Acute glomerulonephritis (AGN) is a clinical syndrome caused by an immune-mediated injury to the glomerulus. Clinical features are reduction in glomerular filtration rate (GFR), oliguria or anuria, azotemia, proteinuria (possibly nephrotic range), microscopic or gross hematuria with RBC casts, pyuria, and evidence of volume overload (hypertension, peripheral edema, vascular congestion). The degree of renal dysfunction and azotemia can range from very mild (subclinical) to severe.
Most cases of AGN result from deposition of preformed immune complexes in glomerular structures (systemic lupus erythematosus [SLE]) or in situ fixation of complement and specific antibody with antigen trapped within glomeruli (post-infectious glomerulonephritis [PIGN]). Other forms of AGN are caused by activation of the classical or alternative complement pathway (membranoproliferative glomerulonephritis [MPGN]), direct antibody-mediated injury (Goodpasture’s syndrome), or damage from infiltrated inflammatory cells (Wegener’s granulomatosis).
Although hereditary nephritis (Alport syndrome) is considered a form of nephritis, it is caused by a genetic mutation resulting in a structural abnormality of the glomerular basement membrane with subsequent glomerular dysfunction. In IgA nephropathy (Berger’s disease), deposition of IgA in the glomerular tuft leads to secondary inflammation. Systemic etiologies that can cause secondary renal injury, but are not a form of glomerulonephritis by definition, include vasculitis (Henoch–Schönlein purpura [HSP]), thrombotic microangiopathy (hemolytic-uremic syndrome [HUS]), subacute bacterial endocarditis (SBE), and shunt (ventriculoatrial) nephritis.
As the GFR falls, oliguria/anuria ensues, leading to the clinical symptoms that are the hallmark of AGN: edema (gravity-dependent: periorbital in the morning and lower extremities in the evening), weight gain, hypertension (both systolic and diastolic), decreased urine output, and tea- or cola-colored urine due to gross hematuria (80% of patients). There may be constitutional symptoms, such as back or abdominal pain, and nausea and vomiting, in addition to the clinical features of the underlying disease. CNS symptoms such as lethargy, irritability, headache, mental status changes, and seizures may occur due to a rapid rise in blood pressure and/or azotemia. Water and salt retention can lead to congestive heart failure and pulmonary edema.
The most common etiology of PIGN is Group A beta-hemolytic Streptococcus (GAS). The disease is most common in school-aged males and typically starts 1–3 weeks after a sore throat during winter months. Impetigo can precede nephritis by up to six weeks and this presentation is most frequently seen in preschool-aged children during the summer months. Onset of PIGN that is synchronous with pharyngitis is suggestive of IgA nephropathy, but may still be caused by GAS (synpharyngitic PIGN). The onset of the AGN is abrupt, with microscopic/macroscopic hematuria, periorbital edema, and mild–moderate hypertension. More than 90% of children with PIGN will have a full recovery.
Systemic Lupus Erythematosus
AGN with or without nephrotic syndrome can be the initial presentation of SLE. Other manifestations of the disease are also usually present, including weight loss, fatigue, rashes, polyserositis, or arthritis.
MPGN causes an illness that may be indistinguishable from PIGN. However, it is more common in older children, particularly adolescent girls, and is characterized by persistent (more than six weeks) hypocomplementemia.
Obtain a careful history, including whether there is a family history of persistent microscopic hematuria, hearing loss, autoimmune diseases, or kidney failure. On physical examination, check the blood pressure manually with an appropriate-sized cuff, note the presence of edema, examine the fundi, skin, heart, lungs, and joints, and assess hearing, mental status, and neurologic function.
If AGN is suspected, order a urinalysis. In glomerular disease, regardless of the etiology, dysmorphic RBCs and RBC casts are almost always present and are diagnostic of this disorder. In renal diseases associated with non-glomerular hematuria, such as nephrolithiasis, trauma, or a bleeding diathesis, the RBCs are eumorphic and RBC casts are not seen. If there is gross hematuria, examine an unspun urine specimen. WBCs may predominate over RBCs early in the course of the disease, suggesting the diagnosis of a urinary tract infection, but the urine culture remains negative. Proteinuria >2+ on a dipstick is virtually always present. Also obtain a CBC, platelet count, ESR, CRP, serum electrolytes, calcium, BUN, creatinine, total protein, albumin, cholesterol, triglycerides, and complement (C3, C4, C50). Hypocomplementemic forms of AGN include PIGN, MPGN, shunt nephritis, and embolic renal disease (SBE).
If the clinical picture is compatible with PIGN, obtain a throat culture, or a skin culture if the patient has impetigo. Antistreptolysin (ASLO) or streptozyme titers will be positive in PIGN caused by GAS, but will be negative with other infections. If SLE is a consideration, obtain an ANA and anti-dsDNA antibody titer.
Consult a nephrologist for all patients with AGN. Immediate priorities include management of hypertension and hyperkalemia. Because hypertensive encephalopathy can occur at a minimally increased blood pressure, especially in PIGN, treat hypertension promptly and aggressively. For an asymptomatic patient, use oral nifedipine (0.25 mg/kg, 10 mg maximum). The onset of action of nifedipine is immediate after the patient bites the capsule and swallows its contents. For a slower reduction in BP in an asymptomatic patient, give amlodipine (0.1 mg/kg/dose), or if the child does not have a history of asthma, oral labetalol (2 mg/kg/dose).
For a patient with acute symptoms (headache, seizures, altered mental status, chest pain, blurred vision), treat with IV nicardipine or labetalol (contraindicated in asthma and pulmonary edema) (see Hypertension, pp. 684–688). The goal of the initial antihypertensive therapy is a 20% reduction in the mean blood pressure (diastolic BP + 1/3 [systolic BP – diastolic BP]).
The cornerstone of medical management is fluid and sodium restriction (see Acute Kidney Injury, pp. 674–679). Restrict fluids to insensible losses plus urine output, regardless of whether the patient is oliguric. Withhold potassium until the patient voids and eukalemia is documented (see Hyperkalemia, pp. 186–188). When the child can eat, limit the sodium to 2 g/day.
Conservative medical therapy is the rule, with renal replacement therapy reserved for severe volume overload with pulmonary edema, life-threatening hyperkalemia (≥7 mEq/L), intractable acidosis, intractable hypocalcemia with seizures, or symptomatic uremia (pleuritis, pericarditis, GI bleeding, encephalopathy).
Indications for Admission
Acute kidney injury (AKI; formerly acute renal failure) is characterized by an acute decrease in the glomerular filtration rate (GFR), associated with increases in blood urea nitrogen and serum creatinine concentrations (azotemia). Oliguria (≤0.5 mL/kg/h) is a frequent, but not invariable, finding.
The causes of AKI can be divided into three pathophysiologic categories: prerenal, postrenal, and renal parenchymal disease (Table 22.1). Prerenal AKI reflects a decline in renal function in the absence of primary structural injury. It is a consequence of inadequate kidney perfusion secondary to hypovolemia (dehydration or blood loss), hypotension, or ischemia/hypoxia. The GFR is rapidly restored to normal when renal blood flow is increased; however, severe renal hypoperfusion may lead to acute tubular necrosis (ATN). Postrenal AKI is secondary to urinary tract obstruction affecting both kidneys (i.e., at the level of the bladder or the urethra). Intrarenal AKI can result from glomerular diseases (AGN, HUS), or tubular injury secondary to nephrotoxins, rhabdomyolysis, or tubular ischemia, as well as acute interstitial nephritis.
|Hypotension||Obstruction – mechanical||Ischemia|
|Hypovolemia||Obstruction – functional||Glomerulonephritis|
|Anaphylaxis||Neurogenic (HSV, MS, spina bifida)||Antibiotics (amphotericin, gentamicin, vancomycin)|
|Antihypertensives||Intra-abdominal tumor||Acute interstitial nephritis|
|Burn||Posterior urethral valves||ATN not treated expeditiously|
|Cardiopulmonary arrest||Renal vein thrombosis||Heavy metals|
|Congestive heart failure||Myo- or hemoglobinuria|
ATN: acute tubular necrosis; HSV: herpes simplex virus; MS: multiple sclerosis
The clinical presentation of AKI depends on the etiology, but signs of significant renal dysfunction such as fluid overload, hypertension, nausea and vomiting, hypocalcemic tetany, as well as neurologic symptoms (coma, seizures) can occur in all forms. Prerenal AKI is suggested by loss of peripheral pulses, prolonged capillary refill time or hypotension (hypovolemic shock), lethargy and fever (sepsis), cutaneous burns, or bleeding. Difficulty voiding and an abnormal urinary stream (obstruction) suggest postrenal AKI. Illnesses associated with jaundice (hemoglobinuria), rhabdomyolysis (myoglobinuria), pallor and bloody diarrhea (HUS), rash, abdominal pain, arthralgias (HSP), or gross hematuria in the context of an antecedent sore throat or URI (PIGN) are associated with intrarenal AKI.
Make a rapid assessment of the patient’s volume status, looking for clinical signs of dehydration (orthostatic vital sign changes, poor capillary refill, weak peripheral pulses, cool extremities, hypotension) or volume overload (edema, rales, palpable liver, cardiac gallop). It is essential to identify the cause of oliguria as quickly as possible and to institute immediate treatment. Prerenal azotemia is a reversible condition early in its course, but failure to recognize a prerenal etiology (hypovolemia) can lead to ATN.
Estimate the GFR by using the modified Schwartz formula:
The constant k depends on age and sex of the patient; LBW infants: k = 0.33; AGA and term infants: k = 0.45; children; and adolescent females: k = 0.55, adolescent males: k = 0.7.
An increase in creatinine of 0.3 mg/dL from baseline is suspicious for kidney injury, despite a serum creatinine level that is still within the range of normal
If the patient is unable or unwilling to void spontaneously, insert a Foley catheter to obtain urine and monitor the urine output. To differentiate among the causes of oliguria, obtain urine for specific gravity, sodium and creatinine, and microscopy. Look for blood, protein, and RBC casts (AGN) or pyuria >5 WBC/hpf). Concentrated urine with a high specific gravity is a feature of prerenal AKI, while isosthenuria with a specific gravity ≤1.010 and few or no cells or proteinuria is seen in interstitial nephritis. Hematuria on dipstick examination, but without RBCs seen on microscopy, is consistent with myoglobinuria or hemoglobinuria. Hematuria with macroscopic clots or microscopic crystals suggests kidney stones.
Obtain blood for electrolytes, BUN, and creatinine. Calculate the fractional excretion of sodium (FENa, Table 22.2):
|Diagnosis||USG1||UNA2 (mEq/L)||BUN/Cr3||FENA4 (%)||U/A5|
|Acute glomerulonephritis (early)||>1.020||<20||>20||<1||RBC casts, dysmorphic RBCs|
|Acute tubular necrosis||1.008–1.012||>40||<20||>1||Tubular epithelial cells|
1 USG = urine specific gravity.
2 UNa = urine sodium concentration.
3 BUN/Cr = ratio of BUN to creatinine.
4 FENA = fractional excretion of sodium; (UNa × PCr)/(PNa × UCr).
5 U/A = typical urinalysis finding.
When urine is unavailable or the urinary findings are pending, but there is no evidence of volume overload and obstruction has been ruled out (sonogram), attempt to discriminate intrarenal AKI from prerenal azotemia by rapidly infusing 20 mL/kg of an isotonic solution (normal saline). If oliguria persists and there are no signs of volume overload, repeat the bolus until it is clear that the patient is not volume-depleted (based on vital signs and capillary refill). If there is no diuresis, place a Foley catheter and give one dose of IV furosemide (1–2 mg/kg; higher doses increase the risk of ototoxicity). If oliguria continues, the diagnosis of intrinsic renal disease (frequently ATN) is probable. If urine output increases with these measures, the patient has prerenal insufficiency, which will return to normal provided adequate maintenance fluid therapy is given. If a sonogram cannot be obtained immediately, a distended bladder suggests a postrenal problem.
If a hemodynamically stable patient remains oliguric, fluid restriction is required: Limit fluids to insensible losses plus urine output. Estimate insensible losses to be 400 mL/m2/day; losses are higher with fever and burns and lower with mechanical ventilation.
If the patient is dehydrated and hyponatremic, the goal is to correct the sodium to at least 135 mEq/L. In a patient with sodium >120 mEq/L, restore the deficit slowly, (2–4 mEq/L q 4h) using the following calculation for the sodium deficit:
Obtain repeat electrolytes every 3–4 hours and adjust the correction rate as needed.
Initiate a rapid correction for patients who are seizing, or are symptomatic and have a sodium <120 mEq/L. Administer hypertonic (3%) saline, which contains 513 mEq/L of Na (every 2 mL contains 1 mEq Na). Calculate the amount of 3% NaCl as follows:
Multiply this result by 2 to determine the volume in mL.
Hyperkalemia often occurs in AKI as a result of renal dysfunction and an acidosis-induced shift of potassium to the extracellular space. Dietary restriction (1 g/day) is sufficient if the potassium is <6 mEq/L. If the potassium is ≥6 mEq/L, immediately obtain an ECG to identify cardiac conduction abnormalities such as peaked T-waves (T-wave ≥ one-half the R- or S-wave) and a shortened QT interval. Later changes include lengthening of the PR interval and QRS duration.
The treatment of hyperkalemia primarily entails enhancing potassium excretion or increasing the movement of potassium into cells as a temporary measure, as well as minimizing cardiac effects. Aggressive IV therapy is necessary for patients who are symptomatic (muscle weakness or cramps/tetany) or have ECG changes. Give 0.5–1 g/kg of glucose (2–4 mL/kg of a 25% dextrose solution) over 30 minutes concurrently with regular insulin (1 unit per 5 g of glucose given). The potassium-lowering effect occurs in 10–20 minutes, but carefully monitor the serum glucose for both hyper- and hypoglycemia. In an infant, IV dextrose alone may be sufficient. Nebulized β-agonists, such as albuterol, are also effective at shifting potassium into the cells, but are less predictable than other therapies. The peak effect is 40–80 minutes after administration. The dose is 10–20 mg in 4 mL normal saline (4–8 times the dose used for the treatment of asthma).
In the absence of peaked T-waves, treat with polystyrene sulfonate (Kayexalate), 1 g/kg dissolved in 4 mL of water, with sorbitol (PO or PR). This dose lowers the serum potassium by 0.5–1 mEq/L by enhancing GI excretion, but the onset is slow and duration is variable. In a patient who is not anuric, give furosemide (1–2 mg/kg). The onset of action is within one hour, and the dose may be repeated every six hours.
In a patient with hyperkalemia, calcium will stabilize the myocardium without affecting the serum potassium level. If there are EKG changes or a cardiac arrhythmia is noted, give IV 10% calcium gluconate solution (100 mg/kg), which will be effective in 1–3 minutes. Do not exceed a rate of 100 mg/min. Complications include hypercalcemia and bradycardia; continuously monitor the EKG, and stop the calcium if the patient becomes bradycardic. Use the same regimen to treat hypocalcemia causing tetany, laryngospasm, arrhythmias, or seizures. When the symptoms have resolved, add maintenance calcium to the IV solution (100 mg elemental calcium/kg/day).
Absolute indications for dialysis include life-threatening hyperkalemia (serum potassium ≥7 mEq/L) not responsive to pharmacological treatment, anuria, intractable acidosis, symptomatic volume overload (CHF, pulmonary edema), and symptomatic uremia (pleuritis, pericarditis, encephalopathy, GI bleeding).
Indications for Admission
Hematuria is defined as ≥2–5 RBCs/hpf in fresh unspun urine or ≥5–10 RBCs/hpf in centrifuged fresh urine. Up to 5% of school-age children have microscopic hematuria on a single specimen, and 1–2% have this finding subsequently confirmed. The incidence increases with age and is greater in girls. Gross hematuria reflects RBCs in the urine that are visible upon inspection.
Hematuria can be classified as either traumatic or non-traumatic in origin. Non-traumatic hematuria can be divided into upper and lower genitourinary tract. Upper tract bleeding usually refers to glomerular causes, but can be of non-glomerular origin (e.g., papillary necrosis in a patient with sickle cell disease).