foreign [Music] syndrome is a collection of signs and symptoms that result from damage to the kidneys and is often confused with nephritic syndrome in nephrotic syndrome there is a substantial amount of protein being lost through the kidneys in the urine defined as more than 3.5 grams per day this leads to hypoalbaminemia a low level of albumin in the blood as albumin is the most abundant protein normally in the blood these two are defining features in nephrotic syndrome nephritic syndrome is different in that there is less proteinuria but also the presence of hematuria and red blood cell or white blood cell casts in the urine hypertension and oligo urea which is a reduced urine output typically between 80 and 400 milliliters per day the functional unit of the kidney is the nephron and normally in the glomerulus of the Nephron there is a specialized membrane that forms the filter made up of a fenestrated endothelium glomerular basement membrane and the food processes of podocytes which are cells that wrap around the capillary giving this additional filtration layer altogether these structures normally act as a filter and prevent large molecules from passing through into the Bowman's capsule and renal tubules they have a net negative charge which may mean that they can repel other negatively charged molecules albumin is negatively charged in nephrotic syndrome there is sufficient injury to these structures to change the permeability and allow albumin and other molecules to pass into the urine leading to hypoalbaminemia the signs and symptoms are linked to hypoalbaminemia which includes peripheral edema and fluid overload particularly in children this can be evident as facial swelling but can also occur in adults particularly around the eyes fluid overload can mean weight gain peripheral edema and even the development of ascites or pleural effusion which can manifest as shortness of breath known as dyspnea the reduction in the blood levels of albumin causes the oncotic pressure of the blood to fall meaning fluid will more readily leak into the surrounding tissues causing edema this is sensed as hypovolemia because less fluid is in the vessels which then triggers the renin Angiotensin aldosterone system causing retention of salt and water this is known as the underfill hypothesis while another is the overfill hypothesis where it is thought that defective renal tubules result in reduced sodium excretion promoting fluid retention hypoalbaminemia also predisposes to hypercoagulability because the liver is stimulated to produce more proteins ultimately leading to an imbalance between pro-coagulant and pro-thrombotic proteins in particular there is a loss of antithrombin 3 through the urine which favors hypercoagulability this can predispose to venous thromboembolisms like DVT and Pulmonary embolism in particular but can also cause arterial thrombosis like myocardial infarction and stroke hyperlipidemia is also a feature the liver is stimulated to produce more proteins and therefore more lipoproteins are also produced however due to the protein deficient State there are less lipoprotein enzymes available and so less enzymes to break down the lipoproteins this hyperlipidemia can manifest xanthelasma which are deposits of cholesterol under the skin most typically around the eyes people can also suffer from recurrent infections due to reduced levels of immunoglobulins and also because edema can act as a site of infection the urine can become frothy or foamy as the higher protein content reduces the surface tension of the urine and it is common to experience a loss of appetite lethargy and tiredness the causes for nephrotic syndrome are divided into primary and secondary where primary means a pathology affecting the kidney directly often idiopathically which means without a clear cause and secondary causes where a condition affecting another part of the body also has an effect on the kidney histological patterns are often used to describe the causes such as minimal change disease which is the most common case in children getting its name because only with an electron microscope do pathological findings become visible it is mostly primary but can be associated with secondary causes such as Hodgkin's lymphoma or the use of non-steroidal anti-inflammatories another is focal segmental glomerulosclerosis characterized by scaring of the glomerulus where focal means some glomeruli and segmental means only parts of the individual glomerulus it can be Primary in nature but it is often linked to a secondary cause like HIV obesity reflux nephropathy and drugs like lithium or bisphosphonates there can be some genetic mutations in genes coding for nephrine a component of the slit diaphragm or laminin 2 a component of the glomerular basement membrane that can also cause this and these are thought to make up 85 percent of steroid resistant nephrotic syndromes in children membranous nephropathy is characterized by thickening of the basement membrane described as having a spike and Dome pattern of immune deposits in the sub-epithelial space most cases are primary while one in three are due to secondary causes like malignancy Hepatitis B or C syphilis autoimmune conditions like lupus and drugs such as penicillamine and again non-steroidal anti-inflammatories another potential cause is diabetic nephropathy which initially begins as a microalbuminuria and in some cases progresses to significant proteinuria and nephrotic syndrome there's also amyloidosis which is the deposition and accumulation of abnormal protein known as amyloid within tissues examples could be amyloid light chain amyloidosis transthereutin amyloidosis which is hereditary and serum amyloid A amyloidosis overall one in two cases are thought to be triggered by infections particularly upper respiratory tract infections and one in three from allergic reactions although any age can be affected it is more common in adults particularly around the age of 40 than it is in children however in children males are affected around twice as commonly as females but this difference seems to even out after adolescence the prognosis depends on age and the underlying cause it is thought that around 50 percent of people with nephrotic syndrome will die or develop CKD within around 14 years the first part of the diagnosis involves confirming the significant protein urea which may be first indicated by a urine dip followed then by urinalysis where urine is collected over 24 hours and protein content assessed looking for the 3.5 grams per day threshold or more than 40 milligrams per hour per square meter of body surface area in children more recently though spot urinary protein to creatinine ratio has replaced this as a ratio of 300 milligrams per millimole is diagnostic for nephrotic syndrome blood tests will include albumin looking for hypoalbaminemia as well as lipid levels and electrolytes urea and creatinine that would also be included to evaluate renal function to determine the underlying cause of the nephrotic syndrome further tests can include immune markers and imaging like CT or ultrasound a kidney biopsy may be needed but this is mostly in adults treatment is aimed at reducing the symptoms and addressing the underlying cause steroid to the Mainstay mostly prednisone or its metabolite prednisolone however 10 to 20 percent of cases will not achieve complete remission after the initial course termed steroid resistant nephrotic syndrome these patients have a higher risk of progressing to end-stage renal disease and in some cases immunosuppressive agents like cyclophosphamide are needed fluid overload is treated with diuretics typically furosemide and diet is modified to provide adequate protein however it is limited to around 1 gram per kilo per day as too much can worsen protein urea salt and overall fluid intake should also be restricted to allow overall fluid loss statins may be started for hyperlipidemia and prophylactic Heparin used to reduce the risk of thromboembolic events both of these particularly in steroid resistant cases where there is a prolonged period of risk