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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
CASE REPORT  
Year : 2014  |  Volume : 25  |  Issue : 1  |  Page : 113-116
Secondary oxalosis due to excess vitamin C intake: A cause of graft loss in a renal transplant recipient


1 Department of Nephrology, Hedi Chaker Hospital, Sfax, Tunisia
2 Department of Anatomopathology, Habib Bourguiba Hospital, Sfax, Tunisia

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Date of Web Publication7-Jan-2014
 

   Abstract 

Renal oxalate deposition can be seen with primary hyperoxaluria, malabsorptive states, ethylene glycol toxicity and, rarely, with excessive vitamin C ingestion. We report a case of secondary hyperoxaluria in which the diagnosis was not considered initially because there was no past history of urinary calculi and no evidence of nephrocalcinosis on plain X-ray of the abdomen and ultrasonography. The disease was detected and diagnosed only after kidney transplantation. Secondary oxalosis can cause graft loss or delayed graft function. Biopsy of the allograft should be carefully examined for oxalate deposits even in the absence of a family history. When oxalosis is diagnosed, intensifying hemodialysis (HD) to eliminate calcium oxalate can help in the recovery of renal function in some cases. Systematic vitamin C supplementation in HD patients should be avoided as it can be a cause of secondary oxalosis.

How to cite this article:
Yaich S, Chaabouni Y, Charfeddine K, Zaghdane S, Kharrat M, Kammoun K, Makni S, Boudawara T, Hachicha J. Secondary oxalosis due to excess vitamin C intake: A cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl 2014;25:113-6

How to cite this URL:
Yaich S, Chaabouni Y, Charfeddine K, Zaghdane S, Kharrat M, Kammoun K, Makni S, Boudawara T, Hachicha J. Secondary oxalosis due to excess vitamin C intake: A cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl [serial online] 2014 [cited 2019 Nov 15];25:113-6. Available from: http://www.sjkdt.org/text.asp?2014/25/1/113/124518

   Introduction Top


Oxalosis may develop in patients with gen­etic disorders of oxalate metabolism or can be secondary to other diseases in patients with no personal or family history of lithiasis.

Secondary oxalosis is the result of excessive oxalate accumulation because of increased ingestion, increased production or decreased excretion. [1] Several substances may cause secondary oxalosis, such as ascorbic acid (AA, vitamin C), ethylene glycol, xylitol and methoxyflurane.

Many studies have shown low levels of AA in dialysis patients, which is due to low intake and intra-dialytic losses. [2],[3] AA is well known to have antioxidant action and is also reported to optimize erythropoietin response. [3],[4],[5] Hence, AA supplementation has been recommended in patients on chronic hemodialysis (HD). [1],[6]


   Case Report Top


A 33-year-old female was on chronic HD for end-stage renal disease of unknown etiology. She had first presented ten years earlier with renal failure when she was found to have bila­teral small kidneys on ultrasound examination. She had no personal or family history of urolithiasis. Abdominal radiography was normal. Serum and urinary oxalate were not tested because no obvious indication existed then. She received a renal allograft from a living related donor (mother) with a two HLA mis­match. The donor also had no personal or family history of lithiasis, and her abdominal radiograph was normal. The operation course was uneventful. Cold ischemia time was 30 min and warm ischemia time was 3.5 min. Post-transplant immunosuppressive treatment included induction with anti-thymoglobulin antibodies, and she was maintained on corticosteroids, mycophenolate mofetil and tacrolimus. After surgery, diuresis occurred immediately and her serum creatinine levels fell to 300 μmol/L by the third day. However, on day six post-transplantation, the creatinine levels went up to 587 μmol/L, associated with a drop in urine output. The blood tacrolimus level at this stage was 12 ng/mL. Doppler ultrasound of the graft was normal and there were no features of obstruction or vascular thrombosis. She under­went an allograft biopsy, which revealed wide­spread tubular degenerative changes typical of acute tubular necrosis and intra-tubular oxalate crystals. When viewed under polarized light, the tubular oxalate deposits appeared birefringent [Figure 1] and [Figure 2]. After the biopsy, the patient admitted to having taken at least 2 g/day of vitamin C daily for several years. There was no specific indication for vitamin C, but it was prescribed systematically for all patients in her dialysis unit, probably to opti­mize iron therapy. A 24-h urinary oxalate mea­surement performed in the donor was 117 μmol/L (normal values, 100-700 μmol/24 h). Bone marrow aspiration was performed, which showed extensive calcium oxalate deposits [Figure 3]. After reviewing the biopsy reports, beside advising to avoid high oxalate foods, we prescribed diuretics (furosemide 1000 mg/ d) and pyridoxine 300 mg/d to try and elimi­nate the excess oxalate load. She also received daily HD sessions; however, there was no im­provement in her graft function and the patient returned to chronic HD.
Figure 1: Proximal tubules with diffuse degenerative changes typical of acute necrosis and tubular calcium oxalate crystals (hematoxylin and eosin, original magnification ×200).

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Figure 2: Tubular calcium oxalate deposits appear birefringent under polarized light (hematoxylin and eosin, original magnification ×200).

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Figure 3: Bone marrow aspiration showing calcium oxalate deposits.

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   Discussion Top


Our patient had no personal or family history of lithiasis, and the donor urinary oxalate was normal. These findings are not consistent with a diagnosis of primary oxalosis. It is very likely that vitamin C was involved in the de­velopment of oxalosis in this patient because she was taking supra-normal doses of this drug for more than ten years. Moreover, bone mar­row aspiration showed oxalate deposits, suggesting high blood concentrations and a super-saturation environment.

Metabolic history and prevalence of secon­dary oxalosis are less well studied than that of primary hyperoxaluria (PH). Secondary hyperoxaluria is due either to increased intestinal absorption of oxalate or the result of excessive intake; it may also be secondary to vitamin de­ficiency (thiamine and pyridoxine) or decreased renal excretion of oxalate. The urinary oxalate excretion is generally lower in patients with secondary hyperoxaluria compared with PH. Nevertheless, it can lead to significant morbi­dity, namely recurrent nephrolithiasis or nephrocalcinosis. [1],[7],[8]

Vitamin C is a water-soluble vitamin that is eliminated by the kidney via filtration and active tubular reabsorption. AA is metabolized to oxalate. Dihydroascorbic acid, a metabolite of AA, gets hydrolyzed to diketogluconic acid, which then undergoes oxidation to oxalic acid and L-threose. [3],[9],[10]

In the general population, ingestion of a large quantity of vitamin C is not problematic as it can be eliminated by the kidneys. However, patients on HD can develop secondary oxalosis.

Several studies have shown that ingestion of high doses of vitamin C can lead to calcium oxalate deposition in the kidneys. In fact, Hatch et al have demonstrated that taking high doses of vitamin C led to significantly elevated levels of serum and urinary oxalate levels. [11] Some case reports have shown an association of vitamin C intake with secondary oxalosis. Nasr et al reported a case of a woman pre­senting with acute renal failure (ARF), in whom renal biopsy revealed acute tubular necrosis with prominent tubular calcium oxalate depo­sition. After the biopsy, the patient admitted to taking vitamin C daily for several months. [12] A similar case was also described by Mashour et al. [9] Alkhunaizi et al described a patient admit­ted for third-degree burns and circulatory shock requiring parenteral nutrition with vitamin C supplementation (1 g/day for two months). The patient developed anuric ARF and kidney biopsy showed extensive calcium oxalate de­position. Renal function improved after dis­continuing vitamin C. [1]

Vitamin C intake is advised for patients on HD not only because of its low level in this population but also because it optimizes iron therapy and improves response to erythropoietin therapy. [3],[4] However, little is known about its safety and, particularly, the risk of secon­dary oxalosis in this population. The majority of authors advise a dose not exceeding 100 mg after each HD session (300 mg/week). [3] Canavese et al tried to establish the safety/efficacy profiles of ascorbate and oxalate in 30 patients with ascorbate deficiency, defined by a plasma ascorbate level <2.6 mg/L on regular dialysis treatment. [3] Eighteen patients were adminis­tered intravenous ascorbate for 18 months (250 mg/week increased to 500 mg); the remaining 12 patients were taken as reference untreated cases. The majority of patients (94%) norma­lized their ascorbate level with high dosage for several months. However, plasma oxalate le­vels also increased significantly with increa­sing vitamin C doses. [3]

Our case illustrates the importance of data obtained with proper history in patients with ARF or in those without improvement in renal function after transplantation and the conse­quences of systematic prescription of some drugs considered benign. Also, allograft biopsy should be carefully examined for oxalate de­posits even in the absence of a family history.

The risk of secondary oxalosis should always be borne in mind while prescribing vitamin C in patients on HD. We should also consider oxalate measurements in patients taking high doses of vitamin C. Physicians must be aware of the complication of secondary oxalosis and vitamin C should no longer be viewed as a benign drug that can be systematically pres­cribed.

 
   References Top

1.Alkhunaizi AM, Chan L. Secondary oxalosis: A cause of delayed recovery of renal function in the setting of acute renal failure. J Am Soc Nephrol 1996;7:2320-6.  Back to cited text no. 1
[PUBMED]    
2.Deicher R, Horl WH. Vitamin C in chronic kidney disease and hemodialysis patients. Kidney Blood Press Res 2003;26:100-6.  Back to cited text no. 2
    
3.Canavese C, Petrarulo M, Massarenti P, et al. Long-term, low dose, intravenous vitamin C leads to plasma calcium oxalate supersaturation in hemodialysis patients. Am J Kidney Dis 2005;45:540-9.  Back to cited text no. 3
[PUBMED]    
4.Tarng DC, Wei YH, Huang TP. Intravenous ascorbic acid as an adjuvant therapy for recombinant erythropoietin in hemodialysis patients with hyperferritinemia. Kidney Int 1999;55:2477-86.  Back to cited text no. 4
    
5.Keven K, Kutlay S, Nergizoglu G, Erturk S. Randomized, crossover study of the effect of vitamin c on EPO response in hemodialysis patients. Am J Kidney Dis 2003;41:1233-9.  Back to cited text no. 5
    
6.Deved V, Poyah P, James MT, et al. Ascorbic acid for anemia management in hemodialysis patients: A systematic review and meta-analysis. Am J Kidney Dis 2009;54:1089-97.  Back to cited text no. 6
[PUBMED]    
7.Urivetzky M, Kessaris D, Smith AD. Ascorbic acid overdosing: A risk factor for calcium oxalate nephrolithiasis. J Urol 1992;147:1215-8.  Back to cited text no. 7
[PUBMED]    
8.Wong K, Thomson C, Bailey RR, McDiarmid S, Gardner J. Acute oxalate nephropathy after a massive intravenous dose of vitamin C. Aust N Z Med 1994;24:410-1.  Back to cited text no. 8
    
9.Mashour S, Turner JF Jr, Merell R. Acute renal failure, oxalosis, and vitamin C supplemen­tation: A case report and review of the lite­rature. Chest 2000;118:561-3.  Back to cited text no. 9
    
10.Baker EM, Saari JC, Tolbert BM. Ascorbic acid metabolism in man. Am J Clin Nutr 1966;19:371-8.  Back to cited text no. 10
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11.Hatch M, Mulgrew S, Bourke E. Effect of mega doses of ascorbic acid on serum and urinary oxalate. Eur Urol 1980;6:166-9.  Back to cited text no. 11
    
12.Nasr SH, Kashtanova Y, Levchuk V, Markowitz GS. Secondary oxalosis due to excess Vitamin C intake. Kidney Int 2006;70:1672.  Back to cited text no. 12
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Correspondence Address:
S Yaich
Department of Nephrology, Hedi Chaker Hospital, Sfax
Tunisia
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DOI: 10.4103/1319-2442.124518

PMID: 24434393

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    Abstract
   Introduction
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    References
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