Nutritional Issues Surrounding Acute Kidney Injury ...

Nutritional Issues Surrounding Acute Kidney Injury and Chronic Kidney Disease in Newborn Infants Allison Prince MS, RD, LD1, Sreekanth Viswanathan MD1, Sharon Groh-Wargo PhD, RD, LD2 1 2

Rainbow Babies and Children’s Hospital, Cleveland, Ohio, USA MetroHealth Medical Center, Cleveland, Ohio, USA

Key Words: Acute Kidney Injury, Chronic Kidney Disease, Newborn, Preterm Infants, Nutrition

ABSTRACT

Introduction

Newborns are more susceptible to renal injury than older infants and children because of the functional and developmental immaturity of the neonatal kidney. Acute kidney injury (AKI) is often transient and part of multiorgan dysfunction especially in premature infants, but could produce long lasting damage to the developing nephrons. The advances in obstetric and neonatal care have improved the survival of the smallest premature infants and infants with renal anomalies–an increasing population at high risk for AKI with the potential for progression to chronic kidney disease (CKD). Nutritional interventions are crucial to therapeutic treatment and optimal outcomes in both AKI and CKD in newborns. Research evidence specific to nutritional management of newborns with AKI/CKD is limited and recommendations often stem from studies in older children with AKI/CKD. This article discusses the nutritional issues surrounding AKI/CKD in infants admitted to the neonatal intensive care unit and recommendations for management based on available evidence to achieve optimal outcomes.

Acute kidney injury (AKI) is characterized by sudden decline in glomerular filtration rate (GFR) which leads to the failure of kidneys to maintain fluid and electrolyte homeostasis.1,2 AKI is encountered in 3–24% of all admissions to neonatal intensive care units.1,3 While AKI is mostly reversible, a small percentage of AKI progresses to chronic kidney disease (CKD) which is defined as persistent abnormalities in structural or functional renal defects that persist for more than 3 months.4 Both disorders are characterized by a decline in GFR, result in impaired nitrogenous waste excretion, and have altered regulation of water, electrolytes and acid-base balance, erythropoietin synthesis, and gluconeogenesis.2,5 These physiologic and metabolic changes create a challenge to provide appropriate nutrition to the affected newborns. AKI is often present as part of multiorgan dysfunction in a critically ill newborn, so the main nutritional management goal is on reducing the impact of acute malnutrition related to the AKI event, while CKD is often present as an established disorder requiring long term nutritional support to promote adequate growth and development.

Correspondence : Sharon Groh-Wargo Professor of Pediatrics and Nutrition Case Western Reserve University School of Medicine Neonatal Nutritionist Department of Pediatrics R240 MetroHealth Medical Center 2500 MetroHealth Drive Cleveland, Ohio 44109-1998 Office (216) 778-5902 Fax (216) 778-3252 Email : [email protected]

Conservative management of AKI and CKD in newborns is intertwined with nutrition in the management of fluid and electrolytes. Prevention of protein-calorie malnutrition optimizes outcomes in this population, especially in premature infants. This article is focused on the nutritional issues of newborn infants admitted to the Neonatal Intensive Care Unit (NICU) with AKI and CKD and provides nutrition support recommendations to achieve optimal growth and prevent malnutrition. Renal Functional Development Though nephrogenesis is complete by 34–36 weeks of

Journal of Clinical Pediatric Nephrology (Vol. 2./January - June 2014)

gestation, the neonatal kidney is different from the adult kidney. The term newborn has similar number of nephrons as adults, but the GFR is only about 30% of the normal adult GFR primarily due to low surface area of glomerular basement membrane.6,7 In preterm infants born before 34 weeks, the lack of full complement of nephrons also contributes to the low GFR.7 The GFR progressively increases in the postnatal life because of changes in renal hemodynamics and changes to the existing glomeruli basement membrane. The mean GFR for a full term infant is about 26 ml/min per 1.73 m2. The GFR doubles by 1–2 weeks of age to 54 ml/min per 1.73 m2.6 Similarly the permeability characteristics of the neonatal proximal and distal tubule are quite different from the adult kidneys, which affect the transport of water and electrolytes. The premature infant has even less mature tubular function compared to the term newborn. This can lead to significant metabolic acidosis and glucosuria in preterm infants due to the reduced bicarbonate and glucose reabsorption in the proximal tubules.7 Also, generalized aminoaciduria due to renal immaturity potentiates the protein loss and can leads to protein-calorie mismatch.8 Preterm infants are exquisitely sensitive to states of water imbalance; the relative inefficiency in concentrating capacity makes them particularly vulnerable to water depletion and dehydration, while the limitation imposed by an overall low GFR, they have limited capacity to excrete a large water load, thus making preterm newborns susceptible to water overload states.8 The diluting segment of neonatal kidney can excrete urine with an osmolality (50 mOsm/kg water) comparable to the adult, however, their maximum urine concentration capacity (600 mOsm/ kg water) is only half of the adult function and reaches the matching adult levels only around 2 years of age.7 Acute Kidney Injury (AKI) The different definitions of AKI used in various studies make it difficult to compare and calculate the true incidence of AKI in the NICU. One of the widely used definitions of neonatal AKI is rising or persistently high level of serum creatinine > 1.5 mg/dl after 48-72 hours of life regardless of the urine output.3 Currently a standardized categorical definition of AKI is recommended based on the level of increase in serum creatinine from the trough level such as modifications of the Acute Kidney Injury Network (AKIN) staging system and the risk, injury, failure, loss and endstage renal disease (RIFLE) classification.9 AKI may be oliguric (urine volume < 0.5-1 ml/kg/hr) or non-oliguric, depending upon the severity of the reduction in GFR and the degree of tubular reabsorption. The impaired GFR causes fluid and salt retention leading to oliguria while a predominant tubular injury results in excessive urine output.

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However, AKI is rarely an isolated disease in newborns. It complicates sepsis, perinatal hypoxic ischemic encephalopathy (HIE), or conditions leading to multiple organ failure (Table 1). Acute critical illness is characterized by catabolism exceeding anabo-lism; therefore they are at risk of nutritional depletion. Most patients with AKI have some degree of net protein breakdown (protein synthesis minus degradation) and have disturbance in fluid, electrolyte, or acid-base status. The net protein breakdown in infants with AKI can increase the rate of rise in plasma potassium, phosphorus, and urea, and the fall in blood pH. Nutritional management for AKI is not very different from other critically ill infants, but it is more complicated as it needs adjustment for the complex alterations in metabolic and nutrient balances associated with AKI. Major problem in management of AKI is retention of water and products of amino acid metabolism because of impaired excretory functions which restricts the administration of fluid and electrolytes. It is important to ensure adequate caloric intake during the AKI phase to prevent catabolism, encourage anabolism, and reverse protein-energy wasting, but it is often not possible to achieve this goal without instituting some form of renal replacement therapy because of the limitations on prescribed fluid intake.10,11 Fluid Management Maintenance of proper fluid homeostasis is critical to the successful management of AKI. Most of AKI in newborns are pre-renal in origin and it is logical to give a fluid challenge to an infant with AKI presenting with oliguria/anuria. The fluid challenge consists of the intravenous administration of 10–20 ml/kg of isotonic saline given over 1 to 2 hours. A positive response of increasing urine output to > 1 ml/kg/ hr indicates a pre-renal cause for the AKI. In infants who respond, the urine output should be maintained by adequate fluid maintenance and replacement that takes into account ongoing urinary and insensible losses, and allows for other losses due to a radiant warmer, phototherapy, and nasogastric or surgical drainage. In infants who don’t respond, a second fluid challenge ± diuretics can be given and absence of a response to a repeated fluid and diuretic challenge generally indicates intrinsic renal failure. Such infants require conservative treatment, including fluid restriction, careful monitoring of fluid balance and serum electrolytes, and dialysis when needed. Fluid administration should be limited to estimated insensible water losses plus the urine output.1,12 Fluid input calculations should include drug volumes, blood products and continuous infusions concentrated where possible.10,11 Infants with renal failure should ideally be weighed every 12 hours and fluid administration adjusted accordingly.13 Weight loss is usually anticipated during the oliguric phase of AKI, and any weight gain during this phase indicates

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Table 1: Common etiologies of acute kidney injury and chronic kidney disease in newborn Congenital Malformations •

Renal agenesis

•

Renal hypoplasia/dysplasia

•

Cystic diseases of kidney, e.g., autosomal recessive polycystic kidney

Acquired Renal Disorders •

Pre-renal –

•

•

•

Hypovolemia: Dehydration, severe patent ductus arteriosus, twin to twin transfusion, perinatal hemorrhage (i.e., abruptio placentae)

Acute tubular necrosis (Vasomotor nephropathy) –

Hypovolemia: Prolonged with insufficient fluid resuscitation

–

Perinatal asphyxia

–

Perinatal hypoxia due to respiratory distress syndrome, traumatic delivery

–

Sepsis/necrotizing enterocolitis due to the third spacing of fluids

Drugs –

Maternal use of ACE inhibitors, NSAID drugs

–

Exposure to NSAID (Ibuprofen, indomethacin), tolazoline, antibiotics (aminoglycosides, vancomycin, cephalosporins, amphotericin B), contrast agents

Vascular –

Arterial thrombosis or embolism or stenosis

–

Venous thrombosis

Obstructive Uropathy •

Posterior urethral valves

•

Pelviureteric obstruction, ureterovesical obstruction

fluid overload.1 If the infant has a greater than expected change in weight, a “dry weight” is often estimated to base the medication doses as well as protein and calorie calculations. Urinary output should be monitored closely, and bladder catheterization may be considered if necessary.10,12 Daily insensible loss in newborns increases with decreasing birth weight (> 2500 g ~15–25 ml/kg, 1500– 2500g ~15–35 ml/kg, < 1500g ~ 30–60 ml/kg).13,14 The use of humidified air on ventilator circuits and maintaining appropriate humidity inside the incubator will help to reduce the insensible water loss in smaller premature infants.12

condition safely allows will help achieve the protective gastrointestinal benefits of enteral nutrition. In animal models, enteral feeds have been shown to exert local gastrointestinal anti-inflammatory responses and strengthen hepatic and even pulmonary immune mechanisms. Adult patients have demonstrated reduced episodes of hyperglycemia with enteral nutrition, which may promote better metabolic control in the infant with AKI.16

Most affected infants are critically ill and require parenteral nutrition. The concentration of glucose and solutes such as sodium, potassium, calcium, and phosphorus in parenteral nutrition depend upon the infant’s weight, serum electrolyte concentrations, the severity of the renal injury, and whether or not the patient is on dialysis.13 Attempts should be made to use the gut if clinically appropriate. Enteral nutrition is the preferred method as it maintains gut integrity, prevents bacterial translocation, is associated with fewer complications, and is less expensive compared to other methods.15 Initiation of trophic feeds as promptly as the infant’s medical

Estimates of energy and protein needs in premature and term infants with AKI are mostly extrapolated from pediatric or adult studies. Approximately 120 kcal/kg/day is required in a neonate with AKI,15 however basing calorie needs on length, i.e., 8 to 12 kcal/cm/day, is also suggested to eliminate fluid interference.15,17,18 Parenteral energy needs are estimated to be 10–15% lower than enteral needs due to reduced stool losses and the absence of digestion and absorption which are energy-requiring processes.19 Minimal provision of 25% of the caloric needs should initially be provided to reduce inevitable catabolism followed by advancing the feeds to goal calorie and protein needs as

Calorie and Protein Management


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tolerated.1 Both parenteral and enteral nutrition can be concentrated to maximize nutrition and minimize the fluid volume. Infants generally require at least 115 ml of fluid for every 100 kcal given.19,20 Infants who are able to take enteral feedings should be given human milk, if available, or a formula that has a low renal solute load and low phosphate content when human milk is unavailable. Similac® PM 60/40 (Abbott Nutrition, Columbus, Ohio) contains low mineral content approximate to human milk, thus is appropriate for infants with impaired renal function. Table 2 compares the composition of Similac® PM 60/ 40 to standard term and preterm formula. However, the need for fluid restriction often makes it difficult to meet the caloric needs of an oliguric infant, resulting in continued daily loss of 0.2–1% of body weight beyond the 1st week of age. The weight loss is not reversed until the underlying clinical condition improves and nutrition is adequate. When fluid limitations prevent infants from receiving optimal nutrition, renal replacement therapy (RRT) is indicated.2,12

that have identified exact amino acid requirements for infants and children with AKI. This is particularly relevant in preterm infants who have higher baseline protein requirements. Infants with AKI are highly catabolic and the release of amino acids from increased muscle protein breakdown can cause further strain on the already limited protein stores of the premature infants. Instead of using protein for anabolism for growth, the released amino acids are used by the liver to synthesize acute-phase proteins.5,22 It is suggested to base protein requirements on age and clinical condition.2 Term infants with AKI, not receiving RRT, should receive amino acids up to a maximum of 1.5 g/kg/ day. Preterm infants with AKI have estimated protein ranges from 1.5 to 2.5 g/kg/day. Protein needs are adjusted based on individual need and laboratory data including electrolytes, acid-base balance and the presence of uremia.2,15,18 A summary of energy and protein requirements in infants with AKI is given in Table 3.

Premature infants have increased protein needs at baseline and amino acids are promptly provided at 3.5 4.5 g/kg/day to the healthy preterm infant within a few days after birth to prevent protein deficit and promote adequate growth of lean body mass.21 There are no studies

Electrolytes Abnormalities Metabolic acidosis: Acid-base balance is normally maintained by renal excretion of the acid load (approximately 1 mEq/kg/day), derived mostly from the metabolism of sulfur-containing amino acids. Elimination

Table 2: Key nutrient composition of human milk and formula milk options for preterm infants (Nutrients are per 100ml) Nutrient

Preterm Human Milka

Preterm Human Milk with HMFb

Premature Formulab

Term Infant Formulab

Similac PM 60/40a

Energy, kcal

67

80

81

68

68

Protein, g

1.4

2.7

2.4

1.4

1.5

Fat, g

3.9

4.7

4.3

3.7

3.8

Carbohydrates, g

6.6

8.8

8.6

7.4

6.9

Vitamin D, IU

2

60

158

46

41

Calcium, mg

25

128

140

53

38

Phosphorous, mg

13

70

74

29

19

Magnesium, mg

3.1

7.0

8.5

4.7

4.1

Iron, mg

0.12

1.0

1.5

1.2

0.5

Sodium, mg

24.8

38.2

41.0

17.1

16.2

Potassium, mg

57.0

92.5

92.4

71.7

54.1

Zinc, mg

0.3

1.2

1.2

0.6

0.5

Abbreviations: HMF: Human Milk Fortifier. a Values obtained from Pediatric Nutrition Product Guide 2013, Abbott Nutrition, Columbus, Ohio, 84805/October 2012. b Average of products commercially available.

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Table 3: Recommendations for calorie and protein intakes in infants with AKI/CKD in the first year of life Recommended intake for healthy infants

AKI

CKD

Peritoneal dialysis

Hemodialysis

Premature infants

110-130

120

110-130

120-150

120-150

0-3 months

(89 x wt [kg] – 100) +175b

100% EER

100% EER

100% EER

100% EER

4-6 months

(89 x wt [kg] – 100) + 56b

7-12 months

(89 x wt [kg] – 100) + 22b

Energy (kcal/kg/day)a

Protein (g/kg/day) Premature infants

3.4-4.2

1.5-2.5d

1.5-2.5e

4-6f

4-6f

0-6 months

1.5c

1.5

1.5-2.1e

1.8

1.6

7-12 months

1.2 c

1.2

1.2-1.7e

1.5

1.3

Abbreviations: AKI Acute kidney injury, CKD Chronic kidney disease, EER Estimated Energy Requirement, DRI Dietary Reference Intake a Energy intake is expressed as kcal/kg/day except where otherwise noted. Parenteral energy needs are estimated to be 10–15% lower than enteral needs. b Equals 100% of the EER for age in kcal/day. c Equals 100% of the DRI for age in g/kg/day. d Extrapolated from data previously published. Recommendations vary. e Maximum protein needs decrease as stages of CKD progress without renal replacement therapy. f Extrapolated from published case studies providing additional protein needs above that of a healthy preterm infant.39

of this acid load is achieved by the urinary excretion of hydrogen ions.14,23 The most effective intervention for neonatal metabolic acidosis is treating the underlying cause. The safety and efficacy of intravenous bicarbonate therapy to correct acidosis is not very clear, and in neonates, bicarbonate therapy has been associated with intraventricular hemorrhage (IVH), myocardial injury, deterioration of cardiac function, and worsening of intracellular acidosis.13

extracellular fluid into the cells by sodium bicarbonate particularly if the infant is acidemic (1–2 mEq/kg IV over 5 minutes), and/or insulin as a bolus (0.05 units/kg human regular insulin with 2 mL/kg of 10% dextrose in water), followed by a continuous infusion of insulin (0.1 units/kg/ hr with 2–4 mL/kg/hr of 10% dextrose in water).24 If these treatments are ineffective, beta adrenergic receptor agonists, such as albuterol can be used to stimulate the cellular potassium uptake.

Hyperkalemia: Depending upon the severity and the rate of onset, hyperkalemia can be mild and asymptomatic or so severe as to constitute a medical emergency as it can cause life-threatening cardiac arrhythmias. 2,15 Potassium excretion generally remains unaffected in patients with renal disease as long as both aldosterone secretion and distal flow are maintained. Thus, hyperkalemia usually develops in a newborn with oliguria or when there is excessive tissue breakdown or impaired aldosterone secretion due to congenital adrenal hyperplasia. Plasma potassium concentration above 6–7 mEq/L is potentially life-threatening, but regardless of the degree of hyperkalemia, immediate therapy is indicated if there are electrocardiographic changes of potassium toxicity. Emergency management includes reversal of the effect of hyperkalemia on the cell membrane by infusion of 10% calcium gluconate (0.5–1.0 ml/kg IV over 5 minutes) and to facilitate potassium movement from the

The above interventions only transiently lower the plasma potassium concentration. Further management focuses on continued removal potassium from the body and tries to eliminate potassium intake. In infants with anuric or oliguric AKI, potassium is often withheld in intravenous fluids and restricted in enterally fed infants. In infants with adequate urine output, diuretics like furosemide (1 mg/kg per dose) can be used to increase the urine output.3 Hyperkalemia in infants with nonoliguric AKI, receiving enteral feeds can be treated with ion exchange resins like sodium polysteryne sulfonate (SPS). The process of treatment with SPS is relatively easy to perform and helps to promotes serum potassium levels towards normal ranges.25 A prescribed dose of SPS (typically 1 g/100ml for slightly elevated serum potassium levels between 5.6-6.5 mEq/L) is added to a container of formula or breast milk, shaken for two minutes, and then


allowed to sit for 60-120 minutes. SPS works as a resin which exchanges sodium ions for potassium, thus retaining the potassium in the resin while releasing sodium into the fluid. The formula is decanted leaving the resin at the bottom of the container and the formula or breast milk is emptied into a separate container, which can be fed to the infant. A recent retrospective study observed significant reduction in serum potassium levels (6.5mEq/L pretreatment to 4.95mEq/L post-treatment) in 13 infants with CKD or AKI within 48 hours after consuming SPS pretreated expressed breast milk or Similac® PM 60/40.25 Careful attention to laboratory values of other electrolytes during treatment is needed as breast milk or formula pretreated with SPS can cause retention of calcium, magnesium, and iron in the resin along with potassium, and can cause significant increase in the sodium content of breast milk or formula. SPS should not be administered orally in premature infants or those infants with severe gastric immotility as slow SPS transit may increase the risk of damage to the mucosal lining from a high osmotic load and is associated with necrotizing enterocolitis.26 Therefore, decanting the feed is an effective alternative method.25-29 One procedure for decanting formula has been developed by a Level III NICU in Ohio and is available online (http:// ohioneonatalnutritionists.homestead.com/Safe_ Administration_of_Kayexalate_ February_2011.pdf). The procedure outlines example dosing and guidelines for practitioners to feasibly decant formula in the unit. Hyponatremia: Hyponatremia in newborns is almost always due to dilution that results from the fluid overload. Management generally consists of restricting free water intake, which usually results in a gradual return of the serum sodium to normal levels.1 However, if neurologic signs such as seizures or lethargy develop or if the serum sodium concentration is extremely low (< 120 mEq/L), urgent partial correction is needed with hypertonic saline. Otherwise total sodium deficit is calculated with the formula [Sodium chloride dose = 0.8 × body weight (kg) × (desired serum sodium – actual serum sodium)] and a slow partial correction with normal saline is given over 12-24 hours. However, in infants with non-oliguric AKI, significant sodium loss in urine can produce hyponatremia. Urine should be analyzed for sodium and potassium content and may need replacement at equal volumes and constituents.1 Hypocalcemia and Hyperphosphatemia: Hypocalcemia is a relatively rare in AKI and often associated with hyperphosphatemia. If the patient is symptomatic or hypocalcemia is severe, it is treated with intravenous calcium gluconate (10% calcium gluconate 0.5–1.0 mL/kg over 5–10 minutes with cardiac monitoring). Among patients who are hyperphosphatemic, lowering the

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serum phosphate concentration will also tend to raise the serum calcium. Careful attention is needed to rising serum phosphorous levels in the infant with AKI due to the risk of hypocalcemia.2,15 Hyperphosphatemia is often managed by restriction or manipulation of phosphorous content in oral, enteral, or parenteral nutrition. For infants on parenteral nutrition, decreasing phosphorous content by 30 to 50% may help normalize serum phosphorous.17 Premature infant formulas and human milk fortifiers contain high levels of calcium and phosphorous compared to standard infant formulas (Table 2). For an enterally fed premature infant, providing strictly human milk or a low phosphorous containing formula (e.g.: Similac® PM 60/40) will restrict dietary phosphorous. Phosphorous binders like calcium carbonate can be administered when dietary restrictions alone do not suffice, however use of aluminum hydroxide binders should be used with caution in this population due to aluminum neurotoxicity.2,15,17,30 Enteral Considerations Human milk provides modest amounts of phosphorous and calcium and is the gold standard for all infants including those with renal disease. Table 2 lists nutrient content of human milk and select formulas used in the term and preterm infant. Human colostrum and human milk provide an array of antimicrobial and immunological components such as secretory immunoglobulin A, lactoferrin, and cytokines that are advantageous to the preterm and term infant whether healthy or in critical condition.31 Without availability of human milk, use of Similac® PM 60/40 in infants with renal impairment may be indicated. Formulas designed for feeding intolerance including soy, protein hydrolysate, and amino acid-based formulas are not usually indicated or recommended; however, special circumstances may require the use of these formulas for issues of intolerance and allergies. Similac® PM 60/40 contains sodium caseinate and is not appropriate to use with a milk protein allergy. In this case, a tolerance formula should be prescribed, and serum levels of phosphorous, calcium, and potassium should be closely monitored. SPS may be required to help treat hyperkalemia in this situation. Soy formulas contain amounts of calcium and phosphorous ~20% higher than standard milk-based formulas to account for minerals bound by phytates which compete for calcium and phosphorous absorption. Studies have shown an increase in osteopenia in preterm infants fed soy-based formulas and therefore are not recommended for this population. Additionally, soy-based formulas have relatively high amounts of aluminum from the mineral salts used in formula production. Aluminum retention and risk of toxicity is enhanced in the presence of reduced renal function in term and preterm infants receiving a soy formula and should be avoided.32

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Parenteral Considerations Infants receiving intravenous nutrition therapy require careful monitoring of the calories, protein, electrolytes, and minerals provided in parenteral nutrition (PN) solutions. Trace elements should also be individualized to the infant with renal compromise. Trace element packages consisting of zinc, selenium, copper, manganese, and chromium are typically added to parenteral solutions after 2-4 weeks of exclusive PN. Both selenium and chromium are primarily excreted via the kidneys and should be reduced or eliminated in PN for infants with renal dysfunction.33-35 Neonates on long-term PN may likely receive sufficient chromium without additional supplementation due to the presence of chromium as a contaminant to the solution.33,34 Zinc supplementation is the only trace element that should be given at the start of PN to prevent deficiency, especially in preterm infants.34 Excessive loss of urinary zinc should be considered in the polyruric infant as urinary zinc has been shown to increase postoperatively in response to surgical stress.34 While toxicity from water-soluble vitamins rarely occurs, toxicities may develop in infants with renal impairment from large doses provided parenterally, especially in the preterm neonate if not adjusted for body weight.35 Water-soluble vitamins are often dosed in greater than required amounts due to the concern for additional losses without storage in the body and the ability of a normal functioning kidney to excrete.35 Nevertheless, PN should be provided when indicated to promote anabolism and prevent any catabolism of lean body mass. Renal Replacement Therapy (RRT) In order to administer proper nutrition and prevent malnutrition, RRT should be considered if appropriate fluid and electrolyte balance and adequate nutrition cannot be maintained because of persistent oliguria or anuria. Also, RRT should be considered in infants who, despite appropriate therapy, have severe acidosis (serum bicarbonate concentration < 12 mEq/L), hyperkalemia (plasma potassium concentration > 8 mEq/L), hyponatremia (serum sodium concentration < 120 mEq/L), or volume overload with heart failure or pulmonary edema. Detailed nutritional management during hemodialysis (HD), peritoneal dialysis (PD), or continuous renal replacement therapy (CRRT) is beyond the scope of this article; however each have important nutrition implications depending on the modality. PD is the preferred method of dialysis in newborns due to the large peritoneal surface area to body ratio.36 The accounts of long-term PD for AKI in low birth weight infants are sparse and described in relatively few case studies.36-38 The Kidney Disease

Outcomes Quality Initiative (KDOQI) update in pediatrics patients recommends 1.8 g/kg/day of protein in a 0-6 month old term infant receiving PD, however no suggestions were made for preterm infants.30 A successful case study of long-term PD in a 930 g infant born at 29 weeks’ gestation was reported.39 The authors attribute much success to the optimal nutrition provided enterally (150 kcal/kg and 6 g/kg/day of protein) with a combination of breast milk, human milk fortifier, and supplemental protein.39 Proper treatment with long-term PD may promote normal vision, hearing, and neurologic development in term and preterm infants, although these infants may still ultimately require long-term dialysis or transplant later in life.36,39 Patients on continuous renal replacement therapy (CCRT) including continuous venovenous hemodiafiltration (CVVHD) and continuous venovenous hemofiltration (CVVH) have higher protein needs due to increased catabolism and amino acid losses across the hemofilters.40 In one randomized control trial, pediatric patients who received either method of CRRT remained in negative nitrogen balance with elevated mean urinary nitrogen appearance (UNA) regardless of modality despite receiving parenteral nutrition at 20-30% above measured resting energy expenditure and amino acids provided at 1.5g/kg/ day.40 While protein requirements for hemodialysis and peritoneal dialysis vary, the most recent recommendations are to provide an additional 0.1 to 0.3 g/kg protein up until one year of age, secondary to dialytic protein and amino acid losses.30 Energy should be provided based on the estimated energy requirement (EER) or based on the caloric needs of the primary condition, and adjusted as needed for growth.15 Infants on dialysis should also receive a supplement of a renal multivitamin to account for water soluble vitamin losses. Often a small dose of a liquid adult-renal multivitamin can be given enterally to meet the daily requirements.15 Chronic Kidney Disease (CKD) Based upon the chronic renal insufficiency (CRI) registry of the North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) database, congenital renal anomalies were the most common cause of CKD in infants and children (57%) followed by glomerular diseases (17%) and idiopathic causes (18%).41 The main congenital anomalies causing CKD include obstructive uropathy (21%), renal aplasia/hypoplasia/dysplasia (18%), reflux nephropathy (8%), and polycystic kidney disease (4 %).41 Even in infants with normal anatomical kidneys, the damage to the nephrons from a significant neonatal AKI could lead to hyperfiltration of remaining nephrons which could eventually lead to glomerular changes, progressive nephron damage and set the stage for evolution of chronic kidney disease (CKD). Prematurity is also proving to be a


significant risk factor without the presence of AKI as recent observational data suggest increased risk of CKD for low birth weight infants. A systematic review noted 70% increase in adult CKD who were former low birth weight infants.42,43 It is important to follow up infants who had sustained neonatal AKI with regular assessment of growth and nutrition, blood pressure, serum creatinine and urinalysis for proteinuria and albumin/creatinine ratio.44,45 Typically, the late development of CKD will first become evident with the development of hypertension, proteinuria and eventually elevation of blood urea nitrogen and serum creatinine. Nutrition Management of CKD Anorexia and emesis are common manifestations of CKD, and spontaneous oral intake decreases with the decline in kidney function.46 Along with decline in GFR over time, the loss of several other functions of the kidneys results in development of anemia of CKD, malnutrition, and metabolic bone disease.4 Numerous factors in CKD impact growth including acidosis, growth hormone disturbances, and poor nutrition.47-49 Therefore, nutrition assessments and interventions in the NICU are critical to better long-term outcomes as poor growth has been implicated in poor neurodevelopmental outcomes and increased mortality in pediatric patients with CKD.50 Approximately 21% to 40% of children with mild or moderate CKD fall below average in IQ and additional cognitive testing.43 Developmental outcomes tend to be worse when renal failure is associated with neonatal hypoxia or genetic syndromes.36 Few infants continue to stay in the NICU beyond the initial treatment for AKI/CKD, and long term management of CKD often occurs outside the neonatal intensive care setting. The primary objectives of nutritional therapy in infants with CKD are to promote optimal linear growth and weight gain while preventing malnutrition and uremic toxicity.30 Energy should be provided at 100% of the EER for age and sex regardless of stages of CKD.30 As in infants without CKD, when growth is either inadequate or excessive based on estimated requirements, energy intake should either be supplemented to allow for catch-up growth, or adjusted downward to prevent excessive adiposity.30,50 For breastfed infants who require more calories, supplementation after feedings with an approved formula may be necessary. Supplementation with Similac® PM 60/40 may be indicated in infants with calcium and phosphorous restrictions, otherwise standard infant formula can be used. Modular products (Duocal®, Nutricia, Gaithersburg, Maryland or SolCarb, Solace Nutrition, Pawcatuck, Connecticut) provide either a source of fat, carbohydrate, or both and can be added to feedings to provide calories without additional micronutrients and protein. Modulars are often a good choice for infants who are already on

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formula and unable to be concentrated due to excessive protein concentration. Given the need for optimal growth and nutrition in infants with CKD, reduction in dietary protein is not advised. In the setting of inadequate caloric intake, protein will be used a source of calories to maintain growth, which is not ideal.4,30 As with AKI, infants with CKD will often require caloric supplementation to meet nutritional requirements and may require tube feeds if they cannot do so orally. A nasogastric tube can be used as short-term nutrition support, but a more permanent gastrostomy tube with or without fundoplication may be required to provide optimal nutrition depending on the infant’s ability to meet needs orally.30 Enteral feedings are the preferred route of nutrition, and the risk of placing a permenant gastrostomy or gastrojejunostomy tubes outweighs the heavy risk of parenteral nutrition. Management of gastroesophageal reflux symptoms should also be considered to alleviate discomfort, anorexia, and loss of nutrition from emesis. Concentrating feeds to reduce volumes and provision of formula in the supine position may be helpful. Prokinetic agents may also be considered.30,50 Summary Very low birth weight infants and infants with intra and extrauterine growth restriction are subject to a permanent reduction in nephron number when associated with an early deficit in protein-calorie intake. With increasing survival of extremely low birth weight infants, the group with highest risk of AKI, the population of infants at risk of progression to CKD is increasing. Conservative fluid and electrolyte management are the first line of defense in AKI, however circumstances may eventually require RRT to manage and enable provision of adequate nutrition. More research is certainly required in this field especially in premature infants, as there are few studies that focus on their unique nutritional needs during AKI and while undergoing RRT. Since the development of CKD is associated with poor growth and neuro-developmental outcomes, it is crucial to understand the nutritional needs of the neonates with AKI or CKD in order to achieve optimal growth and development. References 1.

Chan JC, Williams DM, Roth KS. Kidney failure in infants and children. Pediatr Rev 2002;23(2): 47-60.

2.

Rodig NM, Spinozzi N, Harmon W. Persistant Renal Disease. In Duggan C, Watkins JB, Walker WA.ed. Nutrition in pediatrics: Basic science, clinical applications. 4th ed. Hamilton, Ontario; Lewiston, NY: B.C. Decker; 2008.

3.

Viswanathan S, Mhanna MJ. Acute Kidney Injury in Premature Infants. Journal of Clinical Pediatric Nephrology 2013;1:2028.

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