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Saudi Journal of Kidney Diseases and Transplantation
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Year : 2015  |  Volume : 26  |  Issue : 4  |  Page : 783-785
Primary hyperoxaluria type 1 diagnosed after kidney transplantation: The importance of pre-transplantation metabolic screening in recurrent urolithiasis

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 Publication8-Jul-2015

How to cite this article:
Naderi G, Tabassomi F, Latif A, Ganji M. Primary hyperoxaluria type 1 diagnosed after kidney transplantation: The importance of pre-transplantation metabolic screening in recurrent urolithiasis. Saudi J Kidney Dis Transpl 2015;26:783-5

How to cite this URL:
Naderi G, Tabassomi F, Latif A, Ganji M. Primary hyperoxaluria type 1 diagnosed after kidney transplantation: The importance of pre-transplantation metabolic screening in recurrent urolithiasis. Saudi J Kidney Dis Transpl [serial online] 2015 [cited 2020 Aug 10];26:783-5. Available from: http://www.sjkdt.org/text.asp?2015/26/4/783/160216
To the Editor,

Primary hyperoxaluria type-1 (PH1) is a genetic metabolic disorder in which oxalate overproduction leads to enhanced urinary oxalate excretion and systemic oxalosis. [1],[2] Its main manifestations include recurrent urolithiasis, nephrocalcinosis and early end-stage renal disease (ESRD). [3],[4] As PH1 is a rare disorder with an initial manifestation of renal stones, the diagnosis might be missed or delayed in 20-50% of patients, and, in 10% of patients, the diagnosis may be made after transplantation, especially when there is a negative family history or there are no systemic manifestations. [5],[6],[7]

We herein report a patient with PH1 that was diagnosed after allograft failure following kidney transplantation. The patient was a 20year-old Iraqi man who was referred to our center, Dr. Shariati Hospital at Tehran, Iran for kidney transplantation.

His past medical history revealed an operation on the right kidney due to kidney stone at the age of 2.5 years and several sessions of extracorporeal shock wave lithotripsy in the following years because of recurrent renal stones. The report of stone analysis was not available. At the age of 14 years, ESRD was established and he had been on regular hemodialysis (HD) three times per week since then. His family history was negative for renal stones. On physical examination, he had mild hepatosplenomegaly. On radiologic studies, abdominal X-ray showed diffuse nephrocalcinosis and small kidneys. The voiding cystourethrogram revealed grade III and I reflux in the right and left kidneys, respectively.

The patient underwent a living related donor kidney transplantation in April 2013 when he was 20 years old. The donor was his 53-year old father. The operation was uneventful. The immunosuppressive therapy included prednisolone and cellcept. The urine output in the first 24 h was 7950 mL and his serum creatinine levels were 1.6 and 1.1 mg/dL on the 1 st and 5 th post-op days, respectively. On the 10 th post-op day, his serum creatinine level started to rise and reached 1.8 mg/dL. A graft biopsy was performed and a three-day corticosteroid pulse therapy followed by thymoglobulin was administered with suspicion of acute rejection. The biopsy revealed acute tubular necrosis and diffuse calcium oxalate deposits in the grafted kidney. Doppler ultrasonography was normal.

After ruling out secondary hyperoxaluria, with suspicion of PH, pyridoxine and potassium citrate solution were started along with vigorous serum therapy and daily HD as the plasma and urine oxalate levels were elevated.

The diagnosis was then confirmed by low alanine glyoxylate aminotransferase (AGT) enzyme activity on liver biopsy. When the radiologic findings were retrospectively reviewed, interestingly increased density of vertebral bones was seen. Other radiologic findings were unremarkable.

On the 20 th post-op day, the serum creatinine level started to decrease and thymoglobulin was replaced with tacrolimus. On this day, another graft biopsy was obtained that again showed diffuse tubular calcium oxalate deposition with no evidence of acute rejection. The patient was then discharged with prednisolone, cellcept, tacrolimus, pyridoxine, potassium citrate solution and calcium carbonate; on the 24 th post-op day, the serum creatinine level was 1.6 mg/dL. He was also recommended to be under regular HD, three times per week. The family was informed about the need of screening for PH1 too.

The patient went back to his country with no problems till the 3 rd post-op month, when he returned to Iran due to a rise of his serum creatinine level. During this period, he was undergoing regular HD and had used his medications properly. An allograft biopsy was performed and again diffuse tubular deposition of calcium oxalate crystals was seen. He was hospitalized and treated with vigorous serum therapy and daily HD along with previous medications.

Unfortunately, these treatments could not control the process of oxalosis and the patient underwent graft nephrectomy on the 98 th postop day. Pathologic study of the graft showed extensive infarction, luminal thrombosis of hilar vessels and extensive calcium oxalate crystal deposition in the renal parenchyma. The patient is now under treatment with pyridoxine, potassium citrate and regular HD, looking forward to a chance of combined liver- kidney transplantation in the future.

Primary hyperoxaluria is an autosomal recessive disorder, with prevalence ranging from 1 to 3 per million population. [2],[3] To date, three types of PH are identified and, among them, PH1 is the most common and severe type. [6],[7],[8],[9] PH1 occurs due to hepatic AGT deficiency, and results in excessive oxalate excretion and deposition in different tissues such as kidneys, bone, heart, eyes, skin, blood vessels and other organs. [1],[8],[9],[10],[11] Among these, kidneys are affected earlier with recurrent urolithiasis, nephrocalcinosis and, often, rapid progression to ESRD in childhood. Bone lesions are also common and the skeletal system is one of the main oxalate storage areas. [7],[12],[13]

Characteristic manifestations of PH include recurrent renal stone formation, increased urinary excretion of oxalate and glycolate in addition to high blood oxalate levels. The diagnosis should be confirmed by liver biopsy for enzyme activity level or genetic testing of AGXT gene. [2],[3],[11],[13],[14],[15]

Because of heterogeneous clinical features and variable age of onset or severity of involvement of the kidneys, the diagnosis of PH remains difficult and it may be delayed for several years, particularly when kidneys are solely involved. [2],[7],[12],[13],[14] In chronic renal failure, regardless of cause, because of the impaired clearance, increased plasma oxalate level and deposition of calcium oxalate in different tissues is detected. It should be noted that both plasma and urine oxalate levels are significantly higher in ESRD patients with PH1 than in those without PH1. [13]

Our patient presented with chronic renal failure due to recurrent renal stones without significant systemic features of oxalosis. He was referred to our center many years after his first presentation with inadequate past history and documents. Therefore, he underwent transplantation and doubts about PH1 arose only after graft failure. Because of our limitation to measure urinary glycolic acid and genetic studies, we confirmed the diagnosis with liver biopsy, which showed decreased enzyme activity.

As an inevitable fact, PH1 is a disorder of both liver and kidney. Thus, in misdiagnosed patients who undergo isolated kidney transplantation, as we observed, rapid recurrence and acute graft rejection may occur. This happens especially in patients with significant systemic oxalosis or no enzyme activity level [7],[10],[11],[12],[13],[14].

In patients with a clinical suspicion of primary oxalosis, large fluid intake, daily pyridoxine and inhibition of calcium oxalate crystallization should be provided. [12],[14] Early use of pyridoxine can significantly decrease urinary oxalate excretion in pyridoxine-responsive genotypes and can therefore prevent or delay the development of ESRD in more than 30% of patients. [2],[5],[15] Because there is increased endogenous oxalate overproduction, diet modification such as restricted oxalate-containing food intake might not be very useful, but normal intake of calcium and avoidance of excessive vitamin C or D should be considered. [3],[4]

As previously shown, isolated kidney transplantation is not a good choice anymore and combined liver-kidney transplantation is recommended in the treatment of PH1 to replace both deficient enzyme and damaged kidneys. [8],[9] It is important to protect the transplanted kidney with intensive hydration, pyridoxine and crystallization inhibitors, as systemic oxalate crystallization will progress slowly and may continue over years. [2],[5],[9]

In conclusion, this case suggests that complete diagnostic work-up and metabolic screening should be performed in any patient with renal failure and PH should be kept in mind in any patient with recurrent renal stones.

   Acknowledgment Top

The authors would like to express their thanks to the patient who let them publish his information. This study was not supported or funded by any organization or grant.

Conflict of interest: None

   References Top

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. 1
Rumsby G, Cochat P. Primary hyperoxaluria. N Engl J Med 2013;369:2163.  Back to cited text no. 2
Harambat J, Fargue S, Bacchetta J, Acquaviva C, Cochat P. Primary hyperoxaluria. Int J Nephrol 2011;2011:864580.  Back to cited text no. 3
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. 4
Hoppe B. An update on primary hyperoxaluria. Nat Rev Nephrol 2012;8:467-75.  Back to cited text no. 5
Jacob DE, Grohe B, Geßner M, Beck BB, Hoppe B. Kidney stones in primary hyperoxaluria: New lessons learnt. PLoS One 2013;8:e70617.  Back to cited text no. 6
Alsuwaida A, Hayat A, Alwakeel JS. Oxalosis presenting as early renal allograft failure. Saudi J Kidney Dis Transpl 2007;18:253-6.  Back to cited text no. 7
[PUBMED]  Medknow Journal  
Harambat J, van Stralen KJ, Espinosa L, Groothoff JW, Hulton SA, Cerkauskiene R, 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. 8
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. 9
Madiwale C, Murlidharan P, Hase NK. Recurrence of primary hyperoxaluria: An avoidable catastrophe following kidney transplant. J Postgrad Med 2008;54:206-8.  Back to cited text no. 10
[PUBMED]  Medknow Journal  
Malakoutian T, Asgari M, Houshmand M, et al. Recurrence of primary hyperoxaluria after kidney transplantation. Iran J Kidney Dis 2011;5:429-33.  Back to cited text no. 11
Shang MH, Jun H, Fan Y, et al. Recurrence of primary hyperoxaluria after kidney transplantation: The report of two cases. Chin Med J (Engl) 2009;122:2794-7.  Back to cited text no. 12
Kim HH, Koh HI, Ku BI, Lee HS. Late-onset primary hyperoxaluria diagnosed after renal transplantation presented with early recurrence of disease. Nephrol Dial Transplant 2005;20:1738-40.  Back to cited text no. 13
Riksen NP, Timmers HJ, Assmann KJ, Huysmans FT. Renal graft failure due to type 1 primary hyperoxaluria. Neth J Med 2002;60:407-10.  Back to cited text no. 14
van Woerden CS, Groothoff JW, Wijburg FA, et al. Primary hyperoxaluria remains undiagnosed in patients with hyperoxaluria and recurrent urolithiasis. Clin Chem 2007;53:1553-5.  Back to cited text no. 15

Correspondence Address:
Dr. GholamHossein Naderi
Department of Kidney Transplantation, Dr. Shariati Hospital, Tehran University of Medical Sciences, Tehran
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DOI: 10.4103/1319-2442.160216

PMID: 26178557

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