Overview
It is a syndrome with acute and chronic damage to the renal tubular mesenchyme as the main pathological manifestation Common symptoms include abnormal urine output, nocturia, foamy urine, hematuria, fatigue, back pain, nausea, etc. Drugs and infections are the most common causes, which also include a history of nephrotoxic exposure, tumors, and autoimmune disorders, etc. Treatments include general treatment, medication, and symptomatic supportive treatment
Definition
Interstitial nephritis is a syndrome originating in the renal interstitium with acute and chronic damage to the renal tubular interstitium as the main pathologic manifestation.
It is also known as tubulointerstitial nephritis because of the frequent involvement of renal tubules in interstitial nephritis, which causes tubular dysfunction.
Classification
Interstitial nephritis is categorized into acute interstitial nephritis and chronic interstitial nephritis according to the degree of urgency and slowness of the onset of the disease and the different pathological changes.
Acute interstitial nephritis
Multiple causes, drugs and infections are the most common causes.
The onset of disease is rapid.
The main pathological manifestations are inflammatory cell infiltration and renal interstitial edema.
Glomeruli and renal blood vessels are not involved or the lesions are mild.
Renal tubular dysfunction is the main manifestation, with or without decreased glomerular filtration function.
Chronic interstitial nephritis
It is caused by a variety of etiological factors, such as history of exposure to nephrotoxic substances, infection, tumor, autoimmune disease, etc..
It has an insidious onset and a long course.
Pathologic manifestations are dominated by chronic lesions, in which renal interstitial fibrosis, renal interstitial inflammatory cell infiltration and renal tubular atrophy are more prominent.
Usually, early glomeruli and renal vessels are not involved or are relatively mildly involved, but in the late stage of the disease, glomerulosclerosis and thickening of the wall of small blood vessels or tubular lumen occlusion can be seen if the glomeruli are involved in the late stage of the disease.
Causes
Causes
The most common cause of interstitial nephritis is drugs. Other causes include autoimmune diseases, infections, tumors, metabolic diseases, and some hereditary diseases.
The causes of acute and chronic interstitial nephritis are not identical.
Acute interstitial nephritis
Drugs
Antibiotics such as penicillins (e.g., penicillin G) and cephalosporins (e.g., ceftriaxone, cefoperazone), macrolides (e.g., azithromycin, erythromycin, etc.) and others (e.g., lincomycin, chloramphenicol, tetracycline, vancomycin, and sulfamethoxazole, etc.).
Nonsteroidal anti-inflammatory drugs (e.g., aspirin, ibuprofen, naproxen, salazosulfapyridine, indomethacin, diclofenac, and meloxicam) and antipyretic and analgesic drugs (e.g., aminophenazone, antifungal, etc.).
H2 receptor blockers (e.g. cimetidine, famotidine, ranitidine) and proton pump inhibitors (e.g. omeprazole, lansoprazole, pantoprazole, etc.).
Diuretics (e.g. furosemide, hydrochlorothiazide, indapamide, aminopterin, etc.).
Other medications (e.g., allopurinol, azathioprine, penicillamine, captopril, warfarin, etc.)
Infections
Systemic infections (including brucellosis, streptococcal infections, Mycoplasma pneumonia, infectious mononucleosis, cytomegalovirus disease, leptospirosis, etc.)
Primary renal infections (including pyelonephritis, renal tuberculosis, and renal fungal infections, etc.)
Immunologic
Including secondary connective tissue diseases (e.g., systemic lupus erythematosus, primary dry syndrome, necrotizing vasculitis, and IgG4-related diseases) and acute rejection disease of transplanted kidneys.
Idiopathic
Substances mediating immune injury, including endogenous renal tubular basement membrane components, etc., and exogenous, such as drugs and chemicals, causing delayed hypersensitivity reactions and cytotoxic T-lymphocyte damage, leading to increased extracellular interstitium, renal interstitial fibrosis, and tubulopenia.
Chronic interstitial nephritis
Primary
Drug-induced (e.g., analgesics, 5-aminosalicylic acid, nonsteroidal anti-inflammatory drugs, herbs, etc.)
Toxic substances (e.g. lithium, lead, cadmium, Balkan regional nephropathy)
Metabolic abnormalities (e.g., abnormal uric acid metabolism, hypokalemia, hypercalcemia, hyperoxaluria, etc.)
Immune-mediated (e.g., tuberculosis, dry syndrome, etc.)
Infections (e.g., bacterial pyelonephritis, hantavirus, leptospirosis, etc.)
Blood disorders (e.g. sickle cell disease, light chain disease, amyloidosis, etc.)
Secondary
Chronic tubulointerstitial nephritis caused by further development of lesions originating in the renal vasculature and glomeruli to the tubulointerstitial sites.
Symptoms
Interstitial nephritis is mainly characterized by renal tubular dysfunction. The clinical manifestations of acute interstitial nephritis vary in severity and are not specific. Chronic interstitial nephritis is characterized by slow progress. In addition to this, other systemic symptoms are also included.
Acute interstitial nephritis (AIN)
The clinical manifestations of AIN vary in severity and are non-specific, and the following symptomatic manifestations are often seen.
Allergic symptoms
Drug-associated AIN, which may develop 2 to 3 weeks after drug administration. Fever, rash, joint pain and low back pain are often present, but blood pressure is mostly normal and there is no edema.
Abnormal urine output
20%～50% of patients may have oliguria or anuria, accompanied by varying degrees of azotemia, about 1/3 of patients with severe uremia symptoms, the development of acute renal failure, oliguria or non-oliguria type can be seen.
Urinalysis abnormalities
95% of patients have hematuria, and a few of them may have microscopic hematuria; some patients may have aseptic pyuria, and a few patients may have eosinophilic granulocyturia. Proteinuria is often mild to moderate, usually less than 2 g. A small number of AINs due to NSAIDs or interferons may be associated with large amounts of proteinuria, which is associated with microscopic glomerular lesions.
Renal tubular function impairment
Renal tubular function impairment is prominent, with common renal glycosuria, small molecule proteinuria, increased urinary β2-MG and NAG excretion, and decreased urine specific gravity and osmolality. Type I renal tubular acidosis, occasional Fanconi syndrome, and electrolyte disorders are seen.
Chronic interstitial nephritis (CIN)
CIN presents with signs and symptoms of renal tubular insufficiency, with a slow and insidious clinical progression.
Pre-existing manifestations
Proximal tubular reabsorption dysfunction leads to nephrogenic diabetes mellitus. Impairment of distal renal tubular concentrating function leads to hypospecific gravity urine, decreased urine osmolality and increased nocturia prominently. Thereafter, proteinuria gradually appears, which is tubular proteinuria, and proteinuria rarely exceeds 2 g/d. Aseptic pyuria is often seen. Aseptic pyuria is often seen, and renal tubular acidosis is common.
Late stage
Progressive glomerular hypoplasia occurs in the late stage, and uremia eventually develops. 60% to 90% of patients have varying degrees of anemia, which is not parallel to the degree of impaired glomerular function.
Consultation
Department of Medicine
Nephrology
It is recommended to consult the Nephrology Department when there is abnormal urine output, increased nocturia, foamy urine, hematuria, and so on.
Emergency Department
If you experience severe pain in the kidney area, nausea, vomiting, etc., it is recommended that you consult the Emergency Department promptly.
Preparation for medical treatment
Preparation for medical consultation: registration, preparation of documents, common problems
Tips for seeking medical treatment
Try to keep a record of your 24-hour urine output before going to the doctor, and you can approximate it by recording the number of times you urinate.
Preparation Checklist
Symptom list
Pay particular attention to the time of onset of symptoms, special manifestations, etc.
How many times did you urinate during the day? Is there any change in the color or character of the urine? Is there an increase in nocturia?
Are there any symptoms of fever and any recent infections?
Are there any symptoms of pain or colic in the kidney area?
Are there any symptoms of nausea, vomiting, and generalized weakness?
List of medical history
Have certain medications (e.g., antibiotics, painkillers, etc.) been applied in the last 2 to 3 weeks?
Is there any history of exposure to radioactive or heavy metal substances?
Any autoimmune disease?
Is there any history of chronic pyelonephritis, polycystic kidney disease, obstructive nephropathy?
Is there any tumor or other related disease?
Has there been any kidney transplantation?
Checklist
Test results in the last six months, which can be brought to the doctor’s office
Laboratory examination: blood routine, urine examination, blood biochemistry (renal function, electrolytes, carbon dioxide binding capacity), immunological examination (anti-nuclear antibody, anti-double-stranded DNA antibody, anti-SSA, anti-SSB, IgG, etc.).
Imaging examination: renal ultrasound, CT examination.
Other tests: renal pathology biopsy.
List of medications used
Medication used in the last 3 months, if there is a box or package of medication, you can bring it with you to the doctor’s office
Glucocorticoid: prednisone, etc.
Immunosuppressants: cyclophosphamide, mertiomacrolide, etc.
Diagnosis
Diagnosis based on
Medical history
A clear history of drug use, heavy metal exposure, infection, chronic pyelonephritis, immune system disorders and other systemic diseases.
Clinical manifestations
The clinical manifestations of acute interstitial nephritis vary in severity and are not specific. Chronic interstitial nephritis is characterized by slow progress.
The clinical manifestations of interstitial nephritis vary with different causes. However, all interstitial nephritis usually has renal tubular dysfunction as the main clinical symptom.
Symptoms include abnormal urine output, increased nocturia, proteinuria, hematuria, malaise, nausea, joint pain, muscle weakness, and renal colic. Acidosis and anemia to a degree not parallel to renal function may also occur in advanced stages.
Laboratory Tests
Routine blood tests
To find out whether the patient has developed hematologic damage.
The presence of increased peripheral blood eosinophils may guide the etiologic determination of acute interstitial nephritis. Decrease in hemoglobin may be of significance in the diagnosis of chronic interstitial nephritis.
Urinalysis
It is mainly used to evaluate the presence of microscopic hematuria, proteinuria, leukocyturia and the presence of tubular damage.
The presence of hematuria, aseptic pyuria, eosinophilic granulocyturia, mild to moderate proteinuria, or nephrogenic glycosuria, increased urinary β2-microglobulin (MG), N-acetyl-β-D-glucosidase (NAG) and other excretion, and decreased specific gravity and osmolality of the urine, etc., are conducive to the diagnosis of interstitial nephritis.
Blood biochemistry
It mainly includes renal function, electrolytes, carbon dioxide binding capacity and so on.
It is mainly to check whether the patient’s renal function is impaired, whether there are electrolyte disorders and metabolic acidosis.
The presence of elevated blood creatinine, normal or mildly elevated blood uric acid, and progressive glomerular hypoplasia may suggest impaired renal function.
Low blood potassium, low blood calcium, low blood phosphorus, low carbon dioxide, etc. may suggest electrolyte disorders, metabolic acidosis, and may assist in the diagnosis of interstitial nephritis.
Immunologic examination
Including anti-nuclear antibody, anti-double-stranded DNA antibody, anti-SSA, SSB and IgG.
Positive antinuclear antibodies, anti-double-stranded DNA antibodies, anti-SSA, and anti-SSB antibodies usually indicate the presence of immune system disorders, such as systemic lupus erythematosus and desiccation syndrome, which may lead to interstitial nephritis.
The presence of elevated serum IgG4 subtype is mostly suggestive of IgG4-related diseases.
Imaging examination
Renal ultrasound
Renal ultrasound can indicate the condition of renal lesions and observe whether the volume of the kidney changes.
Acute interstitial nephritis has normal or mildly enlarged size of both kidneys and enhanced cortical echogenicity, but these manifestations are not unique to acute interstitial nephritis, so ultrasound is not specific for the diagnosis of acute interstitial nephritis.
Chronic interstitial nephritis renal ultrasound examination can see bilateral kidney shrinkage, which helps the diagnosis of chronic lesions.
CT examination
CT examination is usually helpful in determining certain specific etiologies, such as urinary tract obstruction, vesicoureteral reflux, and cystic disease of the kidneys.
It can check the size of the kidneys, and for patients with chronic interstitial nephritis, it shows the manifestations of bilateral kidney shrinkage and irregular renal contour; CT urography can show the signs of renal papillary necrosis characteristic of painkiller nephropathy, all of which are conducive to the diagnosis of the disease.
Pathologic biopsy
Renal biopsy is the gold standard for the diagnosis of interstitial nephritis.
Acute interstitial nephritis is characterized by inflammatory cell infiltration and renal interstitial edema, and glomeruli and renal blood vessels are usually uninvolved or have very mild lesions.
Chronic interstitial nephritis is mainly characterized by renal interstitial fibrosis, chronic inflammatory cell infiltration, and renal tubular atrophy. In the advanced stage, the glomeruli are surrounded by fibrous tissue and sclerosis occurs.
Differential diagnosis
Incomplete obstructive nephropathy
Similarities: both characterized by tubulointerstitial damage.
Differences: Obstructive nephropathy has a history of obstructive diseases such as tumors and stones, and interstitial nephritis should be differentiated from it in terms of history of medications, exposures, and history of underlying diseases, in addition to obstructive nephropathy as a causative factor.
Hypertensive renal damage
Similarity: both are characterized by tubulointerstitial damage.
Differences: hypertensive renal damage has a history of hypertensive disease and poor blood pressure control. Blood pressure is usually normal in acute interstitial nephritis, and hypertension with renal failure can occur in the later stages of chronic interstitial nephritis. However, patients with hypertensive damage have a long history of hypertension with target organ damage to the heart and fundus to help differentiate them.
Treatment
Treatment aims: to promote the recovery of renal function, protect the residual renal function, delay further deterioration of renal function, and control and eliminate the causes of the disease.
Treatment principle: Interstitial nephritis treatment should firstly actively remove the pathogenic factors, such as suspicious drugs, infections and so on. At the same time, symptomatic treatment should be given for renal failure, anemia, electrolyte disorders and so on.
General treatment
Removal of causative factors
Remove the causative factors of interstitial nephritis by discontinuing the suspected drugs, fighting infection and treating the primary disease.
Immediately stop all drugs that may cause interstitial damage, if not, other safe drugs should be used instead.
In case of co-infections, antibiotics should be rationally applied to treat infectious interstitial nephritis.
If interstitial nephritis is induced by autoimmune diseases, tumors and other diseases, the primary disease should be actively treated to maximize the improvement and delay of further damage to the renal interstitium by the underlying disease.
Drug therapy
Glucocorticoid
It is mainly used for idiopathic acute interstitial nephritis, acute interstitial nephritis caused by immune diseases.
If drug-associated acute interstitial nephritis and infection-associated acute interstitial nephritis do not improve renal function after stopping sensitive drugs or controlling infection, or if the pathology suggests that the renal interstitium is infiltrated by diffuse inflammatory cells or granulomatous interstitial nephritis, it is necessary to give glucocorticoid treatment at an early stage.
Commonly used drugs are prednisone, etc.
It is recommended to use 4-6 weeks and then slowly reduce the dosage. If the drug is ineffective for 6 weeks, it suggests that the lesion has become chronic, and the hormone should be gradually stopped, and the drug should not be used for too long. Prolonged use is prone to secondary infections, osteoporosis, hypokalemia, hyperglycemia and so on.
Immunosuppressant
It is suitable for those who have no sign of remission or progressive deterioration of renal injury after 2 weeks of glucocorticoid application, and renal biopsy shows no or only mild interstitial fibrosis.
Commonly used drugs include cyclophosphamide, mertiomacrophenol ester and so on.
Note that if there is no improvement in renal function after 6 weeks of use, it suggests that the lesion may have become chronic and should be discontinued, while liver function should be checked during use. Adverse reactions include myelosuppression, nausea, vomiting, hyperuricemia, and alopecia.
Symptomatic supportive therapy
Acute interstitial nephritis
In case of oliguric acute renal failure, combined with hyperkalemia, pulmonary edema and other indications for renal replacement therapy, blood purification supportive therapy should be performed.
Blood purification treatment can choose continuous renal replacement, hemodialysis and so on.
Chronic interstitial nephritis
Correct electrolyte disorder and acid-base balance imbalance.
Supplement erythropoietin to correct renal anemia.
Control blood pressure.
If obvious uremic symptoms appear and there are indications for blood purification treatment, blood purification treatment should be carried out, and continuous renal replacement, hemodialysis, peritoneal dialysis, etc. can be chosen, and renal transplantation can also be carried out if conditions permit.
Prognosis
Cure
Acute interstitial nephritis
Most patients with acute interstitial nephritis have a good prognosis, while those with severe pathological damage or untimely or inappropriate treatment may be left with renal insufficiency and permanent renal impairment.
Chronic interstitial nephritis
The prognosis of chronic interstitial nephritis is closely related to the etiology, interstitial lesions and the degree of renal function impairment.
Thoroughly removing the cause of the disease can slow down the progression of chronic interstitial nephritis, and renal function may be relatively stable or improve to some extent in a few mild patients after stopping the drug, but renal function continues to progress in the majority of patients until they enter end-stage renal failure requiring dialysis or renal transplantation.
Prognostic factors
Pathogenic factors, duration of the disease, degree of renal function impairment, severity of interstitial inflammation and fibrosis, and whether the treatment is timely and appropriate may affect the efficacy, recovery time and degree of recovery.
Daily
Daily management
Dietary management
High-quality low-protein diet should be provided, such as lean meat and eggs.
Balanced nutrition, supplement foods rich in vitamins and fiber to promote metabolism and enhance immunity.
Pay attention to limiting potassium and sodium intake so as not to increase the burden on the kidneys and the risk of hyperkalemia and sodium retention.
Life management
Quit smoking and limit alcohol, ensure sufficient sleep, avoid staying up late, and increase or decrease clothing according to the temperature to prevent infection and aggravation of interstitial nephritis.
Maintain regular and moderate physical exercise. Avoid excessive exercise if renal failure has been reached.
Psychological support
Accept health education, understand the knowledge about interstitial nephritis, avoid wrong perception of the disease, and enhance the confidence of cure.
Maintain good mood and avoid anxiety. In case of anxiety, insomnia, depression, irritability, etc., friends and relatives should provide timely counseling to avoid psychological problems affecting the therapeutic effect.
Disease monitoring
Pay attention to record and monitor the 24-hour urine output, and observe the changes in urine color and character.
Monitor the blood pressure daily and control it under the doctor’s guidance if it rises.
Follow-up and review
Patients with interstitial nephritis should follow up regularly to monitor the changes of various indexes, so as to adjust the treatment plan in time and prevent the occurrence of complications.
Follow the doctor’s instructions for regular checkups, which should be done once a month for patients in acute stage and every 3-6 months for patients in chronic stage.
The review may need to do blood routine, urine routine, renal function, 24-hour urine protein quantification, urine NAG, urine β2-MG, renal ultrasound and other examination items.
Prevention
Interstitial nephritis cannot be prevented completely and effectively, but the risk of the disease can be reduced by avoiding nephrotoxic drugs, controlling infections, and actively correcting and treating the primary disease.
Avoid taking nephrotoxic drugs, avoid long-term reliance on analgesics, avoid exposure to harmful chemicals and radioactive substances, and actively fight infection if there is co-infection.
Regular physical examination, active correction and treatment of primary diseases, such as chronic pyelonephritis, renal tuberculosis, obstructive nephropathy, autoimmune diseases, tumors and so on.