Nephrotic syndrome natural history, complications and prognosis: Difference between revisions
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===Anemia=== | ===Anemia=== | ||
Anemia is commonly seen in patients with nephrotic syndrome but has been poorly evaluated. Recent studies have shown that perhaps the association between anemia and nephrotic syndrome are exaggerated and may not be as important as once believed.<ref name="pmid16129203">{{cite journal| author=Mähr N, Neyer U, Prischl F, Kramar R, Mayer G, Kronenberg F et al.| title=Proteinuria and hemoglobin levels in patients with primary glomerular disease. | journal=Am J Kidney Dis | year= 2005 | volume= 46 | issue= 3 | pages= 424-31 | pmid=16129203 | doi=10.1053/j.ajkd.2005.06.002 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16129203 }} </ref> Anemia be present even without the presence of worsening kidney function. Several reasons predispose patients with nephrotic syndrome to the development of anemia, but the true pathogenesis has not been revealed yet. Some hypothesize that urinary loss of erythropoetin (EPO) and abnormal physiological response to EPO are the culprit of anemia.<ref name="pmid1443172">{{cite journal| author=Zhou XJ, Vaziri ND| title=Erythropoietin metabolism and pharmacokinetics in experimental nephrosis. | journal=Am J Physiol | year= 1992 | volume= 263 | issue= 5 Pt 2 | pages= F812-5 | pmid=1443172 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1443172 }} </ref><ref name="pmid11273873">{{cite journal| author=Feinstein S, Becker-Cohen R, Algur N, Raveh D, Shalev H, Shvil Y et al.| title=Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function. | journal=Am J Kidney Dis | year= 2001 | volume= 37 | issue= 4 | pages= 736-42 | pmid=11273873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11273873 }} </ref> Nonetheless, these claims have not been validated in the literature and are still prone to debate. | Anemia is commonly seen in patients with nephrotic syndrome but has been poorly evaluated. Recent studies have shown that perhaps the association between anemia and nephrotic syndrome are exaggerated and may not be as important as once believed.<ref name="pmid16129203">{{cite journal| author=Mähr N, Neyer U, Prischl F, Kramar R, Mayer G, Kronenberg F et al.| title=Proteinuria and hemoglobin levels in patients with primary glomerular disease. | journal=Am J Kidney Dis | year= 2005 | volume= 46 | issue= 3 | pages= 424-31 | pmid=16129203 | doi=10.1053/j.ajkd.2005.06.002 | pmc= |url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16129203 }} </ref> Anemia be present even without the presence of worsening kidney function. Several reasons predispose patients with nephrotic syndrome to the development of anemia, but the true pathogenesis has not been revealed yet. Some hypothesize that urinary loss of erythropoetin (EPO) and abnormal physiological response to EPO are the culprit of anemia.<ref name="pmid1443172">{{cite journal| author=Zhou XJ, Vaziri ND| title=Erythropoietin metabolism and pharmacokinetics in experimental nephrosis. | journal=Am J Physiol | year= 1992 | volume= 263 | issue= 5 Pt 2 | pages= F812-5 | pmid=1443172 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1443172 }} </ref><ref name="pmid11273873">{{cite journal| author=Feinstein S, Becker-Cohen R, Algur N, Raveh D, Shalev H, Shvil Y et al.| title=Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function. | journal=Am J Kidney Dis | year= 2001 | volume= 37 | issue= 4 | pages= 736-42 | pmid=11273873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11273873 }} </ref> Nonetheless, these claims have not been validated in the literature and are still prone to debate.<ref name="pmid7933664">{{cite journal| author=Shibasaki T, Misawa T, Matsumoto H, Abe S, Nakano H, Matsuda H et al.| title=Characteristics of anemia in patients with nephrotic syndrome. | journal=Nihon Jinzo Gakkai Shi | year= 1994 | volume= 36 | issue= 8 | pages= 896-901 | pmid=7933664 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7933664 }} </ref><ref name="pmid8768925">{{cite journal| author=Gansevoort RT, Vaziri ND, de Jong PE| title=Treatment of anemia of nephrotic syndrome with recombinant erythropoietin. | journal=Am J Kidney Dis | year= 1996 | volume= 28 | issue= 2 | pages= 274-7 | pmid=8768925 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8768925 }} </ref><ref name="pmid8938689">{{cite journal| author=Ishimitsu T, Ono H, Sugiyama M, Asakawa H, Oka K, Numabe A et al.| title=Successful erythropoietin treatment for severe anemia in nephrotic syndrome without renal dysfunction. | journal=Nephron | year= 1996 | volume= 74 | issue= 3 | pages= 607-10 | pmid=8938689 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8938689 }} </ref><ref name="pmid7492766">{{cite journal| author=Misaizu T, Matsuki S, Strickland TW, Takeuchi M, Kobata A, Takasaki S| title=Role of antennary structure of N-linked sugar chains in renal handling of recombinant human erythropoietin. | journal=Blood | year= 1995 | volume= 86 | issue= 11 | pages= 4097-104 | pmid=7492766 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7492766 }} </ref> Additionally, iron stores are thought to be depleted in nephrotic syndrome with urinary loss of transferrin, contributing to the pathogenesis as an iron-resistant microcytic hypochromic anemia. Similarly, some researchers noted that ferritin is in fact increased in patients with nephrotic syndrome, not decreased as once postulated.<ref name="pmid15316097">{{cite journal| author=Branten AJ, Swinkels DW, Klasen IS, Wetzels JF| title=Serum ferritin levels are increased in patients with glomerular diseases and proteinuria. | journal=Nephrol Dial Transplant | year= 2004 | volume= 19 | issue= 11 | pages= 2754-60 | pmid=15316097 | doi=10.1093/ndt/gfh454 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15316097 }} </ref><ref name="pmid16129203">{{cite journal| author=Mähr N, Neyer U, Prischl F, Kramar R, Mayer G, Kronenberg F et al.| title=Proteinuria and hemoglobin levels in patients with primary glomerular disease. | journal=Am J Kidney Dis | year= 2005 | volume= 46 | issue= 3 | pages= 424-31 | pmid=16129203 | doi=10.1053/j.ajkd.2005.06.002 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16129203 }} </ref> The reason behind such elevation in ferritin remains unclear. | ||
Generally, administration of EPO resolves the anemia in these patients.<ref name="pmid11273873">{{cite journal| author=Feinstein S, Becker-Cohen R, Algur N, Raveh D, Shalev H, Shvil Y et al.| title=Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function. | journal=Am J Kidney Dis | year= 2001 | volume= 37 | issue= 4 | pages= 736-42 | pmid=11273873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11273873 }} </ref> | Generally, administration of EPO resolves the anemia in these patients.<ref name="pmid11273873">{{cite journal| author=Feinstein S, Becker-Cohen R, Algur N, Raveh D, Shalev H, Shvil Y et al.| title=Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function. | journal=Am J Kidney Dis | year= 2001 | volume= 37 | issue= 4 | pages= 736-42 | pmid=11273873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11273873 }} </ref> | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Complications
Infections
Patients with nephrotic syndrome are at increased risk of infections due to several mechanisms:
- Urinary loss of immunoglobulins
- Delay in complement-dependent opsonisation of encapsulated organisms, such as S. pneumoniae[1]
- Reduction in factors B and I[1]
- Decrease of blood flow to mesenteric regions
Patients with nephrotic syndrome who complain of abdominal pain must always be assessed for peritonitis that requires paracentesis. The rate of spontaneous bacterial peritonitis is 2-6%[2] which contributed to 1-2% of mortality in these patients. Gram-negative bacterial organisms, such as E. coli, are especially important infectious agents in patients with nephrotic syndrome.[3] Urinary tract infections and skin infections are also common, such as cellulitis, erysipelas, and lymphangitis.[4] Since patients are often treated with immunosuppressants, the susceptibility to infections is further heightened in these patients.[5][1]
Thromboembolism
The rate of thromboembolism may be as high as 40% in adults(120); whereas it is much lower in children at a rate of 2-5%.(121) Several factors contribute to thromboembolism in nephrotic syndrome[6]:
- Increase in platelet aggregation
- Increase in concentration of fibrinogen
- Urinary Loss of antithrombin III
- Increase in blood viscosity
- Decrease in blood flow
Thromboembolism is considered the second most important cause of mortality in nephrotic syndrome. The risk of thromboembolism increases as other risk factors of thrombosis are also present, such as immobility, indwelling catheters, use of diuretics or steroids.[4] Thromboembolism may occur at any site; common locations include deep veins of the extremities, cerebral veins, renal veins, and pulmonary veins. Although arterial occlusion is much less common, its prognostic significance is much graver than venous thromboembolism and is associated with mortality.[6] Considerably, the use of heparin may not be as efficient in nephrotic syndrome due to the insufficiency of antithrombin III required by the drug for anticoagulation.[7]
Cardiovascular Disease
The clinical presentation of nephrotic syndrome per represents a high-risk profile for cardiovascular disease. Patients may present with hypertension, hyperlipidemia, anemia, renal disease, and exposure to steroids, all of which are considered risk factors for the development of cardiovascular disease and cardiovascular events.[8][9]
Osteoporosis
Osteoporosis is generally a complication of corticosteroid use in nephrotic syndrome. However, medication-induced osteoporosis is not the only factor that predisposes patients to loss of bone density, urinary loss of components required for osteogenesis, such as vitamin D-binding protein is also involved.[10][11][12]
Anemia
Anemia is commonly seen in patients with nephrotic syndrome but has been poorly evaluated. Recent studies have shown that perhaps the association between anemia and nephrotic syndrome are exaggerated and may not be as important as once believed.[13] Anemia be present even without the presence of worsening kidney function. Several reasons predispose patients with nephrotic syndrome to the development of anemia, but the true pathogenesis has not been revealed yet. Some hypothesize that urinary loss of erythropoetin (EPO) and abnormal physiological response to EPO are the culprit of anemia.[14][8] Nonetheless, these claims have not been validated in the literature and are still prone to debate.[15][16][17][18] Additionally, iron stores are thought to be depleted in nephrotic syndrome with urinary loss of transferrin, contributing to the pathogenesis as an iron-resistant microcytic hypochromic anemia. Similarly, some researchers noted that ferritin is in fact increased in patients with nephrotic syndrome, not decreased as once postulated.[19][13] The reason behind such elevation in ferritin remains unclear.
Generally, administration of EPO resolves the anemia in these patients.[8]
Growth Retardation
Urinary loss of insulin-like growth factor (IGF) binding proteins may cause a decrease in serum concentration of IGF-I and IGF-II. Corticosteroids, often used in the treatment of nephrotic syndrome, may also suppress growth.[6]
Prognosis
The prognosis depends on the cause of nephrotic syndrome. It is usually good in children, because minimal change disease responds very well to steroids and does not cause chronic renal failure. However, other causes such as focal segmental glomerulosclerosis frequently lead to end stage renal disease. Factors associated with a poorer prognosis in these cases include level of proteinuria, blood pressure control and kidney function (GFR).
References
- ↑ 1.0 1.1 1.2 Patiroglu T, Melikoglu A, Dusunsel R (1998). "Serum levels of C3 and factors I and B in minimal change disease". Acta Paediatr Jpn. 40 (4): 333–6. PMID 9745775.
- ↑ Feinstein EI, Chesney RW, Zelikovic I (1988). "Peritonitis in childhood renal disease". Am J Nephrol. 8 (2): 147–65. PMID 3293444.
- ↑ Tain YL, Lin G, Cher TW (1999). "Microbiological spectrum of septicemia and peritonitis in nephrotic children". Pediatr Nephrol. 13 (9): 835–7. PMID 10603131.
- ↑ 4.0 4.1 Eddy AA, Symons JM (2003). "Nephrotic syndrome in childhood". Lancet. 362 (9384): 629–39. doi:10.1016/S0140-6736(03)14184-0. PMID 12944064.
- ↑ Goldstein SL, Somers MJ, Lande MB, Brewer ED, Jabs KL (2000). "Acyclovir prophylaxis of varicella in children with renal disease receiving steroids". Pediatr Nephrol. 14 (4): 305–8. PMID 10775074.
- ↑ 6.0 6.1 6.2 Roth KS, Amaker BH, Chan JC (2002). "Nephrotic syndrome: pathogenesis and management". Pediatr Rev. 23 (7): 237–48. PMID 12093934.
- ↑ Andrew M, Michelson AD, Bovill E, Leaker M, Massicotte MP (1998). "Guidelines for antithrombotic therapy in pediatric patients". J Pediatr. 132 (4): 575–88. PMID 9580753.
- ↑ 8.0 8.1 8.2 Feinstein S, Becker-Cohen R, Algur N, Raveh D, Shalev H, Shvil Y; et al. (2001). "Erythropoietin deficiency causes anemia in nephrotic children with normal kidney function". Am J Kidney Dis. 37 (4): 736–42. PMID 11273873.
- ↑ Vaziri ND (2001). "Erythropoietin and transferrin metabolism in nephrotic syndrome". Am J Kidney Dis. 38 (1): 1–8. doi:10.1053/ajkd.2001.25174. PMID 11431174.
- ↑ Auwerx J, De Keyser L, Bouillon R, De Moor P (1986). "Decreased free 1,25-dihydroxycholecalciferol index in patients with the nephrotic syndrome". Nephron. 42 (3): 231–5. PMID 3753749.
- ↑ Freundlich M, Bourgoignie JJ, Zilleruelo G, Abitbol C, Canterbury JM, Strauss J (1986). "Calcium and vitamin D metabolism in children with nephrotic syndrome". J Pediatr. 108 (3): 383–7. PMID 3485195.
- ↑ Malluche HH, Goldstein DA, Massry SG (1979). "Osteomalacia and hyperparathyroid bone disease in patients with nephrotic syndrome". J Clin Invest. 63 (3): 494–500. doi:10.1172/JCI109327. PMC 371978. PMID 429568.
- ↑ 13.0 13.1 Mähr N, Neyer U, Prischl F, Kramar R, Mayer G, Kronenberg F; et al. (2005). "Proteinuria and hemoglobin levels in patients with primary glomerular disease". Am J Kidney Dis. 46 (3): 424–31. doi:10.1053/j.ajkd.2005.06.002. PMID 16129203.
- ↑ Zhou XJ, Vaziri ND (1992). "Erythropoietin metabolism and pharmacokinetics in experimental nephrosis". Am J Physiol. 263 (5 Pt 2): F812–5. PMID 1443172.
- ↑ Shibasaki T, Misawa T, Matsumoto H, Abe S, Nakano H, Matsuda H; et al. (1994). "Characteristics of anemia in patients with nephrotic syndrome". Nihon Jinzo Gakkai Shi. 36 (8): 896–901. PMID 7933664.
- ↑ Gansevoort RT, Vaziri ND, de Jong PE (1996). "Treatment of anemia of nephrotic syndrome with recombinant erythropoietin". Am J Kidney Dis. 28 (2): 274–7. PMID 8768925.
- ↑ Ishimitsu T, Ono H, Sugiyama M, Asakawa H, Oka K, Numabe A; et al. (1996). "Successful erythropoietin treatment for severe anemia in nephrotic syndrome without renal dysfunction". Nephron. 74 (3): 607–10. PMID 8938689.
- ↑ Misaizu T, Matsuki S, Strickland TW, Takeuchi M, Kobata A, Takasaki S (1995). "Role of antennary structure of N-linked sugar chains in renal handling of recombinant human erythropoietin". Blood. 86 (11): 4097–104. PMID 7492766.
- ↑ Branten AJ, Swinkels DW, Klasen IS, Wetzels JF (2004). "Serum ferritin levels are increased in patients with glomerular diseases and proteinuria". Nephrol Dial Transplant. 19 (11): 2754–60. doi:10.1093/ndt/gfh454. PMID 15316097.