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A case of “bright myocardium” (not all that glitters is gold)

Case Presentation:
A 37 year old man, who received a renal transplant aged 35, is admitted to a nephrology ward for worsening renal failure associated with heart failure.
The patient had a history of recurrent, bilateral, renal colics with calculi expulsion from a young age. Aged 33 the patient started hemodialytic treatment for end-stage renal failure (aetiology was not fully investigated). One month after starting dialysis he underwent bilateral nephrectomy for an acute post-dialytic hematoma of the left kidney.
After two years of three-weekly dialysis regime, the patient underwent a renal transplant from a living donor (wife).
Myocardial Disease

About a year from the transplantation he suffered repeated renal colics associated with a progressive worsening of  renal function leading to his current hospitalization.

On admission, blood pressure was 140/80 mmHg, heart rate was 100 bpm and pitting ankle oedema was present. Cardiac and abdominal examinations were normal while chest examination revealed bilateral basal pulmonary crepitations. The ECG (Figure 1) showed sinus tachycardia (heart rate,106 bpm), left anterior hemiblock and non-specific alterations of the ventricular repolarization. The chest X-ray showed bilateral congestion of the pulmonary bases without signs of pleural effusion.

Fig. 1:
Standard ECG, showing left anterior hemiblock and non-specific alterations of the ventricular repolarization

The laboratory exams documented: leucocytes 10.17 x 10³/uL (n.v. 4.80-8.50 x 10³/uL), haemoglobin 9,9 g/dl (n.v. 13,0-16,5 g/dl), haematocrit 30.8 % (n.v. 40.0-54.0%), platelets 220 x 10³/uL (150-400 x 10³/uL), urea 1,45 g/L (n.v. 0,15-0,50 g/L), creatinine 4.30 mg/dl (n.v. 0.50-1.20 mg/dl), total proteins 5.7 g/dl (n.v. 6.0-8.0 g/dl), alkaline phosphatase 477 U/L (n.v. 98-220 U/L), sodium 137 mEq/L (135-146 mEq/L), potassium 4.5 mEq/L (3.5-5.3 mEq/L).

Urine test: incolor, limpid, PH 5.5 (n.v. 5.5-6.5), specific gravity 1.010 (n.v. 1.014-1.028), proteins: 69 mg/dL (n.v. <20 mg/dL), red blood cells 19/ul (n.v. 0-15), leucocytes 33/ul (n.v. 0-18/ul), bacteria 10.000/ul (n.v. 0-8000/ul), crystals 734/ul.

Due to the coexistence of heart failure, a cardiological consultation and an echocardiogram were requested. The echocardiogram (Figures 2) showed: a hyperechogenic appearance of the myocardium of the “granular sparkling” type, a slight concentric hypertrophy of the left ventricle (interventricular septum 12 mm, posterior wall 13 mm), an increase of ventricular volumes (end-diastolic/end-systolic 136/63 ml), a slight hypokynesia of the inferior wall, a left ventricular ejection fraction within the normal limits (55%), a slight dilation of the left atrium (longitudinal M-mode diameter 45 mm), minimal mitral regurgitation, slight anterior and posterior pericardial effusion.


Fig 2:
Two-dimensional echocardiogram. a) parasternal, longitudinal view and b) 4-chamber view. The myocardium appears hyperechogenic. A slight concentric hypertrophy of the left ventricle is present (interventricular septum 12 mm, posterior wall 13 mm) as well as increase of ventricular volumes (end-diastolic/end-systolic 136/63 ml

In the light of the patient’s history, examination and tests, what do you think is the correct diagnosis and what further investigations should be performed?

Diagnosis, case resolution and treatment

The clinical history of the patient is definitely characterized by “nephrological problems” i.e. recurrent renal colics and renal insufficiency leading to chronic hemodialysis and kidney transplantation.  Can we use the term (and the concept of) “uraemic” cardiomyopathy” to  explain the abnormal cardiologic findings of this case? Indeed, in patients with end-stage renal disease from any cause, left ventricular remodeling frequently occurs, leading to eccentric left ventricular hypertrophy with varying degrees of ventricular dilatation and dysfunction and frequent calcifications of valves’ anula and leaflets (especially when secondary hyperparathyroidism coexists). However, this “simple” diagnostic hypothesis would not explain all the key findings of the present case, including the recurrence of renal colics and the “bright” hyper reflecting aspect of ventricular myocardium.

During hospitalization a urine morphological exam documented numerous granular casts, calcium oxalate crystals and amorphous urates. Urinary oxalate was 57 mg/1000 cc in 24 hours (n.v. <34 mg/1000 cc in 24 h). 

The hypothesis of primary hyperoxaluria was considered and two further examinations were performed: renal biopsy and molecular analysis.  The biopsy of the transplanted kidney documented a modest increase in cell count in the glomeruli and mesangial matrix, numerous birefringent oxalate crystals (at polarized light)  in the tubular lumen and in the epithelial cells. Extensive diffuse limpho-monocyte interstitial infiltrate, a number of giant cells surrounding the crystals and a discrete amount of fibrosis were also found (Figure 1). The ultrastructural exam showed numerous sizeable crystalline deposits that could morphologically be identified as calcium oxalate crystals in the tubuli and in the interstitium (where a rich inflammatory infiltrate was also present).

 Figure 1: Histology of the kidney (hematoxilin/eosin; 400 x) showing calcium oxalate crystals in the tubular lumen (arrows). 

Figure 1
: Histology of the kidney (hematoxilin/eosin; 400 x) showing calcium oxalate crystals in the tubular lumen (arrows).

To confirm the hypothesis of primary hyperoxaluria, molecular analysis of the two encoding genes was peformed [alanine-glyoxylate aminotransferase (AGXT) and glyoxylate reductase/hydroxypyruvate reductase (GRHPR)]. The molecular analysis of  the AGXT gene showed the presence of a 508G>>A mutation in the IV exon in heterozygosis that determines an aminoacid substitution in the codon 170 of a glycine with an arginine (G170R) in the encoded protein and a 33insC mutation in the I exon that determines a shift in the reading code of the protein. The result therefore confirmed the diagnosis of type I primary hyperoxaluria.

Due to worsening renal function the patient resumed dialysis and received an indication to a combined liver-kidney transplant. The patient successfully underwent the transplant a few months later.


Primary Hyperoxaluria is a rare genetic disease, inherited with an autosomal recessive pattern, characterized by a liver peroxisome enzyme deficiency that causes an abnormal glyoxylate metabolism. It is classified into 2 variants: type I, with a deficiency of alanine-glyoxylate aminotransferase (AGXT) and type II, with a shortage of glyoxylate reductase/hydroxypyruvate reductase (GRHPR). The disease is characterized by a marked hyperoxaluria, calcium oxalate nephrolithiasis, nephrocalcinosis and progressive kidney function reduction. It may also involve the heart through myocardial calcium oxalate deposition, predominantly at intracellular level, determining a storage cardiomyopathy with an echocardiographical appearance of ventricular hypertrophy and a pronounced “granular sparkling” effect. The specialized conduction tissue may also be involved causing electrical conduction blocks. Calcium oxalate may also precipitate in the tunica media of arteries, including coronaries,  and may cause non-atheromasic coronary disease in the young .


Since the enzyme deficiency is localized in the hepatic peroxisomes, the only decisive therapy is a liver transplant which represents a “surgical gene therapy”.
In this specific case a number of elements are congruent with a diagnosis of primary hyperoxaluria and must elicit the clinical diagnostic suspicion: history of recurrent nephrolitiasis from a young age, renal insufficiency progression, recurrence of nephrolitiasis even after kidney transplantation, and myocardial storage disease with a “granular sparkling”, bright appearance on echocardiogram.


Hoppe B, Beck BB, Milliner DS. The primary hyperoxalurias. Kidney Int. 2009;75:1264-71.
Bobrowski AE, Langman CB. The primary hyperoxalurias. Semin Nephrol. 2008;28:152-62.
Cochat P, Liutkus A, Fargue S, Basmaison O, Ranchin B, Rolland MO. Primary hyperoxaluria type 1: still challenging! Pediatr Nephrol. 2006;21:1075-81.

Meyburg J, Hoffmann GF. Liver transplantation for inborn errors of metabolism. Transplantation. 2005;80 (1 Suppl) :S135-7.

Pais VM Jr, Assimos DG. Pitfalls in the management of patients with primary hyperoxaluria: a urologist's perspective. Urol Res. 2005;33:390-3.

Rumsby G. An overview of the role of genotyping in the diagnosis of the primary hyperoxalurias. Urol Res. 2005;33:318-20.

Danpure CJ. Molecular etiology of primary hyperoxaluria type 1: new directions for treatment. Am J Nephrol. 2005;25:303-10

Notes to editor

Presented by Massimiliano Lorenzini, Claudio Rapezzi
University of Bologna and S.Orsola-Malpighi Hospital, Bologna, Italy
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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