Glomerulonephrosis

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Glomerulonephrosis
Specialty Nephrology

Glomerulonephrosis is a non-inflammatory disease of the kidney (nephrosis) presenting primarily in the glomerulus (a glomerulopathy) as nephrotic syndrome. The nephron is the functional unit of the kidney and it contains the glomerulus, which acts as a filter for blood to retain proteins and blood lipids. Damage to these filtration units results in important blood contents being released as waste in urine. This disease can be characterized by symptoms such as fatigue, swelling, and foamy urine, and can lead to chronic kidney disease and ultimately end-stage renal disease, as well as cardiovascular diseases. [1] Glomerulonephrosis can present as either primary glomerulonephrosis or secondary glomerulonephrosis.

Contents

It can be contrasted to glomerulonephritis, which implies inflammation.

Signs and symptoms

Peripheral edema of the lower extremity (left leg) as a result of fluid leaking into the interstitium. Leg Edema 02.jpg
Peripheral edema of the lower extremity (left leg) as a result of fluid leaking into the interstitium.

The primary sign of glomerulonephrosis is proteinuria, [2] the loss of greater than 3.5g of protein in one day, and this can cause the urine to be visibly foamy. One key protein lost in proteinuria can be albumin, a crucial transport protein found in plasma. [3] Proteinuria will lead to other symptoms including swelling known as edema, primarily in the legs, and can eventually progress to generalized edema throughout the body in chronic kidney damage, known as anasarca. In primary stages of glomerulonephrosis, edema will be most visible in the feet and ankles, especially for individuals who spend long amounts of time on their feet. This is due to fluid being pulled down within the body by gravity.[ citation needed ]

Other symptoms include: [4] [5]

Causes

A diagram illustrating the changes in a podocyte in minimal change disease. Minimal Change Disease Pathology Diagram.svg
A diagram illustrating the changes in a podocyte in minimal change disease.

Rather than solely being caused by other diseases or processes, glomerulonephrosis can also present as a result of protein conditions or mutations that cause damage. As a result, it can have primary causes that are a direct result of mutation, or secondary causes such as other chronic conditions.[ citation needed ]

Primary glomerulonephrosis

Secondary glomerulonephrosis

Other forms of secondary glomerulonephrosis can be caused by autoimmune disorders such as HIV, Sjögren's Syndrome, and hepatitis B, and some cancers, including multiple myeloma. [10]

Mechanism

A normal podocyte without damage. 2613 Podocytes.jpg
A normal podocyte without damage.

Podocytes are specialized cells that make up parts of the lining of the glomerulus that normally help prevent protein loss. In glomerulonephrosis, these cells are damaged, which allows proteins to pass through glomerular filtration and be lost in urine (proteinuria). Immunoglobulins, proteins of the immune system, can also be lost due to proteinuria, thus weakening the immune system and making the body more prone to infection. The decreased number of proteins triggers the liver to produce greater numbers of proteins and cholesterol. The increase in cholesterol production leads to hypercholesterolemia, which can lead to cardiovascular issues. Despite the liver’s overproduction of proteins, they will still be filtered into urine. A decreased amount of proteins in the blood vessels will reduce the total plasma oncotic pressure. This pressure results from water, electrolytes, proteins, and other substrates interacting in the blood vessels, but the loss of protein reduces the number of interactions, thus reducing the total pressure. Decreased pressure will cause water and electrolytes to move into the surrounding interstitium, the space that separates internal structures of the body and skin, leading to swelling (peripheral edema). The leakage of water into peripheral structures decreases the total fluid volume in circulation, which will activate the Renin-Angiotensin-Aldosterone system. This system increases blood pressure by retaining sodium, which retains water. However, water will continue to be lost as edema because glomerulonephrosis will continue to cause proteinuria, and prolonged activation of the Renin-Angiotensin-Aldosterone system will cause blood pressure to remain elevated and cause hypertension.[ citation needed ]

Diagnosis

Due to its close connection with other diseases and disorders, glomerulonephrosis is rarely diagnosed independently and is superseded by those other conditions. The primary test to diagnose a form of glomerulonephrosis is a urinalysis to look for any proteinuria. [1] This is a very important step as an otherwise healthy individual will have low protein levels in the urine. A comprehensive metabolic panel (CMP) is also often used to test for hypoalbuminemia, levels of albumin lower than ≤2.5 g/dL. This is a key step in differentiating glomerulonephrosis from conditions that also cause proteinuria, such as multiple myeloma and diabetes mellitus, that are not marked by hypoalbuminemia. A creatinine clearanceCR test will also be used to determine the glomerular filtration rate (GFR), or the rate at which blood flows through the glomerulus. Creatinine is a byproduct of creatine metabolism that will be released as waste in urine, so it is a good benchmark for estimating how much fluid is being filtered through the glomerulus. To differentiate it from glomerulonephritis, microscopy may be used to examine a urinary cast, which is caused by inflammation. In cases involving Minimal Change Disease, an electron microscope [12] can be used to visualize changes in podocyte structure. Additional tests such as a kidney biopsy, lipid profile, ultrasound, and electrolyte, urea, creatinine (EUC) tests can also be performed, but these evaluate overall kidney function rather than the glomerulus specifically. [ citation needed ]

The degree to which an electron microscope can visualize cells. This device is instrumental in diagnosing minimal change disease to view lesions in the glomeruli. Scanning electron microscopy (SEM) of echinocytes.png
The degree to which an electron microscope can visualize cells. This device is instrumental in diagnosing minimal change disease to view lesions in the glomeruli.

Treatment

Treatment of glomerulonephrosis involves treatment of both symptoms and the glomerulus itself. A majority of complications of this condition result from edema, proteinuria, hypercholesterolemia, and hypoalbuminemia so it is important to correct these imbalances.

Symptomatic treatment

Depending on the severity of edema, treatment will vary. Fluid can be managed through rest to counteract the effects of gravity that would otherwise cause it to settle into the legs and feet. Individuals may also need to undergo medical nutrition therapy to make dietary changes and counteract the loss of protein. Similarly to individuals with chronic kidney disease, this diet should consist of an increase the amount of protein consumed while limiting the amount of sodium and fat intake. A balanced nutritional intake can help prevent glomerulonephrosis in some cases, but cannot prevent those with a genetic cause. [13] This type of diet will also assist in counteracting hypoalbuminemia and hypercholesterolemia. In more severe cases of edema, diuretic medications may be used. These medications promote the production of urine and help remove some of the excess fluid in the interstitium. [14]

Glomerular damage treatment

The progressive damage of the glomerulus can be prevented, and in some cases reversed, with the use of corticosteroids, a class of hormonal steroids used as medication. [15] Adults with a new onset of glomerulonephrosis can be treated with prednisone. In children with Minimal Change Disease and adults relapsing into glomerulonephrosis, prednisolone is commonly used until proteinuria is no longer present, but children have a much quicker remission than adults and are less prone to relapse. [16] Direct treatment of proteinuria is the goal of corticosteroid use as this is the primary issue causing other symptoms. In severe cases where the condition has progressed to chronic kidney disease, kidney transplantation will be ultimately be required.[ citation needed ]

Prognosis

Depending on the cause/type of glomerulonephrosis, especially in the case of secondary forms, there may be an array of treatments that may be required and some may be untreatable. In Minimal Change Disease, children usually recover due to their positive response to corticosteroid use. In other forms, such as Focal Segmental Sclerosis, the progression to kidney disease is very common and individuals will inevitably require kidney transplant. If left untreated completely, glomerulonephrosis will almost always develop into nephrotic syndrome and eventually kidney failure within months. [16] Kidney failure severely affects other bodily systems including the cardiovascular system in the forms of atherosclerosis, coronary artery disease, heart failure, stroke, and peripheral artery disease. [17]

Epidemiology

Primary forms of glomerulonephrosis can occur at any age, although it is found in adults more commonly than children. The most common cause of glomerulonephrosis in children is Minimal Change Disease where they make up a majority of cases. There are 10-50 cases per 100,000 children, with male cases being twice as common as female cases. [16] In adults, the opposite is true with Focal Segmental Glomerulosclerosis being the more common. This form is found to be 1.5 times more common in men than women, and some studies suggest that it is found in higher incidences in Blacks than Whites and Hispanics. [18]

Research directions

Due to the connection between glomerulonephrosis and other renal conditions, and its presentation as nephrotic syndrome, a majority of the research is focused on these other causes and the effects of drugs. One recent study of the effect of a drug, silymarin, on kidney tissue of rats with cadmium toxicity found that rats in the cadmium had incidences of glomerulonephrosis, making cadmium a potential cause. Another recent study in rats that investigated the effect of high doses of metformin with the SIRT1 activator, SRT1720, showed high cases of glomerulonephrosis and death. [19] Studies such as this allow for improved clinical practices in renal patients and help physicians make informed decision on the combinations of medications used to prevent glomerulonephrosis.

Related Research Articles

<span class="mw-page-title-main">Kidney</span> Organ that filters blood and produces urine

In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and right in the retroperitoneal space, and in adult humans are about 12 centimetres in length. They receive blood from the paired renal arteries; blood exits into the paired renal veins. Each kidney is attached to a ureter, a tube that carries excreted urine to the bladder.

<span class="mw-page-title-main">Proteinuria</span> Presence of an excess of serum proteins in the urine

Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy. Severe proteinuria can cause nephrotic syndrome in which there is worsening swelling of the body.

<span class="mw-page-title-main">Nephrotic syndrome</span> Collection of symptoms due to kidney damage

Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy urine. Complications may include blood clots, infections, and high blood pressure.

<span class="mw-page-title-main">Kidney failure</span> Disease where the kidneys fail to adequately filter waste products from the blood

Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as either acute kidney failure, which develops rapidly and may resolve; and chronic kidney failure, which develops slowly and can often be irreversible. Symptoms may include leg swelling, feeling tired, vomiting, loss of appetite, and confusion. Complications of acute and chronic failure include uremia, hyperkalaemia, and volume overload. Complications of chronic failure also include heart disease, high blood pressure, and anaemia.

<span class="mw-page-title-main">Assessment of kidney function</span> Ways of assessing the function of the kidneys

Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging.

<span class="mw-page-title-main">Podocyte</span> Type of kidney cell

Podocytes are cells in Bowman's capsule in the kidneys that wrap around capillaries of the glomerulus. Podocytes make up the epithelial lining of Bowman's capsule, the third layer through which filtration of blood takes place. Bowman's capsule filters the blood, retaining large molecules such as proteins while smaller molecules such as water, salts, and sugars are filtered as the first step in the formation of urine. Although various viscera have epithelial layers, the name visceral epithelial cells usually refers specifically to podocytes, which are specialized epithelial cells that reside in the visceral layer of the capsule. One type of specialized epithelial cell is podocalyxin.

<span class="mw-page-title-main">Glomerulonephritis</span> Term for several kidney diseases

Glomerulonephritis (GN) is a term used to refer to several kidney diseases. Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.

<span class="mw-page-title-main">Diabetic nephropathy</span> Chronic loss of kidney function

Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease (ESRD) globally. The triad of protein leaking into the urine, rising blood pressure with hypertension and then falling renal function is common to many forms of CKD. Protein loss in the urine due to damage of the glomeruli may become massive, and cause a low serum albumin with resulting generalized body swelling (edema) so called nephrotic syndrome. Likewise, the estimated glomerular filtration rate (eGFR) may progressively fall from a normal of over 90 ml/min/1.73m2 to less than 15, at which point the patient is said to have end-stage renal disease. It usually is slowly progressive over years.

<span class="mw-page-title-main">Membranous glomerulonephritis</span> Medical condition

Membranous glomerulonephritis (MGN) is a slowly progressive disease of the kidney affecting mostly people between ages of 30 and 50 years, usually white people.

<span class="mw-page-title-main">Minimal change disease</span> Medical condition

Minimal change disease is a disease affecting the kidneys which causes nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein in the urine, which causes the widespread edema and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 6 years of age. MCD is responsible for 10–25% of nephrotic syndrome cases in adults. It is also the most common cause of nephrotic syndrome of unclear cause (idiopathic) in children.

<span class="mw-page-title-main">Nephritic syndrome</span> Medical condition

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. By contrast, nephrotic syndrome is characterized by proteinuria and a constellation of other symptoms that specifically do not include hematuria. 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.

<span class="mw-page-title-main">Focal segmental glomerulosclerosis</span> Kidney disease

Focal segmental glomerulosclerosis (FSGS) is a histopathologic finding of scarring (sclerosis) of glomeruli and damage to renal podocytes. This process damages the filtration function of the kidney, resulting in protein presence in the urine due to protein loss. FSGS is a leading cause of excess protein loss—nephrotic syndrome—in children and adults. Signs and symptoms include proteinuria and edema. Kidney failure is a common long-term complication of the disease. FSGS can be classified as primary, secondary, or genetic, depending on whether a particular toxic or pathologic stressor or genetic predisposition can be identified as the cause. Diagnosis is established by renal biopsy, and treatment consists of glucocorticoids and other immune-modulatory drugs. Response to therapy is variable, with a significant portion of patients progressing to end-stage kidney failure. An American epidemiological study 20 years ago demonstrated that FSGS is estimated to occur in 7 persons per million, with males and African-Americans at higher risk.

<span class="mw-page-title-main">Renal vein thrombosis</span> Medical condition

Renal vein thrombosis (RVT) is the formation of a clot in the vein that drains blood from the kidneys, ultimately leading to a reduction in the drainage of one or both kidneys and the possible migration of the clot to other parts of the body. First described by German pathologist Friedrich Daniel von Recklinghausen in 1861, RVT most commonly affects two subpopulations: newly born infants with blood clotting abnormalities or dehydration and adults with nephrotic syndrome.

<span class="mw-page-title-main">Hypoalbuminemia</span> Medical condition

Hypoalbuminemia is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or abnormal distribution between body compartments. Patients often present with hypoalbuminemia as a result of another disease process such as malnutrition as a result of severe anorexia nervosa, sepsis, cirrhosis in the liver, nephrotic syndrome in the kidneys, or protein-losing enteropathy in the gastrointestinal tract. One of the roles of albumin is being the major driver of oncotic pressure in the bloodstream and the body. Thus, hypoalbuminemia leads to abnormal distributions of fluids within the body and its compartments. As a result, associated symptoms include edema in the lower legs, ascites in the abdomen, and effusions around internal organs. Laboratory tests aimed at assessing liver function diagnose hypoalbuminemia. Once identified, it is a poor prognostic indicator for patients with a variety of different diseases. Yet, it is only treated in very specific indications in patients with cirrhosis and nephrotic syndrome. Treatment instead focuses on the underlying cause of the hypoalbuminemia. Albumin is an acute negative phase respondent and not a reliable indicator of nutrition status.

<span class="mw-page-title-main">Acute proliferative glomerulonephritis</span> Medical condition

Acute proliferative glomerulonephritis is a disorder of the small blood vessels of the kidney. It is a common complication of bacterial infections, typically skin infection by Streptococcus bacteria types 12, 4 and 1 (impetigo) but also after streptococcal pharyngitis, for which it is also known as postinfectious glomerulonephritis (PIGN) or poststreptococcal glomerulonephritis (PSGN). It can be a risk factor for future albuminuria. In adults, the signs and symptoms of infection may still be present at the time when the kidney problems develop, and the terms infection-related glomerulonephritis or bacterial infection-related glomerulonephritis are also used. Acute glomerulonephritis resulted in 19,000 deaths in 2013, down from 24,000 deaths in 1990 worldwide.

Congenital nephrotic syndrome is a rare kidney disease which manifests in infants during the first 3 months of life, and is characterized by high levels of protein in the urine (proteinuria), low levels of protein in the blood, and swelling. This disease is primarily caused by genetic mutations which result in damage to components of the glomerular filtration barrier and allow for leakage of plasma proteins into the urinary space.

<span class="mw-page-title-main">Glomerular basement membrane</span>

The glomerular basement membrane of the kidney is the basal lamina layer of the glomerulus. The glomerular endothelial cells, the glomerular basement membrane, and the filtration slits between the podocytes perform the filtration function of the glomerulus, separating the blood in the capillaries from the filtrate that forms in Bowman's capsule. The glomerular basement membrane is a fusion of the endothelial cell and podocyte basal laminas, and is the main site of restriction of water flow. Glomerular basement membrane is secreted and maintained by podocyte cells.

Podocin is a protein component of the filtration slits of podocytes. Glomerular capillary endothelial cells, the glomerular basement membrane and the filtration slits function as the filtration barrier of the kidney glomerulus. Mutations in the podocin gene NPHS2 can cause nephrotic syndrome, such as focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Symptoms may develop in the first few months of life or later in childhood.

Diffuse proliferative glomerulonephritis (DPGN) is a type of glomerulonephritis that is the most serious form of renal lesions in SLE and is also the most common, occurring in 35% to 60% of patients. In absence of SLE, DPGN pathology looks more like Membranoproliferative glomerulonephritis

Sickle cell nephropathy is a type of nephropathy associated with sickle cell disease which causes kidney complications as a result of sickling of red blood cells in the small blood vessels. The hypertonic and relatively hypoxic environment of the renal medulla, coupled with the slow blood flow in the vasa recta, favors sickling of red blood cells, with resultant local infarction. Functional tubule defects in patients with sickle cell disease are likely the result of partial ischemic injury to the renal tubules.

References

  1. 1 2 "Nephrosis (Nephrotic Syndrome)". Cancer Therapy Advisor. 2019-01-17. Retrieved 2020-12-17.
  2. ↑ Gansevoort RT, Navis GJ, Wapstra FH, de Jong PE, de Zeeuw D. Proteinuria and progression of renal disease: therapeutic implications. Current Opinion in Nephrology and Hypertension. 1997 Mar;6(2):133-140. DOI: 10.1097/00041552-199703000-00005.
  3. ↑ Wiedermann, Christian J; Wiedermann, Wolfgang; Joannidis, Michael (2017-07-06). "Causal relationship between hypoalbuminemia and acute kidney injury". World Journal of Nephrology. 6 (4): 176–187. doi: 10.5527/wjn.v6.i4.176 . ISSN   2220-6124. PMC   5500455 . PMID   28729966.
  4. ↑ "Nephrotic Syndrome in Adults | NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 2020-12-16.
  5. ↑ "Hyperlipidemia Symptoms and Treatment | UPMC". UPMC Heart and Vascular Institute. Retrieved 2020-12-16.
  6. ↑ Vivarelli, Marina; Massella, Laura; Ruggiero, Barbara; Emma, Francesco (2017-02-07). "Minimal Change Disease". Clinical Journal of the American Society of Nephrology. 12 (2): 332–345. doi: 10.2215/CJN.05000516 . ISSN   1555-9041. PMC   5293332 . PMID   27940460.
  7. ↑ "Focal segmental glomerulosclerosis (FSGS) - Symptoms and causes". Mayo Clinic. Retrieved 2020-12-17.
  8. ↑ "Lupus and Kidney Disease (Lupus Nephritis) | NIDDK". National Institute of Diabetes and Digestive and Kidney Diseases. Retrieved 2020-12-17.
  9. ↑ Ghafoor, Azam; Almakki, Akram (2014). "Renal confined sarcoidosis: Natural history and diagnostic challenge". Avicenna Journal of Medicine. 4 (2): 44–47. doi: 10.4103/2231-0770.130346 . ISSN   2231-0770. PMC   3994709 . PMID   24761384.
  10. 1 2 "Nephrotic syndrome - Symptoms and causes". Mayo Clinic. Retrieved 2020-12-17.
  11. ↑ "AL Amyloidosis". UNC Kidney Center. Retrieved 2020-12-17.
  12. ↑ "Minimal change disease". www.kidneypathology.com. Retrieved 2020-12-16.
  13. ↑ "Renal Diet: Sodium, Potassium, Phosphorus Intake & Foods to Avoid". Cleveland Clinic. Retrieved 2020-12-17.
  14. ↑ Ellison, David H. (2019-08-07). "Clinical Pharmacology in Diuretic Use". Clinical Journal of the American Society of Nephrology. 14 (8): 1248–1257. doi: 10.2215/CJN.09630818 . ISSN   1555-9041. PMC   6682831 . PMID   30936153.
  15. ↑ Hahn, Deirdre; Hodson, Elisabeth M; Willis, Narelle S; Craig, Jonathan C (2015-03-18). "Corticosteroid therapy for nephrotic syndrome in children". The Cochrane Database of Systematic Reviews. 2015 (3): CD001533. doi:10.1002/14651858.CD001533.pub5. ISSN   1469-493X. PMC   7025788 . PMID   25785660.
  16. 1 2 3 Vivarelli, Marina; Massella, Laura; Ruggiero, Barbara; Emma, Francesco (2017-02-07). "Minimal Change Disease". Clinical Journal of the American Society of Nephrology. 12 (2): 332–345. doi:10.2215/CJN.05000516. ISSN   1555-9041. PMC   5293332 . PMID   27940460.
  17. ↑ Vallianou, Natalia G.; Mitesh, Shah; Gkogkou, Agathoniki; Geladari, Eleni (February 2019). "Chronic Kidney Disease and Cardiovascular Disease: Is there Any Relationship?". Current Cardiology Reviews. 15 (1): 55–63. doi:10.2174/1573403X14666180711124825. ISSN   1573-403X. PMC   6367692 . PMID   29992892.
  18. ↑ "UpToDate". www.uptodate.com. Retrieved 2020-12-17.
  19. ↑ Palliyaguru, Dushani L.; Minor, Robin K.; Mitchell, Sarah J.; Palacios, Hector H.; Licata, Jordan J.; Ward, Theresa M.; Abulwerdi, Gelareh; Elliott, Peter; Westphal, Christoph; Ellis, James L.; Sinclair, David A. (2020-10-15). "Combining a High Dose of Metformin With the SIRT1 Activator, SRT1720, Reduces Life Span in Aged Mice Fed a High-Fat Diet". The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. 75 (11): 2037–2041. doi: 10.1093/gerona/glaa148 . ISSN   1758-535X. PMC   7750506 . PMID   32556267.
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