Acute tubular necrosis

A Case Report and Review of the Literature

With the increased use of nonprescription vitamin supplementation, physicians involved in critical care must be aware of the potential complications of these medications. We report the case of a 31-year-old African-American man presenting to the emergency department with acute renal failure. He had previously been wet and initially denied the use of any drugs except for vitamin C tablets obtained at a local health food store. This case report and review of the literature is utilized to illustrate the importance of historical data in patients presenting with acute renal failure to a critical care service.

(CHEST 2000; 118:561-563)

Key words: acute renal failure; ascorbic acid; oxalosis

A 31-year-old African-American man presented to the emergency department at the University Medical Center with a 6-day history of headache and a 3-day history of nausea and vomiting. His history was otherwise unremarkable. He denied any recent travel or use of illicit medications, but admitted to the daily use of vitamin C (500 mg tablets, four to five tablets daily) purchased at a local health food store. The following results of physical examination were normal: sodium, 141 mEq/L; potassium, 4.5 mEq/L; chloride, 103 mEq/L; and [CO.sub.2], 15 mEq/L. The BUN level was 22 mg/d, with a creatinine level of 10.1 mg/dL. A urinalysis showed 2+ protein, 2+ blood, and 0 to 2 WBCs per high-power field without crystals or eosinophils. The total creatine phosphokinase level was 72 U/L, with a serum osmolality of 303 mg/dL. The results of a quantitative toxicology screen for ethanol intoxication and ethylene glycol proved negative. Renal ultrasound revealed increased cortical echogenicity of the kidneys measuring 10 cm and 11.6 cm. A renal biopsy was performed on day 2 (Fig 1) and demonstrated acute tubular necrosis and massive oxalate deposition. Treatment with pyridoxine was started on hospital day 4 and was continued until day 9. On further inquiry, the patient was able to recall that he had begun taking even larger numbers of vitamin C tablets a few days prior to the onset of symptoms, up to 10 tablets daily (5,000 mg) due to a recent upper respiratory infection. Antinuclear antibody, antineutrophil cytoplasmic antibody, and antistreptolysin O antibody titers were negative. Complement levels were within normal limits, and HIV serology was negative. The patient underwent two sessions of hemodialysis, with serial measurements of BUN and creatinine showing improvement in renal function. On day 14, measurements showed a BUN of 14 mg/dL and a creatinine level of 2.2 mg/dL; the patient was discharged home, with follow-up in his hometown.

[Figure 1 ILLUSTRATION OMITTED]

DISCUSSION

Ralli et al[1] described the process by which vitamin C is eliminated by the kidney via filtration and active tubular resorption, and the metabolic conversion of vitamin C to oxalate was elucidated in the 1960s (Fig 2).[2,3] The effect of large doses of vitamin C on serum and urine oxalate levels has been examined in both animal models and human volunteers.[4-6] Ono et al[7] demonstrated that rats treated with supernormal levels of vitamin C supplementation developed calcium oxalate crystal deposition in their renal tubules with the development of glomerular and interstitial fibrosis. Vitamin C supplementation has been studied in patients with normal renal function, as well as in those requiring chronic dialysis.[4,5] In 1980, Hatch et al[6] demonstrated that megadosing of vitamin C (2 g qid for 10 days) led to significantly elevated levels of serum and urinary oxalate levels consistent with the metabolic pathway of vitamin C established in earlier studies. Balcke et al,[8] working with long-term dialysis patients, demonstrated that increased levels of oxalate concentrations indicated a most important risk factor for calcium oxalate deposits in uremic patients. A number of case reports have also detailed the association of vitamin C intake and oxalosis.[9-16] Wong et al[9] detail the history of a patient similar to ours, a 61-year-old man who consulted an alternative therapist and was given 60 g vitamin C IV. On admission, the patient was anuric, with urinalysis showing massive oxalate crystals and granular casts. A kidney biopsy showed extensive oxalate deposition in the renal tubules and associated acute tubular necrosis. More often reported is a type of intoxication characterized in the case report by Alkhunaizi and Chan.[10] The patient was admitted with third-degree burns and placed on total parenteral nutrition containing 1 g vitamin C daily. This therapy was continued for 2 months, with the patient subsequently becoming anuric and dependent on hemodialysis. A renal biopsy was obtained, showing extensive calcium oxalate deposition in the interstitium and renal tubules. The vitamin C was discontinued, renal function improved, and the patient was able to discontinue dialysis.

[Figure 2 ILLUSTRATION OMITTED]

In summary, a number of studies have been performed to elucidate the biochemical pathway of vitamin C, specifically its conversion to oxalic acid. Our patient's course and our review of the literature again support the contention that vitamin C ingestion may cause significant morbidity and mortality. Vitamin C should therefore not be viewed as a benign, water-soluble drug but rather as a drug that is potentially toxic, not only for diseased kidneys, but also for normal ones given the proper circumstances. This case illustrates the importance of historical data in patients presenting with acute renal failure to a critical care service. As the use of nonprescription supplements continues to increase, critical care physicians must recognize the importance of the ingestions and the presentation of acute disease process.

REFERENCES

[1] Ralli EP, Friedman GJ, Rubin SH. The mechanism of the excretion of vitamin C by the human kidney. J Clin Invest 1938; 17:765-770

[2] Baker EM, Saari JC, Tolbert BM. Ascorbic acid metabolism in man. Am J Clin Nutr 1966; 19:371-378

[3] Atkins GL, Dean BM, Griffin WJ, et al. Quantitative aspects of ascorbic acid metabolism in man. J Biol Chem 1964; 239:2975-2980

[4] Sullivan JF, Eisenstein AB. Ascorbic acid depletion in patients undergoing chronic hemodialysis. Am J Clin Nutr 1970; 23:1339 -1346

[5] Sullivan JF, Eisenstein AB. Ascorbic acid depletion during hemodialysis. JAMA 1972; 220:1697-1699

[6] Hatch M, Mulgrew S, Bourke E, et al. Effect of megadoses of ascorbic acid on serum and urinary oxalate. Eur Urol 1980; 6:166-169

[7] Ono K, Ono H, Ono T, et al. Effect of vitamin C supplementation on renal oxalate deposits in five-sixths nephrectomized rats. Nephron 1989; 51:536-539

[8] Balcke P, Schmidt P, Zazgornik A, et al. Ascorbic acid aggravates secondary hyperoxalemia in patients on chronic hemodialysis. Ann Intern Med 1984; 101:344-345

[9] Wong K, Thomson C, Bailey R, et al. Acute oxalate nephropathy after a massive intravenous dose of vitamin C. Aust N Z J Med 1994; 24:410-411

[10] 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; 7:2320-2326

[11] Ponka A, Kuhlback B. Serum ascorbic acid in patients undergoing chronic hemodialysis. Acta Med Scand 1983; 213:305-307

[12] Pru C, Eaton J, Kjellstrand C. Vitamin C intoxication and hyperoxalemia in chronic hemodialysis patients. Nephron 1985; 39:112-116

[13] Ono K. Secondary hyperoxalemia caused by vitamin C supplementation in regular hemodialysis patients. Clin Nephrol 1986; 26:239-243

[14] Friedman AL, Chesney RW, Gilbert EF, et al. Secondary oxalosis as a complication of parenteral alimentation in acute renal failure. Am J Nephrol 1983; 3:248-252

[15] Swartz RD, Wesley JR, Somermeyer MG, et al. Hyperoxaluria and renal insufficiency due to ascorbic acid administration during total parenteral nutrition, Ann Intern Med 1984; 100:530-531

[16] Lawton JM, Conway LT, Crosson JT, et al. Acute oxalate nephropathy after massive ascorbic acid administration. Arch Intern Med 1985; 145:950-951

(*) From the Division of Pulmonary and Critical Care Medicine (Drs. Mashour and Turner) and the Division of Nephrology (Dr. Merrell), Department of Medicine, University of Nevada School of Medicine, Las Vegas, NV.

Manuscript received April 22, 1999; revision accepted January 30, 2000.

Correspondence to: J. Francis Turner, Jr., MD, FCCP, Division of Pulmonary and Critical Care Medicine, University of Nevada School of Medicine, 2040 W. Charleston, Suite 300, Las Vegas, NV 89102; e-mail:jturner@med.unr.edu

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