Table 3.
Crystalline nephropathies associated with inherited disorders
| Inherited disorder (inheritance and defect) | Urinary crystal morphology | Kidney syndromes | Histologic findings | Therapy |
|---|---|---|---|---|
| Cystinosis (autosomal recessive; lysosomal storage disease) | Translucent needles, rods, or geometric shapes; Positively birefringent on polarization |
Fanconi syndrome, AKI, CKD, and ESKD | Needle- or geometric-shaped crystal footprints in podocytes, mesangial cells, and interstitial macrophages; less common in tubular cells and tubules; positively birefringent on polarization | Oral cysteamine; treat metabolic abnormalities (hypokalemia, metabolic acidosis, etc.) of Fanconi syndrome; supportive care including dialysis and kidney transplantation |
| 2,8-Dihydroxyadeninuria or APRT deficiency (autosomal recessive; deficiency of adenine phosphoribosyltransferase) | Round with central spicules, reddish-brown color and dark outline; positively birefringent on polarization | Crystalluria, cylinduria, nephrolithiasis, AKI, CKD, and ESKD | Crystals that are brown to green color on H&E and PAS, light blue on trichrome, black on JS; irregular or fan-shaped crystals within tubules; positively birefringent on polarization | Xanthine oxidase inhibition (allopurinol or febuxostat) therapy early in the course; supportive care including dialysis and kidney transplantation |
| Primary hyperoxalurias 1, 2, and 3 (autosomal recessive; hepatic deficiency of glyoxylate metabolism) | Calcium oxalate -Dihydrated: translucent bipyramidal shapes; positively birefringent (weak) on polarization -Monohydrated: translucent ovoids, dumbbells, and rods; positively birefringent on polarization |
Crystalluria, cylinduria, nephrolithiasis, AKI, CKD, and ESKD | Crystals that are translucent to pale blue crystals with fan-like or sunburst shapes within tubular lumens, tubular cells, and interstitium; interstitial inflammation near crystals also noted; positively birefringent on polarization | Administer IVFs if hypovolemic; oral citrate and pyridoxine; supportive care with dialysis, kidney ± liver transplantation; lumasiran approved by FDA and EU; stiripentol being studied in clinical trials |
| Dent disease type 1 (X-linked recessive; mutation in CLCN5 gene) Dent disease type 2 (X-linked recessive; mutation in OCRL1 gene) |
Calcium oxalate, calcium phosphate, mixed -See calcium oxalate crystals Calcium phosphate -Amorphous or thick rods |
Type 1: crystalluria, proximal tubulopathy/Fanconi syndrome, hypercalciuria, nephrocalcinosis, nephrolithiasis, CKD, and ESKD Type 2: same as type 1 |
Rare calcium phosphate crystals in corticomedullary junction; focal global glomerulosclerosis; nonspecific findings with tubular atrophy, interstitial inflammation, and fibrosis | Reduction in hypercalciuria with thiazide diuretics; oral citrate: oral potassium, phosphate, and vitamin D; supportive care with dialysis/transplantation for ESKD |
| Lowe syndrome (X-linked recessive; mutation in OCRL1 gene) | Calcium oxalate, calcium phosphate, mixed -See calcium oxalate crystals Calcium phosphate -Amorphous or thick rods |
Crystalluria, proximal tubulopathy/Fanconi syndrome, distal RTA, hypercalciuria, nephrocalcinosis, nephrolithiasis, CKD, and ESKD | Rare calcium-phosphate crystals are found; focal glomerulosclerosis; nonspecific findings with tubular atrophy, interstitial inflammation, and fibrosis | Oral bicarbonate, potassium, phosphate and vitamin D; supportive care with dialysis/transplantation for ESKD |
AKI, acute kidney injury; APRT, adenine phosphoribosyltransferase; CKD, chronic kidney disease; ESKD, end-stage kidney disease, EU, European Union; FDA, US Food and Drug Administration; H&E, hematoxylin and eosin; IVF, i.v. fluid; JS, Jones methenamine silver; PAS, periodic acid–Schiff; RTA, renal tubular acidosis.