Minimal-Change Disease Workup
- Author: Abeera Mansur, MD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Urinalysis findings are benign in minimal-change disease (MCD), but profound proteinuria and oval fat bodies may be observed. In children, the critical level for diagnosis is proteinuria of more than 40 mg/h/m2. In adults, the threshold is more than 3.5 g/d/1.73 m2.
A random albumin-to-creatinine concentration ratio is in excess of 5. Urine specific gravity is high because of proteinuria. A 24-hour urine measurement should be obtained for protein and creatinine clearance.
Hypoalbuminemia is an important marker of nephrotic syndrome. The level at which edema occurs varies, but it tends to be lower in children than in adults. Nephrotic syndrome in children is defined by a serum albumin of less than 2.5 g/dL. Hyperlipidemia also is a feature of a nephrotic state.
Other laboratory findings are as follows:
Renal function usually is normal except in cases of undiagnosed focal segmental glomerulosclerosis (FSGS) or in those cases that progress to acute renal failure
Hyponatremia is often observed and is in part a spurious finding secondary to the hyperlipidemic state; it also occurs from water retention caused by hypovolemia and antidiuretic hormone release
Renal sonogram results are normal in patients with MCD.
Because MCD accounts for 90% of all cases of idiopathic nephrotic syndrome in children, renal biopsy is not part of the initial workup for MCD in that age group. Instead, biopsy is performed only in those children who fail to achieve remission with an empiric course of corticosteroids. In contrast, a renal biopsy is performed in all adult patients with nephrotic syndrome, before the initiation of treatment for MCD.
In patients with MCD, the glomerulus is, by definition, normal or nearly so when examined with the light microscope; however, the precise limits of normal are not clearly defined. This creates difficulty in differentiating the appearance of minimal change with mild mesangial proliferation from a mesangial proliferative glomerulonephritis. Diagnosis can be even more difficult because, at the peak age of onset (approximately 3 y), the mesangial and epithelial cells are more prominent. In adult patients, diagnosis is made more challenging by superimposed arterionephrosclerosis secondary to hypertension.
In children with frequently relapsing MCD, some involuted glomeruli may be present. These lesions are small and sclerotic but retain their podocyte and parietal epithelial cell constituents. The presence of these glomeruli is related to the duration of the disease.
The most common tubular lesion is protein and lipid droplets in epithelial cells due to increased reabsorption. The presence of areas of tubular atrophy and interstitial fibrosis should raise the suspicion of FSGS.
These studies usually do not demonstrate significant glomerular deposition of immunoglobulins or complement components in patients with MCD. Some biopsy specimens may be positive for low-level IgM deposits not accompanied by mesangial dense deposits.
Retraction of the epithelial foot processes is observed consistently in patients with MCD. This is, at times, erroneously described as foot-process fusion and results from disordered epithelial cell structure with withdrawal of the dendritic process. This finding is not unique to MCD, and the diagnosis is one of exclusion of other diseases based on lack of other processes on light microscopy, immunohistology, or electron microscopy.
Shao YN, Chen YC, Jenq CC, et al. Serum immunoglobulin E can predict minimal change disease before renal biopsy. Am J Med Sci. 2009 Oct. 338(4):264-7. [Medline].
Lai KW, Wei CL, Tan LK, et al. Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats. J Am Soc Nephrol. 2007 May. 18(5):1476-85. [Medline].
Izzedine H, Brocheriou I, Eymard B, et al. Loss of podocyte dysferlin expression is associated with minimal change nephropathy. Am J Kidney Dis. 2006 Jul. 48(1):143-50. [Medline].
Garin EH, Mu W, Arthur JM, Rivard CJ, Araya CE, Shimada M, et al. Urinary CD80 is elevated in minimal change disease but not in focal segmental glomerulosclerosis. Kidney Int. 2010 Aug. 78(3):296-302.
Ling C, Liu X, Shen Y, Chen Z, Fan J, Jiang Y, et al. Urinary CD80 levels as a diagnostic biomarker of minimal change disease. Pediatr Nephrol. 2015 Feb. 30(2):309-16. [Medline].
Kontchou LM, Liccioli G, Pela I. Blood pressure in children with minimal change nephrotic syndrome during oedema and after steroid therapy: the influence of familial essential hypertension. Kidney Blood Press Res. 2009. 32(4):258-62. [Medline].
Hamasaki Y, Yoshikawa N, Hattori S, et al. Cyclosporine and steroid therapy in children with steroid-resistant nephrotic syndrome. Pediatr Nephrol. 2009 Nov. 24(11):2177-85. [Medline].
Swartz SJ, Eldin KW, Hicks MJ, Feig DI. Minimal change disease with IgM+ immunofluorescence: a subtype of nephrotic syndrome. Pediatr Nephrol. 2009 Jun. 24(6):1187-92. [Medline].
Cattran DC, Alexopoulos E, Heering P, et al. Cyclosporin in idiopathic glomerular disease associated with the nephrotic syndrome : workshop recommendations. Kidney Int. 2007 Dec. 72(12):1429-47. [Medline].
Sellier-Leclerc AL, Macher MA, Loirat C, Guerin V, Watier H, Peuchmaur M. Rituximab efficiency in children with steroid-dependent nephrotic syndrome. Pediatr Nephrol. 2010 Jun. 25(6):1109-15. [Medline].
Hoxha E, Stahl RA, Harendza S. Rituximab in adult patients with immunosuppressive-dependent minimal change disease. Clin Nephrol. 2011 Aug. 76(2):151-8. [Medline].
Munyentwali H, Bouachi K, Audard V, Remy P, Lang P, Mojaat R. Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease. Kidney Int. 2013 Jan 16. [Medline].
Caridi G, Gigante M, Ravani P, et al. Clinical features and long-term outcome of nephrotic syndrome associated with heterozygous NPHS1 and NPHS2 mutations. Clin J Am Soc Nephrol. 2009 Jun. 4(6):1065-72. [Medline]. [Full Text].
Li X, Li H, Chen J, et al. Tacrolimus as a steroid-sparing agent for adults with steroid-dependent minimal change nephrotic syndrome. Nephrol Dial Transplant. 2008 Jun. 23(6):1919-25. [Medline].
Sinha MD, MacLeod R, Rigby E, Clark AG. Treatment of severe steroid-dependent nephrotic syndrome (SDNS) in children with tacrolimus. Nephrol Dial Transplant. 2006 Jul. 21(7):1848-54. [Medline].
Westhoff TH, Schmidt S, Zidek W, Beige J, van der Giet M. Tacrolimus in steroid-resistant and steroid-dependent nephrotic syndrome. Clin Nephrol. 2006 Jun. 65(6):393-400. [Medline].
Gulati A, Sinha A, Gupta A, Kanitkar M, Sreenivas V, Sharma J. Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide as the initial therapy for children with steroid-resistant nephrotic syndrome. Kidney Int. 2012 Nov. 82(10):1130-5. [Medline].
Fujinaga S, Hirano D, Nishizaki N, Kamei K, Ito S, Ohtomo Y, et al. Single infusion of rituximab for persistent steroid-dependent minimal-change nephrotic syndrome after long-term cyclosporine. Pediatr Nephrol. 2010. 25(3:359.
Guitard J, Hebral AL, Fakhouri F, Joly D, Daugas E, Rivalan J, et al. Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance. Nephrol Dial Transplant. 2014 Nov. 29(11):2084-91. [Medline].
Waldman M, Crew RJ, Valeri A, et al. Adult minimal-change disease: clinical characteristics, treatment, and outcomes. Clin J Am Soc Nephrol. 2007 May. 2(3):445-53. [Medline].
Ahmad H, Tejani A. Predictive value of repeat renal biopsies in children with nephrotic syndrome. Nephron. 2000 Apr. 84(4):342-6. [Medline].
Araya CE, Wasserfall CH, Brusko TM, et al. A case of unfulfilled expectations. Cytokines in idiopathic minimal lesion nephrotic syndrome. Pediatr Nephrol. 2006 May. 21(5):603-10. [Medline].
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 Jun. 69(12):2251-60. [Medline].
Bagga A, Hari P, Moudgil A, Jordan SC. Mycophenolate mofetil and prednisolone therapy in children with steroid-dependent nephrotic syndrome. Am J Kidney Dis. 2003 Dec. 42(6):1114-20. [Medline].
Bonilla-Felix M, Parra C, Dajani T, et al. Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. Kidney Int. 1999 May. 55(5):1885-90. [Medline].
Cho BS, Yoon SR, Jang JY, Pyun KH, Lee CE. Up-regulation of interleukin-4 and CD23/FcepsilonRII in minimal change nephrotic syndrome. Pediatr Nephrol. 1999 Apr. 13(3):199-204. [Medline].
Choi MJ, Eustace JA, Gimenez LF, et al. Mycophenolate mofetil treatment for primary glomerular diseases. Kidney Int. 2002 Mar. 61(3):1098-114. [Medline].
Day CJ, Cockwell P, Lipkin GW, Savage CO, Howie AJ, Adu D. Mycophenolate mofetil in the treatment of resistant idiopathic nephrotic syndrome. Nephrol Dial Transplant. 2002 Nov. 17(11):2011-3. [Medline].
Dijkman HB, Wetzels JF, Gemmink JH, Baede J, Levtchenko EN, Steenbergen EJ. Glomerular involution in children with frequently relapsing minimal change nephrotic syndrome: an unrecognized form of glomerulosclerosis?. Kidney Int. 2007 Jan. 71(1):44-52. [Medline].
Donia AF, Gazareen SH, Ahmed HA, et al. Pulse cyclophosphamide inadequately suppresses reoccurrence of minimal change nephrotic syndrome in corticoid-dependent children. Nephrol Dial Transplant. 2003 Oct. 18(10):2054-8. [Medline].
Grimbert P, Audard V, Remy P, Lang P, Sahali D. Recent approaches to the pathogenesis of minimal-change nephrotic syndrome. Nephrol Dial Transplant. 2003 Feb. 18(2):245-8. [Medline].
Humphreys BD, Vanguri VK, Henderson J, Antin JH. Minimal-change nephrotic syndrome in a hematopoietic stem-cell transplant recipient. Nat Clin Pract Nephrol. 2006 Sep. 2(9):535-9; quiz 540. [Medline].
Jennette JC, Falk RJ. Adult minimal change glomerulopathy with acute renal failure. Am J Kidney Dis. 1990 Nov. 16(5):432-7. [Medline].
Kyrieleis HA, Lowik MM, Pronk I, et al. Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children. Clin J Am Soc Nephrol. 2009 Oct. 4(10):1593-600. [Medline]. [Full Text].
Lahdenkari AT, Kestila M, Holmberg C, Koskimies O, Jalanko H. Nephrin gene (NPHS1) in patients with minimal change nephrotic syndrome (MCNS). Kidney Int. 2004 May. 65(5):1856-63. [Medline].
Nakayama M, Katafuchi R, Yanase T, Ikeda K, Tanaka H, Fujimi S. Steroid responsiveness and frequency of relapse in adult-onset minimal change nephrotic syndrome. Am J Kidney Dis. 2002 Mar. 39(3):503-12. [Medline].
Niaudet P. Treatment of childhood steroid-resistant idiopathic nephrosis with a combination of cyclosporine and prednisone. French Society of Pediatric Nephrology. J Pediatr. 1994 Dec. 125(6 Pt 1):981-6. [Medline].
Nolasco F, Cameron JS, Heywood EF, Hicks J, Ogg C, Williams DG. Adult-onset minimal change nephrotic syndrome: a long-term follow-up. Kidney Int. 1986 Jun. 29(6):1215-23. [Medline].
Prasad GV, Vincent L, Hamilton R, Lim K. Minimal change disease in association with fire coral (Millepora species) exposure. Am J Kidney Dis. 2006 Jan. 47(1):e15-6. [Medline].
Smith JD, Hayslett JP. Reversible renal failure in the nephrotic syndrome. Am J Kidney Dis. 1992 Mar. 19(3):201-13. [Medline].
Tang HL, Chu KH, Mak YF, et al. Minimal change disease following exposure to mercury-containing skin lightening cream. Hong Kong Med J. 2006 Aug. 12(4):316-8. [Medline].
Tarshish P, Tobin JN, Bernstein J, Edelmann CM Jr. 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. 1997 May. 8(5):769-76. [Medline].
The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr. 1981 Apr. 98(4):561-4. [Medline].
Wei CL, Cheung W, Heng CK, et al. Interleukin-13 genetic polymorphisms in Singapore Chinese children correlate with long-term outcome of minimal-change disease. Nephrol Dial Transplant. 2005 Apr. 20(4):728-34. [Medline].