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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2016  |  Volume : 27  |  Issue : 4  |  Page : 791-794
The first experience of sequential liver-kidney transplantation for the treatment of primary hyperoxaluria type-1 in Iran as a developing country

1 Department of Kidney Transplantation, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
2 Department of Nephrology, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran

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Date of Web Publication5-Jul-2016


Primary hyperoxaluria Type-1 (PH-1) is caused by a deficiency of alanine-glyoxylate aminotransferase manifesting as urolithiasis, nephrocalcinosis, and end-stage renal disease (ESRD). Among treatment options, best outcomes have been achieved by sequential liver-kidney transplantation (Seq-LKT). Herein, we report a patient with PH-1 and ESRD who underwent Seq-LKT in Iran. Criteria for diagnosis included a history of recurring calcium oxalate renal stones and elevated urine oxalate level combined with liver biopsy and absent enzymatic activity at the age of 13 years. Conservative treatment including pyridoxine, potassium citrate solution, high fluid intake, and hemodialysis was administered initially. Liver transplantation was performed at the age of 17 years from a deceased donor followed 4½ months later by a living-unrelated donor kidney transplantation. After two years of follow-up, the patient experienced no complications and had normal liver and renal function. This is the first successful experience of Seq-LKT in the treatment of PH-1 in Iran as a developing country with limited access to equipment and medications.

How to cite this article:
Naderi G, Tabassomi F, Latif A, Ganji M. The first experience of sequential liver-kidney transplantation for the treatment of primary hyperoxaluria type-1 in Iran as a developing country. Saudi J Kidney Dis Transpl 2016;27:791-4

How to cite this URL:
Naderi G, Tabassomi F, Latif A, Ganji M. The first experience of sequential liver-kidney transplantation for the treatment of primary hyperoxaluria type-1 in Iran as a developing country. Saudi J Kidney Dis Transpl [serial online] 2016 [cited 2022 Nov 26];27:791-4. Available from: https://www.sjkdt.org/text.asp?2016/27/4/791/185262

   Introduction Top

Primary hyperoxaluria Type-1 (PH-1) is a rare autosomal recessive disorder caused by liver-specific alanine-glyoxylate aminotransferase (AGT) deficiency resulting in increased endogenous oxalate production and urinary excretion. [1],[2],[3] Main manifestations include recurring urolithiasis, nephrocalcinosis, and chronic renal failure that may lead to early end-stage renal disease (ESRD). Reduced renal function in addition to continuous oxalate overproduction by liver may cause systemic oxalosis that affects many organs resulting in severe morbidity and mortality. [2],[3],[4]

Among available treatment options for patients with PH-1 and ESRD, best outcomes have been achieved by combined liver-kidney transplantation, simultaneously, or sequentially, in which sequential transplantation can correct the enzyme defect as well as deplete the oxalate storage before replacing the damaged kidney. [1],[5],[6],[7]

Herein, we report the first experience of sequential liver-kidney transplantation (Seq-LKT) for the treatment of a patient with PH-1 and ESRD in Iran as a developing country.

   Case Report Top

The patient was born of consanguineous parents on November 14, 1994. He was diagnosed to have renal stones following an incidentally detected hematuria when he was three-year-old. An open renal stone surgery was performed on his left kidney for removal of a calcium oxalate stone at the age of six years. Because of recurring renal stones, he underwent six sessions of extracorporeal shock wave lithotripsy (ESWL) till he was 12-yearold. He was referred to our center (Dr. Shariati Hospital, Tehran, Iran) due to rising serum creatinine level and presence of chronic kidney disease (CKD) at the age of 13 years.

A history of recurring calcium oxalate renal stones along with elevated urinary oxalate excretion (24 h urine oxalate level: 1887 μmol/24 h, reference interval: 78-488) were suggestive of PH. Treatment with high fluid intake, pyridoxine, and potassium citrate solution was initiated immediately. Diagnosis of PH-1 was confirmed with a liver biopsy that revealed absent AGT enzyme activity.

Despite the provided treatment, he became anuric and developed ESRD when he was 14-year-old. Therefore, he underwent hemodialysis (HD) for five days per week and was placed in the waiting list for liver followed by kidney transplantation.

On September 27, 2011, liver transplantation was performed from an 18-year-old brain-dead donor in another center (Namazi Hospital, Shiraz, Iran). The immunosuppressive regimen contained prednisolone, mycophenolate mofetil, and tacrolimus plus acyclovir for Cytomegalovirus prophylaxis. The operation and postoperative period were uneventful. Besides the immunosuppressive regimen and conservative treatment, HD for five days per week was continued. The patient had no problems and after about 4½ months, on February 9, 2012, kidney transplantation from a 22-year-old living-unrelated donor was performed. Thymoglobulin was used for induction therapy, and immunosuppressive regimen was the same as for liver transplantation.

The second operation was uneventful too. The initial 24 h urine output was 7700 mL and his serum creatinine level decreased from 389 μmol/L (reference interval: 53-106) on the admission day to 115 μmol/L on day 1. During the hospitalization period, a graft biopsy was obtained that showed calcium oxalate deposition in renal tubules with no signs of acute rejection. Therefore, the patient underwent aggressive HD until day 17 while he was being treated with immunosuppressants, pyridoxine, potassium citrate solution, and oral calcium supplement. HD was also continued three times per week for six months.

After two years of follow-up, he has encountered no problems. His last serum creatinine level was 97 μmol/L and the 24 h urine oxalate level was 444 μmol/24 h. Regarding liver function tests, his last serum aspartate transaminase, alanine transaminase, and alkaline phosphatase levels were 20 IU/L (reference interval: 10-30), 15 IU/L (reference interval:10-40), and 153 IU/L (reference interval: 44-145), respectively.

   Discussion Top

PH is a group of rare autosomal recessive diseases caused by defects in glyoxylate metabolism. [1],[2],[3],[4] They are characterized by oxalate overproduction and classified into three types: PH-1 is caused by specific hepatic AGT enzyme deficiency and is the most severe and common type; [1],[2] the second and third types are caused by deficient glyoxylate reductase/ hydroxypyruvate reductase enzymes and mutation in HOGA1 gene, respectively. [8],[9]

Excessive oxalate production in PH-1 leads to increased urinary oxalate excretion and consequently oxalate depositions in different tissues. [1] Kidney is involved as the first and predominant organ presenting with urolithiasis, nephrocalcinosis, and often early ESRD. [1],[2],[10] Furthermore, decreased glomerular filtration rate (GFR) leads to elevated plasma oxalate concentration and supersaturation of plasma calcium oxalate causing crystal deposits in most solid organs and the bones. [2]

The definite diagnosis of PH-1 is made by low or absent AGT enzyme activity in liver biopsy, or AGTX gene analysis to detect mutations. [1],[2],[3],[4] Our patient was diagnosed using the results of a liver biopsy since the genetic study was not available.

Conservative treatment should be initiated as soon as possible with intensive fluid intake, calcium oxalate crystallization inhibitors, oral calcium supplementation, and pyridoxine as the mainstay of oral treatment. [1],[2],[3] It is also recommended to avoid any unnecessary surgical intervention or nonendoscopic procedures such as ESWL for renal stones as further renal lesions may decrease GFR. [2],[3],[4]

Besides delayed diagnosis, our patient underwent several sessions of ESWL and open renal stone surgery. These factors may have acelerated the decline of GFR and the presence of CKD before the diagnosis. Therefore, conservative therapy could not delay progression of the renal failure and he underwent HD after developing ESRD.

Previous studies recommended HD for oxalate clearance before, during, and after organ transplantation in patients with systemic oxalosis, especially in anuric ones. However, dialysis alone cannot overcome the continuous oxalate overproduction [2],[4],[11] and the only efficient treatment in PH-1 is organ transplantation. [2] Different transplantation strategies are available that should be individualized based on patient's condition. [1],[5],[7]

Preemptive liver transplantation may be considered in patients before advanced chronic renal failure develops. [2],[7] It can be beneficial and performed in early stages of PH-1 before systemic oxalosis, especially in siblings of affected children diagnosed by genetic screening. [12],[13]

Isolated kidney transplantation is not recommended anymore in the treatment of PH-1 because it cannot overcome oxalate excessive production as the defect is in the liver and is associated with a high rate of recurrence. [2],[3],[7],[14] However, it may be used in selected pyridoxine responsive patients, elderly patients with late onset disease and ESRD, and as a temporary solution in some developing countries. It is also the treatment of choice in PH Type-2. [1],[2],[15]

Combined liver-kidney transplantation is recommended as the treatment of choice in patients with PH-1 and ESRD. [3],[6],[7] It can be performed either simultaneously or more preferably sequentially in ESRD patients. [2],[3],[5],[6],[16] In severe systemic oxalosis, it is suggested to transplant liver first, followed by delayed kidney transplantation in order to reduce tissue depositions with intensive HD. [3],[5],[7] The best time for kidney transplantation depends on the body's oxalate pools and varies from one patient to another. The availability of kidney may also affect this period. [3],[5] Although simultaneous combined liver-kidney transplantation subjects patients to one surgical procedure, less surgical complications, and shorter periods of dialysis, high urinary oxalate excretion may lead the new kidney to severe morbidity and mortality. [5]

We performed Seq-LKT for the treatment of PH-1 in our patient as the first experience in Iran and one of the first experiences in the Middle East. [16] The patient experienced no problems during the two years of follow-up. He was recommended to continue high fluid intake and crystallization inhibitor based on the previous recommendations to prevent stone formation as urinary oxalate can remain elevated for several years even after successful transplantation. [2]

It should be mentioned that we had some difficulties regarding the availability of equipment and medications for diagnosis and treatment of our patient. Although many developing countries like Iran may sustain such difficulties; this experience could be used as a model for the treatment of patients with PH-1 in these countries. Hence, this study along with previous successful reports showed the efficacy of Seq-LKT in the treatment of patients with PH-1, even in developing countries with limited access to equipment and medications.

   Acknowledgment Top

We would like to thank the patient and his parents who gave their informed consent before inclusion in the study.

Conflict of interest: None declared.

   References Top

Beck BB, Hoyer-Kuhn H, Göbel H, Habbig S, Hoppe B. Hyperoxaluria and systemic oxalosis: An update on current therapy and future directions. Expert Opin Investig Drugs 2013;22:117-29.  Back to cited text no. 1
Harambat J, Fargue S, Bacchetta J, Acquaviva C, Cochat P. Primary hyperoxaluria. Int J Nephrol 2011;2011:864580.  Back to cited text no. 2
Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med 2013;369:649-58.  Back to cited text no. 3
Cochat P, Hulton SA, Acquaviva C, et al. Primary hyperoxaluria type 1: Indications for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant 2012;27:1729-36.  Back to cited text no. 4
Alkhunaizi AM, Al-Sannaa NA, Raslan WF. Hyperoxaluria and rapid development of renal failure following a combined liver and kidney transplantation: Emphasis on sequential transplantation. JIMD Rep 2012;3:91-5.  Back to cited text no. 5
Sato S, Fuchinoue S, Kimikawa M, et al. Sequential liver-kidney transplantation from a living-related donor in primary hyperoxaluria type 1 (oxalosis). Transplant Proc 2003;35:373-4.  Back to cited text no. 6
Malde DJ, Pararajasingam R, Tavakoli A, et al. Transplantation in adults with primary hyperoxaluria: Single unit experience and treatment algorithm. Ann Transplant 2011;16: 111-7.  Back to cited text no. 7
Cramer SD, Ferree PM, Lin K, Milliner DS, Holmes RP. The gene encoding hydroxypyruvate reductase (GRHPR) is mutated in patients with primary hyperoxaluria type II. Hum Mol Genet 1999;8:2063-9.  Back to cited text no. 8
Monico CG, Rossetti S, Belostotsky R, et al. Primary hyperoxaluria type III gene HOGA1 (formerly DHDPSL) as a possible risk factor for idiopathic calcium oxalate urolithiasis. Clin J Am Soc Nephrol 2011;6:2289-95.  Back to cited text no. 9
van der Hoeven SM, van Woerden CS, Groothoff JW. Primary hyperoxaluria type 1, a too often missed diagnosis and potentially treatable cause of end-stage renal disease in adults: Results of the Dutch cohort. Nephrol Dial Transplant 2012;27:3855-62.  Back to cited text no. 10
Harambat J, van Stralen KJ, Espinosa L, et al. Characteristics and outcomes of children with primary oxalosis requiring renal replacement therapy. Clin J Am Soc Nephrol 2012;7:458-65.  Back to cited text no. 11
Scheinman JI. Liver transplantation in oxalosis prior to advanced chronic kidney disease. Pediatr Nephrol 2010;25:2217-22.  Back to cited text no. 12
Perera MT, Sharif K, Lloyd C, et al. Preemptive liver transplantation for primary hyperoxaluria (PH-I) arrests long-term renal function deterioration. Nephrol Dial Transplant 2011;26:354-9.  Back to cited text no. 13
Naderi G, Tabassomi F, Latif A, Ganji M. Primary hyperoxaluria type 1 diagnosed after kidney transplantation: The importance of pretransplantation metabolic screening in recurrent urolithiasis. Saudi J Kidney Dis Transpl 2015;26:783-5.  Back to cited text no. 14
[PUBMED]  Medknow Journal  
Naderi G, Latif A, Tabassomi F, Esfahani ST. Failure of isolated kidney transplantation in a pediatric patient with primary hyperoxaluria type 2. Pediatr Transplant 2014;18:E69-73.  Back to cited text no. 15
Mor E, Nesher E, Ben-Ari Z, et al. Sequential liver and kidney transplantation from a single living donor in two young adults with primary hyperoxaluria type 1. Liver Transpl 2013;19:646-8.  Back to cited text no. 16

Correspondence Address:
AmirHossein Latif
Department of Kidney Transplantation, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-2442.185262

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