Primary oxalosis is a rare hereditary disorder of metabolism resulting in accumulation of calcium oxalate in almost all tissues of the body. All published data point out the improvement of cardiac function after transplant. Here, we report the first case in the literature of an 8-year-old patient with primary oxalosis in which oxalosis implantations increased in cardiac tissue after liver transplant and manifested as new-onset ventricular tachycardia and cardiomyopathy, leading to death.
Key words : Cardiomyopathy, Intraabdominal infection, Tachyarrhythmia
Primary hyperoxaluria (PH) is an inherited disease in which patients lack hepatic oxalic acid metabolic enzymes, which could lead to accumulation of calcium oxalate in tissues. In some cases, this disease results in a progressive decline in renal function, oxalate retention, and systemic oxalosis involving bone, retina, arterial media, peripheral nerves, skin, and heart.1,2 Myocardial calcium oxalate deposits may induce conduction system abnormalities, tachyarrhythmia and bradyarrhythmia, and cardiomyopathy.3 Cardiac findings are associated with a decline in renal function and appear to correlate with the plasma oxalate level.3 Liver-kidney transplant is curative but is a highly invasive therapy used to treat patients with PH, with liver replacement treating the hepatic enzymatic deficiency and kidney transplant replacing the main target of the disease.1,4
An 8-year-old patient with PH and with chronic kidney failure and malnutrition was reviewed in our transplant clinic. At 1.5 years old, urolithiasis was noticed within his urine. At age of 4 years, the patient had a genetic test, and the result was consistent with homozygous mutation of PH. The patient had a nephrostomy at 6 years old because of obstruction in the ureter. At age of 6 years, 9 months, the patient started having regular dialysis sessions. At the time when he presented to our clinic, he was receiving 3 sessions per week, each lasting for 3 hours. A decision was made to perform sequential liver and kidney transplant.
The patient was admitted to our transplant department. During the preparation procedures, all needed consultations (pediatric nephrology, pediatric gastroenterology, pediatric neurology, pediatric cardiology, and pediatric ophthalmology) were performed with no impediment to perform the surgery. Echocardiography showed hypertrophic changes in the left ventricle with borderline systolic dysfunction, signs of hypertension changes, and second-degree aortic insufficiency. Ejection fraction (EF) was 53%, and the patient was started on valsartan 80 mg, enalapril 5 mg, and amlodipine 15 mg. Preoperative computed tomography (CT) showed no deposition of oxalate in the patient’s myocardium (Figure 1A) with bilateral extensive nephrocalcinosis (Figure 1B).
The living donor was the patient’s aunt. The genetic test for the aunt performed for oxalosis was negative, and 2 times polymerase chain reaction tests for COVID-19 were obtained for the patient and the donor with negative results. The donor’s liver biopsy was within normal limits for transplant.
The patient’s liver transplant procedure was uneventful (Figure 2A). A left lateral lobe was extracted from the living donor with size compatible with patient’s weight (to avoid small for size syndrome). End-to-end duct-to-duct anastomosis was performed for the donor’s bile duct. The immunosuppressive regimen consisted of a standard triple therapy combining mycophenolic acid 250 (twice daily), tacrolimus 1 mg (twice daily), and prednisolone. The patient was started on intravenous prednisolone 100 mg (twice daily) due to gradually decreasing flow rate and resistance revealed by daily ultrasonographic scans, which started on day 2 posttransplant. The patient was put on a daily dialysis program to help the body to remove extra fluids and toxins from the blood.
On posttransplant day 15, the patient developed acute abdominal pain. Upon exploratory laparotomy, a 1-cm perforation was found in the transverse colon with clean abdomen, and it was repaired with the use of primary sutures. The patient was stable after the surgery, and he was discharged 10 days later. A CT scan obtained during this period showed an increased attenuation of subendocardium, compatible with oxalate deposition (Figure 2B).
One week after discharge (posttransplant day 30), the patient presented to his daily hemodialysis session with fever and fatigue. An abdominal ultrasonography showed a 5-cm subdiaphragmatic collection with bile ducts dilatation accompanied by a slight elevation in total bilirubin. Percutaneous transhepatic cholangiography was performed by an intervention radiology specialist, which showed a stenosis at the bile duct anastomosis line with a small bile leak and a dilatation afterward. An 8F internal-external drainage was inserted using a wire duct passing the stenosis into the duodenum. A 10F drainage was placed subdiaphragmatically to drain the collection, and the patient was started on broad-spectrum antibiotics. A whole body follow-up CT scan demonstrated intensive myocardium oxalate deposition, with drainage catheter within an 8 × 6 × 6.6 collection on the right side of the transplanted liver (probably biloma) (Figure 3A).
One week later (posttransplant day 37), under general anesthesia, the internal-external drainage was replaced with an internal stent. After the patient awoke from the anesthesia, he started to develop absent epilepsy-like seizures, in which the patient becomes unresponsive to all external stimuli and then regains consciousness, with each seizure lasting for about 30 seconds every 0.5 hour. While the patient was connected to a monitor, the seizures were concomitant with a pulse of 190 to 230 beats/min, and an electrocardiogram pattern of wide complex ventricle tachycardia was shown (Figure 4). An emergency head CT scan and diffuse magnetic resonance imaging were obtained and were within normal limits. The patient was transferred to the intensive care unit and was given 1 dose of phenytoin 300 mg and was started on oral levetiracetam 200 mg at 3 times per day. Echocardiography showed a decrease of cardiac contraction with enlargement of the left ventricle; the EF was 40%. The patient was put on intravenous bolus amiodarone 100 mg with 5 mg infusion and metoprolol tablet (12.5 mg twice a day). Blood-gas analysis was compatible with metabolic acidosis, and citrate treatment was started.
Three days later (posttransplant day 40), despite the given treatments, the patient still had frequent ventricle tachycardia attacks. He was put on phenobarbital (2× 30 mg), levetiracetam (3× 250 mg), and phenytoin (3× 40 mg) for the absent seizures. Intravenous metoprolol 0.2 mg, propranolol 15 mg, and amiodarone 10 mg were administrated for heart complications. Obtained thorax CT revealed extensive myocardial oxalate deposition (Figure 3B), which explained the cardiomyopathy and tachyarrhythmia. Three days later (posttransplant day 43), patient exhibited bradycardia and hypotension. Despite all attempts of resuscitation, our patient died.
Primary hyperoxaluria type 1 is an autosomal recessive disorder characterized by a deficiency of liver-specific peroxisomal alanine-glyoxylate aminotransferase. This disease induces an increase in oxalate urinary excretion, causing urolithiasis and nephrocalcinosis.5 Oxalate cannot be metabolized; it is cleared by the kidneys, but urine super saturation for calcium oxalate occurs rapidly and results in nephrocalcinosis and recurrent urolithiasis.3 As progressive renal insufficiency occurs, insoluble oxalate deposits accumulate throughout the body, mainly in the musculoskeletal, cardiovascular, and peripheral nervous systems, causing systemic oxalosis.4,6 Cardiac involvement is a major source of mortality in patients with hyperoxaluria who are on dialysis and may manifest as conduction system abnormalities, tachyarrhythmia and bradyarrhythmia, and cardiomyopathy. Although cardiac involvement is uncommon, it is a major source of mortality in patients.7 Cardiac histopathological analyses have reported calcium oxalate deposition within conduction system, small intramyocardial vessels, and myocardium.8
Cardiac biopsy is the gold standard test to diagnose cardiac oxalate deposition, but it is an invasive procedure. In our presented case, we depended on CT images to display those depositions. As mentioned above, preoperative CT images revealed no deposition of oxalate in myocardium. Throughout the follow-up CTs, the amount of depositions started to increase and, in the pre-death period, extensive myocardial oxalate depositions were noticed. This effect occurred despite a new healthy transplanted liver and daily hemodialysis, which may confirm the fact mentioned in many studies that dialysis is a temporary procedure used to compensate for kidney failure by imitating kidney function by removing extra fluids and toxins from the blood; however, dialysis cannot remove oxalate that accumulates elsewhere in the body.9 Our case results do not comply with some clinical research results that have highlighted that sequential liver and kidney transplant suits patients with long-term renal replacement treatment or patients with systemic oxalate, with sequential liver and kidney transplant preferred over combined liver and kidney transplant in these types of patients, which is due to the possibility of oxalate crystals repositioning in myocardium leading to fatal cardiac complications.1,10
Previous data have demonstrated improvement in cardiac function after liver-kidney transplant, and this improvement is noticed starting from the second and third months posttransplant.8 However, this is the first case that elucidated the transverse effect of repositioning of oxalate crystals into the myocardium. In our opinion, this transverse effect is caused by multiple factors, and we believe that intraabdominal infections combined with metabolic acidosis can be part of these factors. We believe that many perioperative period deaths mentioned in the literature can be caused by this effect, which have never been studied before.
Careful attention should be made to myocardium oxalate depositions in cases of infection, especially in patients with sequential liver and kidney transplant in the posttransplant period, where systemic oxalate crystals may reposition in heart tissue causing fatal complications.
Volume : 18
Issue : 6
Pages : 744 - 748
DOI : 10.6002/ect.2020.0401
From the 1Department of General Surgery, Division of Transplantation, and the
2Department of Radiology, Baskent University, Ankara, Turkey
Acknowledgements: The authors have not received any funding or grants in support of the presented research or for the preparation of this work and have no potential declarations of interest.
Corresponding author: Mehmet Haberal, Baskent University, Department of General Surgery, Division of Transplantation, Baskent University, Ankara, Turkey, Yukari Bahçelievler, Mareşal Fevzi Çakmak St. No:45, 06490 Çankaya, Ankara, Turkey
Figure 1. Preoperative Unenhanced Chest and Abdomen Computed Tomography Scans
Figure 2. Postoperative Unenhanced Abdomen and Chest Computed Tomography Scans
Figure 3. Postoperative Day 30 and Day 40 Unenhanced Computed Tomography Scans
Figure 4. Twelve-lead Electrocardiogram Recording During Ventricle Tachycardia Attacks Showing Wide QT Complexes