9.1 Acute interstitial nephritis
The histopathology of acute interstitial nephritis (AIN) includes edema and infiltration of the renal interstitium with inflammatory cells (mononuclear cells, T lymphocytes, plasma cells, and eosinophils), while the glomeruli and blood vessels are usually spared. AIN can eventually lead to interstitial fibrosis (chronic interstitial nephritis).
9.1.1 Causes of AIN
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Drug Induced: 70% to 75% ,
Not dose dependent, can recur/exacerbate with a second exposure to the same or a related drug
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Proton pump inhibitors
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Nonsteroidal antiinflammatory drugs (NSAIDs); may be accompanied by nephrotic syndrome
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COX-2 inhibitors
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Antibiotics (e.g., beta-lactams, rifampin, sulfa, ciprofloxacin)
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Diuretics
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Allopurinol
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Mesalamine
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Cimetidine
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Immune checkpoint inhibitors
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Systemic Diseases
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Systemic lupus erythematosus (SLE)
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Sarcoidosis
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Sjögren’s syndrome
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IgG4-related disease
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Tubulointerstitial nephritis with uveitis (TINU)
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Infections
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Acute bacterial pyelonephritis (polymorphonuclear leukocytes predominate)
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Leptospirosis
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Legionella
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Granuloma formation: mycobacterium, fungi, spirochetes, parasites
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Streptococcus, beta-hemolysis (Councilman’s nephritis)
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Viral: cytomegalovirus, Epstein-Barr virus (EBV), BK (polyoma) virus, HIV
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9.1.2 Clinical presentation of AIN
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“ Full-blown” presentation: Fever, rash, arthralgias, oliguria, renal insufficiency (acute kidney injury [AKI], acute renal failure [ARF]), but typically not all features are present.
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Urinalysis: White blood cells (WBCs), red blood cells (RBCs), WBC casts, eosinophiluria (rarely).
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Proteinuria: 0 to >1 g/day; nephrotic range proteinuria can be seen with NSAIDs due to concurrent minimal change disease (MCD).
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Blood count: Eosinophilia and anemia may be present.
9.1.3 Diagnosis of AIN
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Kidney biopsy is the gold standard: Interstitial edema and a marked interstitial infiltrate consisting primarily of T lymphocytes and monocytes.
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Positron emission test (PET) scan or gallium-67 renal scan uptake in AIN may distinguish it from acute tubular necrosis (ATN) when biopsy is undesirable or contraindicated.
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Response to discontinuation of the suspected offending agent and a therapeutic trial of corticosteroids over 1 to 2 weeks may be used to make a presumptive diagnosis.
9.1.4 Treatment of AIN
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Treatment aimed at identifying and discontinuing specific offending agents above, if possible.
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Supportive care of ARF (manage volume status and electrolytes).
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If renal function does not improve within 3 to 7 days or if patient needs hemodialysis (HD), perform biopsy and start steroid therapy.
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Prednisone 1 mg/kg/day. Start taper in 2 to 4 weeks based on response.
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If AIN fails to respond to steroids or cannot tolerate steroids, can try mycophenolate mofetil (MMF) 1 to 2 g orally daily.
9.2 Chronic interstitial nephritis
Chronic interstitial nephritis is a large and heterogeneous category of diseases leading primarily to interstitial fibrosis and tubular atrophy. Since progressive, sclerosing kidney diseases of all types are associated with eventual interstitial fibrosis and tubular atrophy, it is useful to define chronic interstitial nephritis as those conditions that cause interstitial and tubular damage initially while leaving glomeruli and vasculature intact.
9.2.1 Causes of chronic interstitial nephritis ,
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Infection
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Pyelonephritis
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HIV
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Tuberculosis (TB)
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EBV (Epstein Barr virus)
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BK (polyoma) virus
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Anatomic diseases
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Obstructive uropathy
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Nephronophthisis (a renal ciliopathy)
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Congenital disorders
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Drug/chemical induced
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Lithium nephropathy
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Analgesic nephropathy (>2–3 kg total intake)
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Calcineurin inhibitors
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Chemotherapy (cisplatin, ifosfamide, nitrosoureas)
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Cocaine and heroin
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Lead, cadmium, mercury
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Balkan nephropathy
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Chinese herbal (aristolochic acid) nephropathy
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Agricultural toxins (“Mesoamerican nephropathy”) ,
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Immunological diseases
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SLE
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Sarcoidosis
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Sjögren’s syndrome
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Rheumatoid arthritis
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IgG4-associated AIN
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TINU
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Metabolic disorders
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Nephrocalcinosis
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Oxalosis
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Gouty nephropathy
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Hypokalemic nephropathy
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Other
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Consequence of unresolved AIN or ATN
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Radiation nephritis
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Myeloma kidney, lymphoma
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Sickle cell disease
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Mitochondrial cytopathies
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9.3 Interstitial fibrosis
9.4 Role of NSAIDs in kidney disease
NSAIDs are probably one of the most commonly used medications as they are available over the counter. NSAIDs can affect the kidneys in several ways.
| Renal Effects of NSAIDs | |
|---|---|
| Decreased PGE 2 Can Cause: | Decreased PGI 2 (prostacyclin) Can Cause: |
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| Renal Insufficiency Mechanisms of NSAIDs | |
|---|---|
| Acute | Chronic |
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9.5 PKD and other hereditary cystic kidney diseases
9.5.1 Types of cystic kidney diseases
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Autosomal dominant polycystic kidney disease (ADPKD)
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Autosomal recessive polycystic kidney disease (ARPKD)
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Nephronophthisis: Medullary cystic kidney disease (MCKD) complex
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Bardet-Biedl syndrome
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Oral-facial-digital syndrome (OFDS)
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Miscellaneous hereditary polycystic kidney disease (PKD) syndromes:
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ADPKD associated with tuberous sclerosis
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ADPKD associated with von Hippel-Lindau disease
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9.5.2 Polycystic kidney disease
PKD is relatively common (1 in every 400–1000 live births, accounts for 5%–10% of ESKD). Most patients with PKD also have liver cysts, but only a fraction of patients develop massive polycystic liver disease.
