PEDIATRIC NEPHRITIS

Lecture notes
 Nephritis is an older term used to clinically denote a child with hypertension,
decreased renal function, hematuria, and edema.
 It suggests a noninfectious inflammatory process that involves the nephron; 
glomerulonephritis (GN) generally is a more precise term. 
 A process of inflammation and cell proliferation, in which endothelial,
mesangial, or epithelial cells are stimulated to proliferate in varying degrees,
is initiated, which damages normal renal tissue.
 If the inflammatory process is turned off, as in acute poststreptococcal GN,
recovery occurs.
 If the inflammatory process continues unabated, progressive loss of glomeruli
and nephrons occurs (eg, as in membranoproliferative GN).
 Glomerulonephritis: An important group of generalized parenchymal
diseases mainly of autoimmune origin with similarities in:
 Etiology and pathogenesis
 Clinical presentation
 Morphology( various histological patterns)
 Diseases that produce GN are usually classified as primary (ie, diseases in
which the kidney is the primarily affected organ) or secondary (ie, systemic
disorders that involve the kidneys in addition to other organs, such as 
systemic lupus erythematosus [SLE]).
 The term nephritis is also applied to a group of unrelated inflammatory
disorders known collectively as tubulointerstitial nephritis (TIN).
 TIN initially affects mainly the interstitium and renal tubules.
 In children TIN, some stimulus (eg, an infection, a drug, a metabolic
abnormality) initiates a tubulointerstitial inflammatory process.
 TIN probably occurs as a result of humoral and cell-mediated immune
reactions against a hapten-protein complex.
 Cytokines are released and recruitment/dysregulation of inflammatory cells
continues, leading to injury out of proportion to the initial insult.
 The occurrence of mononuclear cell infiltrates in tubulointerstitial areas is
the principal pathogenic process. Tubular dysfunction is out of proportion to
glomerular dysfunction.
 TIN is often clinically classified as acute or chronic based on the rapidity with
which renal clearance function decreases.
 With acute TIN, treatment or removal of the stimulus leads to resolution.
 In chronic TIN, differing rates of progressive renal damage persist.
 Acute postinfectious (most often poststreptococcal) GN has diminished in
recent years but is still the most frequent type of GN.
 Other conditions that present with GN,  Henoch-Schönlein purpura,
immunoglobulin A (IgA) nephropathy,  Alport syndrome, and SLE, as well as
membranoproliferative GN and mesangial proliferative GN.
 Acute tubulointerstitial nephritis (TIN) in the United States may account for 5-
10% of acute renal failure, and chronic TIN may account for 20% of chronic
renal failure in children.
 TIN is purely a biopsy diagnosis, thus the previous estimates of TIN may be
underrepresentations.
 Most cases of acute TIN in children are virus or medication related.
 Most cases of chronic TIN in children are related to chronic infection, 
vesicoureteral reflux, or metabolic disease (eg Crohn disease).
PROGNOSIS

The overall prognosis for survival in children with all forms of nephritis is good.
 Primary complications associated with hypertension include:
 Seizure
 Encephalopathy
 Stroke
 End-organ damage
 Primary complications associated with kidney failure include:
 Fluid overload
 Electrolyte abnormality
 Uremic symptoms
 Anemia
 Abnormal bone mineralization
 Sexual dysfunction
 Poor growth
 Anorexia
 Endocrine abnormalities
CLINICAL PRESENTATION

 History:
 For Alport syndrome- family history of family members with nephritis or renal
failure.
 For poststreptococcal glomerulonephritis (GN), elicit a history of
streptococcal throat or skin infection.
 Inquire about symptoms of swelling and facial, perioral, or pedal edema or
ascites.
 Symptoms of pulmonary edema or congestive heart failure (eg, dyspnea with
exertion, orthopnea, shortness of breath) may be present.
 Gross hematuria (eg, dark, rust colored, coke colored, tea colored) may be
present.
 With severe hypertension, identify nosebleed, headache, or encephalopathy.
 The parent may note decreased urine frequency.
 Nonspecific symptoms, such as malaise, fever, anorexia, or weakness, may be
present.
 For children with tubulointerstitial nephritis (TIN) who present with allergic
manifestations, most have fever (80-100%) and many have maculopapular rash
(25-50%).
 These symptoms often occur with arthralgias and malaise. When considering
the diagnosis of TIN, attempt to obtain a history of a known etiology (eg,
bacterial, viral, drug-related, metabolic).
 In patients with TIN, a history of polyuria, rather than oliguria, is obtained.
Physical Examination

 Elevated blood pressure is an important physical finding.

 Look for edema. The child may have a pale appearance because of dilutional
anemia. Tachypnea, dyspnea, hepatic congestion, and gallop rhythm suggest
fluid overload with congestive heart failure.
 If a secondary form of glomerulonephritis (GN) is suspected, seek physical
findings of the condition (eg, vasculitis in SLE).
 With tubulointerstitial nephritis (TIN), physical findings include
maculopapular rash, joint pain (with flexion and extension), and fever.
 Rarely, the patient may present with uveitis as part of tubulointerstitial
nephritis and uveitis syndrome (TINU). 
Diagnostic Considerations

 Conditions that produce hematuria, decreased clearance, and, sometimes,

hypertension include all specific types of glomerulonephritis (GN), anatomic
abnormalities of the kidneys, renal stones, tumors, drugs, and infection.
 Differentials to consider include the following:
 Takayasu disease
 Membranoproliferative GN
 Medullary sponge kidney
 MELAS syndrome
 Multicystic renal dysplasia
 Nephrotic syndrome
 Oliguria
 Polycystic kidney disease
 Proteinuria
 Pyelonephritis
 Hepatorenal syndrome
 Hypercalcemia
 Hypertension
 IgA nephropathy
 Rhabdomyolysis
 Sarcoidosis
 Renal cortical necrosis
 Uric acid stones
 Urinary tract infection
 Urolithiasis
 Wilms tumor
 Antiphospholipid antibody syndrome
 Escherichia coli infection
 Systemic sclerosis
 Tumor lysis syndrome
 Systemic lupus erythematosus
INVESTIGATIONS

 Laboratory:
 Electrolyte, creatinine, and blood urea nitrogen (BUN) levels
 Complete blood count (CBC)
 Urinalysis
 Urine culture
 Lupus serologies
 Measurement of complement components (ie, C3, C4)
 Antistreptolysin-O (ASO) titer
 Anti-DNAase B
 Perinuclear antineutrophil cytoplasmic antibody (P-ANCA) measurement
 Cellular antineutrophil cytoplasmic antibody (C-ANCA) assessment
 Serum IgA measurement 
 If the child has a history consistent with acute poststreptococcal
glomerulonephritis (GN), such as low C3, positive ASO, and anti-DNAase B, a
provisional diagnosis of this disorder can be made.
 Supportive care and observation for improvement within 10-14 days is
reasonable.
 If a diagnosis of acute poststreptococcal GN seems unlikely, a percutaneous
renal biopsy is the single most effective mechanism to arrive at a pathologic
diagnosis.
 Laboratory findings in tubulointerstitial nephritis (TIN) include hematuria,
eosinophilia, sterile pyuria, low-grade proteinuria, eosinophiluria, and urinary
white blood cell casts.
 A percutaneous renal biopsy is the criterion standard for diagnosing TIN.
 With TIN, the hallmarks of GN (ie, edema, hypertension, sodium chloride
retention) are not present. Tubular dysfunction is the predominant feature.
 The pattern of tubular dysfunction that develops in TIN depends on the
tubular segment(s) involved.
 Proximal tubular lesions result in aminoaciduria, glucosuria, phosphaturia,
uricosuria, beta2 microglobinuria, and bicarbonaturia, often producing
proximal renal tubular acidosis. 
 Lesions involving the distal tubule result in an inability to acidify urine (distal
renal tubular acidosis), to regulate sodium balance, and to secrete potassium.
 Lesions affecting the medulla and papilla result in an inability to concentrate
urine.
 These tubular functions may be tested by calculating the fractional excretion
of phosphate or bicarbonate, measuring the urinary glucose excretion, and
measuring the urine pH and osmolality with fasting.
 Imaging studies:
 Renal ultrasonography is usually performed to exclude other causes of
hypertension and hematuria, such as renal artery stenosis (ie, small,
abnormal kidney on one side), anatomic abnormalities, a tumor, and stones.
 The kidneys are frequently echodense when GN is present and maybe
abnormally large or small.
 No imaging tests are sensitive or specific for TIN.
 Renal ultrasonography may show large kidneys with normal echogenicity.
 Gallium scanning may reveal increased uptake.
 Renal biopsy: standard for identifying a specific pathology.
 Histologic Findings:
 In glomerulonephritis (GN), light microscopy usually reveals infiltration of the
kidney by lymphocytes, polymorphonuclear leukocytes, or both.
 Immunofluorescence microscopy may reveal IgG, IgA, IgM, or complement in
mesangial or vascular distribution, depending on the type of GN.
 Electron microscopy may reveal deposits in mesangial, subendothelial, or
subepithelial tissue or in a combination of tissues, depending on the type of
GN present.
 Replacement of renal tissue by scar tissue (tubular atrophy and interstitial
fibrosis) is the final common pathway for several types of GN.
 For tubulointerstitial nephritis (TIN), light microscopy reveals focal interstitial
infiltrates of edema that contain lymphocytes and eosinophils. Tubular injury
is usually greater than glomerular or vascular injury.
TREATMENT AND MANAGEMENT

 Medical care for glomerulonephritis (GN) is usually divided into 2 major

components: treatment of primary pathology and supportive care.
 In renal diseases, supportive care involves managing hypertension and fluid
and electrolyte abnormalities and managing decreased renal function.
 The treatment of primary pathology ranges from watchful waiting, as in
postinfectious GN, to treatment with immunosuppressive medication, such as
steroids or cyclophosphamide in lupus.
 Hypertension can be managed with antihypertensives, such as calcium
channel–blocking agents, angiotensin-converting enzyme (ACE) inhibitors,
angiotensin receptor–blocking agents, peripheral vasodilators, and diuretics.
 The most common fluid abnormality, hypervolemia, is managed with fluid
restriction and diuretics or with dialysis if renal function is too poor to
respond to diuretics.
 Hyponatremia is usually dilutional and responds, at least partially, to removal
of excess fluid.
 Hypocalcemia may respond to oral or IV calcium, depending on severity. Mild
metabolic acidosis may be present but rarely requires primary treatment.
 Some recommend a short course of steroids or cyclophosphamide for
tubulointerstitial nephritis (TIN). Prednisone may speed up the recovery from
renal symptoms of TIN. 
 However, these drugs are usually not necessary. Most often, stopping the
 

offending agent leads to recovery.

DIET AND ACTIVITY

 In children with acute renal failure secondary to glomerulonephritis (GN) who have lost
the ability to excrete a water load, fluid restriction may prevent fluid overload.
 Tubulointerstitial nephritis (TIN) usually produces nonoliguric acute renal failure. Fluid
restriction of 300 mL/m2/d plus losses may allow management of acute renal failure
for 2-3 days without dialysis.
 In patients with hypertension, sodium restriction to the recommended daily allowance
(RDA) of 2-4 mEq/kg/d may aid in management.
 In children with renal failure, potassium restriction is justified to prevent
hyperkalemia. A short-term high-carbohydrate diet may prevent catabolism of body
protein as an energy source.
 Calcium supplementation is useful to maintain normal serum calcium.
 In patients with hypertension and renal failure, discourage strenuous activity;
however, walking, playing, and other activities are acceptable.
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