Dietary Oxalate Nephropathy Due to Pureed Feeds

Abstract

An 8-year-old boy with a 5q14.3 deletion presented with an elevated serum creatinine level of 1.8 mg/dL. A kidney biopsy demonstrated tubular injury and extensive oxalate crystals. His serum and urinary oxalate levels were elevated, but genetic testing for primary hyperoxaluria was negative. The patient depended on pureed foods for nutrition, and his mother consistently used a large amount of spinach and nuts when preparing his blenderized feeds. Hence, his dietary intake of oxalate was extremely high. After dietary modification, his serum and urinary oxalate levels decreased, but his serum creatinine levels had increased to 2.1 mg/dL. Unfortunately, the reported outcome of secondary oxalate nephropathy is poor, with no patients having a full recovery and the majority developing kidney failure. Children on pureed foods are at risk of hyperoxaluria if there is a chronic high intake of foods with elevated oxalate content, and caregivers may not realize that healthy foods such as spinach and nuts are high in oxalate. Nutritional counseling of children on pureed foods should include screening for excessive oxalate intake, especially if there is a decrease in kidney function or kidney stones.

Hyperoxaluria can be either primary or secondary. The primary hyperoxalurias are rare autosomal recessive disorders because of overproduction of oxalate in the liver. There are currently 3 known forms, with primary hyperoxaluria type 1 because of pathogenic variants in alanine-glyoxylate aminotransferase causing the most severe clinical manifestations.¹ Primary hyperoxaluria can present in childhood or adulthood, and severity varies. Primary hyperoxaluria can lead to recurrent kidney stones, nephrocalcinosis, and progressive kidney damage, ultimately culminating in end-stage kidney disease.²

There are a variety of different etiologies of secondary hyperoxaluria. Several gastrointestinal conditions, such as inflammatory bowel disease and gastric bypass surgery, cause increased enteric absorption of oxalate. Low dietary calcium can also increase oxalate absorption because of decreased complexing of calcium with oxalate in the gastrointestinal tract.³ Ingestion of oxalate precursors such as vitamin C or ethylene glycol can cause hyperoxaluria. Hyperoxaluria can be secondary to excessive intake of foods high in oxalate, such as spinach, rhubarb, star fruit, nuts, and chocolate. Because there is no mechanism for catabolism of oxalate, most absorbed oxalate is excreted in the urine, leading to hyperoxaluria when intake is excessive.⁴

Hyperoxaluria can lead to kidney stones composed of calcium oxalate, nephrocalcinosis, and oxalate nephropathy, which may be diagnosed by kidney biopsy. Its characteristic findings include the accumulation of calcium oxalate crystals in the kidney tubules, which results in varying degrees of kidney dysfunction and may even cause end-stage kidney disease.⁵

Case Presentation

An 8-year-old boy was initially evaluated for chronic, severe anemia and was found to have an elevated serum creatinine levels. There was no history of recent illnesses or symptoms, such as fever, diarrhea, emesis, decreased intake, or new medications. The patient’s medical history was notable for a 5q14.3 deletion, severely dilated aortic root, global developmental delay, and seizures. He had no history of kidney stones. There was no family history of kidney disease, kidney stones, or consanguinity. His medications included losartan, perampanel, valproic acid, and levocarnitine. The physical examination was notable for normal blood pressure and global developmental delay.

Laboratory evaluation included serum creatinine levels of 1.8 mg/dL (estimated glomerular filtration rate = 24 mL/min/1.73m² using Chronic Kidney Disease in Children U25 equation), albumin 2.9 g/dL, hemoglobin 7.7 g/dL, reticulocyte count 1.4%, normal iron stores, and an erythropoietin level of 9 mU/mL (expected level of >10,000 mU/mL with a hematocrit of 22%). The urinalysis dipstick was negative for blood and protein; microscopy demonstrated 0-5 white blood cells per high powered field. A renal ultrasound (10.7 cm right kidney and 10.3 cm left kidney) demonstrated mild bilateral hydronephrosis and increased echogenicity of the kidney cortex. A kidney biopsy (Fig 1A-D) was notable for chronic interstitial nephritis with tubular injury associated with marked crystal deposition with diffuse mild interstitial fibrosis and mild chronic glomerular damage with podocyte injury. The biopsy findings led to the measurement of a serum oxalate levels (55 mcmol/L [normal < 2 mcmol/L]) and a urine oxalic acid to creatinine ratio (0.9 mg/mg [normal: 0.01-0.05 mg/mg]). A 24-hour urine was not obtained because of urinary incontinence. The family preferred blenderized feeds instead of a complete nutritional formula, and the patient had been receiving a large intake of spinach and nuts daily for 5 years. The patient did not have a gastrostomy tube. Management included increased fluid intake, avoiding foods with elevated oxalate content, and treatment of his chronic kidney disease. After 3 months of decreased dietary oxalate, the serum oxalate level decreased to 33 mcmol/L, and the spot urine oxalic acid to creatinine ratio decreased to 0.17 mg/mg. However, the serum creatinine level had increased to 2.1 mg/dL (estimated glomerular filtration rate = 20 mL/min/1.73m² using Chronic Kidney Disease in Children U25 equation).

Figure 1.

(A) Kidney biopsy images: light microscopy with hematoxylin and eosin (H&E) staining (original magnification, ×100) demonstrates diffuse moderate interstitial fibrosis, tubular atrophy, and a moderate lymphocytic infiltrate with a minor component of eosinophils. Numerous refractile crystals are present. (B) H&E staining at higher magnification (original magnification, ×400) shows that crystals are mainly within the tubular lumens, but some are also in the interstitium, likely a result of tubular rupture. (C) Polarization microscopy (original magnification, ×40) shows crystals that are strongly birefringent. (D) Electron microscopy (original magnification, ×4,000) demonstrates needle-like crystals within the tubular lumens, some with a fan-shaped arrangement.

Discussion

We present a case of a pediatric patient who developed oxalate nephropathy secondary to the consumption of a blenderized diet with a large amount spinach and nuts, foods with a high oxalate content, for 5 years. Urine and serum oxalate levels decreased when the patient changed to a lower oxalate diet.

There is an increasing preference of caregivers to use blenderized foods over commercially produced complete nutritional formulas.⁶ Although blenderized feeds are successfully given to many patients and may be beneficial in reducing gastrointestinal symptoms in some patients, there is more risk for variable energy and nutrient intake when compared with commercially available formulas with clearly quantified nutritional content.⁶ Even commercially available formulas have been found to have highly variable oxalate concentrations ranging from 4-140 mg oxalate/L of formula.⁷ Enteral nutrition formulas in the United States are classified by the Food and Drug Administration as medical foods. Many nutrients must be reported on the label, but there is no requirement to report the oxalate content.

Caregivers preparing blenderized foods may use a limited variety of foods, and this can lead to nutritional deficiencies. Moreover, they may perceive high oxalate foods, such as spinach and nuts as being healthy, not recognizing the dangers of chronic consumption of excessive amounts of oxalate, which can cause oxalate nephropathy and chronic kidney disease.

The management of dietary hyperoxaluria, includes avoiding foods with high oxalate content, adequate dietary calcium to bind dietary oxalate, and high fluid intake to increase the solubility of calcium oxalate.⁴ However, the outcome of secondary oxalate nephropathy is poor, with none having a full recovery and the majority developing kidney failure.⁴ This emphasizes the importance of screening for excessive oxalate consumption in children receiving blenderized foods.

Conclusion

We report a child who developed stage 4 CKD because of excessive consumption of oxalate from blenderized feeds. Children who consume substantial amounts of foods with high oxalate content are at risk for kidney stones and oxalate nephropathy. There is increasing use of blenderized feeds by caregivers of children who would previously be managed with commercial formulas. Such children are at risk of dietary hyperoxaluria if there is chronic utilization of foods with elevated oxalate content. The dietary content of children receiving blenderized foods should be reviewed for excessive intake of oxalate, especially if they develop kidney stones, nephrocalcinosis, or decreased kidney function.