International Journal of Nephrology

International Journal of Nephrology / 2011 / Article

Case Report | Open Access

Volume 2011 |Article ID 146927 |

Jorge Lamarche, Reji Nair, Alfredo Peguero, Craig Courville, "Vitamin C-Induced Oxalate Nephropathy", International Journal of Nephrology, vol. 2011, Article ID 146927, 4 pages, 2011.

Vitamin C-Induced Oxalate Nephropathy

Academic Editor: Tibor Nadasdy
Received04 Nov 2010
Accepted19 Jan 2011
Published16 Mar 2011


Although a multitude of syndromes have been thoroughly described as a result of vitamin deficiencies, over consumption of such substances may also be quite dangerous. Intratubular crystallization of calcium oxalate as a result of hyperoxaluria can cause acute renal failure. This type of renal failure is known as oxalate nephropathy. Hyperoxaluria occurs as a result of inherited enzymatic deficiencies known as primary hyperoxaluria or from exogenous sources known as secondary hyperoxaluria. Extensive literature has reported and explained the mechanism of increased absorption of oxalate in malabsorptive syndromes leading to renal injury. However, other causes of secondary hyperoxaluria may also take place either via direct dietary consumption of oxalate rich products or via other substances which may metabolize into oxalate within the body. Vitamin C is metabolized to oxalate. Oral or parenteral administration of this vitamin has been used in multiple settings such as an alternative treatment of malignancy or as an immune booster. This article presents a clinical case in which ingestion of high amounts of vitamin C lead to oxalate nephropathy. This article further reviews other previously published cases in order to illustrate and highlight the potential renal harm this vitamin poses if consumed in excessive amounts.

1. Introduction

Acute renal failure can occur as a result of acute tubular necrosis secondary to acute oxalate nephropathy due to the deposition of calcium oxalate crystallization within the renal tubules [1]. Oxalate nephropathy can occur in both primary and secondary hyperoxaluria. Primary hyperoxaluria is a group of autosomal recessively inherited enzymatic deficiencies that lead to the increased urinary excretion of oxalate. In Type 1 primary hyperoxaluria, there is a reduction of alanine : glyoxylate aminotransferase (AGT) activity in the liver, leading to an accumulation of oxalate [2]. Type 2 primary hyperoxaluria involves a mutation of glyoxylate reductase/D-glycerate dehydrogenase, leading to the excretion of increased amounts of L-glyceric acid as well as oxalate [3].

Secondary hyperoxaluria can occur due to increased dietary oxalate intake, increased absorption of oxalate from the bowel (also known as enteric hyperoxaluria), and increased production of oxalate.

Increased dietary intake of oxalate is fairly uncommon; however, there have been case reports in the literature describing excessive star fruit juice ingestion [4, 5] and peanut intake [6] leading to oxalate nephropathy. Enteric hyperoxaluria results mainly from fat malabsorption, which leads to increased absorption of soluble oxalate from the colon. Calcium binds to the free fatty acids that cannot be absorbed. This reduces the normal calcium oxalate precipitation in the feces thereby allowing the absorption of soluble oxalate. This mechanism of enteric hyperoxaluria is manifested in several ways, including with orlistat therapy [7, 8], Roux-en-Y gastric bypass surgery [9], celiac disease, and Crohn’s disease. Increased production of oxalate is mainly due to increased levels of oxalate precursors, more commonly glyoxylate, which is associated with ethylene glycol ingestion, and less commonly ascorbic acid [10]. We report, in detail, a case of a patient who presented with this rare occurrence of excessive vitamin C-induced oxalate nephropathy.

2. Case Presentation

Our patient is a 72-year-old white male who was brought to the emergency department after being found down at home and confused. On presentation, he was found to have a BUN level of 102 mg/dL, a creatinine level of 10.6 mg/dL (baseline BUN 3.6 mg/dL and creatinine 1.3 mg/dL), and was also found to be oliguric. An ABG in the emergency department showed a pH of 7.19, PCO2 of 53, HCO3 of 21.4, and a PO2 of 77 mmHg on 2 liters of O2 via nasal cannula. His acidosis was attributed to the patient’s history of COPD and chronic CO2 retention. Urinalysis in the emergency department showed 1 RBC/hpf, 1+ protein, and no WBC or microorganisms present. Urine toxicology was positive for prescribed opiates and negative for recreational substances, including cocaine, ethanol, and amphetamines. The patient’s ethyl alcohol and salicylate levels were undetectable. His FeNa was calculated to be 1.7%. His measured serum osmolality was 321 mOsm/kg whereas his calculated osmolality was 3 mOsm/kg. Lab analysis also showed an elevated anion gap of 19.

Further history was difficult to attain given the fact that the patient was only alert to person but not to place or time. The patient was admitted to the medical ICU and the nephrology service was consulted for further evaluation. Due to his poor renal clearance, he was initiated on hemodialysis (HD).

The patient’s mental status improved after about a week, and his kidney function continued to slowly improve. During his hospital stay, the patient was found to have negative p-ANCA, c-ANCA, and qualitative ANA values. The patient’s C3 and C4 levels were within normal limits.

However, despite continued supportive therapy, the patient’s kidney function had not significantly recovered as expected. A renal biopsy was performed to shed further light on his disease process. The pathology report of the renal biopsy was consistent with findings of oxalate nephropathy as numerous tubules showed birefringent crystals shaped as plates or fine spicules under polarized light (Figure 1). There were also findings of moderate interstitial fibrosis, mild-to-moderate acute tubulointerstitial nephritis and mild hyaline and hyperplastic arteriolosclerosis with moderate-to-severe arteriosclerosis.

Upon further questioning, the patient denied ingestion of any products containing ethylene glycol or any medications other than what was prescribed to him. He also denied any prior gastric surgeries. However, the patient did mention that he had changed his eating habits within the past year as he wanted to include more leafy vegetables that incidentally were rich in oxalate. He also admitted to ingesting between 1.9 L and 3.8 L per day of his favorite beverage for about 3-4 months prior to presentation. This beverage was an orange flavored powder drink, which had about 60 mg of vitamin C per 236.6 mL serving. Therefore, the patient was ingesting approximately 480 mg to 960 mg of vitamin C daily. The patient’s oxalate nephropathy was attributed to excessive vitamin C intake, which anecdotally has a poor prognosis. As the biopsy demonstrated significant interstitial inflammation, prednisone was started at 60 mg and tapered down for a period of six weeks. The patient was discharged from the hospital on HD. Five weeks after discharge, he was able to be dialysis independent. His creatinine level at that time was 1.9 mg/dL.

3. Discussion

As described by Ralli et al. [11] in the 1930s, vitamin C is excreted by the kidneys by filtration and active tubular reabsorption. The metabolism of vitamin C to oxalate was later described in the 1960s by other investigators [12, 13]. Since then, there have been several case reports in the literature mentioning acute oxalate nephropathy in association with excessive vitamin C intake. Wong et al. [19] reports a patient with metastatic carcinoma of the prostate with underlying obstructive renal insufficiency who received a 60 gm bolus of IV vitamin C an an alternative therapy and developed anuric renal failure. Two days later on renal biopsy, the patient had similar findings to our patient. Lawton et al. [14] also describes a patient with similar findings after a single administration of 45 gm of IV ascorbic acid as adjuvant therapy for primary amyloidosis with nephrotic syndrome.

In the 1970s, Sullivan and Eisenstein [15, 16] demonstrated that dialysis patients tended to lose ascorbic acid during dialysis and as a result, should receive vitamin C supplementation. Subsequently, there have been reports of cases of patients on dialysis who developed oxalate crystal deposition in various organs secondary to vitamin C supplementation [17].

Vitamin C induced acute oxalate nephropathy has also been reported in the setting of patients who received parenteral alimentation. Friedman and associates [18] describe a patient with hemolytic uremic syndrome who was given total parenteral nutrition (which included 500 mg/day of ascorbic acid) while in the hospital. The patient ended up passing away with sepsis and severe metabolic acidosis about 4 months after being admitted. An autopsy showed extensive deposition of calcium oxalate in the kidneys and pancreas. Table 1 provides a summary of the various cases reported in the literature of biopsy proven oxalate nephropathy suspected to be secondary to ascorbic acid [10, 14, 1924].

Patient (Ref. Num.)*AgeGenderBaseline Serum creatinine (mg/dl)Renal presentation and serum creatinine (Cr) in mg/dlDose of ascorbic acid per dayDuration of administrationTreatmentOutcome

2071Female1.4Anuria (Cr = 12.1)500 mg (oral)6 monthsHDESRD
15**58Female1.0Oliguria (Cr = 3.5 )45 g (IV)1 dayHDDeath
21***72MaleUnknownAnuria(Cr = 15.3)Grams (oral)MonthsMedicalDeath
2273Male1.2Poor renal clearance
(Cr = 8.4)
680 mg (oral)4 monthsHDRecovery
Cr = 1.8 mg/dl
2331MaleUnknownPoor renal clearance
(Cr = 10.1)
2.5–5.0g (oral)Undisclosed (week to months?)HDRecovery
Cr = 2.2 mg/dl
2449Female0.7Oliguria (Cr = 4.5)4.0 g (oral)Several monthsHDRecovery
Cr = 1.1 gm/dl
1058Male1.4Anuria (undisclosed)1 g (IV)2 monthsHDRecovery
Cr = 1.4 mg/dl
1461Male1.3Anuria (Cr = 13.3)60 g (IV)1 dayMedicalRecovery
Cr = 2.9 mg/dl

The ref. num. identifies the individual case report. Please refer to the listed references at the end of the article to locate any particular case report by its reference number.
The patient died from multiple organ failure. Her systemic illness was amyloidosis.
The patient died from renal failure and associated multiple organ failure as he did not want to undergo dialysis.

Our patient’s renal biopsy findings were similar to the biopsy findings mentioned in the cases above. Although vitamin C induced hyperoxaluria is not as common as ingestion of ethylene glycol leading to oxalate nephropathy, clinicians must consider the potential dangers of large dose ingestion of vitamin C in some individuals, especially those with underlying kidney disease or advanced age.

In conclusion, the use of vitamin C must be scrutinized closely both in patients with normal renal function and with underlying renal insufficiency. According to Auer et al. [25], “surveys have indicated that about 66% of the general public take ascorbic acid either on its own or as part of a multivitamin preparation and that ingestion of megadoses of this vitamin in excess of the recommended daily allowance is common”. This figure is extremely concerning given the increasing percentage of the general public developing chronic kidney disease. We would like to add our case presentation to the literature as further evidence of this overlooked issue. Additionally, considering the improvement of our patient’s condition after being treated empirically with prednisone, it is crucial to further investigate the potential benefits and improvement of prognosis with prednisone therapy in the setting of oxalate nephropathy.


  1. P. Hill, M. Karim, D. R. Davies, I. S. D. Roberts, and C. G. Winearls, “Rapidly progressive irreversible renal failure in patients with pancreatic insufficiency,” American Journal of Kidney Diseases, vol. 42, no. 4, pp. 842–845, 2003. View at: Publisher Site | Google Scholar
  2. R. W. E. Watts, “Primary hyperoxaluria type I,” Quarterly Journal of Medicine, vol. 87, no. 10, pp. 593–600, 1994. View at: Google Scholar
  3. L. E. Seargeant, G. W. De Groot, L. A. Dilling, C. J. Mallory, and J. C. Haworth, “Primary oxaluria type 2 (L-glyceric aciduria): a rare cause of nephrolithiasis in children,” Journal of Pediatrics, vol. 118, no. 6, pp. 912–914, 1991. View at: Google Scholar
  4. C. L. Chen, H. C. Fang, K. J. Chou, J. S. Wang, and H. M. Chung, “Acute oxalate nephropathy after ingestion of star fruit,” American Journal of Kidney Diseases, vol. 37, no. 2, pp. 418–422, 2001. View at: Google Scholar
  5. K. Niticharoenpong, P. Chalermsanyakorn, R. Panvichian, and C. Kitiyakara, “Acute deterioration of renal function induced by star fruit ingestion in a patient with chronic kidney disease,” Journal of Nephrology, vol. 19, no. 5, pp. 682–686, 2006. View at: Google Scholar
  6. M. Sasaki, M. Murakami, K. Matsuo et al., “Oxalate nephropathy with a granulomatous lesion due to excessive intake of peanuts,” Clinical and Experimental Nephrology, vol. 12, no. 4, pp. 305–308, 2008. View at: Publisher Site | Google Scholar
  7. L. Karamadoukis, G. H. Shivashankar, L. Ludeman, and A. J. Williams, “An unusual complication of treatment with orlistat,” Clinical Nephrology, vol. 71, no. 4, pp. 430–432, 2009. View at: Google Scholar
  8. A. Singh, S. R. Sarkar, L. W. Gaber, and M. A. Perazella, “Acute oxalate nephropathy associated with orlistat, a gastrointestinal lipase inhibitor,” American Journal of Kidney Diseases, vol. 49, no. 1, pp. 153–157, 2007. View at: Publisher Site | Google Scholar
  9. W. K. Nelson, S. G. Houghton, D. S. Milliner, J. C. Lieske, and M. G. Sarr, “Enteric hyperoxaluria, nephrolithiasis, and oxalate nephropathy: potentially serious and unappreciated complications of Roux-en-Y gastric bypass,” Surgery for Obesity and Related Diseases, vol. 1, no. 5, pp. 481–485, 2005. View at: Publisher Site | Google Scholar
  10. A. M. Alkhunaizi and L. Chan, “Secondary oxalosis: a cause of delayed recovery of renal function in the setting of acute renal failure,” Journal of the American Society of Nephrology, vol. 7, no. 11, pp. 2320–2326, 1996. View at: Google Scholar
  11. E. P. Ralli, G. J. Friedman, and S. H. Rubin, “The mechanism of the excretion of vitamin C by the human kidney,” The Journal of Clinical Investigation, vol. 17, pp. 765–770, 1938. View at: Google Scholar
  12. E. M. Baker, J. C. Saari, and B. M. Tolbert, “Ascorbic acid metabolism in man,” American Journal of Clinical Nutrition, vol. 19, no. 6, pp. 371–378, 1966. View at: Google Scholar
  13. G. L. Atkins, B. M. Dean, W. J. Griffin, and R. W. Watts, “Quantitative aspects of ascorbic acid metabolism in man,” The Journal of Biological Chemistry, vol. 239, pp. 2975–2980, 1964. View at: Google Scholar
  14. J. M. Lawton, L. T. Conway, and J. T. Crosson, “Acute oxalate nephropathy after massive ascorbic acid administration,” Archives of Internal Medicine, vol. 145, no. 5, pp. 950–951, 1985. View at: Publisher Site | Google Scholar
  15. J. F. Sullivan and A. B. Eisenstein, “Ascorbic acid depletion in patients undergoing chronic hemodialysis,” American Journal of Clinical Nutrition, vol. 23, no. 10, pp. 1339–1346, 1970. View at: Google Scholar
  16. J. F. Sullivan and A. B. Eisenstein, “Ascorbic acid depletion during hemodialysis,” Journal of the American Medical Association, vol. 220, no. 13, pp. 1697–1699, 1972. View at: Publisher Site | Google Scholar
  17. K. Ono, “Secondary hyperoxalemia caused by vitamin C supplementation in regular hemodialysis patients,” Clinical Nephrology, vol. 26, no. 5, pp. 239–243, 1986. View at: Google Scholar
  18. A. L. Friedman, R. W. Chesney, and E. F. Gilbert, “Secondary oxalosis as a complication of parenteral alimentation in acute renal failure,” American Journal of Nephrology, vol. 3, no. 5, pp. 248–252, 1983. View at: Google Scholar
  19. K. Wong, C. Thomson, R. R. Bailey, S. McDiarmid, and J. Gardner, “Acute oxalate nephropathy after a massive intravenous dose of vitamin C,” Australian and New Zealand Journal of Medicine, vol. 24, no. 4, pp. 410–411, 1994. View at: Google Scholar
  20. C. Mousson, E. Justrabo, G. Rifle, C. Sgro, J. M. Chalopin, and C. Gerard, “Piridoxilate-induced oxalate nephropathy can lead to end-stage renal failure,” Nephron, vol. 63, no. 1, pp. 104–106, 1993. View at: Google Scholar
  21. G. J. McHugh, M. L. Graber, and R. C. Freebairn, “Fatal vitamin C-associated acute renal failure,” Anaesthesia and Intensive Care, vol. 36, no. 4, pp. 585–588, 2008. View at: Google Scholar
  22. S. Rathi, W. Kern, and K. Lau, “Vitamin C-induced hyperoxaluria causing reversible tubulointerstitial nephritis and chronic renal failure: a case report,” Journal of Medical Case Reports, vol. 1, article 155, 2007. View at: Publisher Site | Google Scholar
  23. S. Mashour, J. F. Turner, and R. Merrell, “Acute renal failure, oxalosis, and vitamin C supplementation: a case report and review of the literature,” Chest, vol. 118, no. 2, pp. 561–563, 2000. View at: Google Scholar
  24. S. H. Nasr, Y. Kashtanova, V. Levchuk, and G. S. Markowitz, “Secondary oxalosis due to excess vitamin C intake,” Kidney International, vol. 70, no. 10, p. 1672, 2006. View at: Publisher Site | Google Scholar
  25. B. L. Auer, D. Auer, and A. L. Rodgers, “Relative hyperoxaluria, crystalluria and haematuria after megadose ingestion of vitamin C,” European Journal of Clinical Investigation, vol. 28, no. 9, pp. 695–700, 1998. View at: Publisher Site | Google Scholar

Copyright © 2011 Jorge Lamarche et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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