ACUTE KIDNEY INJURY
Acute kidney injury (AKI; previously called acute renal failure) is the sudden loss of renal function necessary to maintain normal fluid and electrolyte balance and clear metabolic waste.1,2 AKI is typically manifested by an increase in serum creatinine, although the increase will not necessarily cause the creatinine to be outside the normal range. Use of serum creatinine alone to define AKI, however, is problematic because creatinine is an inaccurate estimate of glomerular filtration rate (GFR) and can be removed by dialysis, and variable cut-off values for creatinine have been used in AKI. Therefore, the international classification system, Kidney Disease: Improving Global Outcomes (KDIGO) (Table 134-1), is preferred. The system uses creatinine and urine output criteria and can be applied to both children and adults, minimizing practice variation.3
| Stage* | Lab Criteria | Urine Output Criteria | Other Criteria |
|---|---|---|---|
| I | Serum creatinine 1.5–1.9 times baseline or increase of ≥ 0.3 mg/dL | Urine output <0.5 mL/kg/h for 6 h | |
| II | Serum creatinine 2–2.9 times baseline | Urine output <0.5 mL/kg/h for 12 h | |
| III | Serum creatinine 3 times baseline or increase in serum creatinine to ≥4 mg/dL | Urine output <0.3 mL/kg/h for 24 h or anuria for ≥12 h | Initiation or renal replacement therapy |
AKI is the result of nephrotoxic and/or hypoxic injury to the glomeruli and renal tubules.1 Reduced blood flow causes hypoxic injury and damages the proximal tubular cells. Common nephrotoxins include aminoglycosides, contrast agents, calcineurin inhibitors, amphotericin B, and nonsteroidal anti-inflammatory drugs.4 Inflammatory mediators intensify renal tubular damage.2
AKI is frequently classified based on three major anatomic locations of injury: prerenal, renal, and postrenal disease. Prerenal disease is typically caused by inadequate renal perfusion and is the most common class of AKI. Prerenal AKI is typically due to hypovolemia (e.g., bleeding or GI losses such as vomiting and diarrhea), decreased renal artery blood flow, or reduction in effective circulation (e.g., heart failure, cardiogenic shock, third spacing in septic shock). Renal disease or intrinsic renal disease occurs when there is structural damage to the renal parenchyma. Common causes of renal disease include glomerular diseases (e.g., pyelonephritis, nephrotic syndrome, glomerulonephritis, Henoch-Schönlein purpura), vascular diseases (e.g., hemolytic-uremic syndrome, thrombosis, vasculitides), interstitial diseases (e.g., interstitial nephritis, infections), and tubular injuries (e.g., ischemia, nephrotoxins, hypotension). Lastly, postrenal disease is typically due to an obstruction caused by congenital or acquired anomalies to the lower urinary tract. Examples include nephrolithiasis, renal vein thrombosis, pelvic masses (e.g., lymphoma, rhabdomyosarcoma), and urethral obstruction (posterior ureteral valves).
Direct the initial history to determine risk factors or causes for AKI. Many symptoms and signs relate to the underlying disorder, although patients can also be asymptomatic. Vomiting and diarrhea may suggest intravascular depletion and a prerenal cause of AKI. Other important historical features include history of streptococcal infection (suggests poststreptococcal glomerulonephritis), bloody diarrhea (hemolytic-uremic syndrome), and joint symptoms, rash, or purpura (Henoch-Schönlein purpura). Signs of obstruction include complete anuria or poor urinary stream. Symptoms of renal failure itself include nausea, anorexia (secondary to uremia), changes in urine output or color, edema (may be dependent, periorbital, scrotal/labial, or generalized), and headache from hypertension. Perform a full review of systems and obtain the medical history and pertinent family history.1,2 Identify all medications used, including prescription and nonprescription drugs, herbals, and sport supplements.
The physical examination should be thorough, with special emphasis on vital signs (especially blood pressure), weight, hydration status, and joint and skin findings.1 Note the presence or absence of edema. Auscultate the lungs for rales, which suggest fluid overload, and the heart for uremic rubs. Palpate the abdomen for masses and organomegaly, which may indicate fluid overload in young children.
Acute renal failure laboratory findings include alterations of renal function, such as elevated creatinine and BUN or an abnormal urinalysis.
Analysis of the urine can distinguish between prerenal, renal, and postrenal causes of acute renal failure. In children who are not toilet trained, it may be necessary to obtain a urine specimen by catheterization. In prerenal AKI, urinalysis may be normal. Hematuria, presence of casts, and proteinuria characterize the “active sediment” of glomerulonephritis. Proteinuria alone suggests nephrotic syndrome. WBCs and bacteria suggest infection. A urine dipstick test positive for blood in the absence of observed red blood cells (RBCs) suggests myoglobinuria or hemoglobinuria. Hyaline casts may be seen in acute tubular necrosis. Urine specific gravity is often high (>1.025) in prerenal acute renal failure and may be normal to low in acute tubular necrosis.
Obtain serum electrolyte levels when acute renal failure is suspected because hyperkalemia and other electrolyte abnormalities may require emergent treatment. Hyperkalemia may result from a combination of factors including reduced GFR, decreased tubular secretion of potassium, tissue breakdown with release of intracellular potassium, and metabolic acidosis resulting in transcellular movement of potassium. Other electrolyte abnormalities may include hyponatremia secondary to fluid retention or hypernatremia from dehydration in prerenal failure. Hyperphosphatemia from impaired renal excretion may lead to secondary hypocalcemia. A blood gas may show an anion gap metabolic acidosis secondary to impaired renal excretion of acid and reabsorption and regeneration of bicarbonate. A CBC is useful to identify anemia, hemolysis, and thrombocytopenia (characteristic of hemolytic-uremic syndrome), signs of systemic infection, or eosinophilia (interstitial nephritis). Additional studies are dictated by the clinical picture.
An ECG will identify cardiac arrhythmias and hyperkalemia. Renal biopsy is the definitive study for most cases of intrinsic renal disease and may be done on an outpatient or inpatient basis.1,2
A chest radiograph can identify an increase in heart size or pulmonary edema. US identifies anatomic abnormalities, hydronephrosis, and/or hydroureter. Voiding cystourethrogram is obtained in boys with suspected posterior urethral valves. Additional imaging depends on the differential diagnosis.
Treatment of acute renal failure is different for prerenal, renal, and postrenal failure. In all cases, careful monitoring of vital signs, including baseline weight and urine output, is necessary. In prerenal failure, treat dehydration and hypovolemia with a 10- to 20-mL/kg crystalloid bolus of normal saline. If hemorrhagic shock is the cause for hypovolemia, initiate a crystalloid bolus until blood products are available. Packed RBCs are transfused at a volume of 10 mL/kg. Fresh frozen plasma and platelets may be necessary in massive hemorrhage.
In renal failure from intrinsic renal disease, the specific cause must be identified and treated. Depending on the clinical state, manage oliguria with fluid restriction, limiting replacements to insensible losses only. Discontinue all nephrotoxic medications or adjust dose for GFR. Treat hypertension with antihypertensive agents (avoid angiotensin-converting enzyme [ACE] inhibitors and angiotensin receptor blockers) or diuretics (see “Hypertension” below).
Manage oliguria of postrenal failure with fluid restriction and treatment of hypertension. A Foley catheter may be necessary to relieve the obstruction. In all types of AKI, electrolyte management is important. The management of life-threatening hyperkalemia and hyponatremia is discussed in chapter 129, “Fluid and Electrolyte Therapy in Infants and Children.”
When conservative management fails, consider acute renal replacement therapy (dialysis). Indications for acute renal replacement therapy are severe electrolyte abnormalities, fluid overload not relieved by administration of loop diuretics, and intractable metabolic acidosis not responding to bicarbonate therapy. Peritoneal dialysis is the preferred method of acute dialysis for children because it is inexpensive and requires less expertise to perform than hemodialysis.1,2
Although the primary care physician can manage mild renal insufficiency caused by dehydration, pyelonephritis, postinfectious glomerulonephritis, or Henoch-Schönlein purpura on an outpatient basis, consult a pediatric nephrologist for the management of more significant renal insufficiency, which often requires inpatient therapy. Children with hypertension with or without other findings require inpatient evaluation and management. Pediatric urology consultation is needed for postrenal failure.1 Admit children with severe electrolyte abnormalities and fluid overload to a pediatric intensive care unit.
NEPHROTIC SYNDROME
Nephrotic syndrome is a chronic disease in children that alters permeability at the glomerular capillary wall, which causes a urinary loss of protein. The disease is classically characterized by proteinuria (>40 milligrams/m2 in 24 hours), hypoalbuminemia (serum albumin <30 grams/L), hyperlipidemia, and edema. However, hyperlipidemia and edema are not consistently present. Nephrotic syndrome can be primary (involving only the kidney) or secondary (multisystem). The cause is unknown.
The glomerular membrane is damaged, resulting in increased permeability of the glomerulus to proteins normally not able to pass through the glomerular capillary wall. Increased permeability results in the two diagnostic hallmarks of nephrotic syndrome: proteinuria and hypoproteinemia. Nephrotic syndrome also leads to salt and water retention. The combination of low intravascular oncotic pressure from the loss of proteins, coupled with the retention of salt and water, gives rise to the clinical feature of edema. As fluids shift to the extracellular space, the kidney is stimulated through the renin-angiotensin-aldosterone system to increase distal sodium reabsorption, which exacerbates the cycle.5
Although viral upper respiratory tract infection often precedes symptomatic nephrotic syndrome, a causal link has not been established. The classification of primary nephrotic syndromes includes minimal change disease, focal segmental sclerosis, membranous nephropathy, membranoproliferative nephritis, and proliferative nephritis (diffuse, focal, or mesangial). Causes of secondary nephrotic syndrome include systemic diseases such as lupus, Henoch-Schönlein purpura, sickle cell anemia, and systemic infections, as well as potential drug or toxin exposure (e.g., heavy metals). TORCH (toxoplasmosis, syphilis, varicella, rubella, cytomegalovirus, and herpes simplex virus) infections may cause a congenital nephrotic syndrome in neonates.
Edema is the most common complaint. Focus the history on the duration and location of edema. Anasarca consists of marked peripheral edema, ascites, scrotal or vulvar edema, and severe periorbital edema. Shortness of breath, cough, and orthopnea suggests a pleural effusion. Ask about urine output, because oliguria is often associated with more severe edema. Nausea, vomiting, and anorexia suggest ascites or edema of the bowel wall. Review of systems should note fever, fatigue, and headache as well as the character of the urine (foamy, bloody, and tea colored).2 The presence of hematuria, hypertension, or reduced renal function, age at onset, medical and family history of disease, and biopsy findings are all important predictors of disease outcome.
The main life-threatening complications of nephrotic syndrome are severe infection and thromboembolic events (venous and arterial). Serum complements, antibodies, and coagulation factors are lost as protein in the urine, leading to relative immunocompromise. Steroid therapy for nephrotic syndrome increases the risk of infection. Hyperlipidemia may lead to hyperviscosity, and increased levels of fibrinolytic inhibitors increase thrombotic risks.
Rebound abdominal tenderness, ascites, and scrotal or labial swelling are potential findings.5 Perform a full cardiopulmonary and abdominal exam. Auscultate for findings of pleural effusion and pulmonary edema. Be careful not to confuse facial swelling due to nephrotic syndrome with swelling secondary to allergic reaction.
The four diagnostic criteria of nephrotic syndrome are as follows:
Hypoproteinemia with disproportionately low albumin level (<3 grams/dL)
Urine protein (milligrams/deciliter) to urine creatinine (milligrams/deciliter) ratio >2 in a first morning void or a 24-hour urine protein loss that exceeds 50 milligrams/kg or 40 milligrams/m2
Hypercholesterolemia (>200 milligrams/dL)2
Generalized edema
Renal biopsy is not indicated during the initial episode of acute nephrotic syndrome. Renal biopsy may be done when there is a definitive need to make a specific diagnosis for therapeutic reasons or to provide a diagnosis.2,5
In general, blood and urine samples are sent for study to confirm the diagnosis of nephrotic syndrome (tests for proteinuria, hypoproteinemia, and hyperlipidemia), distinguish primary from secondary causes (tests for hematuria, serum immunoglobulin and complement levels, and antinuclear antibody level; hepatitis serologic testing), and aid in management (CBC, serum electrolyte levels, and renal function test). Serum creatinine may be normal for age and height. Total serum calcium is often low, although ionized calcium is usually normal. Serum sodium level is low secondary to increased triglycerides. Imaging studies are rarely indicated unless there is clinical concern for pulmonary edema or effusions. Symptoms or signs suggestive of potential thrombotic complications of nephrotic syndrome should prompt the appropriate evaluation (e.g., duplex US of renal vessels, CT angiography).
The goal is to treat acute symptoms, make the diagnosis of nephrotic syndrome, and arrange for appropriate follow-up. Treat hypovolemic shock with isotonic fluid, even if edema is severe. For the mildly to moderately dehydrated patient, provide oral rehydration with small, frequent aliquots of sodium-deficient solutions. Treat volume overload with furosemide, 1 to 2 milligrams/kg. Diuretics may not be effective when there is profound hypoalbuminemia, and in that situation, infusion of albumin (0.5 to 1.0 gram/kg) followed by furosemide may be effective, but intensive care monitoring is required. Treat infection or thrombotic complications as clinically indicated.
The mainstay of the treatment of nephrotic syndrome is oral corticosteroids, but the response to steroids varies with the cause. Minimal change disease and mesangial proliferative nephritis are often steroid responsive; membranous nephropathy may respond to steroids; focal segmental sclerosis and membranoproliferative nephritis are typically steroid resistant.2,5 When indicated, prednisone is often started at 2 milligrams/kg/d in two or three divided doses, or 60 milligrams/m2 for the initial dose and 40 to 60 milligrams/m2 for the subsequent doses, given daily for 6 weeks with an additional 6 weeks of alternate-day administration. No steroid taper is required for this initial therapy.6 In patients with known steroid-responsive disease who experience relapse, the ED physician may restart steroids as above in consultation with a pediatric nephrologist. In steroid-resistant nephrotic syndrome, the nephrologist must be consulted for initiation of medications. There are three types of medications that can be used for steroid-resistant nephrotic syndrome (5% of cases): immunosuppressive, immunostimulatory, and nonimmunosuppressive medications. Examples include cyclosporine, cyclophosphamide, chlorambucil, and levamisole.6
Admit patients with severe edema, pulmonary effusions or respiratory symptoms, or signs and symptoms suggestive of systemic infection or thrombotic complications to the hospital. Children with mild or moderate edema can often be treated as outpatients with a low-salt (<2 grams/d) diet and close follow-up with their primary care physician or pediatric nephrologist.2
Children with nephrotic syndrome are at high risk for bacterial peritonitis from Streptococcus pneumoniae and should receive the pneumococcal (23-valent) vaccine to avoid peritonitis. The varicella vaccine should also be administered to children with nephrotic syndrome once they are in remission and no longer receiving steroid therapy.5
GLOMERULONEPHRITIS
Glomerulonephritis is a spectrum of inflammatory disorders characterized by hematuria and proteinuria. Signs of glomerulonephritis vary from asymptomatic proteinuria and microscopic hematuria to gross hematuria, nephrotic syndrome, hypertension, and impaired renal functioning requiring renal replacement therapy.2 Glomerulonephritis is caused by several disorders, all of which cause inflammation leading to glomerular injury. Examples of hereditary glomerular diseases include systemic lupus erythematosus nephritis, thin glomerular basement membrane disease, and Alport’s syndrome.2,7 Poststreptococcal glomerulonephritis, immunoglobulin A (IgA) nephropathy, and Henoch-Schönlein purpura will be discussed in this section.
Glomerulonephritis is an inflammatory process affecting the glomerulus. It can be caused by immune-mediated disorders, inherited disorders, or postinfection sequelae. Glomerulonephritis usually results from deposition of immune complexes within the glomeruli. These immune complexes activate a number of processes including complement activation, leukocyte recruitment, and release of growth factors and cytokines. This leads to inflammation and injury. Sclerosis occurs within the glomeruli, and fibrosis occurs in the tubulointerstitial cells.2,7
Glomerulonephritis may be classified as primary (isolated to the kidney) or secondary (a result of a systemic disorder). There are four main presentations: acute glomerulonephritis, rapidly progressive glomerulonephritis, recurrent macroscopic hematuria, and chronic glomerulonephritis. Although glomerulonephritis caused by streptococcal disease or Henoch-Schönlein purpura usually resolves completely and without sequelae, glomerulonephritis from other causes can progress to renal damage and ultimately end-stage renal failure.2
Glomerulonephritis is often associated with hypertension, which may cause headaches when severe. Symptoms related to hypertension may be the chief complaint of a child with undiagnosed glomerulonephritis.2,7 Patients may complain of bloody or foamy urine (a result of proteinuria), oliguria, fatigue, and lethargy.2,7 In glomerulonephritis, the urinalysis demonstrates macroscopic or microscopic hematuria, RBC casts, and proteinuria. Microscopic examination of urinary sediment shows dysmorphic RBCs and RBC casts. The physical examination is often normal. The blood pressure may be elevated. Other examination findings depend on the underlying disorder.
The microscopic urinalysis demonstrates dysmorphic RBCs and RBC casts. Send urine for culture, because proteinuria and hematuria may represent urinary tract infection, although RBC casts are not typical of infection.7
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