Nephrotic syndrome overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Ali Poyan Mehr, M.D. [2] Associate Editor(s)-in-Chief: Olufunmilola Olubukola M.D.[3]
Overview
Nephrotic syndrome is group of signs and symptoms resulting from loss of kidney filtration capabilities leading to massive loss of protein in urine (>3.5g of protein in urine per 24hours), generalized or localized body edema, hyperlipidemia and hypoproteinemia (most importantly, hypoalbuminemia). Causes of Nephrotic Syndrome can be primary (idiopathic) or secondary (from a systemic insult or immune mediated).
Nephrotic syndrome (nephrosis) is defined as heavy proteinuria > 3.5 grams per 24 hours in adults. In children, nephrotic syndrome is defined as protein excretion > 40 mg/m2/h. The accurate diagnosis of nephrotic syndrome thus requires 24-hour urine collection. However, in clinical practice, urine dipstick of a qualitative measure of 3+ urinary proteins, or spot urine protein (mg)/creatinine(mg) ratio > 2 may also reflect nephrotic syndrome.[1]
Clinically, nephrotic syndrome is defined as[2]:
- Heavy proteinuria > 3.5 g/24 hrs
- Peripheral edema
- Hypoalbuminemia
- Hyperlipidemia and lipiduria
- Hypercoagulability
Classification
Nephrotic syndrome can be classified into primary or secondary depending on the underlying etiology. Primary (idiopathic) nephrotic syndrome is defined as nephrotic syndrome due to a primary glomerular disease. Secondary nephrotic syndrome is defined as nephrotic syndrome due to a primary etiology other than glomerular disorders, such as infections, malignancies, systemic conditions, and medications.
Pathophysiology
The pathophysiology of hypoalbuminemia in nephrotic syndrome is multifactorial. Proteinuria plays an important role in the pathogenesis of hyperlipidemia in nephrotic syndrome.[3] Neurohormonal changes in the renin-angiotensin-aldosterone system, vasopressin, atrial natriuretic peptide (ANP), and sympathetic nervous system are is implicated in edema formation in nephrotic syndrome.[4]
Causes
Nephrotic syndrome can be either primary or secondary to diseases. Primary renal disorders, such as primary glomerulonephritides, may cause primary nephrotic syndrome. The most common cause of secondary nephrotic syndrome in adults is diabetes mellitus.
Differential Diagnosis
The differential diagnosis of nephrotic syndrome includes other diseases with similar findings on physical examination, such as lower extremity edema, or similar clinical findings, such as hypoalbuminemia. Differential diagnoses include congestive heart failure, liver cirrhosis, protein losing enteropathy, malignancy, lymphedema, venous insufficiency, and malnutrition.
Epidemiology and Demographics
Idiopathic nephrotic syndrome has an incidence of 2-7 cases per 100,000 and a prevalence of 16 cases per 100,000.[5] Nephrotic syndrome may affect children and adults alike. There is no age or ethnic predominance. The prevalence of nephrotic syndrome in children has a 2 to 1 male to female ratio.[6]
Natural History, Complications and Prognosis
Complications of nephrotic syndrome include infections, thrombotic events, and renal failure. Mortality and overall prognosis depends on the occurrence of complications and adherence to medications.[5]
Diagnosis
History and Symptoms
Symptoms of nephrotic syndrome include edema, dyspnea, abdominal fullness, anorexia, and fatigue.
Physical Examination
A full physical examination should be performed among patients presenting with nephrotic syndrome. Findings on physical examination suggestive of secondary etiologies may be present, such as characteristic rash in systemic lupus erythematosus (SLE), or peripheral neuropathy in diabetes mellitus.
Laboratory Findings
Nephrotic syndrome is characterized by the following laboratory findings: proteinuria > 3.5g/24 hrs on 24-hour urine collection, proteinuria on urine dipstick, and urine protein/creatinine ratio > 3. When nephrotic syndrome is diagnosed (proteinuria > 3.5 g/24 hrs), additional laboratory tests are required such as serum albumin concentration, serum chemistry panel, lipid panel, and serum creatinine concentration.
Chest X-Ray
Chest X-ray may show signs of pleural effusion.[1]
Ultrasound
Renal and abdominal doppler ultrasound may be required to investigate for renal etiologies and complications of disease, such as renal vein thrombosis.[1] Kidney size and signs of obstruction during assessment are also important.[1] Doppler ultrasound of the extremities is indicated if patients with nephrotic syndrome present with suspected deep vein thrombosis.
Other Imaging Findings
Renal vein thrombosis, a complication of nephrotic syndrome, may require any of venography, CT scan, or MRI for appropriate diagnosis.[2]
Biopsy
Ultrasound-guided renal biopsy for visualization under light microscopy, immunofluorescence or immunoperoxidase, and electron microscopy is usually recommended for patients with nephrotic syndrome.[2] Renal biopsy provides diagnostic and prognostic benefit. However, guidelines that define the timing and the circumstances to perform renal biopsy are not present. In minimal change disease, the most common primary cause of nephrotic syndrome in children, and in diabetic nephropathy, the most common secondary cause of nephrotic syndrome in adults, renal biopsy is not generally recommended and is not routinely performed.[1] Nonetheless, patients who present with unknown or unsure etiology of nephrotic syndrome are recommended to undergo renal biopsy for definitive diagnosis.[1]
Treatment
Medical Therapy
There are currently no guidelines for the management of edema associated with nephrotic syndrome. The slow reversal of edema is important at a rate of 0.5-1 kg daily to prevent electrolyte disturbances, hypotension, ischemic acute tubular necrosis, and hemoconcentration associated with aggressive diuretic therapy.[2][2] Since proteinuria is one of the most significant factors for progression of disease and is associated with outcome[7][8], treatment of proteinuria in nephrotic syndrome must always be considered a priority. Angiotensin-converting enzyme inhibitors (ACE-I), with or without angiotensin-II receptor blockers (ARB) have been extensively studied and are well-known to decrease proteinuria and the risk of progression of renal disease in patients with nephrotic syndrome.[9][10][11][12][13] Pneumococcal vaccines are recommended for all patients with nephrotic syndrome.[1]
Primary Prevention
Appropriate treatment of conditions that can cause nephrotic syndrome may help prevent the syndrome.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Kodner C (2009). "Nephrotic syndrome in adults: diagnosis and management". Am Fam Physician. 80 (10): 1129–34. PMID 19904897.
- ↑ 2.0 2.1 2.2 2.3 2.4 Hull RP, Goldsmith DJ (2008). "Nephrotic syndrome in adults". BMJ. 336 (7654): 1185–9. doi:10.1136/bmj.39576.709711.80. PMC 2394708. PMID 18497417.
- ↑ Kaysen GA, Kirkpatrick WG, Couser WG (1984). "Albumin homeostasis in the nephrotic rat: nutritional considerations". Am J Physiol. 247 (1 Pt 2): F192–202. PMID 6742202.
- ↑ Siddall EC, Radhakrishnan J (2012). "The pathophysiology of edema formation in the nephrotic syndrome". Kidney Int. 82 (6): 635–42. doi:10.1038/ki.2012.180. PMID 22718186.
- ↑ 5.0 5.1 Eddy AA, Symons JM (2003). "Nephrotic syndrome in childhood". Lancet. 362 (9384): 629–39. doi:10.1016/S0140-6736(03)14184-0. PMID 12944064.
- ↑ "The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children". J Pediatr. 98 (4): 561–4. 1981. PMID 7205481.
- ↑ Ruggenenti P, Perna A, Mosconi L, Pisoni R, Remuzzi G (1998). "Urinary protein excretion rate is the best independent predictor of ESRF in non-diabetic proteinuric chronic nephropathies. "Gruppo Italiano di Studi Epidemiologici in Nefrologia" (GISEN)". Kidney Int. 53 (5): 1209–16. doi:10.1046/j.1523-1755.1998.00874.x. PMID 9573535.
- ↑ Locatelli F, Marcelli D, Comelli M, Alberti D, Graziani G, Buccianti G; et al. (1996). "Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group". Nephrol Dial Transplant. 11 (3): 461–7. PMID 8710157.
- ↑ Gansevoort RT, Sluiter WJ, Hemmelder MH, de Zeeuw D, de Jong PE (1995). "Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials". Nephrol Dial Transplant. 10 (11): 1963–74. PMID 8643149.
- ↑ "Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia)". Lancet. 349 (9069): 1857–63. 1997. PMID 9217756.
- ↑ Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T (2003). "Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial". Lancet. 361 (9352): 117–24. doi:10.1016/S0140-6736(03)12229-5. PMID 12531578. Review in: ACP J Club. 2003 Sep-Oct;139(2):40
- ↑ Ruggenenti P, Mosconi L, Vendramin G, Moriggi M, Remuzzi A, Sangalli F; et al. (2000). "ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome". Am J Kidney Dis. 35 (3): 381–91. PMID 10692263.
- ↑ Korbet SM (2003). "Angiotensin antagonists and steroids in the treatment of focal segmental glomerulosclerosis". Semin Nephrol. 23 (2): 219–28. doi:10.1053/snep.2003.50020. PMID 12704582.