Nephritic syndrome

Nephritic syndrome is a syndrome comprising signs of nephritis, which is kidney disease involving inflammation. It often occurs in the glomerulus, where it is called glomerulonephritis. Glomerulonephritis is characterized by inflammation and thinning of the glomerular basement membrane and the occurrence of small pores in the podocytes of the glomerulus. These pores become large enough to permit both proteins and red blood cells to pass into the urine (yielding proteinuria and hematuria, respectively). By contrast, nephrotic syndrome is characterized by proteinuria and a constellation of other symptoms that specifically do not include hematuria.[6] Nephritic syndrome, like nephrotic syndrome, may involve low level of albumin in the blood due to the protein albumin moving from the blood to the urine.[7]

Nephritic syndrome
Other namesAcute nephritic syndrome[1]
Hematuria (one of the symptoms of Nephritic syndrome)
SpecialtyNephrology 
SymptomsOliguria[2]
CausesInfectious, autoimmune, or thrombotic[3]
Diagnostic methodUrinalysis, kidney biopsy[4]
TreatmentAntihypertensives[5]
Anatomical Kidney with graphical representation of position

Signs and symptoms

Historically, nephritic syndrome has been characterized by blood in the urine (hematuria), high blood pressure (hypertension), decreased urine output <400 ml/day (oliguria), red blood cell casts, pyuria, and mild to moderate proteinuria.[8][9] If the condition is allowed to progress without treatment, it can eventually lead to azotemia and uremic symptoms.[9] This constellation of symptoms contrasts with the classical presentation of nephrotic syndrome (excessive proteinuria >3.5 g/day, low plasma albumin levels (hypoalbuminemia) <3 g/L, generalized edema, and hyperlipidemia).[8][10]

Signs and symptoms that are consistent with nephritic syndrome include:

Causes

Purpura

Nephritic syndrome is caused by extensive inflammatory damage to the glomerulus capillaries, which is associated with a variety of medical conditions that we will discuss. Furthermore, the cause of this inflammation can be infectious, autoimmune, or thrombotic.[3] The causative conditions can be divided conveniently between age groups as follows, though it is important to note that many of the conditions listed in children/adolescents can also occur in adults with lower frequency, and vice versa:[4]

Children/adolescents

Adults

Pathophysiology

The pathophysiology of nephritic syndrome is dependent on the underlying disease process, which can vary depending on what condition the nephritic syndrome is secondary to. More specifically, different diseases (many of which are mentioned above in the Causes section) affect different segments of the glomerulus and cause disease-specific segments of the glomerulus to become inflamed. Most often, it is dependent on what part of the glomerulus is damaged by antibody-antigen complex (immune complex) deposition.[9] In all cases, however, the inflammatory processes in the glomerulus cause the capillaries to swell and the pores between podocytes become large enough that inappropriate contents in the blood plasma (i.e. red blood cells, protein, etc.) will begin to spill into the urine. This causes a decrease in glomerular filtration rate (GFR) and, if left untreated over time, will eventually produce uremic symptoms and retention of sodium and water in the body, leading to both edema and hypertension.[9]

Diagnosis

The diagnostic approach to nephritic syndrome includes evaluating the patient for any suspected underlying pathology that could cause a nephritic syndrome.

Physical examination

If the person in the office is being examined by a physician, some physical exam findings consistent with nephritic syndrome include the following:

Laboratory testing

If the physician is suspicious of a possible nephritic syndrome, then he/she may order some common lab tests including:

  • Serum electrolytes - The kidney is one of the main regulators of electrolytes in the human body and measuring the different electrolyte levels using either a basic metabolic panel (BMP) or comprehensive metabolic panel (CMP) can be a useful indicator of the underlying pathology.[30]
  • Serum creatinine - Also measured using a BMP or CMP, creatinine is one of the most important indicators of current kidney function and is used to calculate the glomerular filtration rate (GFR). An elevated creatinine level is considered abnormal and may indicate decreased kidney function.[31]
  • Blood urea nitrogen (BUN) - Also measured using a BMP or CMP, blood urea nitrogen is an indicator of how much nitrogen is in the blood at the time of the phlebotomy. The kidney is responsible for excreting nitrogenous substances in the urine, so an elevated BUN usually indicates that the kidney is not functioning appropriately.[32]
  • Urine Analysis (Urinalysis) - After the patient provides a urine specimen, it is sent to the lab for analysis using a variety of methods including urine dipstick testing and microscopic examination. Because the kidney is responsible for making urine, analyzing the urine directly can provide crucial data that can help the physician diagnose nephritic syndrome.[33] Some findings on urinalysis that are consistent with nephritic syndrome include red blood cells (hematuria), red blood cell casts, proteinuria, and possibly white blood cells (pyuria).[9]

If nephritic syndrome is identified and diagnosed, then it is important for the physician to determine the underlying cause. To do this, he/she may order any of a large variety of relevant lab tests, some of which are included here:

Invasive testing

A kidney biopsy will provide a fully definitive diagnosis of nephritic syndrome and may also reveal the underlying cause of the nephritic syndrome depending on the underlying pathological process. On biopsy, a patient with nephritic syndrome would show inflammation of numerous glomeruli.[37]

Treatment

When a patient is confirmed to have nephritic syndrome, the main goal of treatment (regardless of the underlying cause) is to control elevated blood pressures and reduce active inflammation in the kidney itself.[4] Most often, the patient will need to be admitted to the hospital for close monitoring to ensure the efficacy of treatment and make adjustments as needed. Some treatment modalities commonly used to meet these goals include:

Once the acute phase of the nephritic syndrome is controlled, it is crucial to determine the underlying pathology that caused the onset of the acute nephritic syndrome and to treat that condition. If the underlying cause is not determined and treated appropriately, it increases the risk of a recurrence of nephritic syndrome or chronic kidney disease (CKD) in the future.[4]

Prognosis

Because nephritic syndrome is a syndrome and not a disease, the prognosis depends on the underlying cause. Generally, the prognosis of nephritic syndrome in children is better than it is in adults.[5]

Epidemiology

According to the CDC, nephritis/nephrosis/nephritic syndrome was the 9th leading cause of death in the United States in 2017.[45] It was listed as the cause of death for 50,633 out of the total 2,813,503 deaths reported in 2017.[45]

Geography

The southeast region of the United States reported a significantly higher death rate due to kidney disease than any other region in 2017. Mississippi reported the highest death rate due to kidney disease (21.7), followed by Louisiana (20.6) and Arkansas (19.7).[46] Although Vermont reported the lowest death rate due to kidney disease (3.3), the western United States reported the lowest regional average death rate due to kidney disease in 2017.[46]

Gender

Out of the 1,374,392 female deaths reported in the US in 2017, kidney disease was listed as the cause of death for 24,889 women and was reported as the 9th overall cause of death for women in 2017.[45]

Out of the 1,439,111 male deaths reported in the US in 2017, kidney disease was not listed in the top 10 causes of death.[45]

Race and ethnicity

Out of the 2,378,385 deaths reported in individuals who identified as White, kidney disease was ranked 10th overall (39,105 deaths) in causes of death in the US in 2017.[45]

Out of the 340,644 deaths reported in individuals who identified as Black or African American, kidney disease was ranked 8th overall (9,609 deaths) in causes of death in the US in 2017.[45]

Out of the 74,094 deaths reported in individuals who identified as Asian or Pacific Islander, kidney disease was ranked 9th overall (1,563 deaths) in causes of death in the US in 2017.[45]

Out of the 197,249 deaths reported in individuals who identified as Hispanic or Latino, kidney disease was ranked 10th overall (3,928 deaths) in causes of death in the US 2017.[45]

Other countries of world

In a review of Romanian cases, a 10-year review yielded that upon biopsy, nephritic syndrome was the second most common clinical syndrome at 21.9% (nephrotic syndrome was 52.3%)[47]

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Further reading

  • Crutchlow, Eileen M.; Dudac, Pamela J.; MacAvoy, Suzanne; Madara, Bernadette R. (2002-01-01). Pathophysiology. Jones & Bartlett Learning. ISBN 9781556425653.
  • Schrier, Robert W. (2014-05-13). Manual of Nephrology. Lippincott Williams & Wilkins. ISBN 9781469887364.
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