Central Annals of Pediatrics & Child Health

Review Article *Corresponding author Carlos G. Musso, Adult & Internal Millieu Divisions, Hospital Italiano de Buenos Aires, Argentina, Water, Sodium and Potassium Email: Submitted: 09 July 2016 Accepted: 28 August 2016 Imbalance in Peritoneal Published: 02 September 2016 Copyright Pediatric Patients © 2016 Musso et al. OPEN ACCESS Carlos G. Musso¹*, Maritza Contreras², and Paula Coccia² 1Adult Nephrology & Internal Millieu Divisions, Hospital Italiano de Buenos Aires, Keywords • Water Argentina • Sodium 2 Pediatric Nephrology & Internal Millieu Divisions, Hospital Italiano de Buenos Aires, • Potassium Argentina • Peritoneal dialysis • Pediatrics Abstract Water, sodium and potassium regulation is usually altered in end-stage renal disease patients, particularly in frail individuals such as pediatric and elderly people. In this review article, pathophysiology of water, sodium, and potassium imbalance in peritoneal dialysis pediatric patients is in detail described. Understanding the etiological mechanisms of dysnatremia and dyskalemia in this group is crucial for their proper diagnosis and treatment.

INTRODUCTION other diseases: neurological, pulmonary, or paraneoplastic. (c) Excessive water intake: A water income which overcomes renal One of the main renal functions consists of regulation of water, free water excretion capability can induce hyponatremia even sodium and potassium metabolisms. Therefore serum sodium in a context of fully suppressed secretion. This type and potassium levels can be seriously affected, resulting in the of hyponatremia has been documented in patients who suffered appearance of dysnatremias or dyskalemias, respectively, in end- from primary polydipsia. (D) Low intracelular phosphate content: stage renal disease patients, particularly in pediatric patients Low cellular phosphate can lead to intracellular hypo-osmolarity on dialysis [1-3]. In the present article, the pathophysiology of and consequently to water shift into extracellular compartment. water, sodium, and potassium imbalance in peritoneal dialysis (E) Reset osmostat: Reset osmostat hyponatremia is induced by pediatric patients is analyzed in detail, in order to facilitate its a change in the set point for serum sodium tonicity. This sort of understanding, and consequently the implementation of an hyponatremia is usually found in malnourished chronically-ill adequate therapeutic approach. patients, and it should be a diagnosis of exclusion. Regarding Salt & water imbalance: its pathophysiology

Serum sodium level usually results from the relation between (Tablehyponatremia, 2). it is classically classified depending on patient´s salt and water (Na:H2O) body content, thus a low Na:H2O ratio plasma tonicity and patient´s (ECF) status can induce hyponatremia (serum sodium < 135 mmol/L), and Altered serum sodium in peritoneal dialysis a high Na:H2O ratio can induce hypernatremia (serum sodium Hyponatremia is a prevalent electrolyte problem in > 145 mmol/L) (Table 1). Additionally, there are other factors peritoneal dialysis patients; and this disturbance is mainly which can modify Na:H2O ratio, and induce hyponatremia, such as induced in anuric peritoneal dialysis patients by different [4-12]: (A) Low body potassium content: Potassium intracellular mechanisms [1,12-14]: (A) Low sodium / water ratio secondary depletion induces hyponatremia at least by two mechanisms: inducing inadequate vasopressin release. Edelman summarized Table 1: Salt & water imbalance characteristics. this• by concept inducing in sodium the following shift into equation the intracellular [1]: Serum space, sodium •by = volume contraction volume overload body (exchangeable) sodium + body (exchangeable) potassium imbalance negative positive / total (B) Excessive free water retention: Free magnitude mild to severe mild to severe water retention induced by inadequate vasopressin secretion axillary dryness secondary to drugs (opioids, psychotropic medications), hypertension, peripheral clinical manifestation orthostatism, edema, lung congestion endocrinopathies (hypothyroidism, hypoaldosteronism), and hypotension,

Cite this article: Musso CG, Contreras M, Coccia P (2016) Water, Sodium and Potassium Imbalance in Peritoneal Dialysis Pediatric Patients. Ann Pediatr Child Health 4(4): 1110. Musso et al. (2016) Email: Central

Table 2: Hypotonic Hyponatremia Normotonic Hyponatremia Hypertonic Hyponatremia Hyponatremia clinical classification. PO: <280 PO: 280-300 PO: >300 mOsm/L mOsm/L mOsm/L normal free water body content increased free water body content increased free water intravascular content eg: important paraproteinemia eg: classical hyponatremia eg: hyperglicemia or dyslipidemia Hypotonic Hypotonic Hypotonic Hyponatremia Hyponatremia Hyponatremia axillary dryness, orthostatism hypotension normal clinical exam hypertension, peripheral edema, lung congestion low ECF normal ECF high ECF Abbreviations: PO: Plasma Osmolarity;

ECF: Extracellular Fluid to a high oral water intake (water in excess of sodium), and/or volume is low: salt supply should be delivered (orally or intravenously, depending on the acuity of the situation); and if occurs with an increase in body weight, as well as clinical signs of volumelow water overload. excretion (B) (insufficientLow sodium )./ water ratio secondary This situation to an function: consideration should be given to antidiuretic hormone extracellular volume is normal with significant residual renal residual renal function, it could be interpreted as an osmostat extracellularLow potassium fluid bodysodium content deficit due due to tolow a low potassium intake (low intake sodium [low reset- driven [13]. renal Hypernatremia water retention; is usually in associated those without with intermittent significant diet),potassium and/or diet], excess and/or sodium excessive loss (excessive potassium ultrafiltration). loss (diarrhea). (C) peritoneal dialysis which consists of a dialytic schedule based Intracellular potassium depletion induces sodium to shift from on frequent exchanges at 30-60 minutes intervals. This sort the extracellular compartment to the intracellular one, in order to of dysnatremia occurs more commonly when high dialysate

least three mechanisms for the development of hypernatremia leadskeep bodyto extracellular compartments volume electrically contraction. neutral. This The scenario flux of presents sodium glucose concentration is used to achieve ultra [14]. A withfrom a the reduction extracellular in body fluid weight to theand intracellularthere may be compartment, clinical signs of hypovolemia, but not always hypokalemia. (D) Intracellular hyperglycemiahave been proposed which causes [14-16]: osmotic • Dialysate diuresis hypertonicity, (if residual diuresis which isinduces preserved) salt and and water consequently loss in excess increases of water. the •Dialysis serum induced sodium water into the intravascular compartment. This mechanism of dilutionalphosphate hyponatremia deficit due topresents malnutrition itself with which reduced induces body shift weight of concentration and because of that are more likely associated with (lean mass reduction) but without signs of volume contraction. hypernatremia.level. •Shorter exchanges have a lower outflow dialysate sodium residual renal function (RRF): GFR: 15-20 ml/min/1.73 m², such Salt & water imbalance in peritoneal dialysis asRegarding those who peritoneal start peritoneal dialysis dialysis patients earlier who have due to a significant refractory pediatrics patients hyperkalemia or concomitant cardiac failure (incremental Fluid and electrolyte requirements in children vary dialysis), they can also suffer from hyponatremia induced by according to their primary kidney disease, degree of residual free water retention due to an inadequate vasopressin secretion. kidney function, and method of kidney replacement therapy. This hyponatremia presents itself without edema or body weight should rule out the presence of non hypotonic hyponatremia, outputSupplementation and the ability or restriction to concentrate of fluid, , sodium, hydration and status,potassium and change. When evaluating hyponatremic patients, first of all you either normotonic hyponatremia (pseudohyponatremia), theintake presence is individualized or absence andof hypertension influenced by or thehyperkalemia. volume of urineBody as it is documented in cases of severe paraproteinemia or composition also differs considerably in children as compared to dyslipidemia; or hypertonic hyponatremia, as it is documented in adults. Total body water is 75 % in newborns, 60 % in infants hyperglycemia, or icodextrin use. Secondly, evaluate the serum and adolescents and 50 % in elderly men [17,18]. The primary potassium level, and nutritional status. If the patient presents cause of chronic kidney disease needs to be considered. Although hypokalemia, or intracellular potassium depletion is strongly suspected, potassium should be administered cautiously and with chronic nephropathy associated with sodium and water with close monitoring of the serum potassium level. If the patient retention,restriction the of most sodium common and/or causes fluids of is renal appropriate disease inin children is malnourished, adequate nourishment should be provided, but are associated with excessive loss of sodium and chloride. Infants not before assuring the normal serum potassium and phosphorus and children with obstructive uropathy or renal dysplasia have levels, as well as monitoring them during this process in order to avoid re-feeding syndrome. Finally, regarding hypotonic Dehydration frequently occurs in these children in association hyponatremia, the extracellular volume should be evaluated. withpolyuria, gastroenteritis. polydipsia, Soand it hasdifficulty to be takenconserving into consideration sodium chloride. that If extracellular volume is high: negative volume balance should be induced. For this purpose, dextrose-based solutions salt supplementation. Sodium depletion seriously affects (removal by osmosis) may be better than icodextrin (removal extracellularCKD children volume, may develop muscle adevelopment, salt-wasting mineralization state and required of the by colloid osmosis) since they remove water in excess of sodium, bone and growth [17,19]. Infants on peritoneal dialysis therapy particularly with exchanges of shorter duration. If extracellular

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Table 3: Main electrolytes alterations in peritoneal dialysis pediatric tone [22-24]. Potassium retention is one of the dangers associated patients. to advanced chronic renal failure, especially when glomerular mechanism imbalances can leads to either hypokalemia (serum potassium < filtration rate falls below 20 ml/min/1.73 m² [22]. Potassium Dehydration low water income 3.5 mmol/L) or hyperkalemia (serum potassium > 5.5 mmoil/L); diarrheahigh ultrafiltration and the pathophysiology of dyskalemias depends on an altered high dialysis dose external or internal balances (Table 4) [22-24]: Hypotonic Hyponatremia low sodium income high dialysis dose Serum potassium alteration in peritoneal dialysis Hypokalemia low potassium income Despite physical principles applied in peritoneal dialysis low dialysis dose and hemodialysis are the same ones, the rate of potassium drugs removal is markedly slower in the former [25,26]. Peritoneal Hyperkalemia catabolism for potassium averages about 17 ml/minute for metabolic acidosis cytolysis intermittent peritoneal dialysis, and approximately 7 ml/minute are predisposed to substantial sodium losses too, even when values are between those for and creatinine clearances. Interestingly,for continuous ambulatory peritoneal dialysis (CAPD). These clearance is higher (24 ml/minute) than that of the remaining anuric. Higher ultra filtration requirements per kilogram of body period and the duringmost probable the first explanation hour of for a dwell,these high potassium values achieveweight asadequate compared nutrition. to adults But on result the other in removal hand, breast of significant milk or is the release of potassium from the cells that line the peritoneal standardamounts ofcommercial sodium chloride. infant formulasThis high haveultra afiltration low sodium is needed content to cavity. This release may be promoted by the initial low pH (160 mg/L or 7 mmol/L and 160 to 185 mg/L or 7 to 8 mmol/L and/ or by the hyperosmolality of the instilled dialysate. Some solute transport is considerable and addition of oral sodium additional potassium can also be removed by ultra filtration [25- chloriderespectively). supply In such is often children, required ultrafiltration to prevent related a reduce convective body patients have normal or even high intracellular potassium 27]. Contrary to patients on hemodialysis, peritoneal dialysis sodium content, hypotension and neurological sequel [19,20]. related to the continuous glucose absorption from the dialysis content, especially those on CAPD. This phenomenon is probably blindness, and therapy should be individualized based on clinical solutions and the subsequent stimulation of intracellular uptake symptoms,Consequences including of hyponatremia hypotension, includeand a degree cerebral of hyponatremia. edema and of potassium, mediated by insulin release [27]. Hyperkalemia is Sodium balance measurements, determined from dietary and those on chronic hemodialysis [28], The main causes that can considerably less common in stable CAPD patients contrary to considered every 6 months concurrent with the measurement of induce hyperkalemia in peritoneal dialysis patients are: a high dialysismedication adequacy. intake More and frequent dialysate measurement effluent losses, is indicated should after be potassium diet, hyperkalemia generating drugs [angiotensin

(Table 3) [19-21]. blockers (ARBs), low dialysis dose, or an internal fount of significant changes to the dialysis prescription or clinical status potassiumconverting release enzyme (potassium inhibitors shift (ACEIs), from the angiotensin intracellular receptor space Potassium imbalance: its pathophysiology to the intravascular one): rabdomyolisis, gross haematoma, hemolysis, bulky tumour necrosis, or acute hepatitis [24-28]. Total body potassium is mostly located in the intracellular Since it has been documented that peritoneal dialysis patients compartment, especially in muscles, erythrocytes, and liver. were not able to handle an acute potassium overload, it takes a prolonged dialysis (by automatic peritoneal or hemodialysis) to Conversely, the extracellular space contains the minority of this normalize their plasma potassium levels avoiding a hyperkalemic cation. This uneven distribution reflects the large potassium concentration gradient between the intracellular (Ki: 150 [22].mmol/L) Potassium and extracellular has two balances: (Ke: 4 mmol/L)the external fluid b alancecompartments, between organismwhich is generated and environment, by Na-K-ATPase and the internal pump activity balance (Figure between 1) 3 Na + extracellular and intracellular compartments within the organism K+ K+ [23]. Regarding the external balance, it normally depends on P nutrition, renal (80%) and colonic (20%) potassium excretion, and this renal excretion depends on GFR and potassium distal 2 K + tubule secretion, which is mainly stimulated by [23]. In regards with the internal balance, it depends on the potassium shifts between intracellular and extracellular compartments. Lum Insulin and the adrenergic system are the main stimuli for Intersentiti um cell its intracellular shift along with metabolic alkalosis, plasma Lum hypotonicity and beta-adrenergic sympathetic tone, while the enp Lumen main stimuli for its extracellular shift are glucagon, metabolic Figure 1 Uneven potassium distribution between compartments and acidosis, plasma hypertonicity, and alpha-adrenergic sympathetic

Na-K-ATPase pump (p). Ann Pediatr Child Health 4(4): 1110 (2016) 3/5 Musso et al. (2016) Email: Central

Table 4: Potassium imbalance. CONCLUSION Dyskalemia negative pediatric patients on peritoneal dialysis is crucial for their proper hypokalemia external balance diagnosisKnowledge and treatment. of the pathophysiology of electrolyte disorders in positive external hyperkalemia REFERENCES balance 1. Adrogué H, Wesson D. Salt & water. Houston. Libra & Gemini. 1993. internal balance hypokalemia (shift into the cells) 2. Edelman IS, Leibman J, O’Meara MP, Birkenfeld LW. Interrelations internal balance between serum sodium concentration, serum osmolarity and total hyperkalemia (shift out of the cells) exchangeable sodium, total exchangeable potassium and total body rebound in the post-dilaytic period [28]. Regarding hypokalemia 3. water. J Clin Invest. 1958; 37: 1236-1256. potassium for determining plasma water content: application in Nguyen MK, Ornekian V, Butch AW, Kurtz I. A new method supplementation for hypokalemia, and it has been reported that pseudohyponatremia. 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Cite this article Musso CG, Contreras M, Coccia P (2016) Water, Sodium and Potassium Imbalance in Peritoneal Dialysis Pediatric Patients. Ann Pediatr Child Health 4(4): 1110.

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