Home > Kidney nontumor / medical renal > Oxalosis

Kidney nontumor / medical renal

Tubulointerstitial disease

Genetic

Oxalosis

Author: Jonathan E. Zuckerman, M.D., Ph.D.

Editorial Board Member: Nicole K. Andeen, M.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Last author update: 9 February 2022

Last staff update: 10 February 2022

Copyright: 2019-2025, PathologyOutlines.com, Inc.

PubMed Search: Oxalosis[TI] pathology full text[sb]

Table of Contents

Cite this page: Zuckerman JE. Oxalosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/kidneyoxalosis.html. Accessed January 9th, 2025.

Definition / general

Excess oxalate accumulation in the kidney resulting in acute and chronic tubulointerstitial injury
May be primary genetic (primary hyperoxaluria) resulting in oxalate overproduction or secondary due to excess intake or decreased clearance of oxalate

Essential features

Detection of excess calcium oxalate crystals in the kidney
Crystals are rhomboid / fan shaped and polarizable

Terminology

Primary: hyperoxaluria, hyperoxalosis, primary hyperoxaluria
Secondary: oxalate nephropathy, oxalosis

ICD coding

ICD-10:
- E72.53 - primary hyperoxaluria
- N14.2 - nephropathy induced by unspecified drug, medicament or biological substance

Epidemiology

Primary:
- Autosomal recessive
- Prevalence is < 3:1,000,000 individuals worldwide (J Am Soc Nephrol 2015;26:2559)
- 1 - 2% of all children with end stage renal disease (N Engl J Med 2013;369:649, Clin J Am Soc Nephrol 2012;7:458)
- 3 types (Nat Rev Nephrol 2012;8:467)
  - Type 1 is the most common (~80%) and most severe form
  - Type 2 (~10%)
  - Type 3 (~10%)
Secondary:
- 5 - 24% of all patients with gastrointestinal diseases associated with malabsorption including those with a history of (Nephrol Dial Transplant 2016;31:375)
  - Bariatric surgery
  - Celiac
  - Crohn's
  - Pancreatic insufficiency
  - Cystic fibrosis

Sites

Primary:
- Insoluble calcium oxalate salts deposit primarily in the kidneys
- Other sites include retina, myocardium, vascular walls, skin, bone and central nervous system (Kidney Int 2009;75:1264)
Secondary:
- Kidney, both native and allograft

Pathophysiology

Primary:
- Defective glyoxylate metabolism in hepatocytes resulting in excessive oxalate production
- Oxalate is renally cleared as calcium salts
- Excess oxalate results in oversaturation leading to crystallization in the renal tubules
- Crystals cause direct renal tubular toxicity and obstruction resulting in acute tubular injury and chronic renal failure
- Urolithiasis may also occur
Secondary:
- Mechanism of renal injury is similar to primary
- Excess intake of oxalate results in increased deposition within the kidney, usually mild
- Enteric hyperoxaluria (Nephrol Dial Transplant 2016;31:375):
  - Fat malabsorption results in increased calcium sequestration in the gut resulting in increased oxalate absorption from the small intestine and, to some degree, colon
  - Free fat and bile acids may also contribute to colonic permeability of oxalate
  - Oxalate degrading bacteria such as Oxalobacter formigenes may be a factor (Kidney Int 2013;83:1144)

Etiology

Primary:
- 3 most common subtypes are caused by mutations in the AGXT (type 1), GRHPR (type 2) and HOGA1 (type 3) genes
Secondary:
- Increased oxalate intake of foods or supplements rich in oxalate (Curr Rheumatol Rep 2013;15:340)
  - Rhubarb
  - Parsley
  - Spinach
  - Black tea
  - Vitamin C (an oxalate precursor)
- Ethylene glycol toxicity
- Increased gut absorption of oxalate in malabsorptive states (enteric hyperoxaluria)
  - Bariatric surgery
  - Inflammatory bowel disease (Crohn's disease)
  - Celiac disease
  - Pancreatic insufficiency
  - Short gut syndrome

Clinical features

Acute renal failure
Chronic renal failure
Recurrent nephrolithiasis
In primary disease, clinical presentation and disease course is quite variable (Am J Nephrol 2005;25:290)
- Median age at symptom onset is ~6 years
- Onset reported to range from birth to > 50 years

Diagnosis

Renal biopsy demonstrating excess oxalate accumulation with compatible clinical history
Presence of characteristic molecular findings in hereditary forms

Laboratory

Urinalysis / stone analysis with oxalate stones
Molecular testing

Prognostic factors

Primary:
- Type 1 is most severe form
  - Patients with the Gly170Arg or Phe152Ile mutation in AGXT gene have better overall outcome due to sensitivity to pyridoxine (Kidney Int 2005;67:1704)
- Type 2 has less severe course
- Type 3 is least severe; nephrocalcinosis and chronic kidney failure are uncommon (N Engl J Med 2013;369:649)
Secondary (Kidney Int Rep 2018;3:1363):
- Prognosis is guarded with up to 58% progressing to end stage renal disease
- Complete recovery of renal function is rare

Case reports

3 month old boy with hyperoxaluria type 1 and autosomal dominant polycystic kidney diesease (Pediatr Radiol 2011;41:107)
4 year old girl with end stage renal disease and primary hyperoxaluria type 1 (Pediatr Dev Pathol 2009;12:229)
51 year old man with hyperoxaluria nephropathy after Roux-en-Y bypass induced by vitamin C (Oxf Med Case Reports 2016;2016:omw054)
57 year old woman with oxalate nephropathy following vitamin C intake (Clin Nephrol 2017;88:354)
65 year old woman with oxalate rich green smoothie juice cleanse causing acute oxalate nephropathy (Am J Kidney Dis 2018;71:281)
67 year old man with calcium oxalate crystal related kidney injury after Roux-en-Y hepaticojejunostomy (BMC Nephrol 2017;18:106)
70 year old woman with calcium oxalate nephropathy due to short bowel syndrome and cholecystectomy (Case Rep Nephrol Dial 2018;8:147)
Acute kidney injury due to oxalate nephropathy after chelating therapy with oral ethylenediamine tetra acetic acid (Am J Kidney Dis 2017;70:722)
Acute oxalate nephropathy due to pancreatic atrophy in newly diagnosed pancreatic carcinoma (Hum Pathol 2016;48:163)

Treatment

Primary:
- Hydration
- Pyridoxine supplementation for type 1 (N Engl J Med 2013;369:649)
- Combined liver / kidney transplant (inevitable recurrence without liver transplantation in type 1 disease)
Secondary:
- Elimination of sources of excess oxalate
- Enteric oxalosis (Nephrol Dial Transplant 2016;31:375):
  - Oxalate binding agents, calcium
  - Calcium supplementation
  - Citrate supplements
- Hemodialysis
- Otherwise supportive care

Microscopic (histologic) description

Specific findings:
- Translucent polyhedral, rhomboid and fan-like calcium oxalate crystals found within cortical and medullary tubular lumens and interstitial spaces
- Crystals are birefringent under polarized light
- Crystal deposition can be associated with giant cell reaction
- Occasionally arterial / arteriolar deposits (usually in cases of primary hyperoxaluria)
- Advanced primary hyperoxaluria generally shows massive oxalate deposition with extensive interstitial fibrosis / tubular atrophy
Nonspecific findings:
- Acute tubular injury
- Interstitial fibrosis and tubular atrophy
- Generally mild tubulointerstitial inflammation
Early primary hyperoxaluria difficult to distinguish from secondary causes

Microscopic (histologic) images

Contributed by Jonathan E. Zuckerman, M.D., Ph.D.

Type 1 primary hyperoxaluria

Secondary oxalosis: calcium phosphate deposition

Secondary oxalosis: intraluminal calcium phosphate deposition

Fan shaped calcium oxalate deposits

Immunofluorescence description

No immunofluorescence staining of oxalate depositions
Usual nonspecific background IgA and light chain staining of adjacent tubular casts

Immunohistochemistry & special stains

von Kossa stain: oxalate crystals will be negative (calcium phosphate crystals will be positive)

Electron microscopy description

Oxalate crystals or outlines of crystals (may not survive processing) may be seen in tubule lumens or interstitial spaces

Electron microscopy images

Contributed by Jonathan E. Zuckerman, M.D., Ph.D.

Oxalate crystals

Molecular / cytogenetics description

Primary:
- All forms autosomal recessive
- AGXT gene mutations (type 1), which encodes the hepatic peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT)
- GRHPR gene (type 2), which encodes the GRHPR enzyme
- HOGA1 gene (type 3), which encodes the mitochondrial 4-hydroxy-2-oxoglutarate (HOG) aldolase enzyme
- ~5% do not have demonstrable mutations in any of these 3 genes (N Engl J Med 2013;369:649, J Am Soc Nephrol 2015;26:2559)

Sample pathology report

Left kidney, biopsy:
- Acute tubular injury (acute tubular necrosis) with marked calcium oxalate deposition suggestive of oxalate nephropathy
- Comment: The differential diagnosis for these findings includes both secondary and primary causes. Secondary hyperoxaluria / oxalate nephropathy can be seen in the setting of gastrointestinal malabsorption (enteric hyperoxaluria) or exogenous / dietary oxalate ingestion (e.g. excess vitamin C, rhubarb, parsley, spinach, beet greens, star fruit, nuts, black tea) usually in a background of underlying chronic kidney disease. Of note, oxalate deposition can also be seen in the setting of ethylene glycol ingestion. Primary oxaluria can present in adulthood; however, this possibility should be investigated after all secondary causes are excluded.

Differential diagnosis

Calcium phosphate:
- Purple crystals, not polarizable
2,8-Dihydroxyadenine (DHA) crystals / adenine phosphoribosyltransferase deficiency:
- Crystals polarizable, brown in color (Clin J Am Soc Nephrol 2012;7:1521)
Urate crystals:
- Needle shaped birefringent crystal
- Positive for uric acid stain (Arch Pathol Lab Med 2000;124:774)
Drug crystals:
- E.g. triamterene (Am J Kidney Dis 2014;63:148)
Acute tubular injury:
- May show nonspecific calcium oxalate crystals in tubular lumens
- Usually less extensive deposition than in cases of true oxalosis
- May be difficult to distinguish from secondary oxalosis; requires clinical correlation
Nonspecific accumulation can be seen in end stage kidney disease due to any cause:
- Usually more focal than in true oxalosis; clinical correlation

Board review style question #1

A 60 year old man presents with acute kidney injury. His past medical history is significant for morbid obesity treated by gastric bypass therapy. He also notes that he recently went on a green smoothie juice cleanse. What is the most likely cause of this patient's acute kidney injury?

Acute interstitial nephritis
Obesity related glomerulopathy
Oxalate nephropathy
Phosphate nephropathy
Urate nephropathy

Board review style answer #1

C. Oxalate nephropathy

Comment Here

Reference: Oxalosis

Board review style question #2

You receive a liver and bilateral kidneys from an 8 year old boy undergoing combined liver / kidney transplantation. The liver shows no significant gross or histologic findings. The kidneys appear atrophic with a gritty cut surface. Microscopic examination reveals extensive rhomboid and fan shaped translucent crystals that are polarizable and shows extensive cortical scarring. This boy most likely suffers from which of the following conditions?

Adenine phosphoribosyltransferase deficiency
Congenital nephrocalcinosis
Primary hyperoxaluria type 1
Primary hyperoxaluria type 2
Uromodulin kidney disease (ADTKD-UMOD)

Board review style answer #2

C. Primary hyperoxaluria type 1

Comment Here

Reference: Oxalosis

Home > Kidney nontumor / medical renal > Oxalosis