Minimal change disease natural history, complications and prognosis: Difference between revisions
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==Overview== | ==Overview== | ||
Complications associated with the pathogenesis of the disease as a nephrotic syndrome include thromboembolic events and disorders of hemostasis, hyperlipidemia, vulnerability to | Complications associated with the pathogenesis of the disease as a nephrotic syndrome include [[thromboembolic]] events and disorders of [[hemostasis]], [[hyperlipidemia]], vulnerability to [[infection]]s, and [[hypertension]].<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> Before the steroid era, patients died of [[renal failure]] and from [[infection]]s.<ref name="pmid19808243">{{cite journal| author=Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ et al.| title=Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1593-600 | pmid=19808243 | doi=10.2215/CJN.05691108 | pmc=PMC2758253 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808243 }} </ref> Nowadays, patients have excellent renal outcomes when they are still steroid-responsive and virtually all patients survive with a normal creatinine clearance.<ref name="pmid19808243">{{cite journal| author=Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ et al.| title=Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1593-600 | pmid=19808243 | doi=10.2215/CJN.05691108 | pmc=PMC2758253 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808243 }} </ref><ref name="pmid19808239">{{cite journal| author=Niaudet P| title=Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1547-8 | pmid=19808239 | doi=10.2215/CJN.05950809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808239 }} </ref> Although renal outcomes are considered excellent with appropriate therapy, the risk of chronic renal disease cannot be completely ruled out, especially among patients receiving nephrotoxic medications for prolonged periods of time.<ref name="pmid19808239">{{cite journal| author=Niaudet P| title=Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1547-8 | pmid=19808239 | doi=10.2215/CJN.05950809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808239 }} </ref> | ||
==Natural History and Prognosis== | ==Natural History and Prognosis== | ||
Outcomes in minimal change disease have been mostly studied in the pediatric population, with very little knowledge in in adults. Before the steroid era, patients died of renal failure and from | Outcomes in minimal change disease have been mostly studied in the pediatric population, with very little knowledge in in adults. Before the [[steroid]] era, patients died of [[renal failure]] and from [[infection]]s.<ref name="pmid19808243">{{cite journal| author=Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ et al.| title=Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1593-600 | pmid=19808243 | doi=10.2215/CJN.05691108 | pmc=PMC2758253 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808243 }} </ref> Nowadays, patients have excellent renal outcomes when they are still steroid-responsive and virtually all patients survive with a normal [[creatinine]] clearance.<ref name="pmid19808243">{{cite journal| author=Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ et al.| title=Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1593-600 | pmid=19808243 | doi=10.2215/CJN.05691108 | pmc=PMC2758253 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808243 }} </ref><ref name="pmid19808239">{{cite journal| author=Niaudet P| title=Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1547-8 | pmid=19808239 | doi=10.2215/CJN.05950809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808239 }} </ref> Up to 80% of children with nephrotic syndrome respond to [[corticosteroid]]s and become in full remission within 1 month of [[steroid therapy]]. Of those, 30% require only 1 course of [[steroid]]s, 20% require several courses, and 30-50% suffer from frequently relapsing nephrotic syndrome (FRNS) when steroids are discontinued.<ref name="pmid9176846">{{cite journal| author=Tarshish P, Tobin JN, Bernstein J, Edelmann CM| title=Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children. | journal=J Am Soc Nephrol | year= 1997 | volume= 8 | issue= 5 | pages= 769-76 | pmid=9176846 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9176846 }} </ref><ref name="pmid19808239">{{cite journal| author=Niaudet P| title=Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1547-8 | pmid=19808239 | doi=10.2215/CJN.05950809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808239 }} </ref> Age at disease onset is strongly associated with the frequency of relapses in children. | ||
It was once believed that only 10% of children with minimal change disease persist into adulthood.<ref name="pmid7103547">{{cite journal| author=Koskimies O, Vilska J, Rapola J, Hallman N| title=Long-term outcome of primary nephrotic syndrome. | journal=Arch Dis Child | year= 1982 | volume= 57 | issue= 7 | pages= 544-8 | pmid=7103547 | doi= | pmc=PMC1627702 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7103547 }} </ref><ref name="pmid2857421">{{cite journal| author=Trompeter RS, Lloyd BW, Hicks J, White RH, Cameron JS| title=Long-term outcome for children with minimal-change nephrotic syndrome. | journal=Lancet | year= 1985 | volume= 1 | issue= 8425 | pages= 368-70 | pmid=2857421 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2857421 }} </ref> More recent data shows that the rate is in fact higher, reaching approximately 25-42%. Risk factors for persistence of minimal change disease into adulthood are as follows<ref name="pmid19808239">{{cite journal| author=Niaudet P| title=Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1547-8 | pmid=19808239 | doi=10.2215/CJN.05950809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808239 }} </ref><ref name="pmid16126050">{{cite journal| author=Rüth EM, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ| title=Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. | journal=J Pediatr | year= 2005 | volume= 147 | issue= 2 | pages= 202-7 | pmid=16126050 | doi=10.1016/j.jpeds.2005.03.050 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16126050 }} </ref><ref name="pmid19808243">{{cite journal| author=Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ et al.| title=Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1593-600 | pmid=19808243 | doi=10.2215/CJN.05691108 | pmc=PMC2758253 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808243 }} </ref> | It was once believed that only 10% of children with minimal change disease persist into adulthood.<ref name="pmid7103547">{{cite journal| author=Koskimies O, Vilska J, Rapola J, Hallman N| title=Long-term outcome of primary nephrotic syndrome. | journal=Arch Dis Child | year= 1982 | volume= 57 | issue= 7 | pages= 544-8 | pmid=7103547 | doi= | pmc=PMC1627702 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7103547 }} </ref><ref name="pmid2857421">{{cite journal| author=Trompeter RS, Lloyd BW, Hicks J, White RH, Cameron JS| title=Long-term outcome for children with minimal-change nephrotic syndrome. | journal=Lancet | year= 1985 | volume= 1 | issue= 8425 | pages= 368-70 | pmid=2857421 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2857421 }} </ref> More recent data shows that the rate is in fact higher, reaching approximately 25-42%. Risk factors for persistence of minimal change disease into adulthood are as follows:<ref name="pmid19808239">{{cite journal| author=Niaudet P| title=Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1547-8 | pmid=19808239 | doi=10.2215/CJN.05950809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808239 }} </ref><ref name="pmid16126050">{{cite journal| author=Rüth EM, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ| title=Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome. | journal=J Pediatr | year= 2005 | volume= 147 | issue= 2 | pages= 202-7 | pmid=16126050 | doi=10.1016/j.jpeds.2005.03.050 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16126050 }} </ref><ref name="pmid19808243">{{cite journal| author=Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ et al.| title=Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1593-600 | pmid=19808243 | doi=10.2215/CJN.05691108 | pmc=PMC2758253 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808243 }} </ref> | ||
*Young age at diagnosis | *Young age at diagnosis | ||
*Increased number of relapses | *Increased number of relapses | ||
*Use of alkylating agents and cyclosporine | *Use of alkylating agents and [[cyclosporine]] | ||
Although renal outcomes are considered excellent with appropriate therapy, the risk of chronic renal disease cannot be completely ruled out, especially among patients receiving nephrotoxic medications for prolonged periods of time.<ref name="pmid19808239">{{cite journal| author=Niaudet P| title=Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1547-8 | pmid=19808239 | doi=10.2215/CJN.05950809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808239 }} </ref> | Although renal outcomes are considered excellent with appropriate therapy, the risk of chronic renal disease cannot be completely ruled out, especially among patients receiving nephrotoxic medications for prolonged periods of time.<ref name="pmid19808239">{{cite journal| author=Niaudet P| title=Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1547-8 | pmid=19808239 | doi=10.2215/CJN.05950809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808239 }} </ref> | ||
There are much less knowledge of outcomes and prognosis of adult-onset minimal change disease. In adults, 90% achieve remission with | There are much less knowledge of outcomes and prognosis of adult-onset minimal change disease. In adults, 90% achieve remission with [[corticosteroid]]s, but the rate of relapse of the first episode of nephrotic syndrome is as high as 70%, where approximately 30% have frequent relapses.<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> Young patients < 40 years at onset of disease are found in some studies to experience recurrence of disease than their older peers; these findings, however, have not been consistent in the literature.<ref name="pmid11877569">{{cite journal| author=Nakayama M, Katafuchi R, Yanase T, Ikeda K, Tanaka H, Fujimi S| title=Steroid responsiveness and frequency of relapse in adult-onset minimal change nephrotic syndrome. | journal=Am J Kidney Dis | year= 2002 | volume= 39 | issue= 3 | pages= 503-12 | pmid=11877569 | doi=10.1053/ajkd.2002.31400 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11877569 }} </ref><ref name="pmid3189423">{{cite journal| author=Korbet SM, Schwartz MM, Lewis EJ| title=Minimal-change glomerulopathy of adulthood. | journal=Am J Nephrol | year= 1988 | volume= 8 | issue= 4 | pages= 291-7 | pmid=3189423 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3189423 }} </ref><ref name="pmid11275629">{{cite journal| author=Huang JJ, Hsu SC, Chen FF, Sung JM, Tseng CC, Wang MC| title=Adult-onset minimal change disease among Taiwanese: clinical features, therapeutic response, and prognosis. | journal=Am J Nephrol | year= 2001 | volume= 21 | issue= 1 | pages= 28-34 | pmid=11275629 | doi=46215 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11275629 }} </ref><ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> The number of relapses is ultimately associated with long-term renal outcomes and steroid dependence.<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> | ||
==Complications== | ==Complications== | ||
Complications associated with the pathogenesis of the disease as a nephrotic syndrome include thromboembolic events and disorders of hemostasis, hyperlipidemia, vulnerability to | Complications associated with the pathogenesis of the disease as a nephrotic syndrome include [[thromboembolic]] events and disorders of [[hemostasis]], [[hyperlipidemia]], vulnerability to [[infection]]s, and [[hypertension]].<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> The frequency of [[acute kidney injury]] (AKI) associated with minimal change disease is also higher. According to Waldman and colleagues<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref>, who studied 95 patients with adult-onset minimal change disease, the rate of acute kidney injury was approximately 25%. Whereas early reports showed that AKI is a reversible complication, larger trials suggested that creatinine was still significantly higher in these patients at 15-year follow-up.<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> Accordingly, the true renal outcome following AKI in minimal change disease is still controversial and requires further investigation. The presence of [[chronic kidney disease]] raises the suspicion of [[focal segmental glomerulosclerosis]] (FSGS). Waldman and colleagues described the following risk factors for acute kidney injury<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref>: | ||
*Male gender | *Male gender | ||
| Line 26: | Line 26: | ||
*Older age > 54.5 years | *Older age > 54.5 years | ||
*Hypertension | *[[Hypertension]] | ||
*Hypoalbuminemia | *[[Hypoalbuminemia]] | ||
Steroid resistance, defined as steroid therapy for more than 4 months, is not uncommon in adults.<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> A subset of patients becomes steroid-resistant and is thus associated with the progression of disease into focal segmental glomerulosclerosis (FSGS). Cyclosporine may induce remission in approximately 60% of patients<ref name="pmid8072258">{{cite journal| author=Meyrier A, Noël LH, Auriche P, Callard P| title=Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Société de Néphrologie. | journal=Kidney Int | year= 1994 | volume= 45 | issue= 5 | pages= 1446-56 | pmid=8072258 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8072258 }} </ref><ref name="pmid2966873">{{cite journal| author=Tejani AT, Butt K, Trachtman H, Suthanthiran M, Rosenthal CJ, Khawar MR| title=Cyclosporine A induced remission of relapsing nephrotic syndrome in children. | journal=Kidney Int | year= 1988 | volume= 33 | issue= 3 | pages= 729-34 | pmid=2966873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2966873 }} </ref><ref name="pmid8159300">{{cite journal| author=Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R et al.| title=Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. | journal=Nephrol Dial Transplant | year= 1993 | volume= 8 | issue= 12 | pages= 1326-32 | pmid=8159300 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8159300 }} </ref> | [[Steroid]] resistance, defined as steroid therapy for more than 4 months, is not uncommon in adults.<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> A subset of patients becomes steroid-resistant and is thus associated with the progression of disease into [[focal segmental glomerulosclerosis]] (FSGS). [[Cyclosporine]] may induce remission in approximately 60% of patients,<ref name="pmid8072258">{{cite journal| author=Meyrier A, Noël LH, Auriche P, Callard P| title=Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Société de Néphrologie. | journal=Kidney Int | year= 1994 | volume= 45 | issue= 5 | pages= 1446-56 | pmid=8072258 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8072258 }} </ref><ref name="pmid2966873">{{cite journal| author=Tejani AT, Butt K, Trachtman H, Suthanthiran M, Rosenthal CJ, Khawar MR| title=Cyclosporine A induced remission of relapsing nephrotic syndrome in children. | journal=Kidney Int | year= 1988 | volume= 33 | issue= 3 | pages= 729-34 | pmid=2966873 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2966873 }} </ref><ref name="pmid8159300">{{cite journal| author=Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R et al.| title=Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial. | journal=Nephrol Dial Transplant | year= 1993 | volume= 8 | issue= 12 | pages= 1326-32 | pmid=8159300 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8159300 }} </ref> whereas cyclophosphamide may induce remission in approximately 25-60% of patients for five years. Resistance to [[cyclosporine]] and [[cyclophosphamide]] has also been described.<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> Similarly, the diagnosis of FSGS in patients who fail to respond to alternative therapy should also be highly considered.<ref name="pmid17699450">{{cite journal| author=Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G et al.| title=Adult minimal-change disease: clinical characteristics, treatment, and outcomes. | journal=Clin J Am Soc Nephrol | year= 2007 | volume= 2 | issue= 3 | pages= 445-53 | pmid=17699450 | doi=10.2215/CJN.03531006 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17699450 }} </ref> | ||
Complications of minimal change disease may be due in fact complications of medications, such as weight gain, osteoporosis, cataract, diabetes, and cardiovascular events associated with | Complications of minimal change disease may be due in fact complications of medications, such as [[weight gain]], [[osteoporosis]], [[cataract]], [[diabetes]], and cardiovascular events associated with [[corticosteroid]]s.<ref name="pmid19808243">{{cite journal| author=Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ et al.| title=Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1593-600 | pmid=19808243 | doi=10.2215/CJN.05691108 | pmc=PMC2758253 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808243 }} </ref><ref name="pmid15956073">{{cite journal| author=Gulati S, Sharma RK, Gulati K, Singh U, Srivastava A| title=Longitudinal follow-up of bone mineral density in children with nephrotic syndrome and the role of calcium and vitamin D supplements. | journal=Nephrol Dial Transplant | year= 2005 | volume= 20 | issue= 8 | pages= 1598-603 | pmid=15956073 | doi=10.1093/ndt/gfh809 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15956073 }} </ref><ref name="pmid16679793">{{cite journal| author=Hayasaka Y, Hayasaka S, Matsukura H| title=Ocular findings in Japanese children with nephrotic syndrome receiving prolonged corticosteroid therapy. | journal=Ophthalmologica | year= 2006 | volume= 220 | issue= 3 | pages= 181-5 | pmid=16679793 | doi=10.1159/000091762 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16679793 }} </ref><ref name="pmid12612977">{{cite journal| author=Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P et al.| title=Steroid-sensitive nephrotic syndrome: from childhood to adulthood. | journal=Am J Kidney Dis | year= 2003 | volume= 41 | issue= 3 | pages= 550-7 | pmid=12612977 | doi=10.1053/ajkd.2003.50116 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12612977 }} </ref> The rate of these complications has become much less frequent with the use of steroid-sparing agents and the use of “alternate-day” steroid therapy.<ref name="pmid19808243">{{cite journal| author=Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ et al.| title=Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. | journal=Clin J Am Soc Nephrol | year= 2009 | volume= 4 | issue= 10 | pages= 1593-600 | pmid=19808243 | doi=10.2215/CJN.05691108 | pmc=PMC2758253 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19808243 }} </ref><ref name="pmid15329424">{{cite journal| author=Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA| title=Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 9 | pages= 868-75 | pmid=15329424 | doi=10.1056/NEJMoa040367 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15329424 }} </ref> Similarly, the use of alkylating agents, like cyclophosphamide, is also associated with reversible and irreversible azoospermia and oligospermia at higher doses of 150-250 mg/kg.<ref name="pmid761678">{{cite journal| author=Hsu AC, Folami AO, Bain J, Rance CP| title=Gonadal function in males treated with cyclophosphamide for nephrotic syndrome. | journal=Fertil Steril | year= 1979 | volume= 31 | issue= 2 | pages= 173-7 | pmid=761678 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=761678 }} </ref><ref name="pmid4826616">{{cite journal| author=Penso J, Lippe B, Ehrlich R, Smith FG| title=Testicular function in prepubertal and pubertal male patients treated with cyclophosphamide for nephrotic syndrome. | journal=J Pediatr | year= 1974 | volume= 84 | issue= 6 | pages= 831-6 | pmid=4826616 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4826616 }} </ref><ref name="pmid6112527">{{cite journal| author=Trompeter RS, Evans PR, Barratt TM| title=Gonadal function in boys with steroid-responsive nephrotic syndrome treated with cyclophosphamide for short periods. | journal=Lancet | year= 1981 | volume= 1 | issue= 8231 | pages= 1177-9 | pmid=6112527 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=6112527 }} </ref> and higher than 168 mg/kg, according to one meta-analysis.<ref name="pmid15683089">{{cite journal| author=Wetzels JF| title=Cyclophosphamide-induced gonadal toxicity: a treatment dilemma in patients with lupus nephritis? | journal=Neth J Med | year= 2004 | volume= 62 | issue= 10 | pages= 347-52 | pmid=15683089 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15683089 }} </ref> Comparison between control subjects and children with idiopathic nephrotic syndrome receiving a cumulative dose of 23,000 mg of alternate-day steroid therapy for a mean duration of 53 months showed no increased risk in [[osteoporosis]].<ref name="pmid15329424">{{cite journal| author=Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA| title=Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. | journal=N Engl J Med | year= 2004 | volume= 351 | issue= 9 | pages= 868-75 | pmid=15329424 | doi=10.1056/NEJMoa040367 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15329424 }} </ref> Renal outcomes are generally excellent in patients receiving steroid therapy. Nonetheless, [[cyclosporine]]-induced nephrotoxicity, even without a decrease in GFR, is observed in patients receiving [[cyclosporine]] therapy for more than 18-24 months.<ref name="pmid7994931">{{cite journal| author=Habib R, Niaudet P| title=Comparison between pre- and posttreatment renal biopsies in children receiving ciclosporine for idiopathic nephrosis. | journal=Clin Nephrol | year= 1994 | volume= 42 | issue= 3 | pages= 141-6 | pmid=7994931 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7994931 }} </ref><ref name="pmid8072258">{{cite journal| author=Meyrier A, Noël LH, Auriche P, Callard P| title=Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Société de Néphrologie. | journal=Kidney Int | year= 1994 | volume= 45 | issue= 5 | pages= 1446-56 | pmid=8072258 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8072258 }} </ref> | ||
==References== | ==References== | ||
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{{WS}} | {{WS}} | ||
[[Category: | [[Category:Nephrology]] | ||
[[Category:Disease]] | [[Category:Disease]] | ||
[[Category:Kidney diseases]] | [[Category:Kidney diseases]] | ||
[[Category:Urology]] | [[Category:Urology]] | ||
Revision as of 16:07, 5 April 2015
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Minimal Change Disease Microchapters |
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Minimal change disease natural history, complications and prognosis On the Web |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Yazan Daaboul, Serge Korjian
Overview
Complications associated with the pathogenesis of the disease as a nephrotic syndrome include thromboembolic events and disorders of hemostasis, hyperlipidemia, vulnerability to infections, and hypertension.[1] Before the steroid era, patients died of renal failure and from infections.[2] Nowadays, patients have excellent renal outcomes when they are still steroid-responsive and virtually all patients survive with a normal creatinine clearance.[2][3] Although renal outcomes are considered excellent with appropriate therapy, the risk of chronic renal disease cannot be completely ruled out, especially among patients receiving nephrotoxic medications for prolonged periods of time.[3]
Natural History and Prognosis
Outcomes in minimal change disease have been mostly studied in the pediatric population, with very little knowledge in in adults. Before the steroid era, patients died of renal failure and from infections.[2] Nowadays, patients have excellent renal outcomes when they are still steroid-responsive and virtually all patients survive with a normal creatinine clearance.[2][3] Up to 80% of children with nephrotic syndrome respond to corticosteroids and become in full remission within 1 month of steroid therapy. Of those, 30% require only 1 course of steroids, 20% require several courses, and 30-50% suffer from frequently relapsing nephrotic syndrome (FRNS) when steroids are discontinued.[4][3] Age at disease onset is strongly associated with the frequency of relapses in children.
It was once believed that only 10% of children with minimal change disease persist into adulthood.[5][6] More recent data shows that the rate is in fact higher, reaching approximately 25-42%. Risk factors for persistence of minimal change disease into adulthood are as follows:[3][7][2]
- Young age at diagnosis
- Increased number of relapses
- Use of alkylating agents and cyclosporine
Although renal outcomes are considered excellent with appropriate therapy, the risk of chronic renal disease cannot be completely ruled out, especially among patients receiving nephrotoxic medications for prolonged periods of time.[3]
There are much less knowledge of outcomes and prognosis of adult-onset minimal change disease. In adults, 90% achieve remission with corticosteroids, but the rate of relapse of the first episode of nephrotic syndrome is as high as 70%, where approximately 30% have frequent relapses.[1] Young patients < 40 years at onset of disease are found in some studies to experience recurrence of disease than their older peers; these findings, however, have not been consistent in the literature.[8][9][10][1] The number of relapses is ultimately associated with long-term renal outcomes and steroid dependence.[1]
Complications
Complications associated with the pathogenesis of the disease as a nephrotic syndrome include thromboembolic events and disorders of hemostasis, hyperlipidemia, vulnerability to infections, and hypertension.[1] The frequency of acute kidney injury (AKI) associated with minimal change disease is also higher. According to Waldman and colleagues[1], who studied 95 patients with adult-onset minimal change disease, the rate of acute kidney injury was approximately 25%. Whereas early reports showed that AKI is a reversible complication, larger trials suggested that creatinine was still significantly higher in these patients at 15-year follow-up.[1] Accordingly, the true renal outcome following AKI in minimal change disease is still controversial and requires further investigation. The presence of chronic kidney disease raises the suspicion of focal segmental glomerulosclerosis (FSGS). Waldman and colleagues described the following risk factors for acute kidney injury[1]:
- Male gender
- Older age > 54.5 years
Steroid resistance, defined as steroid therapy for more than 4 months, is not uncommon in adults.[1] A subset of patients becomes steroid-resistant and is thus associated with the progression of disease into focal segmental glomerulosclerosis (FSGS). Cyclosporine may induce remission in approximately 60% of patients,[11][12][13] whereas cyclophosphamide may induce remission in approximately 25-60% of patients for five years. Resistance to cyclosporine and cyclophosphamide has also been described.[1] Similarly, the diagnosis of FSGS in patients who fail to respond to alternative therapy should also be highly considered.[1]
Complications of minimal change disease may be due in fact complications of medications, such as weight gain, osteoporosis, cataract, diabetes, and cardiovascular events associated with corticosteroids.[2][14][15][16] The rate of these complications has become much less frequent with the use of steroid-sparing agents and the use of “alternate-day” steroid therapy.[2][17] Similarly, the use of alkylating agents, like cyclophosphamide, is also associated with reversible and irreversible azoospermia and oligospermia at higher doses of 150-250 mg/kg.[18][19][20] and higher than 168 mg/kg, according to one meta-analysis.[21] Comparison between control subjects and children with idiopathic nephrotic syndrome receiving a cumulative dose of 23,000 mg of alternate-day steroid therapy for a mean duration of 53 months showed no increased risk in osteoporosis.[17] Renal outcomes are generally excellent in patients receiving steroid therapy. Nonetheless, cyclosporine-induced nephrotoxicity, even without a decrease in GFR, is observed in patients receiving cyclosporine therapy for more than 18-24 months.[22][11]
References
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Waldman M, Crew RJ, Valeri A, Busch J, Stokes B, Markowitz G; et al. (2007). "Adult minimal-change disease: clinical characteristics, treatment, and outcomes". Clin J Am Soc Nephrol. 2 (3): 445–53. doi:10.2215/CJN.03531006. PMID 17699450.
- ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 Kyrieleis HA, Löwik MM, Pronk I, Cruysberg HR, Kremer JA, Oyen WJ; et al. (2009). "Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children". Clin J Am Soc Nephrol. 4 (10): 1593–600. doi:10.2215/CJN.05691108. PMC 2758253. PMID 19808243.
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Niaudet P (2009). "Long-term outcome of children with steroid-sensitive idiopathic nephrotic syndrome". Clin J Am Soc Nephrol. 4 (10): 1547–8. doi:10.2215/CJN.05950809. PMID 19808239.
- ↑ Tarshish P, Tobin JN, Bernstein J, Edelmann CM (1997). "Prognostic significance of the early course of minimal change nephrotic syndrome: report of the International Study of Kidney Disease in Children". J Am Soc Nephrol. 8 (5): 769–76. PMID 9176846.
- ↑ Koskimies O, Vilska J, Rapola J, Hallman N (1982). "Long-term outcome of primary nephrotic syndrome". Arch Dis Child. 57 (7): 544–8. PMC 1627702. PMID 7103547.
- ↑ Trompeter RS, Lloyd BW, Hicks J, White RH, Cameron JS (1985). "Long-term outcome for children with minimal-change nephrotic syndrome". Lancet. 1 (8425): 368–70. PMID 2857421.
- ↑ Rüth EM, Kemper MJ, Leumann EP, Laube GF, Neuhaus TJ (2005). "Children with steroid-sensitive nephrotic syndrome come of age: long-term outcome". J Pediatr. 147 (2): 202–7. doi:10.1016/j.jpeds.2005.03.050. PMID 16126050.
- ↑ Nakayama M, Katafuchi R, Yanase T, Ikeda K, Tanaka H, Fujimi S (2002). "Steroid responsiveness and frequency of relapse in adult-onset minimal change nephrotic syndrome". Am J Kidney Dis. 39 (3): 503–12. doi:10.1053/ajkd.2002.31400. PMID 11877569.
- ↑ Korbet SM, Schwartz MM, Lewis EJ (1988). "Minimal-change glomerulopathy of adulthood". Am J Nephrol. 8 (4): 291–7. PMID 3189423.
- ↑ Huang JJ, Hsu SC, Chen FF, Sung JM, Tseng CC, Wang MC (2001). "Adult-onset minimal change disease among Taiwanese: clinical features, therapeutic response, and prognosis". Am J Nephrol. 21 (1): 28–34. doi:46215 Check
|doi=value (help). PMID 11275629. - ↑ 11.0 11.1 Meyrier A, Noël LH, Auriche P, Callard P (1994). "Long-term renal tolerance of cyclosporin A treatment in adult idiopathic nephrotic syndrome. Collaborative Group of the Société de Néphrologie". Kidney Int. 45 (5): 1446–56. PMID 8072258.
- ↑ Tejani AT, Butt K, Trachtman H, Suthanthiran M, Rosenthal CJ, Khawar MR (1988). "Cyclosporine A induced remission of relapsing nephrotic syndrome in children". Kidney Int. 33 (3): 729–34. PMID 2966873.
- ↑ Ponticelli C, Edefonti A, Ghio L, Rizzoni G, Rinaldi S, Gusmano R; et al. (1993). "Cyclosporin versus cyclophosphamide for patients with steroid-dependent and frequently relapsing idiopathic nephrotic syndrome: a multicentre randomized controlled trial". Nephrol Dial Transplant. 8 (12): 1326–32. PMID 8159300.
- ↑ Gulati S, Sharma RK, Gulati K, Singh U, Srivastava A (2005). "Longitudinal follow-up of bone mineral density in children with nephrotic syndrome and the role of calcium and vitamin D supplements". Nephrol Dial Transplant. 20 (8): 1598–603. doi:10.1093/ndt/gfh809. PMID 15956073.
- ↑ Hayasaka Y, Hayasaka S, Matsukura H (2006). "Ocular findings in Japanese children with nephrotic syndrome receiving prolonged corticosteroid therapy". Ophthalmologica. 220 (3): 181–5. doi:10.1159/000091762. PMID 16679793.
- ↑ Fakhouri F, Bocquet N, Taupin P, Presne C, Gagnadoux MF, Landais P; et al. (2003). "Steroid-sensitive nephrotic syndrome: from childhood to adulthood". Am J Kidney Dis. 41 (3): 550–7. doi:10.1053/ajkd.2003.50116. PMID 12612977.
- ↑ 17.0 17.1 Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA (2004). "Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome". N Engl J Med. 351 (9): 868–75. doi:10.1056/NEJMoa040367. PMID 15329424.
- ↑ Hsu AC, Folami AO, Bain J, Rance CP (1979). "Gonadal function in males treated with cyclophosphamide for nephrotic syndrome". Fertil Steril. 31 (2): 173–7. PMID 761678.
- ↑ Penso J, Lippe B, Ehrlich R, Smith FG (1974). "Testicular function in prepubertal and pubertal male patients treated with cyclophosphamide for nephrotic syndrome". J Pediatr. 84 (6): 831–6. PMID 4826616.
- ↑ Trompeter RS, Evans PR, Barratt TM (1981). "Gonadal function in boys with steroid-responsive nephrotic syndrome treated with cyclophosphamide for short periods". Lancet. 1 (8231): 1177–9. PMID 6112527.
- ↑ Wetzels JF (2004). "Cyclophosphamide-induced gonadal toxicity: a treatment dilemma in patients with lupus nephritis?". Neth J Med. 62 (10): 347–52. PMID 15683089.
- ↑ Habib R, Niaudet P (1994). "Comparison between pre- and posttreatment renal biopsies in children receiving ciclosporine for idiopathic nephrosis". Clin Nephrol. 42 (3): 141–6. PMID 7994931.