CKD: Nutrition

• Recombinant Growth Hormone (rhGH): Children with CKD are at risk for growth failure/deficiency as part of their disease

• Growth Hormone (various brands) starting at 0.35mg/kg/week, DAILY injections.

• Targeting at least 50th %ile or mid-parental height. It’s an expensive drug, so some people suggest just going to whichever is lower.

• Workup prior to starting GH can include: bone age (L wrist XR), XR hips/pelvis, TSH/FT4, ***

• Monitor for/Contra-indicated in:

  • Increased ICP (headaches, fundoscopic exam)

  • Neoplasia

  • Severe hyperPTH (PTH > 800ng/mL)

  • Closed epiphyses

  • AVN or SCFE (hip pain)

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• Growth failure due to congenital CKD

• Major part of growth happens during the first 3 years of life: 50 cm

  • U-shaped mortality: cardiac death, infection-related death, malignancy-related death

• Factors that contribute to growth failure in CKD:

  • [***] Nature Reviews Nephrology 2019 (Drube et al)

• GH in well-nourhished infants with CKD

  • [***] see: clin J am soc nephrol 2010

  • Age dependent efficacy of GH treatment

    • Earlier initiation leads to improvement

    • Change in growth

• Adult height below 3rd percentile in approximatley 40% of European patients with ESKD

• Short stature impairs quality of life, self-esteem and social rehabilitiation, and is associated with increased mortality in children with ESKD

• Uremia is a state of GH insensitivity which can be overcome by supraphysiological doses of recombinant human growth hormone

• The efficacy and safety of GH has been studied in several controlled, uncontrolled and open-label studies during the last 30 yers

• GH treatment is licensed for CKD-induced growth failurei n Europe, NA and many other high0-incoming countries

• 2018 consensus statement

  • Work up before initiation of GH treatment:

    • Height or supine length should be regularly measured

    • Height velocity should be calculated over a minimum period of six months, and both height and height velocity should be plotted on standardized growth charts

    • Assessment intervals for statural growth in CKD [*** table with intervals]

  • Growth potential should be assessed by genetic target height, based on parental height and the extent to which the epiphysis of the left wrist is open on radiography

    • Factors need to be addressed before initiation: protein-calorie malnutrition, metabolic acidosis, [*** list factors]

    • Labs:

      • Serum creatinine, urea, calcium,p phosphorus, ALP, bicarbonate, PTH, 25(OH) vitamin D, albumin, fasting glucose and HbA1c levels

      • Serum thyroid hormone (TSH, free t3) and IGF1 concentrations

      • Funduscopic examination

      • Radiography of the left wrist

      • Pubertal status according to Tanner

    • Discuss pros and cons with family

      • Must give it every day

      • Particularly important for immobilized patients (being larger and heavier may complicate their care) and syndromic kidney diseases

  • Candidates: stage 3-5 CKD

    • [***] criteria

    • For transplants, wait 1 year after the transplant

      • Ideally, use steroid free immunosuppression

      • May have spontaneous catch up growth after transplant without the use of exogenous growth hormone

    • Nephropathic cystinosis: if persistent growth failure (height <3%ile for age & sex + height velocity <25%ile)

      • GH therapy should be considered at all stages of CKD

  • GH should NOT be started if:

    • Close epiphyses

    • Known hypersensitivity to the active substance or to any of the excipients

    • In case of unwillingness of the patient or the family

    • Patients with severe secondary hyperparathyroidism (PTH >500 pg/mL)

    • During the first year after renal transplantation

    • Acute critical illness

    • Active malignancy

  • Cost-benefit ratio should be considered

• Dosing

  • 0.045 to 0.05 mg/kg body weight day, given every evening, by subcutaneous injection

  • Encourage children from 8-10 years of age to do the GH injections on their own if adequate training and adherence is ensured (should be supervised by parents)

  • 3-6 months, more frequently in young patients in young patients or

• Monitor: height velocity, pubertal development, skeletal maturation on wrist radiography, kidney function, thyroid hormone levels, serum glucose, calcium, phosphorus, bicarbonate, PTH

• Side effects:

  • NO increased risk for: acceleration of CKD progression, acute rejection after KTx, malignancy

  • Promotes insulin resistance, check glucose intolerance (cystinosis)

  • 2ndary hyperparathyroidism

  • Hypothyroidism may occur

  • Peripheral edema (usually transient)

  • Benign intracranial hypertension: if repeatedly complaining of headaches, should have fundoscopic exam

• Adherence:

  • If height velocity in first year of GH treatment is less than 2 cm/year over baseline, assess adherence, measure IGF1, weight adjust doses, assess nutrition and metabolic factors

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  • Some companies provide a pen that has a microchip that records the dose, and some will even verify the skin is consistent with human skin before the dose is administered

• Discontinue if:

  • Epiphyseal closure

  • Renal transplantation

  • ICH

  • Persistent severe secondary hyperparathyroidism

  • SCFE

  • Inadequate response despite optimal nutritional and metabolic control

  • If unexplained decreased in eGFR and treatment is suspected as a possible cause

  • Consider if accelerated bone maturation

  • Consider if:

    • Patient has reached genetic target height percentile

      • Can be reinstituted if catch-down growth occurs

      • When patients reaches genetic target height

  • 
    

• Barriers to optimizing growth and nutritional status

  • Metabolic acidosis

  • Anemia

  • Fluid and electrolyte imbalances

  • Long term use of corticosteroids

  • Alterations in bone metabolism leading to bone diseases

• Growth

  • Postnatal growth:

    • infancy (birth-18 months): growth hormone, nutrition

    • Childhood (18 months-12 years): growth dependent on growth hormone, thyroid hormone, good overall health

    • Pubertal growth: growth hormone, testosterone, estrogen, good overall health

  • [***] nutrition loss

  • If weight is static for 2 weeks in the first 3 months of life, there is a loss of 1 %ile of maximum height

  • Calories and relation to growth velocity

    • >80% DRI: normal growth

    • <80% DRI: reduced growth velocity

    • <40% DRI: cessation of growth velocity

  • Growth assessment frequency: [*** KDOQI guidelines]

  • Measure:

    • Weight infant scale <2 years, standing scale >2 years

    • Recumbent length <2 years, standing height >2 years

    • Head circumference up to 36 months

  • Example: gain of 200 grams should take 6 week old

    • at 6 weeks: 1 week

    • 7 years: 1 month

    • 14 years: 2-3 weeks

  • Treating growth failure

    • Metabolic abnormalities should be corrected and nutrition optimized prior to starting growth hormone

    • Ensure optimal energy intake prior to starting growth hormone

    • When possible, should be initiated pre-transplantation and pre-puberty

  • Overnourishment: Obesity rates increasing

    • Peaked at ~30% in adolescents

    • Rate of metabolic syndrome also on the rise, 15-30% in CKD

  • Other tools: MUAC is validated at a marker of nutrition status

    • [***] other measurements

• Renal modifications

  • There is no one renal diet; each needs to be tailored to the individual

  • CPR: Pediatric Renal Nutrition Taskforce (PRNT) 2017: link

  • Calories: Aim for initial target of 100% of estimated energy requirement (EER) for a healthy child of the same chronological age, with adjustments based on individual weight gain/loss

  • Protein: aim for DRI, and adjust for dialysate losses (add 0.1 mg/kg HD, add 0.15-0.3 g/kg for PD)

    • Estimated to be higher in CKRT: up to 2.5 g/kg/day

  • Sodium: 1-2 mmol/kg/day

    • Sodium awareness should be taught in early stages of CKD

    • More than 25% of adolescents take in >2x the upper limit of recommended intake

    • Must also account for kidney medications (e.g., sodium polystyrene sulfonate [Kayexalate], sodium bicarbonate)

  • Fluids: individualized

    • Depends on method of dialysis, residual function, and primary kidney disease

    • Must be continually assessed, especially with changes in urine output

      • Polyuria and Na wasting: [*** slide]

    • Fluid allowance needs to be clearly documented and regularly discussed

    • Certain amount of fluid is necessary to ensure adequate calories

    • Must be very clear to patients/families about what this entails [***]

  • Potassium: initial target of 1-3 mmol/kg/day in infants and young children

    • Plant based levels, widely considered to be good from CV standpoint, but can be high in potassium

    • May take 3-7 full days to appreciate full effect of any dietary change on serum potassium

    • Natural potassium

      • 50-60% absorbed

      • Fiber ↓ absorption

        • Fruits/vegetables

        • Milk, milk products

        • Meat, chicken, fish

        • Beans, lentils, nuts

    • Added potassium

      • 100% absorbed

        • Flavor agent

        • Sodium substitutes (e.g., Mrs. Dash)

      • Potassium may not be on the nutrition label: look for the ingredients list

        • Examples: potassium sorbate, potassium benzoate, potassium nitrate, potassium propionate, potassium acetate, potassium lactate, potassium citrate, potassium phosphate, potassium chloride, potassium carbonate, potassium sulphate, potassium gluconate, etc.

• Calcium, phosphorus and vitamin D

  • KDOQI:

    • Ca: DRI and no more than 2x DRI

    • Phos: DRI

    • Vitamin D: individualized

  • Bones:

    • Lower GFR can cause disorders in calcium and phosphorus metabolism

      • Lower/higher serum calcium

      • higher phosphorus

      • Higher PTH levels

    • Inadequate activation of vitamin D

      • Lower levels of 1,25 dihydroxyvitamin D

      • [***] tables:

        • NKF, AJKD 2009 KDOQI; McAlister (2019) Ped Neph

  • Phosphorus:

    • Natural phosphorus: 40-60% absorbed

      • Phytates ↓ absorption

      • Found in:

        • Dairy products

        • Meat, poultry, fish

        • Soy (milk, tofu)

        • Nuts, seeds

        • Dried beans and peas

        • Whole grains

    • Added phosphorus: >90% absorbed

      • • Food additives

          • Used to improve texture, taste, shelf life of processed foods

        • Dietary supplements

        • Calcium fortification

      • Also not always on nutrition label, so check ingredients list for anything with "phos" in the name

  • Vitamin D

  • Other vitamins and minerals:

    • [***]

    • Zinc: commonly low on dialysis

    • Copper: can be high or low

    • Selenium: commonly low on dialysis

• If energy requirements not being met:

  • Formula prescription tailored: volume, electrolytes, nutrients, mixture of products

  • No magic renal formula

    • BC children's hospital formula calculator

• Standard infant options:

  • Expressed breast milk

    • Lower in protein, sodium, potassium, and phosphorus

    • Can be fortified with Duocal to increase calories or mixed with renal formula to reduce electrolytes

  • [***]

• Renal formula liquid (Suplena, Novasource)

  • Lower in K

  • Predialysis: lower in protein

  • Dialysis: higher in protein

  • Intended for use in adults

  • Concentrated calories, good for controlled fluids

  • Renal formula powders (Nephea kid, renastart, PM 60/40)

    • Electrolyte/mineral reduced supplement intended for use in children with CKD

    • Short term use, not sole source of nutrition

    • Can be used in combination with other formulas to reduce electrolytes

  • Decanting and pretreatment:

    • Hyperkalemia may require treatment

      • SPS: sodium based cation exchange

      • Patiromer: calcium based cation exchange

    • Provided by mouth or feeding tube: not in infants due to increased risk of NEC

  • May need to pretreat formula for babies/children

    • 6 g/L max dose SPS [***]

• Medical nutrition therapy:

  • Take "shots" of nutrition supplement a few times a day

• Home blenderized tube feeds

  • [***]

  • Benefits:

    • Improvement in GI symptoms

    • Firmer stools, decrease in emesis

    • Decreased retching and gagigng

    • Can tailor recipe to meet patients' needs

  • [***]

• intradialytic parenteral nutrition (IDPN)

  • Noninv asive method to provie carbohydrates, protein and fat to undernourished HD patients

  • Not sole source of nutrition; addiotoin to oral or enteral nutrition

  • Provided during HD via venous access distal to hemolyzer

  • [***]

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