Interstitial nephritis

　　I. Etiology

　　1. Obstructive nephropathy Urinary tract obstruction below the renal papilla is the primary etiology of more than half of interstitial nephritis.

　　2. Renal damage caused by analgesics.

　　3. Chronic (non-obstructive) pyelonephritis In the absence of obstruction or other primary etiologies of kidney disease, chronic progressive pyelonephritis caused by kidney bacterial infection is a rare cause of chronic renal failure.

　　4. Immune interstitial nephritis The immune injury of the interstitium and its related structures can be an important precipitating factor for some chronic kidney diseases.

　　5. Balkan nephritis This is a chronic progressive interstitial disease with insidious onset, unknown etiology, and cases are limited to the Danube River basin.

　　6. Idiopathic interstitial nephritis About 10% of patients with interstitial nephritis cannot find the cause of the disease.

　　II. Pathogenesis

　　The mechanism of renal tubular interstitial injury caused by various reasons can be roughly divided into the following aspects, namely microvascular injury, tubular cell injury, interaction of inflammatory cells, changes in fibroblast phenotype, tubular cell-fibroblast interaction, leading to tubular atrophy, interstitial fibrosis, interstitial infiltration, etc. Chronic tubular injury releases growth factors and cytokines, causing a disorder in the synthesis and degradation of cell components, resulting in tubular atrophy.

　　Growth factors and cytokines cause interstitial fibroblasts to proliferate, leading to increased extracellular matrix deposition and the formation of interstitial fibrosis. The released growth factors and cytokines have a chemical attractive effect, causing cell infiltration and proliferation of infiltrating cells. Tubular atrophy, interstitial fibrosis, interstitial infiltration, and peritubular capillary lesions can all lead to occlusion of the postglomerular capillary lumen, resulting in secondary elevation of glomerular capillary pressure and progressive loss of renal function.

　　Chronic interstitial nephritis can be complicated by renal glycosuria, even Fanconi syndrome; it can also be complicated by tubular acidosis, leading to uremia; in addition, it can also be complicated by renal anemia and hypertension. Acute interstitial nephritis is complicated with acute renal failure. Patients with low resistance are prone to respiratory, urinary tract, and skin infections, and after infection, there may be no obvious symptoms, and treatment is also difficult, so attention should be paid to it.

　　Acute interstitial nephritis manifestations

　　Acute interstitial nephritis, due to different etiologies, has varied clinical manifestations and is non-specific. The main prominent manifestation is oliguric or non-oliguric acute renal insufficiency, which may be accompanied by non-specific symptoms such as fatigue, fever, and joint pain. Tubular function loss may result in low specific gravity and low osmolality urine, tubular proteinuria, and disturbances in water, electrolyte, and acid-base balance, and some patients may present with Fanconi syndrome.

　　Drug-related acute interstitial nephritis often has a more typical course: renal function damage appears several days or weeks after the use of the pathogenic drug, with urine output decreasing or remaining unchanged, abnormal urine tests, and some with gross hematuria, asymptomatic leukocyturia, back pain, and generally without hypertension and edema. It is often accompanied by systemic allergic symptoms such as fever, rash, and the triad of eosinophilia, and most patients have gastrointestinal symptoms such as nausea and vomiting. The clinical manifestations of acute interstitial nephritis caused by different drugs are not entirely the same. Some patients may develop acute interstitial nephritis even if they were previously tolerant to a certain drug and then use it again. Acute interstitial nephritis caused by non-steroidal anti-inflammatory drugs may present with a large amount of proteinuria.

　　Patients with infection-related acute interstitial nephritis often have signs of infection, such as fever, chills, headache, nausea, vomiting, and even sepsis, and may also have symptoms of other organ systems, such as pneumonia, myocarditis, and liver damage. Among them, acute pyelonephritis complicated with renal parenchymal infection is the most common. Most renal parenchymal infections are secondary to bacterial infections in the urethra and bladder, with diverse clinical manifestations ranging from mild discomfort to sepsis symptoms: they often start abruptly, with symptoms such as chills, high fever, costovertebral angle tenderness, and urinary tract irritation. Atypical cases may present with symptoms such as fatigue, back pain, weight loss, recurrent cystitis (difficulty urinating, frequent urination, urgency, suprapubic pain), etc. About 1/3 of elderly patients may not have fever, and 20% of elderly patients may present mainly with gastrointestinal symptoms or pulmonary symptoms. Urine examination may show leukocyteuria, pyuria, and bacteriuria, and urine culture may be positive.

　　For men, urinary tract obstruction caused by prostatitis and benign prostatic hyperplasia is an important cause. Acute interstitial nephritis caused by hemogenous infection is more common in the elderly, diabetics, and patients who have been taking immunosuppressants or NSAIDs for a long time.

　　Idiopathic acute interstitial nephritis is more common in young women, with clinical manifestations including fatigue, fever, rash, muscle pain, and uveitis. Some patients may have lymphadenopathy, and urine examination shows mild to moderate proteinuria, with obvious tubular damage and non-oliguric renal insufficiency. Approximately 1/3 of patients may have ocular symptoms, which may appear several weeks before, simultaneously, or several months after the onset of kidney disease. 80% of cases are mainly localized to the anterior uvea, but there are also reports of involvement of the posterior uvea. Clinically, there may be no symptoms, but eye pain, photophobia, lacrimation, and visual impairment may also occur. Physical examination may reveal conjunctival congestion or mixed congestion, aqueous humor turbidity, corneal posterior deposits, and iris adhesions. 20% of patients may have complications such as posterior iris adhesions and changes in intraocular pressure. Laboratory tests may show anemia, eosinophilia, rapid erythrocyte sedimentation rate, elevated CRP, and globulin. The type of hormone treatment has a significant effect.

　　Other clinical manifestations Acute interstitial nephritis caused by systemic diseases may simultaneously appear the specific clinical manifestations of the systemic disease, such as patients with systemic lupus erythematosus may have facial rash, joint pain, photosensitivity, alopecia, frequent oral ulcers, etc., and patients with Sjögren's syndrome may have dry mouth, dry eyes, multiple dental caries, etc.

　　Second, the manifestations of chronic interstitial nephritis

　　Chronic interstitial nephritis is often insidious, chronic, or acute in onset, due to chronic interstitial inflammation, mainly fibrosis tissue proliferation, tubular atrophy, so it often has common clinical manifestations.

　　1. Patients often present with gradually increasing polyuria or nocturia, accompanied by varying degrees of anorexia, fatigue, weight loss, and non-specific symptoms, generally without edema. Some cases may have no clinical symptoms at all, and mild urinary changes, renal function decline, anemia, and renal osteopathy may be discovered only during physical examination or due to other diseases. Some patients may have a history of medication or exposure to chemical factors. Some may have the manifestations of the primary disease due to systemic diseases.

　　2. Urinalysis usually shows mild proteinuria (qualitative trace to +, quantitative generally

　　3. If there is renal papillary necrosis, high fever, lumbar pain, gross hematuria, and urinary tract irritation may occur during the course, common causes include diabetes, pyelonephritis, analgesic nephropathy, urethral obstruction, or vasculitis. Acute renal papillary necrosis can lead to acute renal failure, and necrotic tissue fragments can be found in the urine sediment. Renal pelvis imaging may show annular shadows or filling defects. In chronic cases, calcification shadows in the renal medulla and renal papillae can be seen, and clinical urine concentration function is reduced.

　　4. Chronic interstitial nephritis can affect glomeruli and blood vessels, leading to corresponding functional damage. In the early stage, there is a decrease in内生肌酐清除率, and the serum creatinine level may increase later. In the late stage, when glomeruli and blood vessels are severely involved, symptoms of chronic renal insufficiency may appear, such as nausea, vomiting, anorexia, etc. Anemia is often very severe and not necessarily proportional to the degree of renal function decline. About half of the patients develop hypertension, but the severity is often not as serious as that caused by glomerulonephritis.

　　1. Avoid overexertion and mental stress, as excessive fatigue, staying up late, and academic pressure can all worsen the condition of chronic nephritis. Maintain a good living habit and keep a regular lifestyle. Arrange daily life and rest properly, participate in moderate activities, strengthen physical exercise, but avoid overexertion. Have a reasonable diet, enhance physical fitness and immune resistance. Pay attention to personal and environmental hygiene, develop good health habits, and always keep a relaxed and pleasant mood, strengthen self-care awareness.

　　2. Be careful to prevent bacterial or viral infections. Bacterial or viral infections are the most common causes of acute nephritis, especially upper respiratory tract infections, asymptomatic bacteriuria, influenza, pharyngitis, bronchitis, etc., which may worsen the symptoms of chronic nephritis.

　　3. Actively prevent and treat infection foci, and actively prevent acute nephritis. Reduce the opportunities for body infection, prevent catching a cold and catching a chill, and prevent diseases such as common cold, suppurative tonsillitis, and skin suppurative infection. Once infected with the above diseases or acute nephritis and other primary glomerular diseases, timely and thorough treatment should be given. For patients with acute nephritis who have chronic infection foci, after the condition is stable for 3 to 6 months, surgery or other methods can be used for radical treatment if necessary, to prevent these diseases from lingering and developing into chronic nephritis.

　　4. Pay attention to diet and nutrition. Renal disease patients should avoid high-protein diets, pay attention to food safety, and eat more fresh fruits and natural foods. The principle should be variety, reasonable matching, and delicious taste.

　　1. Urine tests

　　It is generally a small amount of low molecular weight proteinuria, with urinary protein excretion often between 0.5 to 1.5g/24h, rarely >2g/24h; urinalysis may show microscopic hematuria, leukocytes, and casts, and occasionally eosinophils. Abnormal renal tubular function may present differently depending on the site and extent of tubular involvement, and may include renal glycosuria, renal tubular acidosis, hypotonic urine, Fanconi syndrome, etc.

　　2. Blood tests

　　Some patients may have symptoms such as hypokalemia, hyponatremia, hypophosphatemia, and hyperchloric metabolic acidosis. Blood uric acid is usually normal or slightly elevated. The incidence of anemia in chronic interstitial nephritis is high, and the degree is severe, often presenting as normocytic normochromic anemia. Patients with acute interstitial nephritis may have an increased proportion of eosinophils in peripheral blood, which may be accompanied by elevated IgE. Idiopathic interstitial nephritis may present with anemia, increased eosinophils, rapid sedimentation rate, elevated CRP, and globulin.

　　3. Imaging examinations

　　B-ultrasound for acute interstitial nephritis can show normal kidney size or increased volume, with enhanced cortical echo. B-ultrasound, radionuclide, CT, and other imaging examinations usually show shrinkage of both kidneys and irregular kidney contour. Imaging examinations also help determine certain special causes, such as urinary tract obstruction, vesicoureteral reflux, kidney cystic diseases, etc. Intravenous urography (IVU) can show characteristic renal papillary necrosis in analgesic nephropathy. Due to the tubular toxicity of contrast agents, they should be used with caution in cases of tubular injury.

　　4. Renal biopsy pathology

　　Pathological examination is of great significance for diagnosis. In addition to acute interstitial nephritis related to infection, active renal biopsy should be performed for other types to distinguish the type and degree of interstitial infiltration cells, thereby helping to determine the treatment plan and predict the prognosis.

　　Acute interstitial nephritis has an obvious renal tubular interstitial lesion, mainly manifested as diffuse inflammatory cell infiltration and interstitial edema. The infiltrating cells in acute interstitial nephritis caused by drugs are often distributed in patches, mainly located at the cortex-medulla junction at the beginning of the disease, and in severe acute interstitial nephritis, the infiltrating cells are diffusely distributed. The infiltrating cells are mainly T cells, monocytes, and macrophages; plasma cells, eosinophils, and neutrophils may be present. In some special cases, granulomatous lesions can be seen around the interstitium or damaged tubules. The types of infiltrating cells in acute interstitial nephritis caused by different reasons vary; acute interstitial nephritis related to beta-lactam antibiotics is mainly CD4+ cells; in patients with cimetidine and NSAIDs, CD8+ cells are more than CD4+ cells. More than 50% of patients have CD14+ macrophages in the renal tissue, and granulomas are mainly composed of CD4+ cells and macrophages. Drug-induced allergic interstitial nephritis with more eosinophil infiltration also shows eosinophilic tubulitis. In acute interstitial nephritis associated with infection, there is more neutrophil infiltration in the interstitium, and the infiltrating cells in tubulitis are mostly neutrophils.

　　The basic pathological manifestations of chronic interstitial nephritis are multifocal or large-scale fibrosis of the interstitium under light microscopy, which may be accompanied by infiltration of lymphocytes and monocytes, atrophy,变性, and dilation of renal tubules, thickening of the basement membrane of renal tubules, ischemic contraction or sclerosis of glomeruli, varying degrees of thickening of the intima of small arteries and arterioles, narrowing or occlusion of lumens, but without manifestations of vasculitis. Immunofluorescence is negative. Electron microscopy is not significant for the diagnosis of chronic interstitial nephritis. Under electron microscopy, regenerating renal tubules show new and basement membrane-like substances, leading to TBM stratification. Chronic interstitial nephritis caused by immune diseases can be seen under electron microscopy with dense deposits, and light chain deposition disease shows TBM with clustered needle-like dense deposits.

　　1. Make full use of the inherent flavors of the materials and food

　　Choose fresh seasonal materials and make full use of the inherent flavors of the materials. Whether it is fish, vegetables, or fruits, those produced in the season are fresher, and the same cooking method can produce different flavors.

　　2. Make good use of acidity and fragrance

　　Acetic acid or the fragrance of citrus fruits can be used as vinegar for salads. If the materials are fresh, even a small amount of salt is very delicious. Adding the juice of lemons, limes, oranges, and tangerines to the dishes will enhance the taste and aroma of the cooked dishes.

　　3. Use spicy seasonings for flavoring

　　You can add some coffee cream powder, pepper, ginger, Chinese cabbage, chili, etc. to the dishes, which not only makes the dishes more delicious but also adds to the atmosphere of the dining table.

　　1. Traditional Chinese medicine treatment

　　Treatment and herbal medicine:

　　1. Deficiency of spleen and kidney

　　Treatment method: Strengthening the spleen and kidney.

　　Herbal medicine: For patients with spleen and kidney qi deficiency, use Wu Zi Yan Zong Wan with additional Shen Qi; for those with spleen and kidney yang deficiency, use Wu Bi Shan Yao Wan or modified Shen Qi Wan; for patients with both spleen and kidney qi and yin deficiency, use modified Shen Qi Di Huang Decoction (including dang shen, raw huang qi, mai dong, wu wei zi, raw di huang, Shan yao, Shan yu mu, dan pi, fu ling, ze xie, du zhong, niu xi, chi suo zi).

　　2. Yin deficiency of the Liver and Kidney

　　Treatment method: Tonify the Liver and Kidney.

　　Herbal medicine: Use modified Qijuhua Dihuang Decoction (Gouqizi, Juhua, Shengdi, Shanyao, Shanyao, Danshen, Fuling, Zexie, Duzhong, Niuxi, Sangshen, Danggui, Chishao) or modified Dabuyuan Decoction.

　　3. Deficiency of both Qi and blood

　　Treatment method: Tonify Qi and nourish blood.

　　Herbal medicine: Use Baizhen Decoction or Shiqian Buwei Pill. The medicinal materials include Danshen, Baizhu, Fuling, Gancao, Shengdi, Danggui, Baishao, Chuanxiong, Shanyao, Longyanrou, Chenpi, Banxia, Guangmuxiang, Shaoren.

　　4. Internal Obstruction of Dampness and Turdus

　　Treatment method: For damp-heat, add modified Huanglian Wencan Decoction (Chenpi, Banxia, Fuling, Gancao, Huanglian, Zhishi, Zhuru, Baiziren, Shengdahuang, Shengjiang) and Sanren Decoction; for cold-dampness, use Weifeng Decoction and Shisai Decoction.

　　Second, Western Medicine Treatment

　　1. Symptomatic treatment

　　The natural course of chronic interstitial nephritis varies from person to person. If the primary etiology can be treated in the early stage, it can often delay the progression of the disease, and sometimes the kidney function can also be improved to some extent, the most prominent example being the relief of urinary tract obstruction. If the etiology cannot be removed or the disease progresses to the late stage, at the level of renal insufficiency, the progression to the terminal stage of the disease is slower than that of chronic glomerulonephritis. Proper treatment of hypovolemia, acidosis, hyperkalemia, or hypertension can often reverse the rapidly deteriorating kidney function. Terminal renal failure can be treated with dialysis and kidney transplantation.

　　2. Treatment of the etiology

　　(1) Urinary tract infection: For chronic interstitial nephritis caused by bacterial infection, antibiotics should be used to combat infection. Pay attention to the changes in bacterial sensitivity, dosage, and course of treatment, and adjust the dosage of the drug according to the kidney function status, and try to choose drugs with little kidney toxicity.

　　(2) Analgesic nephritis: Early diagnosis is very important, and the relevant drugs should be stopped as soon as the diagnosis is made. Reducing the dosage of analgesics can help prevent the occurrence of the disease.

　　(3) Obstructive nephritis: Release the obstruction according to the cause of obstruction, control the infection at the same time, and preserve kidney function.

　　(4) Toxic nephritis: For toxic nephritis caused by drugs, the drug should be discontinued. For toxic nephritis caused by heavy metals, the exposure should be reduced and detoxification drugs should be used.

　　(5) Other primary diseases: The treatment can refer to the treatment of relevant diseases.