Paediatric Nephrology/ ACUTE GLOMERULONEPHRITIS

Acute glomerulonephritis is characterized by hematuria(65%), hypertension(75%), and edema(50%). The hematuria is usually grossly evident as tea-colored or cola-colored urine. In some children, however, the hematuria may be microscopic only.

This clinical syndrome can be considered to present in many ways:

acute nephritis with no or mild renal failure
and acute nephritis with rapidly progressive renal failure
or nephritis-nephrotic
or subclinical form.

DISEASES THAT USUALLY PRESENT AS ACUTE GLOMERULONEPHRITIS

Acute poststreptococcal glomerulonephritis 
Acute poststreptococcal glomerulonephritis (APSGN) is a common form of glomerulonephritis in childhood 
Although poststreptococcal nephritis may happen at any age, the peak incidence occurs at age 7 years, with a slight predominance among boys. It is uncommon before age 3 years and in adults

ETIOLOGY

Poststreptococcal nephritis is the consequence of the host's immune response to a nonrenal infection with group A beta-hemolytic streptococci (GABHS


Not all GABHS strains are nephritogenic. Types 12 and 49 are the strains most commonly associated with nephritis
Infection with a nephritogenic strain does not guarantee an episode of nephritis, because a variety of incompletely understood factors determines the host response

CLINICAL PRESENTATION

Mild and subclinical cases are common. Renal involvement characteristically manifests 8 to 14 days after a pharyngeal infection or 14 to 21 days after a skin infection caused by the nephritogenic streptococci


Most patients who have acute poststreptococcal nephritis present as an acute glomerulonephritis, with macroscopic hematuria present in about 65% of the cases.

Patients will usually have oliguria and, in rare cases, anuria.

Fluid retention leads to edema that usually is periorbital and rarely, severe

Intravascular overload caused by salt and water retention can lead to signs of congestive heart failure. 

Approximately 75%of the patients have hypertension also related to salt and water retention.

Patients who have severe hypertension may have symptoms of headache, drowsiness, vomiting, personality and visual changes, and convulsions.
Although arteriolar spasm is commonly found on funduscopic examination, papilledema and hemorrhages are rare, even with severe hypertension


Anorexia and pain in the abdomen or flank are common, although palpation of the abdomen usually reveals no significant findings. 
Although a history of preceding skin or pharyngeal infection supports the diagnosis, such a history cannot be elicited in many cases


In rare cases, in which convulsions or symptoms of cardiovascular dysfunction are the primary complaint, unrecognized poststreptococcal nephritis is the underlying etiology

LABORATORY FINDINGS

The urine usually is tea colored and opaque. 
The specific gravity generally is increased, 
and hemoglobin can be detected by chemical testing. 
Any proteinuria that is present usually parallels the degree of hematuria and rarely reaches the nephrotic syndrome range.
Microscopic examination usually reveals erythrocyturia, pyuria and granular or cellular casts

Measurement of serum complement shows a reduction of C3 in most of the patients and, early in the course, a reduction of C4 in 50%. 

The erythrocyte sedimentation rate (ESR) usually is elevated

With severe oliguria, azotemia and acidosis may been seen.

The plasma volume usually is expanded, causing a decline in hemoglobin, and hematocrit levels by dilution. Hemolysis, a shortened erythrocyte half-life, and reduced erythrocyte production may contribute to these hematological changes.

Salt retention with a decreased fractional excretion of sodium.

. Evaluation of a Child with Hematuria

1. Complete history and physical examination (particularly blood pressure, optic discs, skin, abdomen, genitalia)
2. Confirmation of true hematuria by urine microscopic examination
3. Urine culture
4. Urine calcium, protein, creatinine
5. Complete blood count including platelets, serum electrolytes, BUN/serum creatinine (calculate creatinine clearance), calcium, total protein and albumin
5. Streptozyme, C3, C4, ANA
6. Renal ultrasonography
7. Renal biopsy in selected cases

Evidence of a preceding streptococcal infection is important to support the diagnosis.

The antistreptolysin O (ASO) titer is elevated in 80% of patients, although increases in titer are less common in patients who have skin infection and in those who receive early treatment with antibiotics.
If other streptococcal antibodies (antihyaluronidase, antideoxyribonuclease B) are measured, 95% of patients will have serological evidence of preceding streptococcal infection.

Cultures often are negative for GABHS by the time nephritis develops and are particularly affected by pretreatment with antibiotics 
The chest roentgenogram in patients who have hypertension usually reveals a large heart with prominent pulmonary vasculature& pulmonary edema

Ultrasound examination usually reveals bilaterally enlarged kidneys

TREATMENT

Acute poststreptococcal glomerulonephritis most often resolves spontaneously. Even so, the practitioner must be aggressive in treating hypertension, oliguria, and the resulting vascular overload, pulmonary edema, and encephalopathy that occur in the acute phase of the illness, because these can be fatal.

Although mild hypertension may resolve spontaneously, more severe degrees of hypertension should be controlled with antihypertensive agents that act quickly. Because increased intravascular volume is theorized to be the main determinant of hypertension in acute glomerulonephritis
, diuretics are a mainstay of therapy
.

Control of severe hypertension often will require the use of intravenous

Sodium nitroprusside, labetalol
Oral
minoxidil
in a dose of 0.1 to 0.2 mg/kg may be effective
.Slower-acting, less potent antihypertensive drugs are not good initial choices but can be substituted once blood pressure has been acutely stabilized.

The signs of congestive heart failure usually resolve with control of the hypertension.

Occasionally a patient develops acute renal failure severe enough to require dialysis

A 10-day course of antibiotics usually is given to eradicate any remaining GABHS and, thus, prevent the spread of the organism to others.

There is no evidence that such treatment affects the course of nephritis in the patient.

Close contacts should be screened for streptococcal infection and treated if present

Hospitalization for patients who have this disease needs to be determined individually

Although many children who have mild episodes do well as outpatients,

the sudden development of hypertension and oliguria may produce life-threatening symptoms quite rapidly, necessitating hospitalization.

After the acute phase, the child may be allowed to resume normal activities gradually. Every child should be followed up regularly until the serum complement values return to normal.

To be certain of the diagnosis, a renal biopsy may be indicated for a child whose clinical or laboratory findings are atypical. Any child whose C3 value does not return to normal within 8 weeks should have a kidney biopsy.

COURSE


Diuresis usually ensues by one week from onset, heralding resolution of the acute illness. Creatinine should normalize by 3 to 4 weeks.

Gross hematuria resolves within 1 or 2 weeks, although microscopic hematuria may persist for more than 1 year. 

Proteinuria should resolve by 3 months, and complement levels should normalize by 6 to 8 weeks

PROGNOSIS

Studies have shown that more than 95% of children who have acute poststreptococcal glomerulonephritis recover from their illness.
For most children, the critical period(5_10) early in the illness when potentially fatal hypertension or fluid overload presents a 
danger.
Treating the streptococcal infection does not prevent PSGN; however, if the patient still has active streptococcal infection, antibiotic treatment is warranted 
Recurrences of APSGN are rare.

The presence of nephrotic-range proteinuria or extensive crescents by biopsy indicate a poor prognosis.

The failure of complement levels to normalize by 8 weeks suggests the presence of a form of nephritis other than ASPGN, such as membranoproliferative glomerulonephritis, the nephritis of chronic infection, or lupus nephritis.

The prognosis for renal recovery in other forms of chronic GN and in RPGN is variable and related to the disorder and disease severity at diagnosis.