bubble_chart Overview

Interstitial nephritis is a clinical syndrome primarily characterized by renal interstitial inflammation and renal tubular dysfunction caused by various factors. The renal interstitium refers to the tissue distributed between renal tubules and glomeruli, including fibrous connective tissue, blood vessels, lymphatic vessels, and nerve fibers. The interstitium is sparse and loosely distributed in the cortex, which is rich in glomeruli, while it is denser and more abundant in the medulla, the main region of renal tubules, particularly at the tips of renal pyramids (renal papillae). Therefore, interstitial nephritis rarely affects glomeruli but often occurs concurrently with tubular damage, with a close relationship between the two, hence it is also termed tubulointerstitial nephritis. When the pathological changes are predominantly atrophy, sclerosis, or tumor cell infiltration, it is referred to as tubulointerstitial nephropathy. Tubulointerstitial diseases account for 1.91% of autopsy cases. Among cases of unexplained acute kidney failure, acute interstitial nephritis constitutes 14%. With timely treatment, renal function can often return to normal, and the prognosis is generally favorable.

bubble_chart Etiology

The disease cause and pathogenesis of interstitial nephritis are complex and can be summarized into the following categories:

Interstitial nephritis has a complex disease cause, which can be broadly classified into the following types:

1. **Infection**: Bacteria or viruses directly invade the renal interstitium, or immune reactions triggered by infections damage the tubulointerstitium, such as in pyelonephritis, renal subcutaneous nodules, and various systemic infectious diseases.
2. **Toxicity**: Common nephrotoxic substances include drugs such as antibiotics (aminoglycosides, cephalosporins, polymyxins, ampicillin, amphotericin B, rifampin, etc.), sulfonamides, nonsteroidal analgesics, thiazide and loop diuretics, and antineoplastic agents. Other substances like allopurinol, cimetidine, and captopril can also cause acute interstitial nephritis. Iodinated contrast agents and heavy metals (e.g., lead, cadmium) may also induce it, though less commonly than drugs.
3. **Immune factors**: Drug allergies (e.g., penicillins, sulfonamides, cephalosporins, rifampin) and immune-related diseases (e.g., systemic lupus erythematosus, scleroderma, renal transplant rejection, Sjögren’s syndrome) can cause immune-mediated renal interstitial damage.
4. **Metabolic disorders**: Prolonged presence of high concentrations of metabolites in the urine, such as in diabetes, hyperuricemia, hyperoxaluria, hypercalcemia, Bence Jones proteinuria, and hypokalemia or hyponatremia, can lead to interstitial nephritis.
5. **Circulatory disturbances**: Conditions like renal artery stenosis, renal arteriolosclerosis, acute tubular necrosis, and sickle cell disease can cause insufficient blood supply to the renal interstitium, resulting in damage.
6. **Urinary tract obstruction**: Any cause of urinary tract obstruction leading to hydronephrosis, increased tubular pressure, or urinary tract infections can damage the renal interstitium.
7. **Tumors**: Leukemia and lymphoma can directly infiltrate the renal interstitium, and metastatic cancer cells can also cause interstitial damage.
8. **Genetic factors**: Hereditary conditions such as hereditary nephritis, medullary cystic kidney disease, and congenital polycystic kidney disease often present with interstitial damage as an early manifestation.
9. **Physical factors**: Radiation, electric shock, and heatstroke can also cause interstitial nephropathy.
10. **Unknown causes**: In about 10% of cases, the disease cause is unknown, termed idiopathic interstitial nephritis.

The **pathogenesis** varies depending on the disease cause and can be classified into immune and non-immune mechanisms. Non-immune mechanisms often involve direct damage by causative factors (e.g., infection, toxicity, physical injury, tumor cell infiltration, ischemia). Immune mechanisms involve immune reactions triggered by causative factors entering the body, initially injuring renal tissue and converting it into an antigen, which stimulates antibody production, leading to immune-mediated renal injury.

**Pathology**

1. **Acute interstitial nephritis**: The kidneys are enlarged, with interstitial edema and cellular infiltration, predominantly lymphocytes, monocytes, and plasma cells, often accompanied by eosinophils and neutrophils. Fibrous connective tissue proliferation is mild. Renal tubular epithelial cells show cloudy swelling, varying degrees of focal necrosis, and dilated lumens. In immune-mediated cases, immunoglobulins and C3 deposits are found in the tubular basement membrane and interstitium.
2. **Chronic interstitial nephritis**: The kidneys are asymmetrically shrunken, with a scarred and uneven surface, possibly with renal capsule adhesions. The renal pelvic mucosa thickens, and calyces dilate. The interstitium shows grade I edema with lymphocyte and plasma cell infiltration. Tubular epithelial cells atrophy or flatten, with localized or diffuse fibrosis and scarring, leading to distal tubular distortion and proximal tubular dilation. Fibrotic scar areas show hyaline degeneration and intimal hyperplasia in small and micro-arteries. Glomeruli may exhibit fibrosis and hyalinization, while those outside scarred areas remain normal or show only mild changes. Analgesic nephropathy primarily manifests as renal papillary necrosis, with necrotic papillae partially or completely sloughing off or calcifying. Interstitial nephritis caused by systemic diseases often shows characteristic changes of the primary condition, such as leukemia or other tumor cell infiltration.

bubble_chart Clinical Manifestations

Acute Interstitial Nephritis

(1) Systemic Manifestations

For those caused by infection, the onset is usually abrupt, with sudden high fever, shivering, and systemic sepsis-like symptoms. There is an increase in polymorphonuclear leukocytes in the blood with a left shift. For those caused by drug allergies, there is often a history of sensitizing drug use, with fever, rash, arthralgia, and lymphadenopathy occurring during medication. Blood eosinophils and IgE levels are elevated.

(2) Renal Damage Manifestations

Acute inflammation and edema of the renal interstitium often lead to lumbago and tenderness in the kidney area upon percussion. Urinary protein excretion is less than 1.5g/day, characterized by small-molecular tubular proteinuria, with a small number of red and white blood cells and casts. In cases caused by infection, urine culture reveals corresponding pathogenic bacteria. In drug-induced cases, there may be sterile leukocyturia, with urinary sediment eosinophils accounting for more than 10%. Severe cases may develop acute renal failure.

Chronic Interstitial Nephritis

Clinical manifestations of the primary disease may be present, but the onset is often insidious, with diagnosis sometimes made only after renal impairment appears. Tubulointerstitial damage presents with the following features.

(1) Impaired Urinary Concentration Function

Due to damage to the renal medullary tubules, impaired urinary concentration is a prominent feature, such as polydipsia, polyuria, nocturia, decreased urine specific gravity and osmolality, with maximum urine osmolality <500–600 mOsm/L water, and even diabetes insipidus.

(2) Impaired Urinary Acidification Function

Reduced renal excretion of H⁺ and ammonia leads to renal tubular acidosis, which can easily cause hypokalemia, hyponatremia, and hypocalcemia, resulting in symptoms such as lack of strength, paralysis, and convulsion.

(3) Renal Papillary Necrosis

In the acute phase, symptoms include sudden fever, gross hematuria, lumbago, and urinary tract irritation. Necrotic tissue or blood clots blocking the ureter may cause renal colicky pain. Pyelography may reveal a ring-shaped shadow in the renal papillary area, along with filling defects and deformities.

(4) Chronic Renal Insufficiency

Symptoms of uremia may include nausea, vomiting, lethargy, and anemia. Elevated serum creatinine and hematuria nitrogen levels are observed. Pyelography shows deformities of the renal pelvis and calyces, and B-ultrasound reveals asymmetrical shrinkage of the kidneys.

bubble_chart Treatment Measures

1. Symptomatic treatment: The natural course of chronic interstitial nephropathy varies. If the primary disease cause can be treated early, the progression of the disease can often be delayed, and sometimes kidney function may improve to some extent. The most prominent example is the relief of urinary tract obstruction. If the disease cause cannot be removed or the disease progresses to an advanced stage, the speed at which the disease progresses to the end stage is slower than that of chronic glomerulonephritis when the level of renal insufficiency is comparable. By appropriately treating low volume, acidosis, hyperkalemia, or hypertension, the acute deterioration of renal function can often be reversed. End-stage renal failure can be treated with dialysis and kidney transplantation.
2. Disease cause treatment:
   1. Urinary tract infection: For chronic interstitial nephritis caused by bacterial infection, antibiotics should be used for anti-infection. Pay attention to changes in bacterial sensitivity, dosage, and course of treatment when using medication, and adjust the drug dosage according to the state of renal function. Try to choose drugs with less renal perianal abscess toxicity.
   2. Analgesic nephropathy: Early diagnosis is crucial. Once diagnosed, the relevant drugs should be discontinued immediately. Reducing the dosage of phenacetin helps prevent the occurrence of this disease.
   3. Obstructive nephropathy: The obstruction should be relieved according to the disease cause of the obstruction, while controlling infection and preserving renal function.
   4. Toxic nephropathy: For toxic nephropathy caused by drugs, the drug should be discontinued. For toxic nephropathy caused by heavy metals, exposure should be reduced and removing toxin drugs should be used.
   5. Other primary diseases: Their treatment can refer to the treatment of related diseases.

bubble_chart Prognosis

The prognosis of chronic interstitial nephritis varies depending on the disease cause and the degree of renal function impairment. When the disease cause can be completely eliminated, chronic interstitial nephritis can be cured. If it has progressed to the stage of chronic renal insufficiency, it often leads to chronic renal failure, resulting in a poor prognosis.