Renal tuberculosis

　　The causative bacteria of renal tuberculosis are human and bovine tuberculosis Mycobacterium tuberculosis. They enter the kidney from the primary focus, such as the lung, bone, joint, and lymph nodes, through hematogenous or lymphatic pathways, and can spread to the ureter, bladder, prostate, epididymis, and other places.

　　Humans are easily infected with tuberculosis bacteria, but the body's response to infection depends on both the number and virulence of the bacteria, and to a large extent on the strength of the immune system. Therefore, the response of patients infected with tuberculosis bacteria is related to whether they have had an infection before and the immune response caused by the infection. The first infection is called primary infection or initial infection; the infection that occurs after the body has established an immune response or a delayed-type hypersensitivity reaction is called post-primary infection or re-infection, and the two have different responses in the body. Generally, after 3 to 4 weeks of the initial tuberculosis infection, with the establishment of cell-mediated immunity or delayed-type hypersensitivity reaction, the early nonspecific inflammatory reaction is replaced by granulomatous tuberculosis nodules, which are mainly composed of lymphocytes and macrophages, and often have caseous necrosis at the center. At this time, 90% of the patients' infections are controlled and spread is prevented. Although these patients are infected with tuberculosis bacteria, they do not develop tuberculosis due to their strong immune system, and there are no clinical manifestations. Only a few children and adults with low immunity can directly develop tuberculosis from the primary infection.

　　至于原发后感染或再感染多见于原发感染灶已消退，细胞免疫已建成，但体内又重新出现结核。现在多认为这类感染为早期原发感染播散时留下的病灶重新复发，即为内源性再感染。据报道约5％的患者于原发感染2～5年后，肺部出现结核；另有约5％的患者则于原发感染后10～20年或更长的时间始出现其他肺外结核如肾结核、骨关节结核和淋巴结核等临床症状。由于机体已感染致敏，并已具有细胞免疫的功能，故能限制感染的播散，但组织破坏则较显著，与原发感染有着显著的差别。

　　肾结核几乎都继发于肺结核感染，也偶见继发于骨关节、淋巴及肠结核。结核杆菌到达肾脏的途径有4种，即经血液、尿路、淋巴管和直接蔓延。后两种径路的感染比较少见，只在特殊情况下发生。经尿路感染也只是结核病在泌尿系统的一种蔓延，不是结核菌在泌尿系统最初引起感染的途径。结核杆菌经血行到达肾脏，是已被公认的最主要和最常见的感染途径；而肾结核的血行感染以双侧同时感染机会较多，但在病情发展过程中，一侧病变可能表现严重，而对侧病变发展缓慢。如果患者抵抗力降低，病情迅速发展，可能表现为双侧肾脏严重病变。病理检查证明80％以上的病例是双侧感染。但实际上因大多数患者对侧轻度病变能自行愈合，所以临床上所见的肾结核多以单侧为主，约占85％以上，而双侧肾结核在临床上约占10％。

　　肾结核主要病理变化为肾皮质的阻塞性缺血性萎缩，肾髓质的干酪样坏死空洞形成及尿路的纤维化和梗阻。结核杆菌经血行到达肾脏后进入肾小球毛细血管丛中，若患者免疫力强，菌量少，毒力弱，则病变局限于肾皮质内，形成多个小肉芽肿，多数可全部自愈；若患者免疫力低下，菌量大，毒力强，则结核杆菌到达肾髓质和乳头，病变进行性发展，结核结节彼此融合、坏死，形成干酪样病变，后者液化后排入肾盏形成空洞，则罕有自行愈合者。肾盂、肾盏黏膜上的结核可在肾内经淋巴、血行或直接蔓延累及全肾或播散于肾脏其他部位。若肾盏纤维化狭窄，可形成局限性闭合性脓肿。肾盂结核性纤维化造成梗阻时，可使肾脏病变加速发展，成为无功能的结核性脓肾。肾结核病变扩展至肾周围时，可发生结核性肾周围炎或肾周寒性脓肿，甚至发生结核性窦道或瘘管形成。
　　Another pathological feature of renal tuberculosis is fibrosis and calcification. Perivascular fibrosis causes stenosis of the intrarenal arteries, intimal thickening, and narrowing of the arterial lumen, leading to atrophy of the renal cortex, known as 'obstructive renal cortical atrophy', which is the main pathological change of the renal cortex in renal tuberculosis. Fibrosis of the renal calyx, renal pelvis, and ureteral tuberculosis lesions can cause luminal stenosis, even complete obstruction. In the late stage of renal tuberculosis, calcification can occur, initially appearing at the edge of the cavity, presenting as dot-like spots. Empyema can form a characteristic shell-like calcification. If the affected ureter is completely obstructed, the tuberculous urine from the kidney cannot flow into the bladder, which can improve or even heal the bladder tuberculosis, with complete disappearance of clinical symptoms, known as 'renal autolysis', often discovered incidentally during physical examination with ultrasound or abdominal X-ray film. At this time, there may still be surviving tuberculous bacilli in the caseous tissue within the kidney, so the diseased kidney should also be removed.
　　Tuberculosis bacteria can be transmitted from the kidney to the ureter, invading the mucosal membrane, the固有layer, and the muscular layer. Tuberculous nodules form superficial, creeping ulcers on the mucosa, with granulation tissue as the base, which can cause obvious fibrosis, making the ureter thick and hard, forming rigid strands, segmental narrowing of the lumen, and even complete obstruction. Ureteral stenosis is most common in the bladder wall segment at the ureterovesical junction, followed by the renal pelvis ureteral junction, and less common in the middle segment.
　　Bladder tuberculosis develops secondary to renal tuberculosis. Initially, tuberculous nodules appear near the affected ureteral orifice, then spread to other parts, extending to the trigone and the entire bladder. The tuberculous nodules are light yellow and millet-like, can fuse with each other, and after necrosis, form ulcers. The ulcerative lesions invade the muscular layer, causing severe fibrous tissue hyperplasia and scar contraction, making the bladder capacity decrease to below 50ml, which is called 'contractile bladder'. The hyperplasia of bladder fibrous tissue can lead to stenosis or incomplete closure of the ureteral orifice, forming cave-like structures. Both can cause hydronephrosis due to obstruction or urine reflux into the ureter during urination; incomplete closure can also lead to ascending infection of the opposite kidney by infected urine in the bladder. Severe bladder lesions and deep ulcers can penetrate the bladder wall, forming vesicovaginal fistula or vesicorectal fistula into the vagina or rectum.
　　In addition, about 50% to 70% of male patients with renal tuberculosis have concurrent genitourinary tuberculosis. Although male genitourinary tuberculosis mainly starts from the prostate and seminal vesicle, the most obvious clinical manifestation is epididymal tuberculosis. Among the patients with renal tuberculosis complicated with genitourinary tuberculosis, about 40% of patients have epididymal tuberculosis before or at the same time as renal tuberculosis.

　　When the condition cannot be relieved in time, renal tuberculosis can cause bladder contracture, contralateral hydronephrosis, and spontaneous rupture of the tuberculous bladder, as follows:
　　1. Bladder contracture
　　The causes and pathological changes of bladder contracture come from the tubercle bacilli that frequently and repeatedly invade the bladder from renal tuberculosis, causing severe tuberculous cystitis. In the mucosal and muscular layer of the bladder, there are congestion, edema, tuberculous nodules, tuberculous ulcers, tuberculous granulomas, a large number of lymphocytes infiltration, and the formation of fibrous tissue, finally causing bladder contracture. After the bladder contracture, the bladder wall loses its normal elasticity, and the capacity is significantly reduced. It is generally believed that the capacity of the contracted bladder is below 50ml. In severe cases, the bladder can shrink to a few milliliters of capacity. Due to the repeated infection of the bladder by the tubercle bacilli, the pathological changes in the bladder are an existing process of acute and chronic, inflammation and fibrosis intertwined.
　　The diagnosis of bladder contracture must rely on X-ray examination. Bladder urography can show a significantly reduced appearance of the bladder. Especially, delayed bladder urography can observe the reflux at the ureteral orifice and the expansion and hydronephrosis of the contralateral ureter and renal pelvis. At the time of the examination, attention should be paid to whether there is acute inflammation in the bladder. When there is acute inflammation in the bladder, it is not suitable to perform bladder urography on one hand, and on the other hand, it can be stimulated by the contrast agent, causing bladder contraction and the false appearance of bladder contracture, so it should be paid attention to in order to avoid misdiagnosis.
　　2. Contralateral hydronephrosis
　　Contralateral hydronephrosis is a late complication of renal tuberculosis, caused by bladder tuberculosis. The symptoms of contralateral hydronephrosis are generally the clinical symptoms of renal tuberculosis. The symptoms of contralateral hydronephrosis depend on the degree of hydronephrosis. Mild hydronephrosis may be asymptomatic or have no signs, while severe and obvious hydronephrosis may cause abdominal fullness and pain, or lumbar pain, as well as the presence of a mass in the abdomen or lumbar region.
　　3. Spontaneous rupture of the tuberculous bladder
　　The spontaneous rupture of the bladder is rare, but tuberculosis is the most common cause among the cases of rupture, therefore it should be paid attention to clinically. The symptoms of spontaneous rupture of the bladder due to tuberculosis are that the spontaneous rupture of the bladder often presents as an acute onset process. The patient suddenly experiences lower abdominal pain without any trauma, followed by no urination or only a small amount of hematuria, and abdominal peritoneal irritation. However, due to the history of tuberculosis, the symptoms of urinary system tuberculosis, and the diagnostic criteria for urinary system tuberculosis, the patient exists before the rupture.
　　The diagnosis of spontaneous rupture of the tuberculous bladder in patients with urinary system tuberculosis presents with acute abdominal symptoms, and the lower abdomen is more obvious. Due to the continuous flow of urine into the peritoneal cavity after bladder rupture, abdominal hydroperitoneum is often present. Diagnostic peritoneal puncture can extract a large amount of yellow fluid. Cystoscopy often shows no urine or only a small amount of bloody urine. If bladder perfusion test is performed through the catheter, there may be a significant difference or明显减少(液体进入腹腔)，or明显增多(腹腔内尿液被抽出)in the amount of fluid injected compared to the amount of fluid aspirated. If the catheter enters the peritoneal cavity through the rupture, a large amount of urine can be drained. X-ray cystography can be performed for diagnosis if necessary.

　　Renal tuberculosis is often asymptomatic in the early stage, and there are no abnormalities in urinary tract imaging. The only important positive finding is a small amount of red blood cells and pus cells in the urine. At this time, Mycobacterium tuberculosis can be found in the urine. As the disease progresses, the following symptoms may appear:

　　1. Bladder irritation

　　This is a typical symptom of renal tuberculosis, with about 80% of patients experiencing frequent urination, gradually increasing from 3 to 5 times a day to 10 to 20 times a day. This is due to the stimulation of the bladder mucosa or mucosal ulcers by the pus containing Mycobacterium tuberculosis. In the late stage, bladder stricture, with a small capacity, the number of voidings per day can reach dozens, even呈尿失禁现象，at the same time there is urgency and dysuria.

　　2. Hematuria

　　This is another important symptom of renal tuberculosis, with an incidence of about 70%, generally appearing simultaneously with symptoms such as frequent urination, urgency, and dysuria, mostly terminal hematuria, and in severe cases, there may be blood clots. This is due to bleeding caused by bladder tuberculosis inflammation and ulcers during urination due to bladder contraction. If there is renal tuberculosis bleeding before the bladder lesions, it may manifest as painless gross hematuria.

　　3. Pyuria

　　The incidence of this symptom is about 20%, with a large number of pus cells in the urine, which may also contain caseous material, severe cases may appear like milky, or may be purulent and bloody urine.

　　4. Lumbar pain

　　The incidence of lumbar pain is about 10%, generally asymptomatic in the early stage, but in the late stage of tuberculous pyonephrosis, lumbar pain may occur, such as contralateral hydronephrosis, then contralateral lumbar pain may occur, and a few patients may experience renal colic due to blood clots or pus clots blocking the ureter.

　　5. General symptoms

　　Anemia, low fever, night sweats, decreased appetite, emaciation, and weakness, bilateral renal tuberculosis or unilateral renal tuberculosis with contralateral hydronephrosis, uremia may occur in the late stage, and some patients with renal tuberculosis may have hypertension, which may be related to increased renin secretion due to renal arteriolar stenosis.

　　It is generally believed that the possibility of renal tuberculosis should be considered in the following situations: ① Chronic bladder irritation symptoms such as frequent urination, urgency, dysuria, with protein and red, white blood cells in the urine; ② Young male patients with chronic bladder irritation symptoms; ③ Gradually increasing frequency, urgency, dysuria, or hematuria without efficacy from anti-infection treatment; ④ Urine呈酸性，有脓细胞而普通培养无细菌生长者；⑤ Presence of pulmonary tuberculosis or other extrarenal tuberculosis foci, with small amounts of protein in the urine and red blood cells on microscopic examination; ⑥ Physical examination shows prostate shrinkage, hardness, uneven surface, epididymis, seminal vesicle nodules, or thickened vas deferens, and chronic sinus tracts in the scrotum.

　　The above are the common manifestations of renal tuberculosis, but a considerable number of atypical cases may not have the above manifestations. For example, in a recent report of a group of 349 patients with renal tuberculosis, about 25% of the patients had no自觉 symptoms or only had extremely mild manifestations such as 1 to 2 of the above. These atypical cases are often difficult to diagnose from clinical manifestations and general laboratory tests, but they have the following characteristic manifestations: ① Young and middle-aged patients with recurrent asymptomatic hematuria; ② Only mild back pain without bladder irritation symptoms, intravenous pyelography (IVU) shows unexplained unilateral ureteral obstruction at the lower end; ③ Unsymptomatic and occasionally physical examination IVU shows unilateral kidney non-shadowing; ④ Only persistent urinary frequency without other clear reasons. The above manifestations are very helpful for the diagnosis of renal tuberculosis, but further comprehensive and systematic examinations are still needed to determine the diagnosis.

　　To prevent renal tuberculosis, everyone should establish relevant awareness in daily life, do a good job in vaccination, and seek medical attention in a timely manner if a problem is found. The specific preventive measures are as follows:

　　1. Patients with pulmonary tuberculosis or other tuberculosis should undergo urine examination to detect renal tuberculosis early and receive early treatment.

　　1. Pay attention to rest and emotional adjustment, and have a reasonable diet. It can supplement high-calorie and high-quality protein; eat more fresh vegetables and fruits, keep the bowels and bladder smooth, and strengthen diuresis. Patients with long-standing illness and weakness should eat tonics.

　　4. If renal tuberculosis is diagnosed early and treated properly, it can be cured; if it is found too late, the kidneys may be severely damaged or there may be ureteral stenosis, and surgical treatment may be required, with a poor prognosis.

　　5. Prevent the development of infection into clinical disease by using isoniazid 300mg/d or intermittent medication (three times a week), for 10 to 30 courses. Preventive treatment for those who have had close contact with tuberculosis patients recently and other people who may develop tuberculosis can reduce the incidence of tuberculosis and reduce the spread of the disease.

　　6. Use new technology to study the species and genus specificity of tuberculosis bacteria, surface antigens, produce monoclonal antibodies, and produce specific DNA probes for tuberculosis bacteria, so as to make an early diagnosis of tuberculosis.

　　7. Develop vaccines that are more effective than BCG to enhance immunity and resistance to tuberculosis bacteria.

　　Laboratory examination and imaging examination of renal tuberculosis have the following characteristics:

　　1. Laboratory examination

　　1. Urinalysis

　　About 90% of patients can be found with abnormal urine, which is generally acidic. Microscopic pus in urine and hematuria are the most common, accompanied by a small amount of urinary protein. Urinalysis is an important clue for early screening of renal tuberculosis.

　　2. Tuberculosis Detection

　　Directly smear the sediment of 24-hour urine or the first morning urine for acid-fast staining to detect the presence of tubercle bacilli. Check for 3 times, and 50% to 70% of patients can be detected with tubercle bacilli. However, attention should be paid that if the smear is positive, it cannot be completely determined, as Staphylococcus epidermidis or other acid-fast bacilli can contaminate urine, which is difficult to distinguish from Mycobacterium tuberculosis morphologically, leading to false positives. Especially, one should not rely on a single positive result for diagnosis. Therefore, when collecting urine samples, the vulva and urethral orifice should be cleaned to avoid contamination, and all anti-tuberculosis drugs should be discontinued one week before the examination to increase the positive rate of urine testing.

　　3. Urine Tuberculosis Culture

　　This is an important basis for the diagnosis of renal tuberculosis and can be used for bacterial drug resistance monitoring. It is generally believed that morning urine samples are better than 24-hour urine, as they are easier to collect and have less chance of contamination. However, since the excretion of tubercle bacilli into urine is intermittent, at least 3 days of morning urine should be retained for tubercle bacillus culture before the application of anti-tuberculosis treatment, with a positive rate of up to 80% to 90%. Some scholars suggest collecting 6 times of morning urine cultures for better results.

　　4. Immunological Testing

　　This diagnosis is based on the specific reaction principle between antigens and antibodies, to detect antigens, antibodies, and antigen-antibody complexes in serum and urine, which is helpful for the diagnosis of tuberculosis. Common detection methods include radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA).

　　2. Imaging Examinations

　　Although the detection of tubercle bacilli in urine can make a definitive diagnosis of renal tuberculosis, the specific location of the lesion, the size of the range, whether it is unilateral or bilateral, and the choice of treatment plan all depend on further imaging examinations.

　　1. Plain Film

　　Plain radiography of the urinary system can observe the outline, size, and position of the kidneys, the shadow of the psoas major muscle, and whether there are stones, calcification, or foreign bodies in the kidneys, ureters, and bladder. Renal tuberculosis calcification is often irregular, with uneven density. Caseous cavity type tuberculosis is common around the wall of the cavity,呈圆形或半圆形，usually located in the renal parenchyma. Unless there is extensive renal calcification, calcification of the tuberculous ureter is very rare and should be differentiated from schistosomiasis haematobium. The former is calcification within the ureteral lumen, with the ureter thickened but not dilated; while schistosomiasis haematobium is calcification of the ureteral lumen, usually with ureteral dilatation and tortuosity. Sometimes, calcification of the psoas abscess can be confused with renal calcification, and intravenous urography can be performed for further diagnosis.

　　2. Intravenous Urography (IVU)

　　IVU can not only show the destruction of kidney and ureter tuberculosis, but also understand the renal function status on the opposite side. The renal pelvis margin in the early stage of renal tuberculosis is irregular like worm-eaten, the renal papillae lose the shape of a cup, and in severe cases, caseous necrosis and cavity formation occur in the renal parenchyma. The neck of the renal papilla can become narrow due to tuberculous fibrosis, and even completely obstructed without shadowing. Localized tuberculous abscesses can compress the renal pelvis, causing deformation and pressure marks. If the kidney is completely destroyed or the ureter is completely obstructed due to the lesion, the affected kidney may not be visible, showing as 'non-functional', but it cannot show the degree of kidney destruction. Ureteral tuberculosis shows as the dilatation of the ureter above the ureterovesical junction. If the lesion is severe, it shows as ureteral rigidity and multiple segmental stenosis. Intravenous urography bladder phase can understand the bladder condition, whether there is a contracted bladder or bladder spasm.

　　3. Retrograde pyelography

　　If the diagnosis cannot be made clear by intravenous urography, retrograde pyelography can be considered. In the early stage of renal tuberculosis, cystoscopy can show pale yellow millet-like tuberculosis nodules, which are scattered near the ureteral orifices and in the trigone area. In severe cases, mucosal edema, congestion, and ulcers can be seen. Bladder biopsy can sometimes be performed, and if bladder tuberculosis is diagnosed, it can also explain the diagnosis of renal tuberculosis. If the bladder shows acute tuberculous cystitis changes, bladder biopsy should be contraindicated.

　　In addition, if it is necessary to understand the length of the stricture of the lower segment of the ureter, the degree of obstruction, and the condition of ureteral dilation, or to collect unilateral renal pelvis urine for smears or cultures of tuberculosis bacteria, retrograde pyelography can be performed. As described previously, retrograde pyelography can show the tuberculosis lesions of the kidney and ureter. If dynamic observation is performed under television, it is more helpful for clear diagnosis and the formulation of surgical plans. It is difficult to insert a catheter successfully when the bladder volume is less than 100ml or when the bladder lesions are severe, and it is prone to cause bladder perforation or massive hemorrhage, which is a contraindication for cystoscopy and retrograde urography.

　　4. Percutaneous renal puncture urography

　　It is recently believed that percutaneous renal puncture urography is an important diagnostic method, especially for non-functional kidneys that do not show up on intravenous urography, which is more suitable for understanding the condition of the upper urinary tract above the obstruction. In cases of kidney enlargement, percutaneous renal puncture urography is trending to replace retrograde pyelography. It can puncture into the dilated renal pelvis and inject contrast medium to show the renal pelvis and ureter, and can also extract urine for routine examination and smears for tuberculosis bacteria. It can also determine the concentration of chemotherapy drugs in the tuberculosis cavities and can directly inject anti-tuberculosis chemotherapy drugs for treatment. However, complications such as hemorrhage, retroperitoneal infection, and tuberculous fistula may occur.

　　5. Ultrasound examination

　　It is not significant for the diagnosis of early renal tuberculosis, but it is very helpful for the diagnosis of existing cavities and renal积水. In addition, ultrasound is of great significance for monitoring changes in kidney lesions and bladder volume during the period of anti-tuberculosis drug treatment. After the removal of the affected kidney for renal tuberculosis, regular ultrasound monitoring of the contralateral kidney for the development of renal积水 is more economical and safe than intravenous urography and CT examination.

　　6. CT examination

　　There is some difficulty in diagnosing early renal tuberculosis by CT examination, but it is better than intravenous urography in observing late lesions. In the case of severely damaged and non-functional kidneys, no functional kidneys could be displayed during intravenous urography, and no direct signs of tuberculosis lesions could be obtained. However, CT can clearly show dilated renal calyces, renal pelvis cavities, and calcification, and can also show thickened fibrous renal pelvis and ureteral walls, which are one of the pathological characteristics of renal tuberculosis and are difficult to be detected by other existing examination methods. CT can also observe the thickness of the renal parenchyma, reflecting the degree of destruction of the tuberculosis lesions and providing a reference for determining the surgical method.

　　Kidney tuberculosis patients are suitable for the following foods:

　　1. High-protein diet. Eggs, animal viscera, fish, shrimp, lean meat, tofu are the main sources of protein. And choose more milk and dairy products, because milk is rich in casein and calcium, which can promote the calcification of the tuberculosis focus and is beneficial to the recovery of the body.

　　2. Moderate fat. Tuberculosis patients often have anorexia and poor appetite, so it is advisable to have low-fat food when cooking, such as rice noodles, wheat noodles, red beans, mung beans, fish, honey, etc.

　　3. Supplement foods rich in calcium and iron. Calcium can promote the calcification and healing of the tuberculosis focus, so milk, curd, shrimp shell, tofu, green vegetables and other foods rich in calcium should be eaten regularly.

　　The main treatment for kidney tuberculosis in traditional Chinese medicine is dialectical therapy, as follows:
　　1. Damp-heat retained in the kidney syndrome: frequent urination, urgency, dysuria, hematuria or pyuria, lumbar pain, intermittent fever in the afternoon, thirst, constipation, red tongue, yellow greasy fur, slippery and rapid pulse. Clear heat and promote diuresis. Chu Shi Qing Shen Decoction加减.
　　2. Yin deficiency and fire hyperactivity syndrome: hematuria or turbid urine, frequent urination, weight loss, lumbago, fatigue, low fever in the afternoon, hot palms and soles, seminal emission, night sweats, red cheeks, red tongue, little moisture, fine and rapid pulse. Nourish Yin and reduce fire. Zhi Bai Di Huang Pill加减.
　　3. Qi and Yin deficiency syndrome: hematuria, pale red blood color, fatigue, shortness of breath, reluctance to drink, pale or red cheeks, dry throat, constipation, thin and thin tongue, peeled or cracked fur, weak and rapid pulse. Invigorate the Qi and nourish Yin. Wu Yin Decoction加减.
　　4. Spleen and kidney yang deficiency syndrome: aversion to cold, limbs cold, abdominal distension and loose stools,腰部冷痛, lower back pain, pale complexion, limb edema, frequent night urination, decreased libido or nausea and vomiting, pale and swollen tongue, white fur, slow and weak pulse. Warm and supplement the spleen and kidney. Ji Sheng Shen Qi Pill加减.