Case 5
Helmut HopferInstitute of Pathology, University Hospital Basel
Morphological features
• Intratubular crystals of needle-shaped to rectangular aggregates
• Brownish colour in PAS and HE stains
• Birefringence
• Von Kossa stain negative
• Giant cells
• Interstitial fibrosis and tubular atrophy
Clinical history
• Subacute renal failure, serum creatinine 1250 umol/l (14.1 mg/dl)
• Known autosomal dominant polycystic kidney disease since childhood
• Microhematuria, minimal proteinuria• Hypertension• 2 episodes of renal colics, three and two
years prior to admission, radiolucent stones on X-rays
Differential diagnosis
NephrocalcinosisOxalosisUrate nephropathyCystinosisDrug-induced crystals2,8-Dihydroxyadenine urolithiasis
2,8-DHA urolithiasis
• Autosomal recessive inherited adenine phosphoribosyltransferase deficiency (APRT), homozygosity rate 1:50'000-100'000
• Recurrent urolithiasis
♂ ♀• APRT deficient
(heterozygous)• ADPKD
• APRT deficient (heterozygous)
♂ ♀♂• APRT deficient
(homozygous)• ADPKD
• APRT deficient (heterozygous)
• APRT normal• ADPKD
DNA synthesisRNA synthesisEnergy transfer
2,8-DHA urolithiasis
AdenineAdeninemono-
phosphate
8-Hydroxyadenine
2,8-Dihydroxyadenine
APRT
XO
XO
APRT – Adenine phosphoribosyltransferaseXO – Xanthine oxydase
2,8-DHA urolithiasis
AdenineAdeninemono-
phosphate
8-Hydroxyadenine
2,8-Dihydroxyadenine
APRTmutation
XO
XO
APRT – Adenine phosphoribosyltransferaseXO – Xanthine oxydase
Excretion into the urine Formation of crystals at
physiological pH Urolithiasis
2,8-DHA urolithiasis
AdenineAdeninemono-
phosphate
8-Hydroxyadenine
2,8-Dihydroxyadenine
APRTmutation
XO
XO
APRT – Adenine phosphoribosyltransferaseXO – Xanthine oxydase
Prevention of urolithiasis
Allopurinol
2,8-DHA urolithiasis
• Treatment with allopurinol, low purine diet, high fluid intake
• Clinical DD: urate nephropathy (radiolucent stones, standard chemical test does not differentiate)
• Pathological DD: oxalosis (strong birefringence)
Differential diagnosis
NephrocalcinosisOxalosisUrate nephropathyCystinosisDrug-induced crystals2,8-Dihydroxyadenine urolithiasis
Calcium containing crystalsN
ep
hro
calc
ino
sis
Oxa
losi
s
Oxalate nephropathy
• Shape: round to elongate, mostly rhomboid; clusters or rosette-like
• Location: intraluminal, below the tubular epithelium or interstitium
• Colour: transparent, birefringence in polarized light (H&E stain)
• Special stains: von Kossa black, Alizarin orange/red
Alizarin
Kossa
Urate nephropathy• Shape: needle shaped to
rectangular aggregates within an amorphous matrix
• Location: tophi mostly in the medulla
• Colour: FFPE biopsies – mostly dissolved, alcohol-fixed biopsies – pale to deep blue, birefringence in polarized light
• Special stains: von Kossa negative, Alizarin negative
Cystinosis
• Shape: brick, hexagonal, elongated or flat
• Colour: FFPE biopsies – mostly dissolved, alcohol-fixed biopsies – yellow, brown to sand colour, birefringence under polarized light
• Special stains: von Kossa negative, Alizarin negative
Drug-induced crystals
• Sulfonamides• Acyclovir• Methotrexate• Indinavir• Triamterene• ...
Perazella MA, Am J Med 106:
459-465, 1999
Sulfonamide crystals (1960's)
2,8-DHA urolithiasis
• Brownish intratubular crystals
• Strong birefringence• Giant cells• Von Kossa negative
→ Think of 2,8-DHA urolithiasis in all cases of oxalosis!