Advertisement

Medical Nutrition Therapy for Pediatric Kidney Stone Prevention, Part 3: Cystinuria

      Audience: Pediatrics; Nephrology Outpatient Clinic

      Cystinuria is an inherited, genetic condition that causes hyper-excretion of cystine and other dibasic amino acids (lysine, arginine, and ornithine) in the urine due to impaired transport in the proximal renal tubules. The low solubility of cystine leads to precipitation and the formation of renal stones.
      • Saravakos P.
      • Kokkinou V.
      • Giannatos E.
      Cystinuria: current diagnosis and management.
      • Thomas K.
      • Wong K.
      • Withington J.
      • Bultitude M.
      • Doherty A.
      Cystinuria-a urologist's perspective.
      While rare, this condition accounts for a relatively significant proportion of pediatric nephrolithiasis, up to 10% in children compared to 1% in adults.
      • Chillaron J.
      • Font-Llitjos M.
      • Fort J.
      • et al.
      Pathophysiology and treatment of cystinuria.
      • Andreassen K.H.
      • Pedersen K.V.
      • Osther S.S.
      • Jung H.U.
      • Lildal S.K.
      • Osther P.J.
      How should patients with cystine stone disease be evaluated and treated in the twenty-first century?.
      Furthermore, as compared to other causes of pediatric stone formation, cystinuria is more likely to result in frequent recurrence, morbidity, and need for medical interventions. Careful attention to disease management is required to prevent disease-related complications, specifically chronic kidney disease.
      • Saravakos P.
      • Kokkinou V.
      • Giannatos E.
      Cystinuria: current diagnosis and management.
      • Andreassen K.H.
      • Pedersen K.V.
      • Osther S.S.
      • Jung H.U.
      • Lildal S.K.
      • Osther P.J.
      How should patients with cystine stone disease be evaluated and treated in the twenty-first century?.
      The dietary management of cystinuria is a two-pronged approach involving (1) a reduction in the overall urinary excretion of cystine and (2) an increase in urinary cystine solubility. The first objective may be obtained by restricting dietary intake of animal proteins, which, in comparison to plant-based proteins, are generally higher in cystine and its metabolic precursor methionine.
      • Thomas K.
      • Wong K.
      • Withington J.
      • Bultitude M.
      • Doherty A.
      Cystinuria-a urologist's perspective.
      • Chillaron J.
      • Font-Llitjos M.
      • Fort J.
      • et al.
      Pathophysiology and treatment of cystinuria.
      Avoiding excessive dietary intake of sodium will also reduce urinary excretion of cystine.
      • Chillaron J.
      • Font-Llitjos M.
      • Fort J.
      • et al.
      Pathophysiology and treatment of cystinuria.
      • Andreassen K.H.
      • Pedersen K.V.
      • Osther S.S.
      • Jung H.U.
      • Lildal S.K.
      • Osther P.J.
      How should patients with cystine stone disease be evaluated and treated in the twenty-first century?.
      The second objective, increased urinary cystine solubility, can be improved with increased fluid intake; in pediatric patients, this is commonly estimated using body surface area and approximates 2 L/m2 × body surface area.
      • Chillaron J.
      • Font-Llitjos M.
      • Fort J.
      • et al.
      Pathophysiology and treatment of cystinuria.
      • Carvalho-Salemi J.
      • Moreno L.
      • Michael M.
      Medical nutrition therapy for pediatric kidney stone prevention, part one.
      Cystine solubility also increases with urinary alkalinity, so once again it is important for patients to avoid excessive animal protein, whose sulfur containing amino acid profile acidifies the urine.
      • Chillaron J.
      • Font-Llitjos M.
      • Fort J.
      • et al.
      Pathophysiology and treatment of cystinuria.
      • Han H.
      • Segal A.M.
      • Seifter J.L.
      • Dwyer J.T.
      Nutritional management of kidney stones (nephrolithiasis).
      Finally, it is noted that patients with cystinuria are at higher risk for calcium oxalate stones; therefore, general dietary recommendations for renal stones should be followed, including ensuring adequate amounts of dietary calcium.
      • Thomas K.
      • Wong K.
      • Withington J.
      • Bultitude M.
      • Doherty A.
      Cystinuria-a urologist's perspective.
      Positive outcomes have been noted with an increase in vegetable-based protein and limitation of animal based to 60% of dietary protein intake, including at least two sources of dairy foods.
      • Thomas K.
      • Wong K.
      • Withington J.
      • Bultitude M.
      • Doherty A.
      Cystinuria-a urologist's perspective.
      While randomized clinical trials are the gold standard to confirm such interventions, clinical studies are rare for nutritional therapies and even more so for pediatric populations. The overall health benefits and proven safety of balanced plant-based diets lend itself toward implementation with available evidence—albeit with special precautions to ensure the optimal growth and development of children. As for the safety and efficacy of such diets in children, it is the position of the Academy of Nutrition and Dietetics that vegetarian diets, when well planned, “are appropriate, and they satisfy the nutrient needs and promote normal growth at all stages of the life cycle, including pregnancy and lactation, infancy, childhood, [and] adolescence…”
      • Melina V.
      • Craig W.
      • Levin S.
      Position of the academy of nutrition and dietetics: vegetarian diets.
      That said, it is important to note that removing dietary protein, without substitution with appropriate vegetable protein, can, in fact, be harmful to the growth and development of pediatric patients. A registered dietitian should consult with the family to assess the child's usual intake and nutrition status, as well as food access and social or economic barriers to making dietary changes. Modifications should be appropriate to the patient and caregiver's mealtime routines and level of culinary expertise. A simple recommendation might be to suggest a single food swap that is easy and affordable; examples may include oatmeal or yogurt in place of bacon at breakfast, a peanut butter sandwich substituting for ham at lunch, or bean instead of beef burritos for dinner. Table 1 provides protein intake recommendations for pediatric patients, allowing for a range depending on food choices. Higher protein recommendations are recommended for children limiting animal products (e.g., vegan diets). Children who consume lacto-ovo-vegetarian diets generally meet or exceed recommended protein intake, but clinical judgment as to the nutrition status of the patient is advised.
      Table 1Recommended Daily Protein Intake Based on Age
      Age GroupLower Protein Requirement (g/kg/d)Higher Protein Requirement (g/kg/d)
      Higher protein recommendations for children limiting animal products (e.g., vegan diets).
      Ages 1–3 years
      Recommendations are estimates for children above 13 months of age.7-9
      1.11.5
      Ages 4–80.951.24
      Ages 9–130.951.15
      Ages 14–180.851.02
      Higher protein recommendations for children limiting animal products (e.g., vegan diets).
      ∗∗ Recommendations are estimates for children above 13 months of age.
      • Melina V.
      • Craig W.
      • Levin S.
      Position of the academy of nutrition and dietetics: vegetarian diets.
      Finally, certain vitamins and minerals, and specifically B-12, should be supplemented in any child who regularly avoids or limits animal products.
      • Melina V.
      • Craig W.
      • Levin S.
      Position of the academy of nutrition and dietetics: vegetarian diets.
      In conclusion, protein should not be restricted below the dietary reference intakes in growing children; however, protein foods lower in methionine, such as plant-based foods, may be encouraged. High animal protein diets should be avoided. A registered dietitian can help parents to select low-methionine protein foods and provide recommendations for vitamin supplementation if needed. The educational handout that follows provides a sample list of common foods categorized by methionine content. The following handout can be used to emphasize the differences in methionine content within and among food groups, but should not be used as a recommended food list. For example, all protein foods are presented in two ounce equivalents in order for appropriate comparisons to be made regarding methionine content per serving.

      Note to Educators

      All handouts provided in this series should be utilized as tools to facilitate communication between providers and caregivers and should in no way substitute for complete and thorough medical care.

      References

        • Saravakos P.
        • Kokkinou V.
        • Giannatos E.
        Cystinuria: current diagnosis and management.
        Urology. 2014; 83: 693-699
        • Thomas K.
        • Wong K.
        • Withington J.
        • Bultitude M.
        • Doherty A.
        Cystinuria-a urologist's perspective.
        Nat Rev Urol. 2014; 11: 270-277
        • Chillaron J.
        • Font-Llitjos M.
        • Fort J.
        • et al.
        Pathophysiology and treatment of cystinuria.
        Nat Rev Nephrol. 2010; 6: 424-434
        • Andreassen K.H.
        • Pedersen K.V.
        • Osther S.S.
        • Jung H.U.
        • Lildal S.K.
        • Osther P.J.
        How should patients with cystine stone disease be evaluated and treated in the twenty-first century?.
        Urolithiasis. 2016; 44: 65-76
        • Carvalho-Salemi J.
        • Moreno L.
        • Michael M.
        Medical nutrition therapy for pediatric kidney stone prevention, part one.
        J Ren Nutr. 2017; 27: e5-e8
        • Han H.
        • Segal A.M.
        • Seifter J.L.
        • Dwyer J.T.
        Nutritional management of kidney stones (nephrolithiasis).
        Clin Nutr Res. 2015; 4: 137-152
        • Melina V.
        • Craig W.
        • Levin S.
        Position of the academy of nutrition and dietetics: vegetarian diets.
        J Acad Nutr Diet. 2016; 116: 1970-1980
      1. Texas Children's Hospital Pediatric Nutrition Reference Guide. 11th ed. Texas Children's Hospital, Houston, TX2016
      2. The A.S.P.E.N. Pediatric Nutrition Support Core Curriculum. 2nd ed. American Society for Enteral and Parenteral Nutrition, Silver Spring, MD2015