Tubulointerstitial diseases

They include acute or chronic non-glomerular disorders that involve the renal tubules and/or interstitium. They may cause renal failure and chronic renal disease.

Tubulointerstitial nephritis/ interstitial nephritis or TIN: It is inflammation of the renal interstitium. Most common cause is drug exposure like NSAIDS, beta-lactam antibiotics , rifampin, followed by infectious and inflammatory conditions like CMV, polyoma virus, HIV, adenoviruses, EBV, Mycoplasma pneumoniae, Yersinia pseudotuberculosis, Leptospira, IBD, sarcoidosis, SLE, Sjogren’s disease, tuberculosis, systemic fungal infections, heavy metals like lead, cadmium etc. A wide variety of drugs have been implicated in TIN. It may be acute or chronic. Acute TIN shows interstitial edema, infiltration with lymphocytes and plasma cells, eventually disrupting blood supply to tubulo-interstitial structures that then results in damage, decreased GFR and acute kidney injury or AKI. Chronic TIN is characterized by fibrosis of the tubulo-interstitial structures and decreased GFR. It happens when the inciting stimulus is prolonged leading to local persistence of macrophages, increased TGF-beta and fibrosis. Drug induced TIN is a hypersensitivity reaction to the drug. Biopsy shows inflammatory infiltration with eosinophils and lymphocytes and 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 like lamotrigine. Presentation is non-specific with rash, fever, arthralgia, myalgia, fatigue, flank or abdominal pain, typically 2-3 weeks after drug exposure. TIN with uveitis (TINU syndrome) is seen in Sjogren’s syndrome, IBD and sarcoidosis. Ultrasound shows enlarged kidneys. BUN and creatinine will be elevated. Hyperkalemic hyperchloremic metabolic acidosis may occur. Urine exam will show presence of eosinophils, sterile pyuria, proteinuria, WBC casts and rarely hematuria. Fanconi’s syndrome may result with aminoaciduria, glycosuria, increased fractional excretion of sodium in urine, electrolyte and acid-base abnormalities. Treatment involves stopping the offending drug, corticosteroids, mycophenolate mofetil or other immunosuppressive agents.

Acute tubular necrosis (ATN): It is the destruction of tubular epithelial cells with resultant acute loss of renal function. Common causes are renal ischemia from hypotension, sepsis, major surgery, burns, hemolysis and rhabdomyolysis, multiple myeloma, toxins like 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. ATN presents with renal failure, oliguria, signs of fluid retention like edema, pulmonary edema, seizures, hyperkalemia while recovery phase shows polyuria. 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. Other urine analysis findings in ATN include BUN/creatinine ratio of 10-15/1; urine osmolality < 450; urine specific gravity <1.010, urine sodium > 40 and fractional excretion of sodium >2%. Characteristic muddy brown granular casts made of necrotic tubular epithelial cells are seen. Treatment is supportive. All nephrotoxic agents should be stopped. Diuretics are given to increase urine output. Temporary dialysis may be required. Contrast nephropathy is avoided by hydrating with intravenous saline 6-12 hours before the procedure and acetylcysteine.

Renal papillary necrosis: It is necrosis of renal papillae and inner portions of the renal medulla. It results from factors causing impairment of vascular supply to the inner medulla that results in necrosis and sloughing of the renal papillae. Common causes are 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 hence aggravating the 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. It may involve adjoining cortical areas in severe cases. Patients present with acute renal failure, fever, chills, flank pain, hematuria and anuria or oliguria. Biopsy shows coagulation necrosis. Early changes are seen on CT as poorly delineated areas with hypo-enhancement at the tip of the medullary pyramid. Necrotic areas can be seen when contrast material fills the empty spaces. Calcified areas and blunting of calyces can be seen. Urography can visualize the collecting system. Treatment is with supportive therapy, antibiotics, hydration, blood sugar control, surgical relief of urinary tract obstruction with percutaneous nephrostomy, ureteral stenting and extraction of sloughed papillae. Some patients may need nephrectomy as a life saving measure.