Tubulointerstitial nephritis
How drugs, infections and systemic diseases inflame the tissue between the tubules, why tubular work fails before filtration does, and how oedema and white cells give way to fibrosis and shrunken kidneys when injury persists.
By the end, you can
- Describe the tubules and interstitium, and explain why they meet drugs and toxins at high concentrations.
- Explain how drug hypersensitivity causes acute interstitial nephritis, and why it does not depend on the dose.
- Compare infection-related interstitial nephritis with that of sarcoidosis, Sjögren syndrome, IgG4-related disease and TINU.
- Relate injury to each tubular segment to the urine and blood findings: sterile pyuria, tubular proteinuria, acidosis, abnormal potassium and dilute urine.
- Explain how persistent injury from analgesics, reflux or lead becomes chronic tubulointerstitial nephritis.
- Recognise the tissue picture and tests of tubulointerstitial nephritis, and explain how its treatments act on the mechanism.
What it is
Tubulointerstitial nephritis is inflammation centred on the renal tubules and the interstitium, the connective tissue between them, with the glomeruli and vessels relatively spared at first. The acute form, most often a hypersensitivity reaction to a drug or a response to infection, causes interstitial oedema and a cellular infiltrate and presents as acute kidney injury. The chronic form, from persistent or repeated injury, causes interstitial fibrosis and tubular atrophy and presents as slowly progressive chronic kidney disease.
4 types to tell apart
- Acute drug-induced (hypersensitivity)
- An immune reaction to a drug such as a beta-lactam antibiotic, an NSAID or a proton pump inhibitor; the commonest cause of acute interstitial nephritis.
- Infection-related
- Direct infection of the kidney (bacterial pyelonephritis, leptospires, hantavirus, BK polyomavirus) or an immune reaction to an infection elsewhere (streptococci, Legionella, viruses).
- Systemic immune disease
- Sarcoidosis (granulomas, high calcium), Sjögren syndrome (lymphocytes, distal tubular acidosis), IgG4-related disease (plasma cells, fibrosis) and TINU (with uveitis).
- Chronic tubulointerstitial nephritis
- Slow fibrosis from analgesics, reflux and obstruction, heavy metals such as lead, lithium, metabolic disorders, or acute disease that never resolved.
US spelling: centred → centerd, oedema → edema.
Normal function
Tubules, interstitium and a high exposure to drugs
Tubules make up most of the kidney. The reclaims most of the filtered sodium and bicarbonate and nearly all the glucose, amino acids, phosphate and small proteins. The and the build and use the gradient that concentrates urine, and the and collecting ducts fine-tune potassium and secrete acid. Each tubule rests on a tubular basement membrane.
Between the tubules lies the interstitium: a sparse connective tissue of fibroblasts, a few resident dendritic cells and macrophages, and the peritubular capillaries that carry blood from the glomeruli on to the tubules. Some of its fibroblasts make erythropoietin. Normally it is so thin that neighbouring tubules almost touch; oedema, inflammatory cells or collagen widen it.
The kidneys receive about a fifth to a quarter of the cardiac output and concentrate the filtrate, so tubular cells meet drugs and toxins at far higher concentrations than other tissues do, and carry many of them across their membranes. The medulla, where urine is most concentrated, is the most exposed and the least well supplied with oxygen.
Underlying change · Step 1 of 5
Acute drug-induced interstitial nephritis
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Underlying change · Step 3 of 5
Systemic disease: sarcoidosis, Sjögren, IgG4 and TINU
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Disrupted function · Step 4 of 5
Tubular work fails before filtration does
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Consequences · Step 5 of 5
Chronic disease: fibrosis, atrophy and papillary necrosis
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Symptoms and signs
Symptoms, signs and findings
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Exam detail
Exam detail
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Treatment
How treatment works
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Recap
Recap
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .
Self-check
Check your understanding
The full lesson is part of Student Pro
It takes you through all 5 steps of the mechanism, explains the symptoms, signs and findings each step causes, adds the exam detail and how treatment works where the lesson has them, then recaps it and lets you check yourself with 10 self-check questions. The full pathophysiology library: guided lessons with self-check questions comes with Student Pro, with 100 tutor answers a month and the full available catalogue.
Free to read: the introduction and .