EVALUATION OF A CHILD WITH GLOMERULAR DISEASE

Author:
Patrick Niaudet, MD
Section Editor:
F Bruder Stapleton, MD
Deputy Editor:
Melanie S Kim, MD

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2017. | This topic last updated: Nov 18, 2016.

INTRODUCTION — There are numerous causes of glomerular diseases in children. Many of these conditions vary in
their presentation with mild or no symptoms, to serious renal disease with life-threatening complications. As a result,
the diagnosis of a specific glomerular disease is challenging in children but important so that therapy, if helpful and
needed, can be initiated.

The diagnostic evaluation of children with glomerular disease will be reviewed here. The evaluation of children with
nonglomerular causes of isolated hematuria or proteinuria is discussed separately. (See "Evaluation of microscopic
hematuria in children" and "Evaluation of gross hematuria in children" and "Evaluation of proteinuria in children".)

OVERVIEW — Numerous primary (renal disease alone) and secondary (due to systemic autoimmune disorders,
vasculitis, or infection) disorders produce glomerular disease (table 1).

Findings suggestive of a glomerular disease include proteinuria, hematuria (which may be microscopic or macroscopic),
nephrotic syndrome, arterial hypertension, and renal insufficiency. The presence of these manifestations and their
severity can be used to describe several different clinical patterns that often correspond to different underlying
etiologies.

●An acute nephritic syndrome pattern is associated with active urine sediment with red cells, white cells, granular
and often red cell and other cellular casts, and a variable degree of proteinuria including nephrotic range
proteinuria, and often elevated blood pressure. Histologic examination demonstrates inflammation. This pattern
is most often seen in children with poststreptococcal glomerulonephritis, but may also be secondary to a
membranoproliferative glomerulonephritis. (See "Overview of the pathogenesis and causes of glomerulonephritis
in children" and "Poststreptococcal glomerulonephritis".)
●Isolated nephrotic syndrome presents with nephrotic range proteinuria, and usually an inactive urine sediment
with few cells or casts. Most often, it is secondary to an idiopathic nephrotic syndrome with a rapid onset and
peripheral edema. (See "Etiology, clinical manifestations, and diagnosis of nephrotic syndrome in children",
section on 'Nephrotic syndrome'.)
●Recurrent macroscopic hematuria episodes are commonly seen in patients with an immunoglobulin A (IgA)
nephropathy, but may also be seen in patients with Alport syndrome. (See "Clinical presentation and diagnosis of
IgA nephropathy" and "Clinical manifestations, diagnosis and treatment of hereditary nephritis (Alport
syndrome)".)
●Rapidly progressive glomerulonephritis typically presents with heavy proteinuria, active urine sediment, and
renal failure that does not resolve spontaneously. The renal biopsy of patients shows extensive cellular crescents
in most glomeruli. (See "Overview of the classification and treatment of rapidly progressive (crescentic)
glomerulonephritis" and "Overview of the pathogenesis and causes of glomerulonephritis in children", section on
'Rapidly progressive GN'.)
●Chronic glomerulonephritis is associated with proteinuria, microscopic hematuria, hypertension, and often renal
insufficiency.

Both nephritic and nephrotic patterns can present with an acute or insidious time course, and elements of both may be
also seen in some patients simultaneously or sequentially. Thus, it is important to recognize that patients with
glomerulonephritis may also present with nephrotic syndrome. (See "Differential diagnosis and evaluation of
glomerular disease".)

●Red blood cells that are dysmorphic in appearance (picture 2A-B). and estimating the creatinine clearance based upon the serum creatinine. 0. fever. and. As noted above. a 4+ recording. clinical manifestations. Currently. the gender of the patient (calculator 2).7 in adolescent boys when serum creatinine is measured by the Jaffe method. hypertension. such as decreased renal perfusion due to volume depletion. and diagnosis of nephrotic syndrome in children".INITIAL EVALUATION — The clinical manifestations. height. are indicative of glomerular bleeding and glomerulonephritis. The urine sample should be a first morning void to exclude the possibility of orthostatic proteinuria. The constant k is directly proportional to the muscle component of the body. The GFR can be estimated by using the Schwartz formula. GFR = k X Height (cm) / Screat (mg/dL) Height represents the body height measured in centimeters. and rate of protein excretion are important findings that help guide evaluation and determine the underlying cause of glomerular disease. In contrast. section on 'Definitions and . and respiratory distress caused by pleural effusions. and distinguishes between the patterns of glomerular disease. rash. A reduction in GFR implies either progression of the underlying disease or the development of a superimposed and often reversible problem. which corresponds to a concentration of urinary albumin of 1000 mg/dL. However. most laboratories are using the enzymatic method for creatinine determination rather than the older Jaffe method. the urinalysis of children with idiopathic nephrotic syndrome is associated with heavy proteinuria and lipiduria.33 in premature infants through the first year of life. Patients with secondary causes of glomerular disease often have nonrenal symptoms and signs (eg. the absence of these findings does not exclude glomerulonephritis. 0. section on 'Urine protein excretion'. The following urinalysis findings. urinalysis. and 0. ●The value for k is 0. Nephrotic range proteinuria is confirmed by a quantitative measurement of a timed 24-hour urine collection or by measuring the total protein/creatinine ratio on a spot urine sample (calculator 1). but few cells or cast. arthralgias. Although the urinary dipstick measurement is a qualitative test.55 in children and adolescent girls. is suggestive of nephrotic range proteinuria. The ratio that is indicative of nephrotic range proteinuria is greater than 3 mg protein/mg creatinine (300 mg protein/mmol creatinine). which is based upon serum creatinine. and a rising serum creatinine.413 for all children with chronic kidney disease (CKD) between ages 1 and 16 years when the serum creatinine is determined using enzymatic methodology [2]. Patients with both glomerulonephritis and nephrotic syndrome have an overlap of clinical findings. and varies with age based on the laboratory assay used to measure serum creatinine [1]. age.) Renal function — Once glomerular disease is identified. and course of chronic kidney disease in children". ●The value for k is 0. and pulmonary hemorrhage) that are suggestive of a specific underlying systemic disease. Clinical features — Nephritic syndrome is characterized by a constellation of findings that includes edema. and those with heavy proteinuria are likely to have nephrotic syndrome. Urinalysis and urinary protein — Testing of the urine is the most important noninvasive test in determining whether or not a child has glomerular disease. some patients with glomerulonephritis may have nephrotic range proteinuria. Children who have evidence of glomerular bleeding may have nephritic syndrome secondary to glomerulonephritis. etiology.45 for term infants through the first year of life. and Screat is the serum creatinine in mg/dL. in adolescents. reddish-brown to brown-colored urine. Patients with a nephrotic syndrome may have anasarca with ascites. (See "Etiology. The most common method utilized to estimate the GFR is measuring the serum creatinine concentration. (See "Epidemiology. if present. defined as a urinary protein excretion greater than 50 mg/kg per day or 40 mg/m2 per hour. ●Protein excretion greater than 100 mg/m2 per day at a time when there is no gross bleeding. ●Red cell casts (pathognomonic for glomerular bleeding) (picture 1). the presence or degree of renal dysfunction is assessed by an estimation of the glomerular filtration rate (GFR).

section on 'Complement' and "C3 glomerulopathies: Dense deposit disease and C3 glomerulonephritis". C4. anti-streptolysin. For example. (See "Overview of the pathogenesis and causes of glomerulonephritis in children". However.) ●Antineutrophil cytoplasmic antibodies (ANCA) − ANCA are detected in patients with pauci-immune glomerulonephritis that are seen in patients with systemic vasculitis. as more than 80 percent of patients will respond to this intervention. shunt nephritis. Positive serology indicates a recent streptococcal infection. and nephritis associated with subacute bacterial endocarditis. . MPGN I. children presenting with a different clinical pattern. (See "Acquired deficiencies of the complement system". or hepatitis B and C. section on 'Diagnosis'.) ●Other blood tests that can be performed based upon clinical presentation. Patients with components of both nephritic and nephrotic syndromes are evaluated in a similar manner to those with nephritis because several of the glomerulonephritides may also present with nephrotic syndrome. Glomerulonephritis — Glomerulonephritis represents a variety of disorders that are caused by immunologic injury that results in inflammation of the glomeruli. whereas idiopathic nephrotic syndrome does not typically have an inflammatory component. (See "Clinical manifestations and diagnosis of granulomatosis with polyangiitis and microscopic polyangiitis". (See "Systemic lupus erythematosus (SLE) in children: Clinical manifestations and diagnosis". patients who are suspected of having glomerular disease but don't fit either category are also included in the glomerulonephritis category. whereas they remain persistently low in patients with C3 glomerulopathies. section on 'Serum creatinine and GFR'. For example. (See "Poststreptococcal glomerulonephritis". a child with nephrotic range proteinuria and inactive urine sediment is likely to have idiopathic nephrotic syndrome.) •Low C3 and C4 levels are due to activation of the classic pathway due to immune complex formation.classifications' and "Clinical presentation and evaluation of chronic kidney disease in children". the results of previous testing. in the future.) FURTHER EVALUATION — Based upon the initial evaluation. section on 'Clinical features and renal biopsy findings'. section on 'Diagnosis'.) ●Complement studies including C3. and the clinical judgment of the clinician include: •IgA levels may be elevated in patients with IgA nephropathy or Henoch-Schönlein purpura (IgA vasculitis). In this setting. an empirical course of corticosteroid therapy is a reasonable option. anti- hyaluronidase. such as granulomatosis with polyangiitis (formerly referred to as Wegener's granulomatosis). and CH50. This combination of hypocomplementemia is seen in lupus nephritis. and fulfills a criterion for the diagnosis of poststreptococcal glomerulonephritis. section on 'Systemic lupus erythematosus' and "Renal disease in the setting of infective endocarditis or an infected ventriculoatrial shunt". and anti-DNase B antibodies). section on 'Clinical presentation'. anti-nicotinamide-adenine dinucleotidase. anti-streptokinase. In addition. as they are likely to have a mild course of a glomerulonephritis. These disorders may be primary (only renal involvement) or secondary (due to systemic disease or infection) (table 1). (See "Poststreptococcal glomerulonephritis". require further evaluation to determine the underlying glomerular disease [3]. A promising assay that screens for antibodies to galactose-deficient IgA1 may.) Blood tests — The evaluation of nephritic syndrome in children focuses on identifying the underlying diagnosis and includes the following diagnostic blood tests (algorithm 1): ●Serologic testing to screen for a recent antecedent streptococcal infection (ie. •Low C3 levels due to activation of the alternative pathway of complement are associated with poststreptococcal (PSGN) and C3 glomerulopathies including dense deposit disease. (See "Clinical presentation and diagnosis of IgA nephropathy". section on 'Diagnosis'. section on 'Serology' and "Poststreptococcal glomerulonephritis". be helpful in diagnosing IgA nephropathy. children who present with recurrent gross hematuria after an upper respiratory infection without an active sediment or proteinuria may have a mild course of immunoglobulin A (IgA) nephropathy. The C3 levels typically return to normal within four to six weeks of presentation in patients with PSGN.) ●Antinuclear antibodies (ANA) and antiDNA antibodies − An elevated ANA titer or antiDNA antibody titer fulfills one of the classification criteria for systemic lupus erythematosus (table 2). an underlying disease process may be identified based on the clinical pattern of findings. such as active nephritis.) •Serologic testing for Epstein-Barr virus.

and nephrotic range proteinuria. and early initiation of appropriate therapy are essential to minimize the degree of irreversible renal injury.) ●Primary nephrotic syndrome. •Anti-glomerular basement membrane (GBM) antibody screening. ●Congenital and infantile nephrotic syndrome (see "Congenital and infantile nephrotic syndrome"). antinuclear antibodies (ANA) and antiDNA antibodies. such as red blood cells and red cell casts (picture 1 and picture 2A-B). which is rare in children. ●Secondary nephrotic syndrome. and a rising serum creatinine.) The diagnostic evaluation of children with only nephrotic syndrome is discussed separately. (See "Pathogenesis and diagnosis of anti-GBM antibody (Goodpasture's) disease". and cellular casts). and antineutrophil cytoplasmic antibodies (ANCA). early diagnosis with renal biopsy and serologic testing. especially in a child with concurrent pulmonary symptoms.) ●Children with nephritic syndrome typically will present with edema. clinical manifestations.) Nephrotic syndrome — Nephrotic syndrome in children is classified into three categories. and diagnosis of nephrotic syndrome in children".) . and/or predict renal outcome.) Renal biopsy — A renal biopsy is performed to confirm a diagnosis. rate of protein excretion. determine the extent of renal injury. which refers to nephrotic syndrome in the presence of an identifiable systemic disease. an inactive urine sediment (ie. section on 'Rapidly progressive GN' and "Overview of the classification and treatment of rapidly progressive (crescentic) glomerulonephritis". clinical manifestations. (See "Etiology. (See 'Further evaluation' above. The evaluation of these patients is the same as that of a child with glomerulonephritis alone.) SUMMARY AND RECOMMENDATIONS — Numerous primary (renal disease alone) and secondary (eg. section on 'Diagnosis'. section on 'Diagnosis'. (See "Etiology. The timing of a renal biopsy is dependent upon the clinical setting. reddish brown to brown colored urine. and diagnosis of nephrotic syndrome in children". hypertension. both primary and secondary nephrotic syndromes include patients with glomerulonephritis. urinalysis. section on 'Diagnosis'. determine the extent of renal injury. ●The initial evaluation that includes review of the presenting clinical manifestations.) ●Children with isolated nephrotic syndrome typically present only with edema. may be helpful in diagnosing anti-glomerular basement membrane disease. The timing of a renal biopsy is dependent upon the clinical setting. systemic autoimmune disorders. section on 'Classification and etiology'. clinical manifestations. when there is no gross hematuria. In particular. few or no red blood cells. A renal biopsy is performed to confirm a diagnosis. and renal function can be used to guide the evaluation process to identify the underlying renal condition. (See "Overview of the pathogenesis and causes of glomerulonephritis in children". (See "Etiology. (See 'Glomerulonephritis' above. (See 'Initial evaluation' above. Patients generally have proteinuria greater than 100 mg/m2 per day. and diagnosis of nephrotic syndrome in children". Urinalysis findings include evidence of glomerular bleeding. complement studies. whereas idiopathic nephrotic syndrome does not typically have an inflammatory component. which refers to nephrotic syndrome in the absence of an identifiable systemic disease. In patients with rapidly progressive glomerulonephritis. because many of the glomerulonephritides also present with nephrotic syndrome. or infection) disorders produce glomerular disease in children (table 1). vasculitis. who have an active sediment and glomerular inflammation on renal biopsy.) ●Further evaluation of children with nephritic syndrome includes serologic testing for a recent streptococcal infection. The diagnostic evaluation of children with nephrotic syndrome is presented separately. (See 'Glomerulonephritis' above.) ●Children with both nephritic and nephrotic syndromes are evaluated in a similar manner to those with nephritic syndrome. defined as a urinary protein excretion greater than 50 mg/kg per day or 40 mg/m2 per hour. and/or predict renal outcome. (See 'Initial evaluation' above and "Overview of the pathogenesis and causes of glomerulonephritis in children".