| Abstract|| |
Systemic oxalosis can be either primary or secondary hyperoxaluria. Oxalosis is a phenomenon in which calcium oxalate crystals deposit in various visceral organs leading to bone marrow (BM) failure and recurrent renal stones. We describe two rare cases of BM oxalosis. Hyperoxaluria is strongly associated with nephrolithiasis and nephrocalcinosis. Both the patients presented with recurrent renal stones and a variable degree of BM failure. BM oxalosis should be considered as a possible diagnosis in patients in recurrent nephrolithiasis and cytopenia.
Keywords: End-stage renal disease, nephrolithiasis, oxalosis, pancytopenia
|How to cite this article:|
Sharma S, Rao RN, Pani KC, Paul P. Bone marrow oxalosis: An unusual cause of cytopenia in end-stage renal disease; report of two cases. Indian J Pathol Microbiol 2018;61:268-70
|How to cite this URL:|
Sharma S, Rao RN, Pani KC, Paul P. Bone marrow oxalosis: An unusual cause of cytopenia in end-stage renal disease; report of two cases. Indian J Pathol Microbiol [serial online] 2018 [cited 2019 Jun 19];61:268-70. Available from: http://www.ijpmonline.org/text.asp?2018/61/2/268/230559
| Introduction|| |
Hyperoxaluria is characterized by supersaturation of calcium oxalate in the urine and is associated with nephrolithiasis and nephrocalcinosis. Primary hyperoxaluria is a rare inborn error of metabolism in the metabolic pathway of glyoxylate which causes excessive oxalate production. Secondary hyperoxaluria an acquired disorder secondary to excessive dietary intake or increased absorption of oxalates must be excluded before making the diagnosis of pulmonary hypertension (PH).
Oxalate, when combined with calcium, has a high tendency to deposit in multiple organs. Oxalosis is a phenomenon in which calcium oxalate crystals deposit in renal and extra-renal organs. Tubulointerstitium of renal parenchyma is the first site of calcium oxalate deposition, leading to tubulointerstitial nephritis and nephrolithiasis.,, The other common sites of oxalate deposition are the bones, bone marrow, blood vessels, central nervous system, peripheral nerves, retina, skin, and thyroid. Bone marrow (BM) oxalate deposition has been associated with variable degrees of cytopenias, leukoerythroblastic blood picture, and hepatosplenomegaly.
Here, we present two cases of advanced renal failure due to recurrent renal stones. Diagnosis of oxalosis was made on BM biopsy in both the cases.
| Cases Reports|| |
A 12-year-old male child presented with advanced renal failure. He had a significant history of recurrent bilateral renal stone since 7 years of age. He had pyelolithotomy 10 years ago along with extracorporeal shock wave lithotripsy 3 years ago. Stone analysis revealed calcium oxalate nature of the stones (80% calcium oxalate monohydrate and 20% dihydrate). Since then, he was on conservative management. There was no history of joint pain, cardiac problems, or central nervous system symptoms. On physical examination, he had no clubbing, cyanosis, lymphadenopathy, or organomegaly. Endocrine workup was within normal limits.
Hematological studies showed pancytopenia: hb 81 g/L, total leukocyte count (TLC) 2.6 × 109/L, platelet count 76 × 109/L, and leukoerythroblastic blood picture. His blood urea (106 mg/dL) and serum creatinine (9.1 mg%) were increased. Liver enzymes were within normal limits and viral markers were negative. X-rays kidney, ureter, and bladder showed the presence of multiple stones in bilateral kidneys. Diethylenetriaminepentacetate (DTPA) scan revealed bilateral nephrocalcinosis with multiple renal calculi.
BM biopsy was done for evaluation of pancytopenia. BM smears showed numerous osteoclasts, osteoblasts, and multinucleated giant cells along with few scattered rhomboid to polyhedral refractile crystals. BM biopsy showed fibrocellular marrow spaces replaced by multiple rosettes of rhomboid to polyhedral refractile oxalate crystals surrounded by numerous histiocytes and multinucleate giant cells. The crystals were birefringent under polarized microscopy [Figure 1]a, [Figure 1]b [Figure 1]c.
|Figure 1: Composite picture is showing bone marrow aspiration (a and d), a biopsy (b and e) and polarized microscopy (c and f) features of both the cases. Top panel (a-c) shows images of case 1 and bottom panel (d-f) includes the images of case 2|
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A 28-year-old man presented with vomiting and recurrent fever. He had recurrent episodes of bilateral nephrolithiasis, urolithiasis, and urinary tract infection since the age of 18 years leading to end-stage renal disease (ESRD). For the past 3 years, he required regular hemodialysis and transfusions. On physical examination, no organomegaly was detected. Endocrine workup was within normal limits.
Complete blood count showed hb 87 g/L, TLC 6.7 × 109/L, and platelet count of 196 × 109/L. His creatinine was 18.4 mg/dL and blood urea nitrogen 85 mg/dL. Liver enzymes and bilirubin were within normal limit. Computed tomography scan showed the presence of multiple stones in bilateral kidneys, as well as ureters, and bladder.
Bone marrow biopsy was done for persistent anemia workup. BM smears showed scattered multinucleated giant cells, histiocytes, few osteoblasts, osteoclasts, and numerous oxalate crystals. BM biopsy showed clusters of oxalate crystals which showed a positive birefringence on polarized light [Figure 1]d, [Figure 1]e, [Figure 1]f.
Both the patients are transfusion dependent and awaiting renal transplantation.
| Discussion|| |
Hyperoxaluria is classified as primary or secondary. Primary hyperoxaluria is an autosomal recessive disease which includes three types of enzyme deficiency leading to defective oxalate metabolism. Type I is caused by a mutation in the AGXT gene resulting in a functional defect of the liver enzyme alanine-glyoxylate aminotransferase. With an incidence rate of approximately 1/120,000 live births per year in Europe; it represents 80% cases of primary hyperoxaluria. Type II and III are caused by a deficiency of glyoxylate reductase/hydroxypyruvate reductase (GRHPR) and mitochondrial enzyme HOGA1, respectively.
Secondary hyperoxaluria occurs when dietary and intestinal absorption of oxalate or intake of oxalate precursors is increased, and the intestinal microflora is changed. The clinical presentation of both primary and secondary hyperoxaluria is similar, although systemic oxalosis is less common in secondary oxalosis.
In this case report, we have presented two patients with long duration history of recurrent nephrolithiasis and urolithiasis from childhood with resultant ESRD. Pancytopenia was detected in one patient whereas the second patient had refractory anemia requiring recurrent transfusions. A diagnosis of primary hyperoxaluria was considered based on the history of nephrocalcinosis since a very young age, a stone analysis which revealed the predominance of calcium oxalate monohydrate, absence of gastrointestinal disorder, and BM involvement in both the cases. Although there was no significant family history, a genetic workup could not be performed due to financial constraints.
BM oxalosis is an unusual disease presenting with renal failure and cytopenia. The development of pancytopenia is a rare and late finding. BM biopsy is necessary in most of the cases as aspirate is often hemodiluted due to crystals., Calcium oxalate crystalline deposits surrounded by granulomatous structures are observed on BM biopsy. Polarized microscopy aids to diagnosis. Early diagnosis of patients affected by PH is associated with the improved long term. Kidney or combined liver and kidney transplantation is the treatment of choice for systemic oxalosis.
BM oxalosis should be considered as a possible diagnosis in patients in recurrent nephrolithiasis with pancytopenia- or treatment-resistant anemia.
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Krushna Chandra Pani
Department of Pathology, SGPGIMS, Lucknow, Uttar Pradesh
Source of Support: None, Conflict of Interest: None