Sandbox:Nephritic syndrome

# Overview
Nephritic syndrome is defined as the inflammation of the renal glomeruli. It is characterized by the presence of glomerular microscopic or gross hematuria with active sedimentation of dysmorphic red blood cells in the urine. Due to renal involvement, the syndrome includes a reduced glomerular filtration rate (GFR), oliguria, azotemia, high blood pressure, and edema.  Unlike nephrotic syndrome, proteinuria in nephritic syndrome is not very significant, although frequently present nonetheless. Nephrotic and nephritic syndromes can both still occur concomitantly.

# Historical Perspective
The symptoms of glomerulonephritis were first described by Richard Bright in 1827 when he discovered that several patients died with generalized edema were found to have renal disease. It was not until 1914 that Volhard and Fahr classified renal diseases in Die Brightsche Nierenkrankheit to 3 main categories: nephroses, nephritis, and arteriosclerotic disease.  Acute post-streptococcal glomerulonephritis is thus considered the earliest nephritic syndrome to be described. In 1908, C.F. Wahrer described an epidemic of hemorrhagic nephritis preceded by scarlet fever in 35 patients. Epidemics of nephritis continued in 1915 among British troops during World War I. Clinical and pathological findings from both epidemics were similar. Hemolytic streptococci were isolated from cultures of the oropharynx in many patients.

# Classification
Acute nephritic syndrome can be classified according to the etiology of the underlying disease (renal vs. non-renal etiology). Similarly, acute nephritis may be classified as idiopathic vs. secondary to other conditions. Finally, diseases may be classified according to the proliferative vs. non-proliferative changes seen on pathology.

# Pathophysiology
It is believed that glomerular inflammation requires the activation of both the humoral and the cell-mediated immune system.  Various glomerular disease have different pathophysiology, but the final cellular changes, immunological activation, and renal scarring are shared outcomes.

# Causes
Causes of nephritic syndrome vary by age.  Causes of nephritic syndrome include post-infectious glomerulonephritis, IgA nephropathy (Berger disease), thin basement membrane disease, and rapidly progressive glomerulonephritis.

# Differential Diagnosis
The clinical differentiation between nephritic and nephrotic syndromes is crucial to establish the proper differential diagnosis and determine the appropriate management. In addition, the clinical history and prognosis of nephritic syndrome is different from that of nephrotic syndrome.

# Epidemiology and Demographics
Approximately 25% of patients with acute glomerulonephritis present with nephritic syndrome.  Acute glomerulonephritis accounts for 10-15% of glomerular diseases in the USA.  The reported incidence of glomerulonephritis in adults varies between 0.2 to 2.5/100,000 annually with a male to female ratio reaching 2 to 1. The most common cause of glomerulonephritis worldwide is IgA nephropathy (Berger disease). Approximately 25-30% of patients eventually develop end-stage renal disease (ESRD). The yearly variation of incidence of glomerulonephritis is not validated. While some studies report a decrease in the incidence due to improved healthcare and socioeconomic status, others report an increase in the reported incidence due to increased number of biopsies. Additionally, the true incidence is difficult to predict because the disease might present subclinically.

# Natural History, Complications, and Prognosis
Prognosis, complications, and outcome depend on the underlying etiology. Generally, nephritic syndrome is characterized by an abrupt onset. The course of the disease varies greatly.

# Diagnosis

## History and Symptoms
Symptoms of nephritic syndrome include change in the urine color, decreased urine output, nocturia, and fatigue.  In patients with secondary etiologies of glomerular diseases, clinical presentation might be consistent with the etiology of the disease. Patients must always be inquired about recent illnesses, symptoms of vasculitides or other organ involvement, and constitutional symptoms.

## Physical Examination
The physical examination of patients with nephritic syndrome due to a primary glomerular disease is usually not very remarkable.  Nonetheless, a few signs on physical exam might still be present such as high blood pressure in a minority of patients and signs of fluid overload (peripheral or periorbital edema, pulmonary edema, ascites, and jugular venous distention).  A full physical examination is required when patients present with nephritic syndrome in search for causes of secondary glomerular pathology.

## Laboratory Findings
Laboratory work-up must be directed to first identify the exact diagnosis of nephritic syndrome by ruling out common etiologies, and to monitor disease progression and renal function. Work-up might be different from one individual to another based on the patient's presentation and medical history and physical examination findings.

## Renal Biopsy
A renal biopsy may be helpful to differentiate etiologies of renal disease, monitor disease progression, and estimate prognosis.  Not all cases of nephritic syndrome require renal biopsy. The procedure itself is invasive and may be associated with its own risks. As such, renal biopsy is only indicated if benefit will outweigh the risks. Renal biopsies for patients with initial presentation of nephritic syndrome may be affected greatly by age, progression of symptoms, clinical suspicion, and response to empirical therapy.

## Echocardiography or Ultrasound
Renal ultrasound is useful to estimate the kidney size and echogenicity. Decreased renal size (eg. less than 8 cm) is consistent with irreversible renal injury.  Echocardiography is indicated when a cardiac murmur is noted on physical examination or when there is a high suspicion of bacterial endocarditis causing renal involvement and nephritic syndrome.

# Treatment

## Medical Therapy
Management and therapy vary greatly according to the diagnosis of nephritic syndrome. While most causes of nephritic syndrome are self-resolving and do not require medical intervention, such as post-infectious streptococcal glomerulonephritis, other etiologies require high doses of steroids and immunotherapy, such as rapidly progressing glomerulonephritis.  In secondary etiologies of nephritic syndrome, management of the underlying disease is the mainstay of the management.