Renal Failure

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Chapter 529 Renal Failure

529.1 Acute Renal Failure

Rajasree Sreedharan, Ellis D. Avner

Acute renal failure (ARF), also termed acute renal insufficiency, is a clinical syndrome in which a sudden deterioration in renal function results in the inability of the kidneys to maintain fluid and electrolyte homeostasis. ARF occurs in 2-3% of children admitted to pediatric tertiary care centers and in as many as 8% of infants in neonatal intensive care units. A classification system has been proposed to standardize the definition of acute kidney injury in adults. These criteria of risk, injury, failure, loss, and end-stage renal disease were given the acronym of RIFLE. A modified RIFLE criteria (pRIFLE) has been developed to characterize the pattern of acute kidney injury in critically ill children (Table 529-1). Because RIFLE focuses on glomerular filtration rate (GFR), a modification (Acute Kidney Injury Network, AKIN) categorizes severity by rise in serum creatinine: stage 1 >150%, stage II >200%, stage III >300%.

Table 529-1 PEDIATRIC-MODIFIED RIFLE (PRIFLE) CRITERIA

CRITERIA	ESTIMATED CCl	URINE OUTPUT
Risk	eCCl decrease by 25%	<0.5 mL/kg/hr for 8 hr
Injury	eCCl decrease by 50%	<0.5 mL/kg/hr for 16 hr
Failure	eCCl decrease by 75% or eCCl <35 ml/min/1.73 m²	<0.3 mL/kg/hr for 24 hr or anuric for 12 hr
Loss	Persistent failure >4 wk
End-stage	End-stage renal disease (persistent failure >3 mo)

eCCl, estimated creatinine clearance; pRIFLE, pediatric risk, injury, failure, loss and end-stage renal disease.

Pathogenesis

ARF has been conventionally classified into 3 categories: prerenal, intrinsic renal, and postrenal (Table 529-2).

Prerenal ARF, also called prerenal azotemia, is characterized by diminished effective circulating arterial volume, which leads to inadequate renal perfusion and a decreased GFR. Evidence of kidney damage is absent. Common causes of prerenal ARF include dehydration, sepsis, hemorrhage, severe hypoalbuminemia, and cardiac failure. If the underlying cause of the renal hypoperfusion is reversed promptly, renal function returns to normal. If hypoperfusion is sustained, intrinsic renal parenchymal damage can develop.

Intrinsic renal ARF includes a variety of disorders characterized by renal parenchymal damage, including sustained hypoperfusion and ischemia. Many forms of glomerulonephritis, including postinfectious glomerulonephritis, lupus nephritis, Henoch-Schönlein purpura nephritis, membranoproliferative glomerulonephritis, and anti-glomerular basement membrane nephritis, can cause ARF. Hemolytic-uremic syndrome (HUS) has been described as the most common cause of intrinsic ARF in the USA (Chapter 512).

Acute tubular necrosis (ATN) occurs most often in critically ill infants and children who have been exposed to nephrotoxic and/or perfusion insults. Sepsis, hypovolemic shock, and increased intra-abdominal pressure (abdominal compartment syndrome) are important causes of ATN. The typical pathologic process of ATN is tubular cell necrosis, although significant histologic changes are not consistently seen in patients with clinical ATN. The mechanisms of injury in ATN can include alterations in intrarenal hemodynamics, tubular obstruction, and passive backleak of the glomerular filtrate across injured tubular cells into the peritubular capillaries.

Tumor lysis syndrome is a specific form of ARF related to spontaneous or chemotherapy-induced cell lysis in patients with lymphoproliferative malignancies. This disorder is primarily caused by obstruction of the tubules by uric acid crystals (Chapters 489 and 490). Acute interstitial nephritis is an increasingly common cause of ARF and is usually a result of a hypersensitivity reaction to a therapeutic agent or various infectious agents (Chapter 526).

Postrenal ARF includes a variety of disorders characterized by obstruction of the urinary tract. In neonates and infants, congenital conditions such as posterior urethral valves and bilateral ureteropelvic junction obstruction account for the majority of cases of ARF. Other conditions such as urolithiasis, tumor (intra-abdominal or within the urinary tract), hemorrhagic cystitis, and neurogenic bladder can cause ARF in older children and adolescents. In a patient with 2 functioning kidneys, obstruction must be bilateral to result in ARF. Relief of the obstruction usually results in recovery of renal function except in patients with associated renal dysplasia or prolonged urinary tract obstruction.

Clinical Manifestations and Diagnosis

A carefully taken history is critical in defining the cause of ARF. An infant with a 3-day history of vomiting and diarrhea most likely has prerenal ARF caused by volume depletion, but HUS must be a consideration. A 6 yr old child with a recent pharyngitis who presents with periorbital edema, hypertension, and gross hematuria most likely has intrinsic ARF related to acute postinfectious glomerulonephritis. A critically ill child with a history of protracted hypotension or with exposure to nephrotoxic medications most likely has ATN. A neonate with a history of hydronephrosis on prenatal ultrasound and a palpable bladder and prostate most likely has congenital urinary tract obstruction, probably related to posterior urethral valves.

The physical examination must be thorough, with careful attention to volume status. Tachycardia, dry mucous membranes, and poor peripheral perfusion suggest inadequate circulating volume and the possibility of prerenal ARF (Chapter 54). Peripheral edema, rales, and a cardiac gallop suggest volume overload and the possibility of intrinsic ARF from glomerulonephritis or ATN. The presence of a rash and arthritis might suggest systemic lupus erythematosus (SLE) or Henoch-Schönlein purpura nephritis. Palpable flank masses might suggest renal vein thrombosis, tumors, cystic disease, or urinary tract obstruction.

Laboratory Findings

Laboratory abnormalities can include anemia (the anemia is usually dilutional or hemolytic, as in SLE, renal vein thrombosis, HUS); leukopenia (SLE, sepsis); thrombocytopenia (SLE, renal vein thrombosis, sepsis, HUS); hyponatremia (dilutional); metabolic acidosis; elevated serum concentrations of blood urea nitrogen, creatinine, uric acid, potassium, and phosphate (diminished renal function); and hypocalcemia (hyperphosphatemia).

The serum C3 level may be depressed (postinfectious glomerulonephritis, SLE, or membranoproliferative glomerulonephritis), and antibodies may be detected in the serum to streptococcal (poststreptococcal glomerulonephritis), nuclear (SLE), neutrophil cytoplasmic (Wegener granulomatosis, microscopic polyarteritis), or glomerular basement membrane (Goodpasture disease) antigens.

The presence of hematuria, proteinuria, and red blood cell or granular urinary casts suggests intrinsic ARF, in particular glomerular disease. The presence of white blood cells and white blood cell casts, with low-grade hematuria and proteinuria, suggests tubulointerstitial disease. Urinary eosinophils may be present in children with drug-induced tubulointerstitial nephritis.

Urinary indices may be useful in differentiating prerenal ARF from intrinsic ARF (Table 529-3). Patients whose urine shows an elevated specific gravity (>1.020), elevated urine osmolality (UOsm > 500 mOsm/kg), low urine sodium (UNa < 20 mEq/L), and fractional excretion of sodium (FENa) <1% (<2.5% in neonates) most likely have prerenal ARF. Those with a specific gravity of <1.010, low urine osmolality (UOsm < 350 mOsm/kg), high urine sodium (UNa > 40 mEq/L), and FENa > 2% (>10% in neonates) most likely have intrinsic ARF.

Table 529-3 URINALYSIS, URINE CHEMISTRIES, AND OSMOLALITY IN ACUTE RENAL FAILURE

Chest radiography may reveal cardiomegaly, pulmonary congestion (fluid overload) or pleural effusions. Renal ultrasonography can reveal hydronephrosis and/or hydroureter, which suggest urinary tract obstruction, or nephromegaly, suggesting intrinsic renal disease. Renal biopsy can ultimately be required to determine the precise cause of ARF in patients who do not have clearly defined prerenal or postrenal ARF.

Though serum creatinine is used to measure kidney function, it is an insensitive and delayed measure of decreased kidney function following acute kidney injury. Other biomarkers under investigation include changes in plasma neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C levels and urinary changes in NGAL, interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1).

Treatment

Medical Management

In infants and children with urinary tract obstruction, such as in a newborn with suspected posterior ureteral valves, a bladder catheter should be placed immediately to ensure adequate drainage of the urinary tract. The placement of a bladder catheter may also be considered in nonambulatory older children and adolescents to accurately monitor urine output during ARF.

Determination of the volume status is of critical importance when initially evaluating a patient with ARF. If there is no evidence of volume overload or cardiac failure, intravascular volume should be expanded by intravenous administration of isotonic saline, 20 mL/kg over 30 min. In the absence of blood loss or hypoproteinemia, colloid-containing solutions are not required for volume expansion. Severe hypovolemia may require additional fluid boluses (Chapters 53, 54, and 64). Determination of the central venous pressure may be helpful if adequacy of the blood volume is difficult to determine. After volume resuscitation, hypovolemic patients generally void within 2 hr; failure to do so points to intrinsic or postrenal ARF. Hypotension due to sepsis requires vigorous fluid resuscitation followed by a continuous infusion of norepinephrine.

Diuretic therapy should be considered only after the adequacy of the circulating blood volume has been established. Mannitol (0.5 g/kg) and furosemide (2-4 mg/kg) may be administered as a single IV dose. Bumetanide (0.1 mg/kg) may be given as an alternative to furosemide. If urine output is not improved, then a continuous diuretic infusion may be considered. To increase renal cortical blood flow, many clinicians administer dopamine (2-3 µg/kg/min) in conjunction with diuretic therapy, although no controlled data support this practice. There is little evidence that diuretics or dopamine can prevent ARF or hasten recovery. Mannitol may be effective in pigment (myoglobin, hemoglobin)-induced renal failure. Atrial natriuretic peptide may be of value in preventing or treating acute kidney injury; there is little pediatric evidence.

If there is no response to a diuretic challenge, diuretics should be discontinued and fluid restriction is essential. Patients with a relatively normal intravascular volume should initially be limited to 400 mL/m²/24 hr (insensible losses) plus an amount of fluid equal to the urine output for that day. Extrarenal (blood, gastrointestinal [GI] tract) fluid losses should be replaced, milliliter for milliliter, with appropriate fluids. Markedly hypervolemic patients can require further fluid restriction, omitting the replacement of insensible fluid losses, urine output, and extrarenal losses to diminish the expanded intravascular volume. Fluid intake, urine and stool output, body weight, and serum chemistries should be monitored on a daily basis.

In ARF, rapid development of hyperkalemia (serum potassium level >6 mEq/L) can lead to cardiac arrhythmia, cardiac arrest, and death. The earliest electrocardiographic change seen in patients with developing hyperkalemia is the appearance of peaked T waves. This may be followed by widening of the QRS intervals, ST segment depression, ventricular arrhythmias, and cardiac arrest (Chapter 52.4). Procedures to deplete body potassium stores should be initiated when the serum potassium value rises to >6.0 mEq/L. Exogenous sources of potassium (dietary, intravenous fluids, total parenteral nutrition) should be eliminated. Sodium polystyrene sulfonate resin (Kayexalate), 1 g/kg, should be given orally or by retention enema. This resin exchanges sodium for potassium and can take several hours to take effect. A single dose of 1 g/kg can be expected to lower the serum potassium level by about 1 mEq/L. Resin therapy may be repeated every 2 hr, the frequency being limited primarily by the risk of sodium overload.

More-severe elevations in serum potassium (>7 mEq/L), especially if accompanied by electrocardiographic changes, require emergency measures in addition to Kayexalate. The following agents should be administered:

• Calcium gluconate 10% solution, 1.0 mL/kg IV, over 3-5 min

• Sodium bicarbonate, 1-2 mEq/kg IV, over 5-10 min

• Regular insulin, 0.1 U/kg, with glucose 50% solution, 1 mL/kg, over 1 hr

Calcium gluconate counteracts the potassium-induced increase in myocardial irritability but does not lower the serum potassium level. Administration of sodium bicarbonate, insulin, glucose lowers the serum potassium level by shifting potassium from the extracellular to the intracellular compartment. A similar effect has been reported with the acute administration of β-adrenergic agonists in adults, but there are no controlled data in pediatric patients. Because the duration of action of these emergency measures is just a few hours, persistent hyperkalemia should be managed by dialysis.

Mild metabolic acidosis is common in ARF because of retention of hydrogen ions, phosphate, and sulfate, but it rarely requires treatment. If acidosis is severe (arterial pH < 7.15; serum bicarbonate < 8 mEq/L) or contributes to hyperkalemia, treatment is required. The acidosis should be corrected partially by the intravenous route, generally giving enough bicarbonate to raise the arterial pH to 7.20 (which approximates a serum bicarbonate level of 12 mEq/L). The remainder of the correction may be accomplished by oral administration of sodium bicarbonate after normalization of the serum calcium and phosphorus levels. Correction of metabolic acidosis with intravenous bicarbonate can precipitate tetany in patients with renal failure as rapid correction of acidosis reduces the ionized calcium concentration (Chapter 52).

Hypocalcemia is primarily treated by lowering the serum phosphorus level. Calcium should not be given intravenously, except in cases of tetany, to avoid deposition of calcium salts into tissues. Patients should be instructed to follow a low-phosphorus diet, and phosphate binders should be orally administered to bind any ingested phosphate and increase GI phosphate excretion. Common agents include sevelamer (Renagel), calcium carbonate (Tums tablets or Titralac suspension), and calcium acetate (PhosLo). Aluminum-based binders, commonly employed in the past, should be avoided because of the established risk of aluminum toxicity.

Hyponatremia is most commonly a dilutional disturbance that must be corrected by fluid restriction rather than sodium chloride administration. Administration of hypertonic (3%) saline should be limited to patients with symptomatic hyponatremia (seizures, lethargy) or those with a serum sodium level <120 mEq/L. Acute correction of the serum sodium to 125 mEq/L (mmol/L) should be accomplished using the following formula:

ARF patients are predisposed to GI bleeding because of uremic platelet dysfunction, increased stress, and heparin exposure if on hemodialysis or continuous renal replacement therapy. Oral or intravenous H₂ blockers such as ranitidine are commonly administered to prevent this complication.

Hypertension can result from hyperreninemia associated with the primary disease process and/or expansion of the extracellular fluid volume and is most common in ARF patients with acute glomerulonephritis or HUS. Salt and water restriction is critical, and diuretic administration may be useful (Chapter 439). Isradipine (0.05-0.15 mg/kg/dose, maximum dose 5 mg qid) may be administered for relatively rapid reduction in blood pressure. Longer-acting agents such as calcium channel blockers (amlodipine, 0.1-0.6 mg/kg/24 hr qd or divided bid) or β-blockers (propranolol, 0.5-8 mg/kg/24 hr divided bid or tid; labetalol, 4-40 mg/kg/24 hr divided bid or tid) may be helpful in maintaining control of blood pressure. Children with severe symptomatic hypertension (hypertensive urgency or emergency) should be treated with continuous infusions of sodium nitroprusside (0.5-10 µg/kg/min), labetalol (0.25-3.0 mg/kg/hr), or esmolol (150-300 µg/kg/min) and converted to intermittently dosed antihypertensives when more stable.

Neurologic symptoms in ARF can include headache, seizures, lethargy, and confusion (encephalopathy). Potential etiologic factors include hyponatremia, hypocalcemia, hypertension, cerebral hemorrhage, cerebral vasculitis, and the uremic state. Diazepam is the most effective agent in controlling seizures, and therapy should be directed toward the precipitating cause.

The anemia of ARF is generally mild (hemoglobin 9-10 g/dL) and primarily results from volume expansion (hemodilution). Children with HUS, SLE, active bleeding, or prolonged ARF can require transfusion of packed red blood cells if their hemoglobin level falls below 7 g/dL. In hypervolemic patients, blood transfusion carries the risk of further volume expansion, which can precipitate hypertension, heart failure, and pulmonary edema. Slow (4-6 hr) transfusion with packed red blood cells (10 mL/kg) diminishes the risk of hypervolemia. The use of fresh washed red blood cells minimizes the risk of hyperkalemia. In the presence of severe hypervolemia or hyperkalemia, blood transfusions are most safely administered during dialysis or ultrafiltration.

Nutrition is of critical importance in children who develop ARF. In most cases, sodium, potassium, and phosphorus should be restricted. Protein intake should be restricted moderately while maximizing caloric intake to minimize the accumulation of nitrogenous wastes. In critically ill patients with ARF, parenteral hyperalimentation with essential amino acids should be considered.

Dialysis

Indications for dialysis in ARF include the following:

• Volume overload with evidence of hypertension and/or pulmonary edema refractory to diuretic therapy

• Persistent hyperkalemia

• Severe metabolic acidosis unresponsive to medical management

• Neurologic symptoms (altered mental status, seizures)

• Blood urea nitrogen >100-150 mg/dL (or lower if rapidly rising)

• Calcium:phosphorus imbalance, with hypocalcemic tetany

An additional indication for dialysis is the inability to provide adequate nutritional intake because of the need for severe fluid restriction. In patients with ARF, dialysis support may be necessary for days or for up to 12 wk. Many patients with ARF require dialysis support for 1-3 wk. The advantages and disadvantages of the 3 types of dialysis are shown in Table 529-4.

Table 529-4 COMPARISON OF PERITONEAL DIALYSIS, INTERMITTENT HEMODIALYSIS, AND CONTINUAL RENAL REPLACEMENT THERAPY

Intermittent hemodialysis is useful in patients with relatively stable hemodynamic status. This highly efficient process accomplishes both fluid and electrolyte removal in 3- to 4-hr sessions using a pump-driven extracorporeal circuit and large central venous catheter. Intermittent hemodialysis may be performed 3 to 7 times per week based on the patient’s fluid and electrolyte balance.

Peritoneal dialysis is most commonly employed in neonates and infants with ARF, although this modality may be used in children and adolescents of all ages. Hyperosmolar dialysate is infused into the peritoneal cavity via a surgically or percutaneously placed peritoneal dialysis catheter. The fluid is allowed to dwell for 45-60 min and is then drained from the patient by gravity (manually or with the use of a cycler machine), accomplishing fluid and electrolyte removal. Cycles are repeated for 8-24 hr/day based on the patient’s fluid and electrolyte balance. Anticoagulation is not necessary. Peritoneal dialysis is contraindicated in patients with significant abdominal pathology.

Continuous renal replacement therapy (CRRT) is useful in patients with unstable hemodynamic status, concomitant sepsis, or multiorgan failure in the intensive care setting. CRRT is an extracorporeal therapy in which fluid, electrolytes, and small- and medium-sized solutes are continuously removed from the blood (24 hr/day) using a specialized pump-driven machine. Usually, a double-lumen catheter is placed into the subclavian, internal jugular, or femoral vein. The patient is then connected to the pump-driven CRRT circuit, which continuously passes the patient’s blood across a highly permeable filter.

CRRT may be performed in 3 basic fashions. In continuous venovenous hemofiltration (CVVH), a large amount of fluid moves by pressure across the filter, bringing with it by convection other molecules such as urea, creatinine, phosphorus, and uric acid. The blood volume is reconstituted by IV infusion of a replacement fluid having a desirable electrolyte composition similar to that of blood. Continuous venovenous hemofiltration dialysis (CVVH-D) uses the principle of diffusion by circulating dialysate in a countercurrent direction on the ultrafiltrate side of the membrane. No replacement fluid is used. Continuous hemodiafiltration (CVVH-DF) employs both replacement fluid and dialysate, offering the most effective solute removal of all forms of CRRT.

Table 529-4 compares the relative risks and benefits of the various renal replacement therapies.

Prognosis

The mortality rate in children with ARF is variable and depends entirely on the nature of the underlying disease process rather than on the renal failure itself. Children with ARF caused by a renal-limited condition such as postinfectious glomerulonephritis have a very low mortality rate (<1%); those with ARF related to multiorgan failure have a very high mortality rate (>90%).

The prognosis for recovery of renal function depends on the disorder that precipitated ARF. Recovery of renal function is likely after ARF resulting from prerenal causes, HUS, ATN, acute interstitial nephritis, or tumor lysis syndrome. Recovery of renal function is unusual when ARF results from most types of rapidly progressive glomerulonephritis, bilateral renal vein thrombosis, or bilateral cortical necrosis. Medical management may be necessary for a prolonged period to treat the sequelae of ARF, including chronic renal insufficiency, hypertension, renal tubular acidosis, and urinary concentrating defect.

Bibliography

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Andreoli SP. Acute kidney injury in children. Pediatr Nephrol. 2009;24:253-263.

Borthwick E, Ferguson A. Perioperative acute kidney injury: risk factors, recognition, management, and outcomes. BMJ. 2010;341:85-90.

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Lameire N, Van Biesen W, Vanholder R. Acute kidney injury. Lancet. 2008;372:1863-1865.

Mannix R, Tan ML, Wright R, et al. Acute pediatric rhabdomyolysis: causes and rates of renal failure. Pediatrics. 2006;118(5):2119-2125.

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529.2 Chronic Kidney Disease

Rajasree Sreedharan, Ellis D. Avner

Chronic kidney disease (CKD) is defined as renal injury (proteinuria) and/or a glomerular filtration rate <60 mL/min/1.73 m² for >3 mo. The prevalence of CKD in the pediatric population is approximately 18 per 1 million. The prognosis for the infant, child, or adolescent with CKD has improved dramatically since the 1970s because of improvements in medical management (aggressive nutritional support, recombinant erythropoietin, recombinant growth hormone [rGH]), dialysis techniques, and kidney transplantation.

Etiology

In children, CKD may be the result of congenital, acquired, inherited, or metabolic renal disease, and the underlying cause correlates closely with the age of the patient at the time when the CKD is first detected. CKD in children <5 yr old is most commonly a result of congenital abnormalities such as renal hypoplasia, dysplasia, or obstructive uropathy. Additional causes include congenital nephrotic syndrome, prune belly syndrome, cortical necrosis, focal segmental glomerulosclerosis, polycystic kidney disease, renal vein thrombosis, and hemolytic uremic syndrome.

After 5 yr of age, acquired diseases (various forms of glomerulonephritis including lupus nephritis) and inherited disorders (familial juvenile nephronophthisis, Alport syndrome) predominate. CKD related to metabolic disorders (cystinosis, hyperoxaluria) and certain inherited disorders (polycystic kidney disease) can occur throughout the childhood years.

Pathogenesis

In addition to progressive injury with ongoing structural or metabolic genetic diseases, renal injury can progress despite removal of the original insult.

Hyperfiltration injury may be an important final common pathway of glomerular destruction, independent of the underlying cause of renal injury. As nephrons are lost, the remaining nephrons undergo structural and functional hypertrophy characterized by an increase in glomerular blood flow. The driving force for glomerular filtration is thereby increased in the surviving nephrons. Although this compensatory hyperfiltration temporarily preserves total renal function, it can cause progressive damage to the surviving glomeruli, possibly by a direct effect of the elevated hydrostatic pressure on the integrity of the capillary wall and/or the toxic effect of increased protein traffic across the capillary wall. Over time, as the population of sclerosed nephrons increases, the surviving nephrons suffer an increased excretory burden, resulting in a vicious cycle of increasing glomerular blood flow and hyperfiltration injury.

Proteinuria itself can contribute to renal functional decline, as evidenced by studies that have shown a beneficial effect of reduction in proteinuria. Proteins that traverse the glomerular capillary wall can exert a direct toxic effect on tubular cells and recruit monocytes and macrophages, enhancing the process of glomerular sclerosis and tubulointerstitial fibrosis. Uncontrolled hypertension can exacerbate disease progression by causing arteriolar nephrosclerosis and by increasing the hyperfiltration injury.

Hyperphosphatemia can increase progression of disease by leading to calcium phosphate deposition in the renal interstitium and blood vessels. Hyperlipidemia, a common condition in CKD patients, can adversely affect glomerular function through oxidant-mediated injury.

CKD may be viewed as a continuum of disease, with increasing biochemical and clinical manifestations as renal function deteriorates. The pathophysiologic manifestations of CKD are outlined in Table 529-5. The terminology to describe the stages of chronic kidney disease is standardized (Table 529-6). End-stage renal disease (ESRD) is an administrative term in the USA, defining all patients treated with dialysis or kidney transplantation. Patients with ESRD are a subset of the patients with stage 5 CKD.

Table 529-5 PATHOPHYSIOLOGY OF CHRONIC KIDNEY DISEASE

MANIFESTATION	MECHANISMS
Accumulation of nitrogenous waste products	Decrease in glomerular filtration rate
Acidosis	Decreased ammonia synthesis Impaired bicarbonate reabsorption Decreased net acid excretion

Sodium retention

Excessive renin production

Oliguria

Sodium wasting

Solute diuresis

Tubular damage

Urinary concentrating defect

Solute diuresis

Tubular damage

Hyperkalemia

Decrease in glomerular filtration rate

Metabolic acidosis

Excessive potassium intake

Hyporeninemic hypoaldosteronism

Renal osteodystrophy

Impaired renal production of 1,25-dihydroxycholecalciferol

Hyperphosphatemia

Hypocalcemia

Secondary hyperparathyroidism

Growth retardation

Inadequate caloric intake

Renal osteodystrophy

Metabolic acidosis

Anemia

Growth hormone resistance

Anemia

Decreased erythropoietin production

Iron deficiency

Folate deficiency

Vitamin B₁₂ deficiency

Decreased erythrocyte survival

Bleeding tendency Defective platelet function Infection

Defective granulocyte function

Impaired cellular immune functions

Indwelling dialysis catheters

Neurologic symptoms (fatigue, poor concentration, headache, drowsiness, memory loss, seizures, peripheral neuropathy)

Uremic factor(s)

Aluminum toxicity

Hypertension

Gastrointestinal symptoms (feeding intolerance, abdominal pain)

Gastroesophageal reflux

Decreased gastrointestinal motility

Hypertension

Volume overload

Excessive renin production

Hyperlipidemia Decreased plasma lipoprotein lipase activity Pericarditis, cardiomyopathy

Uremic factor(s)

Hypertension

Fluid overload

Glucose intolerance Tissue insulin resistance

Table 529-6 STANDARDIZED TERMINOLOGY FOR STAGES OF CHRONIC KIDNEY DISEASE

STAGE	DESCRIPTION	GFR (mL/min/1.73 m²)
1	Kidney damage with normal or increased GFR	>90
2	Kidney damage with mild decrease in GFR	60-89
3	Moderate decrease in GFR	30-59
4	Severe decrease in GFR	5-29
5	Kidney failure	<15 or on dialysis

GFR, glomerular filtration rate.

Clinical Manifestations

The clinical presentation of CKD is varied and depends on the underlying renal disease. Children and adolescents with CKD from chronic glomerulonephritis (membranoproliferative glomerulonephritis) can present with edema, hypertension, hematuria, and proteinuria. Infants and children with congenital disorders such as renal dysplasia and obstructive uropathy can present in the neonatal period with failure to thrive, polyuria dehydration, urinary tract infection, or overt renal insufficiency. Congenital kidney disease is diagnosed with prenatal ultrasonography in many infants, allowing early diagnostic and therapeutic intervention. Children with familial juvenile nephronophthisis can have a very subtle presentation with nonspecific complaints such as headache, fatigue, lethargy, anorexia, vomiting, polydipsia, polyuria, and growth failure over a number of years.

The physical examination in patients with CKD can reveal pallor and a sallow appearance. Patients with long-standing untreated CKD can have short stature and the bony abnormalities of renal osteodystrophy (Chapter 523.4). Children with CKD due to chronic glomerulonephritis (or children with advanced renal failure from any cause) can have edema, hypertension, and other signs of extracellular fluid volume overload.

Laboratory Findings

Laboratory findings can include elevations in blood urea nitrogen and serum creatinine. They can also reveal hyperkalemia, hyponatremia (if volume overloaded), acidosis, hypocalcemia, hyperphosphatemia, and an elevation in uric acid. Patients with heavy proteinuria can have hypoalbuminemia. A complete blood cell count shows a normochromic, normocytic anemia. Serum cholesterol and triglyceride levels are often elevated. In children with CKD caused by glomerulonephritis, the urinalysis shows hematuria and proteinuria. In children with CKD from congenital lesions such as renal dysplasia, the urinalysis usually has a low specific gravity and minimal abnormalities by dipstick or microscopy.

Inulin clearance is the gold standard to determine GFR, but it is not easy to measure. Endogenous creatinine clearance is the most widely used marker of GFR, but creatinine secretion falsely elevates the calculated GFR. Several other markers are under investigation to accurately determine GFR in children, such as cystatin C and iohexol. In children, the degree of renal dysfunction may be determined by applying the following formula, which provides an estimation of the patient’s GFR:

where k is 0.33 for low-birthweight infants <1 yr old, 0.45 for term infants <1 yr old whose weight is appropriate for gestational age, 0.55 for children and adolescent girls, and 0.70 for adolescent boys.