Acute and Chronic Renal Failure

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65 Acute and Chronic Renal Failure

Olivera Marsenic, H. Jorge Baluarte

Acute Renal Failure

Acute kidney injury (AKI), previously referred to as acute renal failure (ARF), is defined as an abrupt reduction in kidney function measured by a rapid decline in glomerular filtration rate (GFR). AKI implies that an acute decline in kidney function is secondary to an injury that leads to functional or structural changes in the kidney. AKI is characterized by a disturbance of renal physiologic functions, including impairment of nitrogenous waste product excretion and inability to regulate water, electrolyte, and acid–base homeostasis. The precise incidence and prevalence of AKI in children is difficult to ascertain. The overall incidence of AKI appears to be rising because of advances in pediatric medical technology including bone marrow, hepatic, and cardiac transplantation, in surgery for congenital heart disease, and in the care of very low birth weight infants.

Etiology and Pathogenesis

The causes of AKI can be related to any process that interferes with the structure or function of the renal vasculature, glomeruli, renal tubules, interstitium, or urinary tract. The causes of AKI can be categorized as prerenal, renal (intrinsic renal disorder), or postrenal.

Prerenal

AKI results from either volume depletion caused by bleeding, gastrointestinal (vomiting, diarrhea), urinary (diuretics, diabetes insipidus), cutaneous losses (burns) or decreased effective blood volume (heart failure, cardiac tamponade, hepatorenal syndrome, shock, sepsis). In this type of AKI, the kidneys are intrinsically normal, and AKI is reversible after renal blood flow is restored by correcting the underlying disturbance. However, prolonged prerenal injury results in intrinsic renal AKI.

AKI (intrinsic renal disease) is the result of disorders that involve the renal vascular, glomerular, or tubular–interstitial pathology. Acute tubular necrosis (ATN) results from ischemia caused by decreased renal perfusion or injury from tubular nephrotoxins (Figure 65-1). All causes of prerenal AKI can progress to ATN if renal perfusion is not restored or nephrotoxins are not withdrawn. Nephrotoxic AKI is mostly caused by toxic tubular injury by medications, including aminoglycosides, contrast agents, amphotericin B, chemotherapeutic agents (ifosfamide, cisplatin), and acyclovir. Toxic tubular injury can also be induced by the release of heme pigments, as it occurs from myoglobinuria caused by rhabdomyolysis and hemoglobinuria caused by intravascular hemolysis. Uric acid nephropathy and tumor lysis syndrome are causes of AKI in children with leukemia. During chemotherapy, a rapid breakdown of tumor cells causes increased release and subsequent excretion of uric acid, resulting in precipitation of uric acid crystals in the tubules and renal microvasculature. Hyperphosphatemia in tumor lysis syndrome results in precipitation of calcium phosphate crystals in the tubules. Acute interstitial nephritis most commonly results from hypersensitivity reactions to drugs, including penicillin analogs (e.g., methicillin), cimetidine, sulfonamides, rifampin, nonsteroidal antiinflammatory drugs, and proton pump inhibitors, but can also be idiopathic. Glomerulonephritis of any etiology (including those caused by vasculitis, systemic lupus erythematosus, or Goodpasture’s syndrome) may present with AKI, with postinfectious glomerulonephritis being the most common cause of AKI in this group. Rapidly progressive glomerulonephritis presents as the most severe degree of any form of glomerulonephritis and presents with AKI. Vascular causes of AKI include cortical necrosis (mostly caused by hypoxic or ischemic injury in newborns), renal artery or vein thrombosis, and hemolytic-uremic syndrome (HUS).

Figure 65-1 Acute renal failure.

Postrenal

AKI is caused by bilateral urinary tract obstruction unless there is a solitary kidney or caused by urethral obstruction. Examples of congenital disorders causing obstruction and AKI are posterior urethral valves (PUVs), bilateral ureteropelvic junction obstruction, and bilateral ureteroceles. Examples of acquired causes of obstruction and AKI are kidney stones and tumors.

Clinical Presentation

A careful history and physical examination can frequently identify disease processes that underlie AKI and suggest an underlying diagnosis.

• A history of vomiting, diarrhea, hemorrhage, sepsis, or decreased oral intake resulting in hypovolemia associated with decreased urine output suggests AKI caused by prerenal disease or ATN. Physical examination findings that include tachycardia, dry mucous membranes, sunken eyes, orthostatic blood pressure changes, and decreased skin turgor suggest hypovolemia, resulting in AKI caused by prerenal disease or ATN.

• Nephrotic syndrome, heart failure, and liver failure causing prerenal AKI caused by a decrease in effective intravascular volume present with edema (see Chapter 63).

• In the hospital, history of hypotension (caused by sepsis or intraoperative events), administration of nephrotoxic agents or recent use of chemotherapy for leukemia may be responsible for AKI.

• History of use of medications that are known to cause a hypersensitivity reaction, together with a rash, fever, and arthralgias, suggests AKI caused by acute interstitial nephritis (see Chapter 62).

• Clinical presentation that includes hypertension, edema, and gross hematuria is likely caused by AKI attributable to a glomerulonephritis. A history of pharyngitis or impetigo a few weeks before the onset of gross hematuria suggests postinfectious glomerulonephritis.

• History of bloody diarrhea and pallor and petechiae on physical examination are associated with HUS (see Chapter 64).

• Hemoptysis in the presence of renal impairment suggests a diagnosis of pulmonary–renal syndrome, such as Goodpasture’s syndrome.

• Skin findings, such as purpura, malar rash, or petechiae or joint pain favor a diagnosis of vasculitis, such as systemic lupus erythematosus or Henoch-Schönlein purpura.

• Anuria or oliguria in a newborn suggests a congenital malformation (i.e., PUVs) or bilateral renal vein thrombosis.

Evaluation and Diagnosis

In addition to a careful history and physical examination, the initial evaluation includes additional laboratory studies.

Serum Creatinine Concentration, Acute Kidney Injury Biomarkers, and Classification of Acute Kidney Injury

AKI is diagnosed by an increase in serum creatinine concentration, which strongly suggests a decrease in the GFR. However, it is accepted that the serum creatinine concentration is an insensitive and delayed measure of decreased kidney function after AKI. Biomarkers that allow recognition of the early stages of AKI have been identified. Clinical use of these markers may permit initiation of timely therapy. These biomarkers are serum neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C, urinary NGAL, interlukin-18, and kidney injury molecule-1 (KIM-1). A standardized classification of AKI has recently been proposed in adults (RIFLE criteria) and adapted for children (pediatric [p] RIFLE criteria). pRIFLE stands for risk for renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function, end-stage renal disease. These criteria better characterize AKI and reflect the course of AKI in children admitted to the intensive care unit (ICU).

Prevention and Management

The basic principles of the general management of AKI are shown in Box 65-1.

Box 65-1 General Management Principles of Acute Kidney Injury

• Maintenance of electrolyte and fluid balance

• Adequate nutritional support

• Avoidance of life-threatening complications

• Treatment of the underlying cause

General measures to help prevent AKI include close monitoring of serum levels of nephrotoxic drugs, adequate fluid repletion in patients with hypovolemia, and aggressive hydration and alkalinization of the urine before chemotherapy. Unless contraindicated, a child with a history of fluid loss (vomiting and diarrhea), a physical examination consistent with hypovolemia (hypotension and tachycardia), or oliguria requires immediate intravenous (IV) fluid therapy in an attempt to restore renal function and perhaps prevent ischemic renal injury. Commonly used fluids are crystalloid solutions, such as normal saline (20 mL/kg) administered over 20 to 30 minutes, which may be repeated. If urine output does not increase and renal function fails to improve, invasive monitoring may be required to adequately assess the child’s fluid status and help guide further therapy.

Hyperkalemia is a life-threatening complication of AKI that may result in fatal cardiac arrhythmia. Hyperkalemia is treated by shifting potassium from the intravascular to the intracellular space using IV glucose and insulin, β-agonists (albuterol inhalation), and bicarbonate and by using enteric exchange resins such as polystyrene sulfonate. IV infusion of calcium is used to stabilize cell membranes and decrease the risk of cardiac arrhythmias. Dialysis may be required to remove potassium.

Acid (H+) generated by diet and intermediary metabolism is excreted by the kidney, but in AKI, acid excretion is decreased, resulting in metabolic acidosis. Acidosis can be treated with IV or oral sodium bicarbonate or oral sodium citrate solutions.

Hyperphosphatemia and Hypocalcemia

Because the kidneys normally excrete a large amount of ingested phosphorus, hyperphosphatemia is common in AKI. Hyperphosphatemia is treated with dietary phosphorus restriction and with oral calcium carbonate (or other calcium compounds) that bind phosphorus and prevent gastrointestinal absorption of dietary phosphorus. Aluminum-containing compounds can be used for phosphate binding, but their use must be restricted to limit aluminum absorption. Hypocalcemia in AKI results from hyperphosphatemia and decreased production of 1,25-vitamin D. In the setting of acidosis, less calcium is bound to albumin, and more calcium is free in its ionized form. With the use of bicarbonate therapy for correction of acidosis or hyperkalemia, more calcium binds to albumin, and there is less free ionized calcium, which may cause symptomatic hypocalcemia with tetany. Therefore, if hypocalcemia is severe or bicarbonate therapy is necessary, IV calcium gluconate or calcium chloride should be given. Hypocalcemia may also be treated by oral administration of calcium carbonate or other calcium salts. Treatment of hypocalcaemia in the setting of severe hyperphosphatemia can result in metastatic calcifications because of a high Calcium × Phosphorus product.

Hypertension

Hypertension in AKI may be related to volume overload or alterations in vascular tone (i.e., renin mediated). If hypertension volume-mediated initial therapy with a loop diuretic can be attempted, fluid removal with dialysis or hemofiltration may be required. For severe hypertension, IV infusion therapy with nicardipine, labetalol, or sodium nitroprusside is indicated. Oral nifedipine, diltiazem, or clonidine can be used for initial control of acute less severe hypertension. After the blood pressure has been controlled, oral long-acting agents can be initiated. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) should be used with caution in AKI because they reduce intraglomerular filtration pressure and retain potassium.

Nutrition

AKI can be associated with severe anorexia and subsequent malnutrition. Proper nutrition is essential in the management of children with AKI. If the gastrointestinal tract is intact and functional, enteral feedings with formula should be instituted in infants as soon as possible. Specialized formulations with attention to calcium, phosphorus, and potassium content should be used. In older children, a diet of high biologic value protein, low phosphorus, and low potassium foods can be used. At a minimum, daily maintenance calories should be provided, although calorie needs may be higher because of catabolism. Parenteral nutrition may be needed.

Renal Replacement Therapy

Renal replacement therapy in children with AKI should be initiated for the indications listed in Box 65-2.

Three dialysis modalities are available: peritoneal dialysis (PD), hemodialysis (HD), and continuous renal replacement therapy (CRRT). The choice of modality is influenced by the clinical presentation of the child, the availability of vascular access (necessary for HD), adequacy of the peritoneal membrane (necessary for PD), the presence or absence of multiorgan failure, and the overall goal of the dialysis (HD is most efficient in rapid correction of electrolyte and other solute abnormalities).

Future Directions

Biomarkers of AKI (cystatin C, NGAL, interleukin-18, KIM-1) and their ability to predict the duration and severity of AKI are under investigation. If these biomarkers prove to be sensitive for early detection of AKI, this will allow initiation of therapy in a timely manner, preventing further intrinsic renal disease.

Fenoldopam is a potent, short-acting, selective, dopamine-1 receptor agonist that decreases vascular resistance while increasing renal blood flow. Unlike dopamine, it was shown to decrease the incidence of AKI, the need for dialysis, ICU stays, and mortality. However, only limited experience in children is available at this time.

Chronic Kidney Disease

Chronic kidney disease (CKD) is a state of irreversible kidney damage or reduction of kidney function that can lead to a progressive decrease in kidney function. CKD more clearly defines renal dysfunction as a continuum rather than a discrete change in renal function. The term CKD replaces the clinical terms of chronic renal failure and chronic renal insufficiency. The National Kidney Foundation Kidney Disease Outcomes Quality Initiative (K/DOQI) has defined CKD as (1) the presence of markers of kidney damage for 3 months or longer, as defined by structural or functional abnormalities of the kidney with or without a decreased GFR, which is manifested by either pathologic abnormalities or other markers of kidney damage, including abnormalities in the blood, urine, or in imaging tests, or (2) GFR below 60 mL/min/1.73 m² for 3 months or longer with or without kidney damage. GFR is estimated by creatinine clearance.

The stages of CKD for children older than 2 years of age are based on estimated GFR (using the Schwartz equation) and are aimed at promoting early detection and treatment of CKD.

The annual incidence and prevalence of CKD, including its early stages, is reported as 12.1 per million children and adolescents younger than 20 years. The yearly incidence and prevalence in stages 4 and 5 is reported as 5.7 to 14.8 per million children in different countries. The variability in the worldwide incidence of CKD is thought to be affected by genetic and environmental factors, as well as the ability to detect CKD and provide care to children with significant renal impairment. In North America, the incidence of CKD is greater in African American than white children. The incidence and prevalence of CKD are greater in boys than girls because of the higher incidence of congenital anomalies of the kidney and urinary tract, including obstructive uropathy, renal dysplasia, renal hypoplasia, and prune belly syndrome, in boys.

Etiology and Pathogenesis

Based on the registry of the North American Pediatric Renal Trials and Collaborative Studies, the causes of CKD are as follows: Congenital renal anomalies are present in 57% of cases (obstructive uropathy; renal aplasia, hypoplasia, or dysplasia; reflux nephropathy; and polycystic kidney disease), and glomerular disease is present in 17% of cases, with focal segmental glomerulosclerosis (FSGS) being the most common glomerular disorder (9% of all CKD cases; African American children are three times more likely to develop FSGS than white children). Other causes accounted for 25% of cases and included HUS, genetic disorders (e.g., cystinosis, oxalosis, hereditary nephritis), and interstitial nephritis. In large number of cases (18%), the primary disease is unknown because patients present in late stages of CKD. Unlike in adults, diabetic nephropathy and hypertension are rare causes of CKD in children (Figure 65-2).

Figure 65-2 Etiology of chronic renal failure.

After initial injury to the kidney, there is continued progression of renal disease and functional impairment, often leading to stage 5 CKD. This is a result of repeated and chronic insults to the renal parenchyma, leading to permanent damage or to the adaptive hyperfiltration response of the remaining nephrons in the kidney, which compensates for the loss of nephrons from the initial injury. Over time, the enhanced transglomerular ultrafiltration and glomerular pressure leads to glomerular damage and leakage of protein, resulting in interstitial inflammation and fibrosis. This long-term injury is characterized histologically by glomerulosclerosis, vascular sclerosis, and tubulointerstitial fibrosis and clinically by proteinuria and progressive renal insufficiency. The rate of progression of CKD is usually greatest during the two periods of rapid growth, infancy and puberty, when the sudden increase in body mass results in an increase in the filtration demands of the remaining nephrons. Other factors associated with acceleration of the progressive CKD include hypertension, obesity, dyslipidemia, proteinuria, anemia, intrarenal precipitation of calcium and phosphate, metabolic acidosis, and tubular interstitial disease. Some of these factors are modifiable, and timely therapeutic interventions may result in a reduced rate of deterioration of renal function.

Clinical Presentation

Clinical presentation of CKD depends on the severity of renal disease and the underlying disorder. Stage 1 and 2 CKD are usually asymptomatic. As CKD progresses, patients become increasingly symptomatic. Signs and symptoms of CKD include different amounts of urine output (polyuria or oliguria), edema, hypertension, proteinuria, and hematuria. Glomerular diseases often present with hematuria, proteinuria, hypertension, and edema in the early stages of CKD. Polyuria may be an early presenting symptom as congenital anomalies of the kidney and urinary tract (e.g., obstructive uropathy); inherited disorders (e.g., nephronophthisis); and tubulointerstitial disorders caused by impairment in renal concentrating ability, which generally precedes a significant reduction in GFR. Poor growth is a common manifestation of CKD in children. More severe symptoms and signs of CKD begin to appear with stage 3 disease and worsen with stages 4 and 5.

Complications

A moderate to severe loss of GFR (stage 3-5 disease) is associated with a number of complications caused by impairment of many renal functions, resulting in disorders of fluid and electrolytes, acid–base homeostasis, metabolic bone disease, anemia, hypertension, dyslipidemia, endocrine abnormalities, and growth retardation.

• Sodium and water balance. Normal kidneys can adapt to a wide range of sodium and water intake, and these homeostatic mechanisms are usually maintained until the GFR decreases to advanced stages of CKD. Fluid abnormalities result in fluid retention and hypertension (particularly with glomerular diseases) or dehydration and hyponatremia (caused by polyuria with decreased renal-concentrating ability in nephronophthisis, congenital renal disorders, and obstructive uropathy).

• Hyperkalemia develops primarily because of decreased potassium excretion with reduced GFR as a result of decreased delivery of sodium to the distal tubule (type IV renal tubular acidosis [RTA]). Contributing factors to hyperkalemia include dietary potassium intake, increased tissue breakdown, metabolic acidosis, or hypoaldosteronism (administration of ACEIs or ARBs).

• Metabolic acidosis is a result of decreased ability of the kidney to excrete hydrogen ions (impaired ammoniogenesis), and in addition, there is reduction of titratable acid excretion and bicarbonate reabsorption.

• Metabolic bone disease (renal osteodystrophy)

• Abnormalities in mineral metabolism and bone structure are common findings in stage 3 CKD (Figure 65-3). There is retention of phosphate because of decreased GFR and decreased renal production of 1,25-dihydroxy vitamin D. This leads to decreased serum calcium levels and subsequent elevation of serum parathyroid hormone (PTH). This secondary hyperparathyroidism results in reabsorption of calcium from bone, leading to bone disease that presents with difficulty in walking, bone pain, skeletal deformities, and fractures.

• Anemia of CKD is initially normocytic and normochromic and is caused by reduced renal erythropoietin production. Iron deficiency, which is common, and vitamin B12 or folate deficiency may contribute to the anemia. Anemia results in progressive fatigue and weakness.

• Hypertension is caused by volume expansion or activation of the renin–angiotensin system. It can be present in the earliest stages of CKD. Cardiovascular abnormalities found in CKD include left ventricular hypertrophy (caused by hypertension) and evidence of early atherosclerosis (coronary artery calcification, increased aortic stiffness).

• Dyslipidemia results from abnormal lipid metabolism in CKD, causing an increase in triglyceride-rich lipoproteins and low high-density lipoproteins (HDL) cholesterol levels. This increases the risk of having cardiovascular disease.

• Endocrine dysfunction in CKD is reflected in disorders of growth hormone metabolism (end-organ resistance to growth hormone caused by increased levels of insulin growth factor binding proteins); thyroid function known as “sick euthyroid syndrome” (low total and free T4 and T3, normal thyroid-stimulating hormone and normal thyrotropin-releasing hormone); and reduced gonadal hormones, resulting in delayed puberty and anovulation.

• Growth retardation in CKD is caused by metabolic acidosis, decreased caloric intake, metabolic bone disease, and alterations in growth hormone metabolism.

• Uremia represents a constellation of symptoms and signs present in the final stage of CKD (Figure 65-4). These include anorexia, nausea, vomiting, growth retardation, platelet dysfunction (abnormal platelet adhesion and aggregation), pericardial disease (pericarditis and pericardial effusion), neurologic abnormalities (peripheral neuropathy, lethargy, seizures, coma, and death), and altered cognitive development (loss of concentration, poor school performance, and mental retardation).

Figure 65-3 Renal failure: calcium and phosphorus metabolism.

Figure 65-4 Uremia.

Evaluation

History

The history should include age at onset of symptoms, duration of symptoms, presence of uremic symptoms (weakness, fatigue, anorexia, vomiting), systemic diseases (fever, rash, arthralgias), specific renal disease, diagnosis of congenital anomaly of the kidney or urinary tract antenatally, and family history of renal disease or hypertension. The history is focused on signs of CKD and should include information about growth and development history; fluid and electrolyte abnormalities; elevated blood pressure; anemia; presence of polyuria, polydipsia, or enuresis; recurrent urinary tract infection; urologic abnormalities; bone abnormalities; and seizures.

Physical Examination

The examination should include measurement of growth parameters, blood pressure measurement, assessment for pallor, examination for any bone deformities, assessment for signs of hypervolemia (e.g., edema), and heart examination looking for pericardial rub (pericarditis) or diminished heart sounds (pericardial effusion).

Laboratory Testing

There is no single pattern of laboratory abnormalities that characterizes pediatric CKD, but some abnormalities are commonly present and are indicative of underlying chronic kidney dysfunction. Serum creatinine is the most commonly used test to estimate the GFR (creatinine clearance indirectly represents the GFR) using the Schwartz formula: GFR = kL/SCr, where k is a constant that varies with age and sex, L is length (cm), and SCr is serum creatinine in mg/dL (Table 65-1). The GFR is then used to determine the stage of CKD. Normal levels of GFR vary with age, gender, and body size (Table 65-2). GFR increases with maturation from infancy and approaches adult mean value by 2 years of age.

Table 65-1 Stages of Chronic Kidney Disease for Children Older Than 2 Years of Age

Stage	Glomerular Filtration Rate
1	Normal (≥90 mL/min/1.73 m²)
2	60-89 mL/min/1.73 m²
3	30-59 mL/min/1.73 m²
4	15-29 mL/min/1.73 m²
5	<15 mL/min/1.73 m² or ESRD

ESRD, end-stage renal disease.

Table 65-2 Normal Glomerular Filtration Rate Levels and the Schwartz Equation

Age (Gender)	Schwartz Equation (Serum Creatinine in mg/dL, Length in cm)	Mean GFR ± SD (mL/min/1.73m²)
1 wk (boys and girls)	GFR = 0.33*(Length/SCr) in preterm infants	40.6 ± 14.8
1 wk (boys and girls)	GFR = 0.45*(Length/SCr) in term infants	40.6 ± 14.8
2-8 wk (boys and girls)	GFR = 0.45*(Length/SCr)	65.8 ± 24.8
>8 wk (boys and girls)	GFR = 0.45*(Length/SCr)	95.7 ± 21.7
2-12 y (boys and girls)	GFR = 0.55*(Length/SCr)	133.0 ± 27.0
13-18 y (boys)	GFR = 0.70*(Length/SCr)	140.0 ± 30.0
13-18 y (girls)	GFR = 0.55*(Length/SCr)	126.0 ± 22.0

GFR, glomerular filtration rate; SCr, serum creatinine; SD, standard deviation.

Electrolytes are tested to evaluate for hyperkalemia and metabolic acidosis. Serum calcium, phosphorus, and PTH level are needed to detect abnormalities in bone mineral metabolism. Lipid profile is needed to detect dyslipidemia. A complete blood count will detect anemia, and RBC indices will characterize the anemia and help eliminate other causes of anemia other than CKD, determining the iron profile (serum iron, total iron-binding capacity, percent transferrin saturation) and looking for possible blood losses (test for occult blood) is necessary.

Urinalysis

Urinalysis as described for AKI can identify the underlying cause of both AKI and CKD. Proteinuria is an important biomarker associated with CKD because it may contribute to CKD progression.

Renal Ultrasonography

Renal ultrasonography is the most widely used imaging modality and is a noninvasive procedure. It assesses the renal size and structure. In CKD, the kidneys are usually smaller than normal, which indicates a loss of renal mass from an underlying renal disease, such as a congenital disorder (e.g., renal hypoplasia). It may also identify the cause of CKD such as detecting cystic kidney disease. Other imaging studies such as voiding cystourethrography, computed tomography, and magnetic resonance imaging are used in specific clinical settings.

Kidney Biopsy

Kidney biopsy provides diagnosis of the underlying renal disorder that caused CKD. The results also serve to guide therapy and provide information about disease severity, including whether the findings may be reversible, and about the degree of renal scarring.

Management

The general management of a patient with CKD includes the following components: treatment of reversible renal dysfunction (some renal function may be recovered if treatment is initiated early), prevention of progression of renal disease, treatment of complications, and identification of renal replacement therapy.

Slowing Progression

Slowing the progression of CKD is achieved by treating hypertension and decreasing proteinuria because these are known to accelerate the progression of CKD. ACEIs and ARBs are used in this regard. Additional intervention studies in adults with CKD such as dietary protein restriction, lipid-lowering therapy, and correction of anemia have shown inconclusive results. As far as the low protein restriction in children is concerned, the current consensus is to provide the age-appropriate recommended daily allowance of protein.

Management of Complications

Sodium and water retention occur as GFR becomes severely decreased in stages 4 and 5 CKD. This is treated with dietary sodium restriction and diuretics. Some children with obstructive uropathy or renal dysplasia have a poor urinary concentrating capacity and sodium wasting, making them prone to hypovolemia and hyponatremia.

• Hyperkalemia is treated with a low-potassium diet, loop diuretics, alkali therapy (sodium bicarbonate), and cation exchange resins (Kayexalate).

• Metabolic acidosis is corrected using sodium bicarbonate therapy with the goal of maintaining serum bicarbonate level at or above 22 mEq/L.

• Bone metabolism and bone disease of CKD are treated with dietary phosphate restriction, use of phosphate binding agents, and vitamin D replacement therapy.

• Hypertension is treated with weight reduction, exercise, dietary salt reduction, antihypertensive medications, and diuretics. Strict blood pressure control in all children with CKD is necessary, with a target blood pressure of less than the 90th percentile for age, gender, and height and less than 120/80 mm Hg for adolescents with CKD.

• Anemia is treated with iron supplementation and erythropoietin replacement therapy. K/DOQI guidelines recommend a target hemoglobin between 11 and 12 g/dL.

• Dyslipidemia is managed with fibrates (i.e., gemfibrozil or fenofibrate) for elevated triglyceride level and with statin therapy (i.e., atorvastatin, simvastatin) for elevated low-density lipoprotein levels.

• Nutrition should be managed so that malnutrition of CKD (secondary to poor appetite, decreased intestinal absorption, and metabolic acidosis) is prevented. It is recommended that protein and caloric intake should be at least 100% of the recommended daily allowance for age. Nutritional support using nutritional supplements is often needed.

• Growth retardation is treated with recombinant human growth hormone (GH) therapy (GH resistance of CKD can be overcome using supraphysiologic doses of exogenous GH) and with management of malnutrition, renal osteodystrophy, acid–base abnormalities, and electrolyte disturbances.

• Neurodevelopmental impairment can be minimized by initiating dialysis and by optimal management of anemia and malnutrition. Infants and young children require frequent monitoring of head circumference and age-appropriate developmental evaluations. A more formal assessment is needed in older children, particularly if they have poor school performance.

• Uremic bleeding that occurs in uremia secondary to abnormalities in platelet adhesion and aggregation properties (mostly caused by reduced von Willebrand factor [vWF] in uremia) can be improved by using desmopressin, which increases levels of coagulation factor VIII and vWF by stimulating their release from storage sites.

Renal Replacement Therapy

Renal replacement therapy is achieved by PD, HD, and kidney transplantation. Renal replacement therapy is generally needed with GFR less than 15 mL/min/1.73 m² (stage 5 CKD). However, renal replacement therapy in children may be initiated sooner if there is poor calorie intake resulting in failure to thrive, symptomatic uremia (e.g., pericarditis), and significant delay in psychomotor and cognitive development. The choice among renal replacement options is dictated by family preference and technical, psychosocial and compliance issues.

• PD is more common in infants and younger children largely because of problems of vascular access in that age group (Figure 65-5). A PD catheter is surgically placed into the peritoneal space. PD fluid is pumped into the peritoneal space. Peritoneal membrane serves as a “filter” through which waste products and water are cleared from blood that circulates through blood vessels of the peritoneal membrane. Waste products and water are transferred to the PD fluid in the peritoneal space by processes of diffusion and osmosis. This fluid is then drained out of the peritoneal space. PD can be performed by parents at home, overnight with a cycling machine that allows the least disruption of home life, school, and work attendance.

• HD is more commonly used in older children (Figure 65-6). HD requires vascular access such as placement of an arteriovenous fistula, arteriovenous graft, or central venous catheter. Blood is pumped from the vascular access into the dialyzer, which contains an artificial membrane that serves as a filter through which waste products and water are cleared from the blood into the dialysis fluid by processes of diffusion, convection, and ultrafiltration. Dialysis fluid flows through the dialyzer countercurrent to the blood. HD is done in specialized HD centers using a HD machine and requires at least three weekly treatments that are each 3 to 5 hours long.

• Renal transplantation is performed using a deceased or living (related or unrelated) kidney donor. It can be performed in stage 4 or 5 CKD before dialysis begins (preemptive kidney transplantation). Renal transplantation is accepted as the optimal therapy of choice, which is based on the belief that successful transplantation not only ameliorates uremic symptoms but also allows for significant improvement, and often correction of, delayed skeletal growth, sexual maturation, cognitive performance, and psychosocial functioning.