Etiology, clinical features, and diagnosis of minimal change disease in adults
- Alain Meyrier, MD
Alain Meyrier, MD
- Professor of Medicine (Emeritus)
- Université Paris-Descartes, Paris, France
- Jai Radhakrishnan, MD, MS
Jai Radhakrishnan, MD, MS
- Professor of Medicine
- Columbia University Medical Center
- Section Editors
- Richard J Glassock, MD, MACP
Richard J Glassock, MD, MACP
- Editor-in-Chief — Nephrology
- Section Editor — Glomerular Diseases
- Emeritus Professor
- The David Geffen School of Medicine at UCLA
- Fernando C Fervenza, MD, PhD
Fernando C Fervenza, MD, PhD
- Section Editor — Glomerular Diseases
- Professor of Medicine
- Mayo Clinic College of Medicine
Minimal change disease (MCD) is a major cause of nephrotic syndrome (approximately 90 percent) in children and in a minority of adults (approximately 10 percent). MCD and focal segmental glomerulosclerosis (FSGS) are both examples of pathogenic mechanisms that primarily affect the podocyte ("podocytopathies"). These entities are not characterized by immune deposits, but there may be a role for circulating factors in the pathogenesis of both diseases. (See 'Pathogenesis' below and 'Primary MCD versus primary FSGS' below.)
The pathogenesis, etiology, causes, and diagnosis of MCD in adults will be reviewed here. The treatment of MCD as well as the pathogenesis, diagnosis, and treatment of FSGS are discussed separately. (See "Treatment of minimal change disease in adults" and "Epidemiology, classification, and pathogenesis of focal segmental glomerulosclerosis" and "Treatment of primary focal segmental glomerulosclerosis".)
MCD is the most common cause of nephrotic syndrome in children, with variations in incidence based upon age [1-3] (see "Etiology, clinical manifestations, and diagnosis of nephrotic syndrome in children", section on 'Idiopathic nephrotic syndrome'):
●Among children under age 10 years who present with idiopathic nephrotic syndrome, MCD is the underlying disease in approximately 90 percent.
●Among children over age 10 years, MCD accounts for only 50 percent of cases with an increased percentage of focal segmental glomerulosclerosis (FSGS) in this age group.To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Nephrotic syndrome in children: prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. A report of the International Study of Kidney Disease in Children. Kidney Int 1978; 13:159.
- Eddy AA, Symons JM. Nephrotic syndrome in childhood. Lancet 2003; 362:629.
- Vivarelli M, Massella L, Ruggiero B, Emma F. Minimal Change Disease. Clin J Am Soc Nephrol 2017; 12:332.
- Cameron JS. The nephrotic syndrome and its complications. Am J Kidney Dis 1987; 10:157.
- Filler G, Young E, Geier P, et al. Is there really an increase in non-minimal change nephrotic syndrome in children? Am J Kidney Dis 2003; 42:1107.
- Haas M, Meehan SM, Karrison TG, Spargo BH. Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. Am J Kidney Dis 1997; 30:621.
- Bonilla-Felix M, Parra C, Dajani T, et al. Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. Kidney Int 1999; 55:1885.
- Srivastava T, Simon SD, Alon US. High incidence of focal segmental glomerulosclerosis in nephrotic syndrome of childhood. Pediatr Nephrol 1999; 13:13.
- Feehally J, Kendell NP, Swift PG, Walls J. High incidence of minimal change nephrotic syndrome in Asians. Arch Dis Child 1985; 60:1018.
- Fogo A, Hawkins EP, Berry PL, et al. Glomerular hypertrophy in minimal change disease predicts subsequent progression to focal glomerular sclerosis. Kidney Int 1990; 38:115.
- Schnaper HW, Robson AA, Kopp JB. Nephrotic syndrome: Minimal change nephropathy, focal segmental glomerulosclerosis, and collapsing glomerulopathy. In: Diseases of the Kidney and Urinary Tract, 8th ed, Schrier RW (Ed), Lippincott Williams & Wilkins, Philadelphia 2007. p.1585.
- Shirato I. Podocyte process effacement in vivo. Microsc Res Tech 2002; 57:241.
- Smithies O. Why the kidney glomerulus does not clog: a gel permeation/diffusion hypothesis of renal function. Proc Natl Acad Sci U S A 2003; 100:4108.
- van den Berg JG, van den Bergh Weerman MA, Assmann KJ, et al. Podocyte foot process effacement is not correlated with the level of proteinuria in human glomerulopathies. Kidney Int 2004; 66:1901.
- Shalhoub RJ. Pathogenesis of lipoid nephrosis: a disorder of T-cell function. Lancet 1974; 2:556.
- Le Berre L, Bruneau S, Naulet J, et al. Induction of T regulatory cells attenuates idiopathic nephrotic syndrome. J Am Soc Nephrol 2009; 20:57.
- Sellier-Leclerc AL, Duval A, Riveron S, et al. A humanized mouse model of idiopathic nephrotic syndrome suggests a pathogenic role for immature cells. J Am Soc Nephrol 2007; 18:2732.
- Yang T, Nast CC, Vo A, Jordan SC. Rapid remission of steroid and mycophenolate mofetil (mmf)-resistant minimal change nephrotic syndrome after rituximab therapy. Nephrol Dial Transplant 2008; 23:377.
- Maas RJ, Deegens JK, Wetzels JF. Permeability factors in idiopathic nephrotic syndrome: historical perspectives and lessons for the future. Nephrol Dial Transplant 2014; 29:2207.
- Koyama A, Fujisaki M, Kobayashi M, et al. A glomerular permeability factor produced by human T cell hybridomas. Kidney Int 1991; 40:453.
- Aggarwal N, Batwara R, McCarthy ET, et al. Serum permeability activity in steroid-resistant minimal change nephrotic syndrome is abolished by treatment of Hodgkin disease. Am J Kidney Dis 2007; 50:826.
- Ali AA, Wilson E, Moorhead JF, et al. Minimal-change glomerular nephritis. Normal kidneys in an abnormal environment? Transplantation 1994; 58:849.
- Lai KW, Wei CL, Tan LK, et al. Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats. J Am Soc Nephrol 2007; 18:1476.
- Kimata H, Fujimoto M, Furusho K. Involvement of interleukin (IL)-13, but not IL-4, in spontaneous IgE and IgG4 production in nephrotic syndrome. Eur J Immunol 1995; 25:1497.
- Yap HK, Cheung W, Murugasu B, et al. Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse. J Am Soc Nephrol 1999; 10:529.
- Cheung W, Wei CL, Seah CC, et al. Atopy, serum IgE, and interleukin-13 in steroid-responsive nephrotic syndrome. Pediatr Nephrol 2004; 19:627.
- Van Den Berg JG, Aten J, Chand MA, et al. Interleukin-4 and interleukin-13 act on glomerular visceral epithelial cells. J Am Soc Nephrol 2000; 11:413.
- Van Den Berg JG, Aten J, Annink C, et al. Interleukin-4 and -13 promote basolateral secretion of H(+) and cathepsin L by glomerular epithelial cells. Am J Physiol Renal Physiol 2002; 282:F26.
- Ishimoto T, Shimada M, Araya CE, et al. Minimal change disease: a CD80 podocytopathy? Semin Nephrol 2011; 31:320.
- Carrie BJ, Salyer WR, Myers BD. Minimal change nephropathy: an electrochemical disorder of the glomerular membrane. Am J Med 1981; 70:262.
- Guasch A, Deen WM, Myers BD. Charge selectivity of the glomerular filtration barrier in healthy and nephrotic humans. J Clin Invest 1993; 92:2274.
- Kerjaschki D. Caught flat-footed: podocyte damage and the molecular bases of focal glomerulosclerosis. J Clin Invest 2001; 108:1583.
- Meyrier A. Mechanisms of disease: focal segmental glomerulosclerosis. Nat Clin Pract Nephrol 2005; 1:44.
- Patrakka J, Lahdenkari AT, Koskimies O, et al. The number of podocyte slit diaphragms is decreased in minimal change nephrotic syndrome. Pediatr Res 2002; 52:349.
- Chiang CK, Inagi R. Glomerular diseases: genetic causes and future therapeutics. Nat Rev Nephrol 2010; 6:539.
- Almansori M, Kovithavongs T, Qarni MU. Cyclooxygenase-2 inhibitor-associated minimal-change disease. Clin Nephrol 2005; 63:381.
- Glassock RJ. Secondary minimal change disease. Nephrol Dial Transplant 2003; 18 Suppl 6:vi52.
- Lecoules S, Duvic C, Hérody M, Nédélec G. [Tiopronin-induced nephrotic syndrome with minimal glomerular lesions]. Presse Med 1999; 28:273.
- Aoyama M, Sugimoto T, Yokono T, et al. Minimal-change nephropathy and chronic hepatitis C infection: coincidental or associated? Nephrol Dial Transplant 2007; 22:1479.
- Dabbs DJ, Striker LM, Mignon F, Striker G. Glomerular lesions in lymphomas and leukemias. Am J Med 1986; 80:63.
- Audard V, Larousserie F, Grimbert P, et al. Minimal change nephrotic syndrome and classical Hodgkin's lymphoma: report of 21 cases and review of the literature. Kidney Int 2006; 69:2251.
- Korzets Z, Golan E, Manor Y, et al. Spontaneously remitting minimal change nephropathy preceding a relapse of Hodgkin's disease by 19 months. Clin Nephrol 1992; 38:125.
- Alpers CE, Cotran RS. Neoplasia and glomerular injury. Kidney Int 1986; 30:465.
- Meyrier A, Delahousse M, Callard P, Rainfray M. Minimal change nephrotic syndrome revealing solid tumors. Nephron 1992; 61:220.
- Auguet T, Lorenzo A, Colomer E, et al. Recovery of minimal change nephrotic syndrome and acute renal failure in a patient withRenal cell carcinoma. Am J Nephrol 1998; 18:433.
- Kwiatkowska E, Gołembiewska E, Ciechanowski K, Kędzierska K. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection. Case Rep Nephrol 2012; 2012:294532.
- Boix E, Rivera F, Gil CM, et al. Steroid-responsive nephrotic syndrome with minimal-change disease and IgA deposits in a HIV-infected patient. Nephrol Dial Transplant 2000; 15:412.
- Niaudet P, Meyrier A. Minimal change disease: clinical features and diagnosis. In: Oxford Textbook of Clinical Nephrology, 4th ed, Turner N, Lameire N, Goldsmith DJ, et al (Eds), Oxford University Press, Oxford 2016. Vol 1, p.501.
- Abdel-Hafez M, Shimada M, Lee PY, et al. Idiopathic nephrotic syndrome and atopy: is there a common link? Am J Kidney Dis 2009; 54:945.
- Lagrue G, Laurent J, Rostoker G. Food allergy and idiopathic nephrotic syndrome. Kidney Int Suppl 1989; 27:S147.
- Lai KN, Lai FM, Chan KW, et al. An overlapping syndrome of IgA nephropathy and lipoid nephrosis. Am J Clin Pathol 1986; 86:716.
- Cheng IK, Chan KW, Chan MK. Mesangial IgA nephropathy with steroid-responsive nephrotic syndrome: disappearance of mesangial IgA deposits following steroid-induced remission. Am J Kidney Dis 1989; 14:361.
- Westhoff TH, Waldherr R, Loddenkemper C, et al. Mesangial IgA deposition in minimal change nephrotic syndrome: coincidence of different entities or variant of minimal change disease? Clin Nephrol 2006; 65:203.
- Dube GK, Markowitz GS, Radhakrishnan J, et al. Minimal change disease in systemic lupus erythematosus. Clin Nephrol 2002; 57:120.
- Rao PS. Nephrotic syndrome in patients with peripheral blood stem cell transplant. Am J Kidney Dis 2005; 45:780.
- Lai TS, Lin WC, Wu MS, et al. Primary biliary cirrhosis associated with minimal change disease. Nephrol Dial Transplant 2007; 22:966.
- Rossiñol T, Cervera R, López C, et al. Antiphospholipid syndrome and minimal change nephropathy. Lupus 2006; 15:547.
- Ergün I, Akbostanci MC, Canbakan B, et al. Minimal change nephrotic syndrome with stiff-person syndrome: is there a link? Am J Kidney Dis 2005; 46:e11.
- Waldman M, Crew RJ, Valeri A, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol 2007; 2:445.
- Nakayama M, Katafuchi R, Yanase T, et al. Steroid responsiveness and frequency of relapse in adult-onset minimal change nephrotic syndrome. Am J Kidney Dis 2002; 39:503.
- Maas RJ, Deegens JK, Smeets B, et al. Minimal change disease and idiopathic FSGS: manifestations of the same disease. Nat Rev Nephrol 2016; 12:768.
- Hayslett JP, Krassner LS, Bensch KG, et al. Progression of "lipoid nephrosis" to renal insufficiency. N Engl J Med 1969; 281:181.
- Tejani A. Morphological transition in minimal change nephrotic syndrome. Nephron 1985; 39:157.
- Moutzouris DA, Herlitz L, Appel GB, et al. Renal biopsy in the very elderly. Clin J Am Soc Nephrol 2009; 4:1073.
- T cell dysfunction
- B cell dysfunction
- Glomerular permeability factor
- Role of the glomerular basement membrane
- Role of the slit diaphragm
- Other glomerular diseases
- Other etiologies
- CLINICAL MANIFESTATIONS
- Differential diagnosis
- - Primary MCD versus primary FSGS
- MCD in the older adult
- MCD and acute kidney injury