Glomerulonephritis (GN) is not a specific disease, but rather an inflammatory state within the renal glomerulus. This inflammation causes glomerular injury and results in impaired glomerular filtration with subsequent abnormal urinary sediment and possibly decreased renal function. It is often associated with edema and hypertension. Clinically, GN spans a wide spectrum of disease from a fairly benign, self-limited condition to an aggressive systemic disease that can lead to rapid loss of renal function. This chapter focuses on the four common presentations of GN that are most likely to be found in hospitalized patients: asymptomatic hematuria, acute GN, rapidly progressive GN (RPGN), and chronic GN.

PATHOPHYSIOLOGY

The causative mechanism of glomerulonephritis is not entirely understood, but scientific literature supports an immunologic mechanism as the pathogenesis of glomerular inflammation.¹ The triggering of an autoimmune rather than the direct immune response to foreign antigens is likely responsible.^2,3 Humeral and cellular mediated responses as well as a variety of host factors play a role in the development of glomerulonephritis.³

ASYMPTOMATIC HEMATURIA

Asymptomatic hematuria can be either microscopic or macroscopic and is not associated with hypertension, impaired renal function, or proteinuria. Asymptomatic isolated microscopic hematuria, defined as hematuria unaccompanied by proteinuria or pyuria, can be the result of many different conditions other than GN such as fever, gastrointestinal disturbances, and bladder catheterization. Because this presentation may frequently be misdiagnosed as a urinary tract infection, urine culture is imperative. In cases of asymptomatic isolated microscopic hematuria, experts recommend at least two of three urinalyses show microhematuria over 2 to 3 weeks before further evaluation is performed.⁴ Outpatient follow-up is appropriate in these patients. The combination of hematuria, either microscopic or gross, and proteinuria is concerning for possible GN, and diagnostic evaluation is therefore indicated.

ACUTE GLOMERULONEPHRITIS

Acute GN is characterized by an abrupt onset of gross hematuria, azotemia, and hypertension. Proteinuria is common, although it is rarely within the nephrotic range (nephrotic range is >40 mg urinary protein/m²/hr or a urinary protein/creatinine ratio >2.0). Edema is also common and is usually due to renal sodium retention secondary to an abrupt decrease in renal function, not from hypoalbuminemia. Post-infectious glomerulonephritis (PIGN) is caused by an immunologic response of the kidney to infection.⁵ It is the most common cause of acute GN, but rates of PIGN are declining in most industrialized countries.⁵ Post-streptococcal glomerulonephritis (PSGN) is a common form of PIGN. In its classic form, there is a sudden onset of painless gross hematuria (often described as “tea colored”) 14 to 21 days after a streptococcal infection. Only nephritogenic streptococcal infections cause PSGN, and host and microbial factors determine susceptibility.⁶

PIGN occurs most frequently in children between 4 and 10 years of age. Physical examination often reveals pallor, mild periorbital edema, and hypertension. The latter is the most common reason for hospitalization and can be severe enough to cause hypertensive encephalopathy and seizures. PIGN is a self-limited disease, with normalization of renal function usually occurring within 3 weeks. RPGN and chronic GN can present as acute GN, but the clinical courses of these illnesses are distinctive. In PIGN, renal function and blood pressure should normalize within 4 weeks, serum complement should normalize within 8 weeks, and proteinuria should disappear within 3 months.¹

RAPIDLY PROGRESSIVE GLOMERULONEPHRITIS

RPGN is a clinical syndrome that can be due to a variety of forms of GN. RPGN is characterized by the signs of GN (hematuria, either microscopic or gross, and proteinuria); systemic symptoms such as fever, malaise, fatigue, and anorexia; and rapid deterioration in renal function (Table 112-1). On microscopy, cellular crescents surrounding extensive glomeruli are the pathologic hallmark of RPGN.¹ Although uncommon in children, RPGN can result in end-stage renal failure in up to 50% of afflicted children,^7,8 and if untreated can progress to irreversible renal failure within a number of weeks.⁹ Although RPGN can be the clinical presentation of any form of GN, it is more commonly associated with either immune complex GN (Type II RPGN)¹⁰ or pauci-immune GN (Type III RPGN).^1,10

Immune complex GN consists of a variety of renal diseases characterized by immune complex deposition within the glomeruli, including systemic lupus erythematosus (SLE), membranoproliferative glomerulonephritis (MPGN), and IgA nephropathy. SLE GN presents with systemic signs and symptoms consistent with lupus: arthralgias, joint effusions, fatigue, malaise, leukopenia, anemia, and thrombocytopenia, in addition to hematuria and proteinuria. MPGN and IgA nephropathy tend to be renal-specific diseases, although systemic symptoms are present in patients with RPGN in addition to the findings of GN.

Pauci-immune GN have few or no immune complex deposition, are often antineutrophile cytoplasmic antibody (ANCA) positive, and cause necrotizing crescentic glomerulonephritis.¹¹ ANCA-positive renal vasculitides include microscopic polyangiitis (which presents with systemic signs and symptoms of vasculitis in addition to the renal findings), granulomatosis with polyangiitis (formerly Wegener granulomatosis,¹¹ which presents with pulmonary and/or sinus findings along with kidney disease), and idiopathic crescentic GN (in which the disease process is confined to the kidney).

Anti-glomerular basement antibody nephritis (Anti-GBM) (Type I RPGN)¹⁰ and double-antibody–positive disease (Type IV RPGN)¹⁰ are rare in children. When renal involvement occurs with pulmonary hemorrhage, the disease is referred to as Goodpasture syndrome.¹⁰

CHRONIC GLOMERULONEPHRITIS

Chronic GN can present acutely, but more commonly it presents as persistent hematuria and proteinuria, with or without hypertension or slowly progressive renal failure. Chronic GN can be manifested as isolated renal disease, as is seen with IgA nephropathy, MPGN, and renal vasculitis, or as part of a systemic disease, such as SLE, chronic endocarditis, and Henoch-Schönlein purpura. Hospitalization for chronic GN is relatively unusual, although children with chronic GN may be hospitalized after diagnostic or prognostic renal biopsy.