Tubulointerstitial diseases

These are acute or chronic non-glomerular disorders that involve the renal tubules and/or interstitium. They can lead to renal failure and chronic kidney disease.

Tubulointerstitial nephritis (TIN) / interstitial nephritis: This is inflammation of the renal interstitium. The most common cause is drug exposure, such as NSAIDs, beta-lactam antibiotics, and rifampin. Other causes include infectious and inflammatory conditions such as CMV, polyoma virus, HIV, adenoviruses, EBV, Mycoplasma pneumoniae, Yersinia pseudotuberculosis, Leptospira, IBD, sarcoidosis, SLE, Sjogren’s disease, tuberculosis, systemic fungal infections, and heavy metals such as lead and cadmium. A wide variety of drugs have been implicated in TIN.

TIN may be acute or chronic.

• Acute TIN shows interstitial edema and infiltration with lymphocytes and plasma cells. This can disrupt blood supply to tubulointerstitial structures, leading to damage, decreased GFR, and acute kidney injury (AKI).
• Chronic TIN is characterized by fibrosis of tubulointerstitial structures and decreased GFR. It occurs when the inciting stimulus is prolonged, leading to persistent macrophages, increased TGF-beta, and fibrosis.

Drug-induced TIN is a hypersensitivity reaction to the drug.

• Biopsy shows inflammatory infiltration with eosinophils and lymphocytes, along with interstitial edema.
• Neutrophils may be seen in bacterial infections.
• Granulomas with giant cells may be seen in sarcoidosis, tuberculosis, systemic fungal infections, and certain drugs such as lamotrigine.

Clinical presentation is often non-specific and typically occurs 2-3 weeks after drug exposure. Symptoms may include rash, fever, arthralgia, myalgia, fatigue, and flank or abdominal pain.

• TIN with uveitis (TINU syndrome) is seen in Sjogren’s syndrome, IBD, and sarcoidosis.

Investigations

• Ultrasound shows enlarged kidneys.
• BUN and creatinine are elevated.
• Hyperkalemic hyperchloremic metabolic acidosis may occur.
• Urine exam may show eosinophils, sterile pyuria, proteinuria, WBC casts, and rarely hematuria.

Complications

• Fanconi’s syndrome may occur, with aminoaciduria, glycosuria, increased fractional excretion of sodium in urine, and electrolyte and acid-base abnormalities.

Treatment

• Stop the offending drug.
• Corticosteroids.
• Mycophenolate mofetil or other immunosuppressive agents.

Acute tubular necrosis (ATN): This is destruction of tubular epithelial cells with resulting acute loss of renal function.

Common causes include renal ischemia from hypotension, sepsis, major surgery, burns, hemolysis and rhabdomyolysis, multiple myeloma, and toxins such as ethylene glycol, some herbal medicines, radiocontrast material, cisplatin, aminoglycosides, amphotericin B, NSAIDs, cyclosporine, tacrolimus, vancomycin, and tumor lysis syndrome.

Because of its rich blood supply and ability to concentrate toxins to high levels, the kidney is particularly vulnerable to toxic injury. The risk of renal damage from contrast medium is greatest in older adults, those with diabetes, and those with kidney disease.

Clinical features

• ATN presents with renal failure and oliguria.
• Signs of fluid retention may occur, including edema, pulmonary edema, seizures, and hyperkalemia.
• During the recovery phase, polyuria may be seen.

Diagnosis

• ATN is suspected when serum creatinine rises ≥ 0.3 mg/dL/day above baseline or increases by 1.5-2.0 times from baseline.
• It may occur a few days after the inciting event.
• Unlike pre-renal azotemia, in ATN, intravenous saline typically causes no increase in urine output and no rapid change in serum creatinine.

Urinalysis and related findings

• BUN/creatinine ratio of 10-15/1
• Urine osmolality < 450
• Urine specific gravity < 1.010
• Urine sodium > 40
• Fractional excretion of sodium > 2%
• Characteristic muddy brown granular casts made of necrotic tubular epithelial cells

Treatment

• Supportive care.
• Stop all nephrotoxic agents.
• Diuretics to increase urine output.
• Temporary dialysis may be required.

Prevention of contrast nephropathy

• Hydrate with intravenous saline 6-12 hours before the procedure.
• Acetylcysteine.

Renal papillary necrosis: This is necrosis of the renal papillae and inner portions of the renal medulla. It results from impaired vascular supply to the inner medulla, leading to necrosis and sloughing of the renal papillae.

Common causes include diabetes mellitus, analgesic abuse, sickle cell anemia, pyelonephritis, renal vein thrombosis, ATN, chronic alcoholism, obstructive uropathy, and tuberculosis.

NSAIDs cause vasoconstriction by inhibiting prostaglandin synthesis, which can aggravate medullary ischemia, especially in people with chronic renal and vascular diseases. Persistent medullary ischemia results in irreversible loss of papillary tissues (collecting ducts) and fibrosis. Sloughed papillae can cause mechanical obstruction of the collecting system. In severe cases, adjoining cortical areas may also be involved.

Clinical features

• Acute renal failure
• Fever and chills
• Flank pain
• Hematuria
• Anuria or oliguria

Pathology and imaging

• Biopsy shows coagulation necrosis.
• Early CT changes include poorly delineated areas with hypo-enhancement at the tip of the medullary pyramid.
• Necrotic areas may be seen when contrast material fills the empty spaces.
• Calcified areas and blunting of calyces may be seen.
• Urography can visualize the collecting system.

Treatment

• Supportive therapy
• Antibiotics
• Hydration
• Blood sugar control
• Surgical relief of urinary tract obstruction with percutaneous nephrostomy
• Ureteral stenting
• Extraction of sloughed papillae

Some patients may require nephrectomy as a life-saving measure.