Acute Tubulointerstitial Nephritis Chronic Tubulointerstitial Nephritis
Epidemiology - 10-15% of all kidney diseases (except in Balkans - endemic)
- Lead nephropathy → ↑ in black populations (socioeconomic factors)
- Analgesic nephropathy → 5-6x in women (↑ ingestion & sensitivity to toxicity)
- ↑ in elderly populations (due to ↓ metabolic capacity) & hospitalized pxs
Etiology Hypersensitivity to medications - most common - Drugs: analgesic (most common), lithium,
- NSAIDs cyclosporine & tacrolimus
- Penicillin - Heavy metals
- Sulfa drugs (thiazides, furosemide, - Lead: house paint, occupational (batteries
antibiotics, hypoglycemic) mining)
- Rifampin - Cadmium & mercury
Immunologic diseases - Immune diseases: Sjogren
- SLE - Neoplasia: myeloma, leukemia, amyloidosis
- Goodpasture Sx - Metabolic diseases: hypercalcemia, cystinosis,
Infections hyperoxaluria, K depletion
- Bacterial - MUST have obstruction or reflux - Obstructive uropathy & reflux disease: prostate
- Viral disease, nephrolithiasis, pelvic fibrosis
- Parasitic: leishmania, toxoplasma - Balkan endemic nephropathy & Chinese herb
- Fungal: histoplasmosis nephropathy → aristolochic acid
Acute transplant rejection
- Result of interaction of renal cells w/ inflammatory cells and mediators.
Pathophysiology - Renal cell injury → new antigen expression → inflammatory cell infiltration
- Proinflammatory cytokines and chemokines → tissue damage
- Sublethal, reversible injury - Lethal irreversible injury
- Preserved basement membrane - Injured basement membrane → scarring, fibrosis
→ tubular dysfunction & Could present acute (TGFβ), and tubular atrophy
renal failure - Injury → NFκβ activation (in CTN w/ proteinuria)
Drugs → hypersensitivity reaction → Progressive chronic renal insufficiency
Infectious → direct injury to tubular cells
Clinical features - Abrupt onset as acute renal failure - Insidious-onset disease w/ HTN
- Days after exposure of offending agent - Most often asymptomatic → diagnosed incidentally
- Except in NSAIDs → months later Analgesic nephropathy → Papillary necrosis
- Triad: - all 3 in only 10% of pxs ● NSAIDs, phenacetin, Acetaminophen + caffeine
- Fever ● Present w/ renal insufficiency, modest proteinuria
- Rash and anemia
- Eosinophilia / pyuria Lithium - distal tubular dysfunction (D.I.)
Other symptoms Cyclosporine and tacrolimus - in transplant pxs
- Mild Fanconi Sx ● Due to ↑vasoconstriction → HTN
- Hematuria Lead → almost always w/ HTN
Specific symptoms in different etiologies ● Severe: encephalopathy & Fanconi Sx
- NSAIDs → Nephrotic Sx (MCD) ● Hyperuricemia and gout
- Rifampin → Ig light chain casts, flu-like Obstruction - hyperkalemic RTA & modest proteinuria
- Antibiotics → Nephritic-range proteinuria Atherosclerotic Kidney Disease - older men who smoke
- HIV → w/ glomerular disease, w/o fever & ● Dyslipidemia and vascular diseases
eosinophilia ● ↑ BUN & creatinine, mild proteinuria
Cholesterol microembolic disease - catheter procedure
● Atheroma crystals in kidney vessels, retinal
arteries (Hollenhorst), skin, & livedo reticularis
● ↑ESR & hypocomplementemia
Spares glomerulus on biopsy
Diagnosis
- ↑IgE Lead nephropathy→ EDTA testing (>0.6 g/24 hr)
- Eosinophilia - Sterile pyuria → w/ or w/ eosinophils
- Eosinophiluria / pyuria - Proteinuria → helps distinguish cause
- CT: Calcifications on papillary tips → NSAIDs
Treatment Discontinue and replace offending agent Lead nephropathy→ EDTA (adults) & succimer (children
Epidemiology - 10-15% of all kidney diseases (except in Balkans - endemic)
- Lead nephropathy → ↑ in black populations (socioeconomic factors)
- Analgesic nephropathy → 5-6x in women (↑ ingestion & sensitivity to toxicity)
- ↑ in elderly populations (due to ↓ metabolic capacity) & hospitalized pxs
Etiology Hypersensitivity to medications - most common - Drugs: analgesic (most common), lithium,
- NSAIDs cyclosporine & tacrolimus
- Penicillin - Heavy metals
- Sulfa drugs (thiazides, furosemide, - Lead: house paint, occupational (batteries
antibiotics, hypoglycemic) mining)
- Rifampin - Cadmium & mercury
Immunologic diseases - Immune diseases: Sjogren
- SLE - Neoplasia: myeloma, leukemia, amyloidosis
- Goodpasture Sx - Metabolic diseases: hypercalcemia, cystinosis,
Infections hyperoxaluria, K depletion
- Bacterial - MUST have obstruction or reflux - Obstructive uropathy & reflux disease: prostate
- Viral disease, nephrolithiasis, pelvic fibrosis
- Parasitic: leishmania, toxoplasma - Balkan endemic nephropathy & Chinese herb
- Fungal: histoplasmosis nephropathy → aristolochic acid
Acute transplant rejection
- Result of interaction of renal cells w/ inflammatory cells and mediators.
Pathophysiology - Renal cell injury → new antigen expression → inflammatory cell infiltration
- Proinflammatory cytokines and chemokines → tissue damage
- Sublethal, reversible injury - Lethal irreversible injury
- Preserved basement membrane - Injured basement membrane → scarring, fibrosis
→ tubular dysfunction & Could present acute (TGFβ), and tubular atrophy
renal failure - Injury → NFκβ activation (in CTN w/ proteinuria)
Drugs → hypersensitivity reaction → Progressive chronic renal insufficiency
Infectious → direct injury to tubular cells
Clinical features - Abrupt onset as acute renal failure - Insidious-onset disease w/ HTN
- Days after exposure of offending agent - Most often asymptomatic → diagnosed incidentally
- Except in NSAIDs → months later Analgesic nephropathy → Papillary necrosis
- Triad: - all 3 in only 10% of pxs ● NSAIDs, phenacetin, Acetaminophen + caffeine
- Fever ● Present w/ renal insufficiency, modest proteinuria
- Rash and anemia
- Eosinophilia / pyuria Lithium - distal tubular dysfunction (D.I.)
Other symptoms Cyclosporine and tacrolimus - in transplant pxs
- Mild Fanconi Sx ● Due to ↑vasoconstriction → HTN
- Hematuria Lead → almost always w/ HTN
Specific symptoms in different etiologies ● Severe: encephalopathy & Fanconi Sx
- NSAIDs → Nephrotic Sx (MCD) ● Hyperuricemia and gout
- Rifampin → Ig light chain casts, flu-like Obstruction - hyperkalemic RTA & modest proteinuria
- Antibiotics → Nephritic-range proteinuria Atherosclerotic Kidney Disease - older men who smoke
- HIV → w/ glomerular disease, w/o fever & ● Dyslipidemia and vascular diseases
eosinophilia ● ↑ BUN & creatinine, mild proteinuria
Cholesterol microembolic disease - catheter procedure
● Atheroma crystals in kidney vessels, retinal
arteries (Hollenhorst), skin, & livedo reticularis
● ↑ESR & hypocomplementemia
Spares glomerulus on biopsy
Diagnosis
- ↑IgE Lead nephropathy→ EDTA testing (>0.6 g/24 hr)
- Eosinophilia - Sterile pyuria → w/ or w/ eosinophils
- Eosinophiluria / pyuria - Proteinuria → helps distinguish cause
- CT: Calcifications on papillary tips → NSAIDs
Treatment Discontinue and replace offending agent Lead nephropathy→ EDTA (adults) & succimer (children
