Case Report

Case Report: Secondary Hyperoxaluria Complicated with Systemic Oxalosis

by Van Eycken M1,2*, Rorive S2, Lemoine A3, Pozdzik A3, Clause AL3

1Department of Pathology, HUB (ULB), Brussels, Belgium

2Centre Universitaire inter Régional d’Expertise en anatomie Pathologique Hospitalière, Charleroi, Belgium

3Nephrology Department, Brugmann Hospital (ULB), Brussels, Belgium.

*Corresponding author: Van Eycken M, Department of Pathology, HUB (ULB), Brussels, Belgium.

Received Date: 20 November 2023

Accepted Date: 25 November 2023

Published Date: 28 November 2023

Citation: Van Eycken M, Rorive S, Lemoine A, Pozdzik A, Clause AL (2023) Case Report: Secondary Hyperoxaluria Complicated with Systemic Oxalosis. Ann Case Report 8: 1529. https://doi.org/10.29011/2574-7754.101529

Abstract

Systemic oxalosis is the most severe complication of chronic hyperoxaluria resulting from either inherited disorder of glyoxylate metabolism (primary hyperoxaluria) or more rarely, increased intestinal oxalate absorption (secondary enteric hyperoxaluria). Significant hyperoxaluria may lead to calcium oxalate crystal formation, contributing to oxalate kidney stones and eventually to abundant crystal deposits within the renal parenchyma, a condition referred as oxalate nephropathy. We discuss and illustrate the case of a patient suffering from oxalate-induced nephropathy that evolves to end-stage renal disease (renal oxalosis) and progresses to systemic oxalosis while treated on hemodialysis.

Keywords: Systemic Oxalosis; Hyperoxaluria; Nephropathy; Hemodialysis; Calcium Oxalate Crystal

Case Report

A 72-year-old male patient from African origin presented at the emergency department for severe acute oliguric kidney failure on pre-existing mild chronic kidney disease (8.5 mg/dl, GFR 11 ml/min/1.73m2 following MDRD equation) with a bland sediment and low-grade proteinuria, from unknown origin. His chronic medication included Medrol 16 mg/day, omeprazole 20 mg/day, native vitamin D and association of triamterene/hydrochlorothiazide 25-50 mg/day for recent diagnosis of hypertension. His past medical history was relevant for systemic sarcoidosis, chronic healed hepatitis B and antrectomy associated to truncal vagotomy and gastro-jejunal anastomosis in 2007 (Bilroth II surgery) after which he suffered from chronic diarrhoea and weight loss.

Renal work-up was negative for auto-immune, complement-mediated, or viral disease (low replicative hepatitis B) but renal sarcoidosis could not be excluded without biopsy. Interestingly, ultrasound imaging of kidneys showed slight bilateral hyper echogenicity of both kidneys with the presence of a single non-obstructive microlithiasis on the left kidney.

The renal biopsy realized at this time displayed 8 glomeruli (one of which was sclerotic) with mild interstitial fibrosis surrounding some atrophic tubules (IFTA grade I). Moderate lesions of acute tubular necrosis were observed, as well as several precipitations of crystals at the intratubular level, within the tubular cells and at the interstitial level associated with a discrete to moderate inflammatory infiltrate. These crystals appeared birefringent in polarized light in favor of calcium oxalate (CaOx) crystals (figure 1).

 

Figure 1: Polarized light microscopy renal biopsy sample (haematoxylin and eosin stain, original magnification x20) demonstrating birefringent intratubular, intracellular and interstitial polyhedral or rhomboid crystals of broken glass appearance with interstitial fibrosis surrounding atrophied tubules.

The ratio of CaOx crystals to glomeruli was 1.10 (9 crystals/8 glomeruli) defining acute oxalate nephropathy according to the threshold ratio ≥ 0.25 proposed by Buysschaert and al. There was also moderate chronic vascular involvement (nephrangiosclerosis).

Unfortunately, the patient didn’t recover from his acute kidney failure (AKIN stage III) and evolved within the month to oliguric chronic kidney failure for which conventional thrice weekly haemodialysis through tunnelled CVC has to be started.

He died 4 years later from cardiac tamponade after an invasive complicated procedure of angioplasty to dilate a stenosis in his right brachiocephalic vein. An autopsy was performed as a part of the internal procedure for all iatrogenic death.

Materials and Methods

Autopsy: An external and internal macroscopic examination of the body was performed and samples of various organs (thyroid, trachea, oesophagus, aorta, lungs, hilar nodes, heart, coronary arteries, kidneys, adrenals, spleen, stomach, pancreas, liver, bladder, prostate, vena cava, small intestine and colon) were collected. All specimens were fixed in 4% buffered formalin (pH 7.2-7.4) and included in paraffin (31 blocks). Sections at 5 µm thickness were produced and stained with haematoxylin-eosin (HE). Histological slides were analysed by two pathologists (1 senior and 1 junior).

Immunohistochemestry: Sections (5 µm thick) were subjected to standard immunohistochemestry (IHC). Anti-CD68, CD163, CD3 and CD20 IHC were performed on a Dako Omnis. The slides incubated with the mouse anti-Human CD68 (1/2000 dilution, clone KP1, Dako; Agilent Technologies, Inc., Santa Clara, CA, USA), mouse anti-Human CD20 (1/500 dilution, clone L26, Dako; Agilent Technologies, Inc., Santa Clara, CA, USA) mouse anti-Human CD163 (1/200, clone 10D6, Leica Biosystems, Diegem, Belgium), and mouse anti-Human CD3 (1/200, clone LN10, Leica Biosystems, Diegem, Belgium) antibodies for 20 minutes each. The slides were washed and incubated thought the Flex Detection method for all antibodies, followed by the addition of complex avidin-horseradish peroxidase. Immunostainings were detected by incubation with diaminobenzidine and hydrogen peroxide. All IHC slides were counterstained with Gill's hematoxylin for 2 min at room temperature, dehydrated and mounted. For each staining, an external positive control was performed and verified according to clinical routine.

DNA extraction: We also performed DNA extraction from frozen renal tissue remaining from renal biopsy (rest of the sample dedicated to immunofluorescence). The tissues were embedded in Tissue-Tek O.C.T. (Sakura, California, USA) and stored at −80°C.

Total nucleic acids were extracted from frozen tissues using the QIAamp DNA mini-Kit (Qiagen, Germantown, MD, USA) following manufacturer's instructions and send to the genetics laboratory of the Erasme Hospital.

Pathological Findings

The major lesions found at autopsy were a hemopericardium, as well as a thrombosis stenosis of the superior vena cava and a thrombus of the right ventricle in the context of severe atheromatosis. Post-mortem samples revealed massive birefringent CaOx crystals deposits in the heart, the aorta walls, the kidneys, and the thyroid (figure 2).

In the renal parenchyma, the crystals were found in the intratubular level, within the tubular cells and in the interstitium with the presence of rare multinucleated giant cells. Interstitial fibrosis and tubular atrophy were strongly increased, representing more than 50% of the renal cortex (IFTA grade 3), associated with severe glomerulosclerosis (figure 2A).

For the aortic wall, the crystals were found in the intima which was thickened (atheromatosis) (figure 2B). In the heart, the crystals were found between the muscle fibres without inflammatory reactions or signs of acute infarction (figure 2C). However, there was a background of chronic ischemic cardiomyopathy with fibrous sequelae. Finally, in the thyroid, the crystals were present within the colloid and between the thyroid follicles (not shown).