Correspondence

Histopathological Features of the Kidney after Acute Renal Failure from Melamine

N Engl J Med 2010; 362:662-664February 18, 2010

Article

To the Editor:

An 8-month-old male infant was admitted on June 28, 2008, with prolonged anuria and mild coma. The child had been fed with Sanlu brand milk powder since he was 1 week of age. Initial laboratory data revealed markedly abnormal results that included a potassium level of 8.12 mmol per liter, a total carbon dioxide level of 9.0 mmol per liter, a blood urea nitrogen level of 137 mg per deciliter (49 mmol per liter of urea), and a creatinine level of 10.3 mg per deciliter (908 μmol per liter). Abdominal ultrasonography revealed bilateral urinary calculi causing acute obstructive renal failure. Peritoneal dialysis was performed, and urine output resumed 42 hours later. The renal-function tests on the third hospital day showed normal results: a potassium level of 4.03 mmol per liter, a blood urea nitrogen level of 16 mg per deciliter (6 mmol per liter of urea), and a creatinine level of 0.8 mg per deciliter (73 μmol per liter). Ultrasonography performed on the 10th hospital day revealed complete obstruction of the right ureter because of a calculus.

The parents of the infant requested a percutaneous biopsy of the right kidney, which was performed after they provided written informed consent. The sections showed generalized lymphocytic infiltration in the glomeruli; 2 of 26 glomeruli were sclerotic, with proliferation of fibrous tissue in the glomeruli and Bowman's capsule (Figure 1AFigure 1Micrographs from the Patient's Renal-Biopsy Specimens before and after Treatment.). The tubular cells were swollen, and crystals were seen within the lumen (Figure 1B). There was lymphocytic infiltration and fibrosis within the renal interstitium (Figure 1C). Transmission electron microscopy showed swollen tubular capillary endothelial cells, marked dilatation and abnormal structure of organelles within some renal tubular epithelial cells, and pyknotic nuclei (Figure 1D). Quantitative analysis with the use of high-performance liquid chromatography revealed the content of the calculi: a combination of melamine (29.2%) and uric acid (52.2%), with the remaining material (18.6%) unidentifiable. No cyanuric acid was present, though it has been reported in animals with melamine toxicity.1,2

At a follow-up visit 13 months after discharge, laboratory studies were performed. The blood urea nitrogen level was 10 mg per deciliter (4 mmol per liter of urea), the creatinine level was 0.5 mg per deciliter (44 μmol per liter), the urinary microalbumin level was 1 mg per liter, and a test for urinary protein was negative. Both kidneys appeared to be normal, without evidence of urinary calculi or precipitates on ultrasonography. A repeat percutaneous biopsy of the right kidney revealed no glomerular sclerosis and no glomerular or tubular-cell degeneration or intraluminal crystals (Figure 1E). Transmission electron microscopy revealed no glomerular-cell or basement-membrane abnormalities; the organelles also had a normal appearance (Figure 1F).

The renal damage caused by melamine is generally considered to be caused primarily by obstructive uropathy. In this infant, the tubular damage was prominent at presentation but resolved. We believe that timely treatment of acute melamine toxicity is effective, even in cases of marked obstruction.3 Melamine, which has been detected in various food products, warrants continued global concern.4

Ning Sun, M.D.
Ying Shen, M.D.
Le-jian He, Ph.D.
Beijing Children's Hospital of Capital Medical University, Beijing, China
ying_116sh@sohu.com

Financial and other disclosures provided by the authors are available with the full text of this letter at NEJM.org.

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Citing Articles (5)

Citing Articles

1. 1

   J. Peng, D. Li, Y. K. Chan, Y. Chen, J. R. Lamb, P. K. H. Tam, H. El-Nezami. (2011) Effects of water uptake on melamine renal stone formation in mice. Nephrology Dialysis Transplantation
   CrossRef

2. 2

   Cynthia B. Stine, Renate Reimschuessel, Charles M. Gieseker, Eric R. Evans, Tamara D. Mayer, Nicholas R. Hasbrouck, Elizabeth Tall, Jamie Boehmer, Gonçalo Gamboa da Costa, Jeffrey L. Ward. (2011) A No Observable Adverse Effects Level (NOAEL) for pigs fed melamine and cyanuric acid. Regulatory Toxicology and Pharmacology 60:3, 363-372
   CrossRef

3. 3

   YING SHEN, QIANG SUN, JIE GAO, LI-QUN JIA, NING SUN, YUE-SONG PAN, XIAO-MEI LIU, XIAO-RONG LIU, YU WANG, DONG-XUE WU, YE-PING JIANG. (2011) One year follow up of the outcomes of child patients with melamine-related kidney stones in Beijing and surrounding provinces in China. Nephrology 16:4, 433-439
   CrossRef

4. 4

   Viroj Wiwanitkit. (2010) Melamine nephropathy. Urological Research 38:5, 411-411
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5. 5

   Viroj Wiwanitkit. (2010) Re: Melamine Related Bilateral Renal Calculi in 50 Children: Single Center Experience in Clinical Diagnosis and Treatment. The Journal of Urology 184:3, 1228-1229
   CrossRef