Tubulointerstitial Diseases

Tubulointerstitial Diseases

·        Involve tubules and renal interstitium (not glomerulus)

Acute Tubular Necrosis (ATN)

·        Ischaemic:

o  Patchy areas of tubular necrosis (proximal convoluted tubules and straight segments of the loop of Henle) and thinning of epithelial brush border 

o  Loss of basement membrane ® scarring, loss of architecture ® permanent loss

o  Regeneration if not too severe

·        Toxin-mediated (e.g. aminoglycosides, radio-contrast agents, heavy metals, arsenic, solvents, also from myoglobinuria from muscle damage):

o  Necrosis is continuous not patchy 

o  No loss of basement membrane ® epithelium can regrow down the nephron ® resolution

·        Leads to: 

o  Intra-tubular obstruction ® ¯GFR.  Glomeruli and vessels generally normal

o  Hyaline casts from cellular debris 

o  Reduction in sodium reabsorption & loss of medullary concentration gradient ® inability to concentrate urine ® isoosmolar urine with Na > 20 mmol/L

·        Management:

o  Fluid restrict

o  Correct electrolytes

o  Nutrition

o  Avoid nephrotoxins

o  Dialysis if:

§  Severe hyperkalaemia

§  Pulmonary oedema/severe hypertension

§  Symptomatic uraemia

§  Progressive uraemia with oliguria

§  Severe refractory metabolic acidosis

·        Lasts 1-2 weeks, followed by gradual improvement in serum urea and creatinine, and diuresis (due to reduced medullary gradient) – monitor to avoid hypokalaemia and hypovolaemia 

·        Prevent preoperatively by maintaining hydration ® maintained renal blood flow. No clear benefit from mannitol, dopamine, frusemide, etc

 Acute Papillary Necrosis

·        Diabetes 

·        Also in urinary outflow obstruction ® ­pressure in renal pelvis ® ¯perfusion

Acute Interstitial Nephritis (AIN)

·        =Intense, often patchy, interstitial inflammatory infiltrate of lymphocytes & monocytes

·        Presentation:

o  Similar to RPGN

o  Also skin rash, fevers, eosinophilia of urine

·        Glomeruli normal but may be tubular necrosis 

·        ¯GFR due to tubular obstruction and altered intra-renal haemodynamics 

·         Associated with drugs (e.g. penicillins - especially amoxycillin, and cephalosporins) – sometimes with infections & systemic diseases. Also NSAIDs – but after months of exposure & severe proteinuria 

·        Symptoms: 1 – 2 weeks after exposure (ie delayed hypersensitivity): fever, maculo-papular rash, eosinophilia, arthralgia, flank pain

·        Urine has pyuria, mild haematuria and mild proteinuria

·        Treatment: withdraw drug +/- steroids

Acute Pyelonephritis

·        Caused by suppurative infection: E coli, Proteus, Klebsiella, Enterobacter

·        From ascending UTI or haematogenous spread of infection (eg septicaemia)

Chronic Pyelonephritis

·        Not a disease, but a description of what happens to the kidney – it becomes dilated and replaced by fat

·        Causes:

o   Recurrent infection

o   Obstructive uropathy 

o   Vesicoureteric reflux (especially in kids with malformed vesicoureteric valves. Present in puberty with renal failure – subclinical before that)

o   Kidney stones (® ­infection)