huangqi, Danggui, Buguzhi each 12 grams. Decocted in water for oral administration, one dose per day.

　　4, Daqingye, Banlangen, Zicao, Chishao, Danpi, Xijiao, Wugong, Xionghuang each 90 grams. Decocted in water for oral administration, one dose per day.

　　5, Dahuang, Heiyuan Shen, Shengdi, Daqingye each 9 grams, Tianhuafen 6 grams, Chantui, Renzhonghuang each 4.5 grams, Fendanpi 3 grams. Decocted in water for oral administration, one dose per day. Traditional Chinese medicine search Breakline leukemia renal damage Western treatment methods

　　II. Drug Treatment

　　1. The treatment of leukemia: Acute lymphoblastic leukemia is treated with prednisone, vincristine, or cyclophosphamide, etc., in combination; acute non-lymphoblastic leukemia is mostly treated with tripterygium alkaloids, cyclophosphamide, vincristine, cytarabine, and prednisone in combination; the Department of Hematology of Ruijin Hospital first applies all-trans retinoic acid (retinoic acid) for induction differentiation therapy in the treatment of acute promyelocytic leukemia, achieving significant efficacy, with an efficacy rate of about 90%. Currently, all-trans retinoic acid (retinoic acid) treatment of acute promyelocytic leukemia has been widely applied and carried out outside China, and has created a successful precedent for the induction differentiation treatment of tumors. Chronic myelocytic leukemia is commonly treated with busulfan (busulfan) and indigo carmine, etc., and acute transformation is treated according to the type of acute transformation. Sometimes, as leukemia relieves, its kidney lesions also improve accordingly.

　　2. The treatment of kidney lesions is roughly similar to the treatment of primary kidney disease. Hematuria can be treated with Chinese and Western hemostatic agents; proteinuria can be treated with Raoulia tangutica, Kunming Mountain and Sea Peach, etc.; nephrotic syndrome involving immune mechanisms can be treated with immunosuppressants.

　　3. The prevention and treatment of uric acid nephropathy first requires avoiding factors that induce uric acid deposition, such as dehydration and acidosis. Four hours before chemotherapy, allopurinol 0.1g, 3 times a day, is used to control blood and urine uric acid within the normal range. When uric acid nephropathy has occurred, in addition to continuing to use allopurinol, alkaline drugs and fluid replacement are used to reduce uric acid deposition. In severe cases, pyrazinamide can be used to inhibit the secretion of uric acid by renal tubules, with a maximum dose of 3.0g, taken once. Hemodialysis therapy can be considered when renal insufficiency has occurred.

　　III. Prognosis

      The prognosis of kidney damage mainly depends on the type of primary disease and whether it can be effectively treated. Only a very few die directly from uremia. In recent years, comprehensive measures have been adopted for long-term treatment of integrated traditional Chinese and Western medicine to prevent central nervous system infiltration, etc., which has significantly improved the remission rate and duration of this disease, and some cases can survive for a relatively long time. In terms of kidney disease, due to the application of uric acid synthesis inhibitors and dialysis therapy, the mortality rate of leukemic patients with concurrent uric acid nephropathy and acute renal failure has decreased from 60% twenty years ago to 2.5% at present.