Nephrotic syndrome medical therapy: Difference between revisions
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=== | ===Treatment of Proteinuria=== | ||
Since proteinuria is one of the most significant factors for progression of disease and is associated with outcome<ref name="pmid9573535">{{cite journal| author=Ruggenenti P, Perna A, Mosconi L, Pisoni R, Remuzzi G| title=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). | journal=Kidney Int | year= 1998 | volume= 53 | issue= 5 | pages= 1209-16 | pmid=9573535 | doi=10.1046/j.1523-1755.1998.00874.x | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9573535 }} </ref><ref name="pmid8710157">{{cite journal| author=Locatelli F, Marcelli D, Comelli M, Alberti D, Graziani G, Buccianti G et al.| title=Proteinuria and blood pressure as causal components of progression to end-stage renal failure. Northern Italian Cooperative Study Group. | journal=Nephrol Dial Transplant | year= 1996 | volume= 11 | issue= 3 | pages= 461-7 | pmid=8710157 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8710157 }} </ref>, 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.<ref name="pmid8643149">{{cite journal| author=Gansevoort RT, Sluiter WJ, Hemmelder MH, de Zeeuw D, de Jong PE| title=Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials. | journal=Nephrol Dial Transplant | year= 1995 | volume= 10 | issue= 11 | pages= 1963-74 | pmid=8643149 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8643149 }} </ref><ref name="pmid9217756">{{cite journal| author=| title=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) | journal=Lancet | year= 1997 | volume= 349 | issue= 9069 | pages= 1857-63 | pmid=9217756 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9217756 }} </ref><ref name="pmid12531578">{{cite journal| author=Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T| title=Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. | journal=Lancet | year= 2003 | volume= 361 | issue= 9352 | pages= 117-24 | pmid=12531578 | doi=10.1016/S0140-6736(03)12229-5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12531578 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12954032 Review in: ACP J Club. 2003 Sep-Oct;139(2):40] </ref><ref name="pmid10692263">{{cite journal| author=Ruggenenti P, Mosconi L, Vendramin G, Moriggi M, Remuzzi A, Sangalli F et al.| title=ACE inhibition improves glomerular size selectivity in patients with idiopathic membranous nephropathy and persistent nephrotic syndrome. | journal=Am J Kidney Dis | year= 2000 | volume= 35 | issue= 3 | pages= 381-91 | pmid=10692263 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10692263 }} </ref><ref name="pmid12704582">{{cite journal| author=Korbet SM| title=Angiotensin antagonists and steroids in the treatment of focal segmental glomerulosclerosis. | journal=Semin Nephrol | year= 2003 | volume= 23 | issue= 2 | pages= 219-28 | pmid=12704582 | doi=10.1053/snep.2003.50020 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12704582 }} </ref> In such cases, the indication of ACE-I is beyond blood pressure control. Patients must thus be started on ACE-I regardless of the presence of hypertension or not. | |||
Treatment with combined agents has been shown to effectively reduce proteinuria more than treatment with single agents.<ref name="pmid8643149">{{cite journal| author=Gansevoort RT, Sluiter WJ, Hemmelder MH, de Zeeuw D, de Jong PE| title=Antiproteinuric effect of blood-pressure-lowering agents: a meta-analysis of comparative trials. | journal=Nephrol Dial Transplant | year= 1995 | volume= 10 | issue= 11 | pages= 1963-74 | pmid=8643149 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8643149 }} </ref><ref name="pmid9217756">{{cite journal| author=| title=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) | journal=Lancet | year= 1997 | volume= 349 | issue= 9069 | pages= 1857-63 | pmid=9217756 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9217756 }} </ref><ref name="pmid12531578">{{cite journal| author=Nakao N, Yoshimura A, Morita H, Takada M, Kayano T, Ideura T| title=Combination treatment of angiotensin-II receptor blocker and angiotensin-converting-enzyme inhibitor in non-diabetic renal disease (COOPERATE): a randomised controlled trial. | journal=Lancet | year= 2003 | volume= 361 | issue= 9352 | pages= 117-24 | pmid=12531578 | doi=10.1016/S0140-6736(03)12229-5 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12531578 }} [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12954032 Review in: ACP J Club. 2003 Sep-Oct;139(2):40] </ref><ref name="pmid16703216">{{cite journal| author=Tsouli SG, Liberopoulos EN, Kiortsis DN, Mikhailidis DP, Elisaf MS| title=Combined treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: a review of the current evidence. | journal=J Cardiovasc Pharmacol Ther | year= 2006 | volume= 11 | issue= 1 | pages= 1-15 | pmid=16703216 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16703216 }} </ref> Follow-up with measurements of serum electrolytes is recommended periodically. | |||
In adults, addition of corticosteroids has not been proven to be beneficial, except if the underlying etiology necessitates the use of steroids or if no improvement on conservative therapy takes place.<ref name="pmid16020995">{{cite journal| author=Crook ED, Habeeb D, Gowdy O, Nimmagadda S, Salem M| title=Effects of steroids in focal segmental glomerulosclerosis in a predominantly African-American population. | journal=Am J Med Sci | year= 2005 | volume= 330 | issue= 1 | pages= 19-24 | pmid=16020995 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16020995 }} </ref><ref name="pmid15495098">{{cite journal| author=Schieppati A, Perna A, Zamora J, Giuliano GA, Braun N, Remuzzi G| title=Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome. | journal=Cochrane Database Syst Rev | year= 2004 | volume= | issue= 4 | pages= CD004293 | pmid=15495098 | doi=10.1002/14651858.CD004293.pub2 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15495098 }} </ref> In converse, most children with nephrotic syndrome are diagnosed with minimal change disease (MCD) and require corticosteroids for the resolution of proteinuria. Rarely do individuals require unilateral or bilateral nephrectomies to treat proteinuria these days.<ref name="pmid18497417">{{cite journal| author=Hull RP, Goldsmith DJ| title=Nephrotic syndrome in adults. | journal=BMJ | year= 2008 | volume= 336 | issue= 7654 | pages= 1185-9 | pmid=18497417 | doi=10.1136/bmj.39576.709711.80 | pmc=PMC2394708 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18497417 }} </ref> | |||
===Specific Treatment of Underlying Cause=== | ===Specific Treatment of Underlying Cause=== | ||
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Medical Therapy
Treatment of Edema
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, hypovention, ischemic acute tubular necrosis, and hemoconcentration associated with aggressive diuretic therapy.[1][1]
IV Loop diuretics, like furosemide or bumetanide[2], are mostly used as first line diuretics. The use of oral medications is generally avoided due to poor absorption in cases of interstinal edema and due to presence of hypoalbuminemia[1] Addition of thiazide-type diuretics, metolazone, or potassium-sparing diuretics are also reasonable options.[2] There are currently no guidelines to outline the appropriate dosages and drug selection.
IV albumin, although generally not recommended for hypoalbuminemia due to its transient effects, has been shown to have synergistic effects with diuretics for an increased delivery of protein-bound diuretics to sites of action.[1] Nonetheless, albumin is still not widely recommended, and its risks may at times outweigh the benefits because it is associated with anaphylaxis, hypertension, and pulmonary edema.[1]
Treatment includes:
Treatment of Proteinuria
Since proteinuria is one of the most significant factors for progression of disease and is associated with outcome[3][4], 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.[5][6][7][8][9] In such cases, the indication of ACE-I is beyond blood pressure control. Patients must thus be started on ACE-I regardless of the presence of hypertension or not.
Treatment with combined agents has been shown to effectively reduce proteinuria more than treatment with single agents.[5][6][7][10] Follow-up with measurements of serum electrolytes is recommended periodically.
In adults, addition of corticosteroids has not been proven to be beneficial, except if the underlying etiology necessitates the use of steroids or if no improvement on conservative therapy takes place.[11][12] In converse, most children with nephrotic syndrome are diagnosed with minimal change disease (MCD) and require corticosteroids for the resolution of proteinuria. Rarely do individuals require unilateral or bilateral nephrectomies to treat proteinuria these days.[1]
Specific Treatment of Underlying Cause
- Immunosupression for the glomerulonephritides (steroids,[13] cyclosporin)
- Standard ISKDC Regime for first episode: Prednisolone -60 mg/m2 /day in 3 divided doses for 4 weeks followed by 40mg/m2/day in a single dose on every alternate day for 4 weeks.
- Relapses by prednisolone 2mg/kg/day till urine becomes negetive for protein. Then,1.5mg/kg/day for 4 weeks.
- Frequent Relapses treated by: cyclophosphamide or nitrogen mustard or cyclosporin or levamisole.
- Achieving stricter blood glucose control if diabetic
- BP control. ACE inhibitors are the drug of choice. Independent of their blood pressure lowering effect, they have been shown to decrease protein loss.
Dietary Recommendations
- Limit high protein animal foods to 1 oz per meal (preferably lean cuts of meat, fish, and poultry)
- Limit high phosphorous foods such as cheese, cooked dried beans and peas, nut butters, soy, tofu, and yogurt, including cokes and colas.
- Limit high potassium vegetables and fruits such as artichokes, avocado, bamboo shoots, beets, brussels sprouts, chard, greens (such as beet and collards), kohlrabi, okra, parsnips, potatoes, pumpkin, rutabagas, spinach, sweet potatoes, tomatoes, tomato juice, tomato sauce, wax beens, winter squash, yams. Fruits include, apricots, bananas, dates, honey dew, nectarines, orange juice, oranges, prune juice.
- Avoid saturated fats and eat unsaturated fats in moderation.
- Eat low-fat desserts only.
- Monitor fluid intake which includes all fluids and foods that are liquid at room temperature.
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 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.
- ↑ 2.0 2.1 Brater DC (1998). "Diuretic therapy". N Engl J Med. 339 (6): 387–95. doi:10.1056/NEJM199808063390607. PMID 9691107.
- ↑ 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.
- ↑ 5.0 5.1 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.
- ↑ 6.0 6.1 "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.
- ↑ 7.0 7.1 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.
- ↑ Tsouli SG, Liberopoulos EN, Kiortsis DN, Mikhailidis DP, Elisaf MS (2006). "Combined treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers: a review of the current evidence". J Cardiovasc Pharmacol Ther. 11 (1): 1–15. PMID 16703216.
- ↑ Crook ED, Habeeb D, Gowdy O, Nimmagadda S, Salem M (2005). "Effects of steroids in focal segmental glomerulosclerosis in a predominantly African-American population". Am J Med Sci. 330 (1): 19–24. PMID 16020995.
- ↑ Schieppati A, Perna A, Zamora J, Giuliano GA, Braun N, Remuzzi G (2004). "Immunosuppressive treatment for idiopathic membranous nephropathy in adults with nephrotic syndrome". Cochrane Database Syst Rev (4): CD004293. doi:10.1002/14651858.CD004293.pub2. PMID 15495098.
- ↑ Hodson E, Willis N, Craig J (2007). "Corticosteroid therapy for nephrotic syndrome in children". Cochrane database of systematic reviews (Online) (4): CD001533. doi:10.1002/14651858.CD001533.pub4. PMID 17943754.