* 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, who studied 95 patients with adult-onset minimal change disease, the rate of acute kidney injury was approximately 25%.<ref name="pmid17699450" />
* 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
** Older age > 54.5 years
** [[Hypertension]]
** [[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>
* 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 [[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>
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. Before the steroid era, patients died of renal failure and from infections. Nowadays, patients have excellent renal outcomes when they are still steroid-responsive and virtually all patients survive with a normal creatinineclearance. 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.
Natural History
The hallmark of minimal change disease in children is acute-onset proteinuria that progresses into nephrotic syndrome.
Finally, infections, such as pneumonia in an otherwise healthy individual, may be the first sign of nephrotic syndrome in minimal change disease.[1]
Complications
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.[3] Nowadays, patients have excellent renal outcomes when they are still steroid-responsive and virtually all patients survive with a normal creatinine clearance.[3][4] 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.[5][4] 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.[6][7] 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:[4][8][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.[4]
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.[9][10][11][1] The number of relapses is ultimately associated with long-term renal outcomes and steroid dependence.[1]