The Evidence-Based Approach to Adult-Onset Idiopathic Nephrotic Syndrome

Adult-onset nephrotic syndrome (NS) differs from its pediatric counterpart in several important ways. Most importantly, NS in adults is more etiologically heterogeneous compared to children, and thus treatment approaches rely heavily on the histological diagnosis provided by renal biopsy. The evidence-based approach to treatment of adult NS has been critically examined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines in glomerulonephritis, published in 2012. Here, we examine the strengths and limits of those guidelines and review recent work that expands the evidence-based approach.

[1]  J. Craig,et al.  Corticosteroid therapy for nephrotic syndrome in children. , 2020, The Cochrane database of systematic reviews.

[2]  J. Craig,et al.  Interventions for idiopathic steroid-resistant nephrotic syndrome in children. , 2016, The Cochrane database of systematic reviews.

[3]  A. Adeyemo,et al.  HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome. , 2015, Journal of the American Society of Nephrology : JASN.

[4]  S. Engelmann,et al.  A single-gene cause in 29.5% of cases of steroid-resistant nephrotic syndrome. , 2015, Journal of the American Society of Nephrology : JASN.

[5]  B. C. Kwan,et al.  Long-term outcome of biopsy-proven minimal change nephropathy in Chinese adults. , 2015, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[6]  A. Anarat,et al.  Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort. , 2015, Clinical journal of the American Society of Nephrology : CJASN.

[7]  A. Edefonti,et al.  Rituximab in Children with Steroid-Dependent Nephrotic Syndrome: A Multicenter, Open-Label, Noninferiority, Randomized Controlled Trial. , 2015, Journal of the American Society of Nephrology : JASN.

[8]  E. Daugas,et al.  Rituximab for minimal-change nephrotic syndrome in adulthood: predictive factors for response, long-term outcomes and tolerance. , 2014, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[9]  R. Mori,et al.  Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial , 2014, The Lancet.

[10]  V. Jha,et al.  Tacrolimus therapy in adult-onset steroid-resistant nephrotic syndrome due to a focal segmental glomerulosclerosis single-center experience. , 2014, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[11]  E. Ota,et al.  A multicenter randomized trial indicates initial prednisolone treatment for childhood nephrotic syndrome for two months is not inferior to six-month treatment , 2014, Kidney international.

[12]  J. Wetzels,et al.  Cancer risk after cyclophosphamide treatment in idiopathic membranous nephropathy. , 2014, Clinical journal of the American Society of Nephrology : CJASN.

[13]  A. Bruchfeld,et al.  Rituximab for minimal change disease in adults: long-term follow-up. , 2014, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[14]  M. Rudnicki,et al.  Rituximab in steroid-dependent or frequently relapsing idiopathic nephrotic syndrome. , 2014, Journal of the American Society of Nephrology : JASN.

[15]  Taixiang Wu,et al.  Lipid-lowering agents for nephrotic syndrome. , 2013, The Cochrane database of systematic reviews.

[16]  J. Radhakrishnan,et al.  The treatment of minimal change disease in adults. , 2013, Journal of the American Society of Nephrology : JASN.

[17]  M. Rudnicki,et al.  Rituximab in adult patients with multi-relapsing/steroid-dependent minimal change disease and focal segmental glomerulosclerosis: a report of 5 cases , 2013, Wiener klinische Wochenschrift.

[18]  J. Radhakrishnan,et al.  Impact of the National Institutes of Health Focal Segmental Glomerulosclerosis (NIH FSGS) clinical trial on the treatment of steroid-resistant FSGS. , 2013, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[19]  K. Dahan,et al.  Rituximab is an efficient and safe treatment in adults with steroid-dependent minimal change disease. , 2013, Kidney international.

[20]  Ľ. Podracká,et al.  [Practice guideline and trends for immunosuppressive treatment of glomerulonephritides according to KDIGO (Clinical Practice Guideline for Glomerulonephritis)]. , 2013, Vnitrni lekarstvi.

[21]  N. Chen,et al.  Tacrolimus versus Cyclophosphamide in Steroid-Dependent or Steroid-Resistant Focal Segmental Glomerulosclerosis: A Randomized Controlled Trial , 2013, American Journal of Nephrology.

[22]  A. Sinha,et al.  Treatment with tacrolimus and prednisolone is preferable to intravenous cyclophosphamide as the initial therapy for children with steroid-resistant nephrotic syndrome. , 2012, Kidney international.

[23]  D. Cattran,et al.  The KDIGO practice guideline on glomerulonephritis: reading between the (guide)lines--application to the individual patient. , 2012, Kidney international.

[24]  A. Fornoni,et al.  Podocyte Foot Process Effacement in Postreperfusion Allograft Biopsies Correlates With Early Recurrence of Proteinuria in Focal Segmental Glomerulosclerosis , 2012, Transplantation.

[25]  Jai Radhakrishnan,et al.  Notice , 2012, Kidney International Supplements.

[26]  S. Palmer,et al.  Trial quality in nephrology: how are we measuring up? , 2011, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[27]  B. Tazón-Vega,et al.  Clinical utility of genetic testing in children and adults with steroid-resistant nephrotic syndrome. , 2011, Clinical journal of the American Society of Nephrology : CJASN.

[28]  D. Leaf,et al.  Glomerular disease: why is there a dearth of high quality clinical trials? , 2010, Kidney international.

[29]  C. Antignac,et al.  Hereditary nephrotic syndrome: a systematic approach for genetic testing and a review of associated podocyte gene mutations , 2010, Pediatric Nephrology.

[30]  J. Egido,et al.  Rituximab treatment of adult patients with steroid-resistant focal segmental glomerulosclerosis. , 2009, Clinical journal of the American Society of Nephrology : CJASN.

[31]  J. G. van den Berg,et al.  Podocyte foot process effacement as a diagnostic tool in focal segmental glomerulosclerosis. , 2008, Kidney international.

[32]  V. D’Agati The spectrum of focal segmental glomerulosclerosis: new insights , 2008, Current opinion in nephrology and hypertension.

[33]  J. Nagy,et al.  [Focal segmental glomerulosclerosis]. , 2008, Orvosi hetilap.

[34]  V. D’Agati,et al.  Adult minimal-change disease: clinical characteristics, treatment, and outcomes. , 2007, Clinical journal of the American Society of Nephrology : CJASN.

[35]  A. Sanabria,et al.  Randomized controlled trial. , 2005, World journal of surgery.

[36]  J. Scholey,et al.  Focal and segmental glomerulosclerosis: definition and relevance of a partial remission. , 2005, Journal of the American Society of Nephrology : JASN.

[37]  E. Lewis,et al.  Focal segmental glomerulosclerosis in nephrotic adults: presentation, prognosis, and response to therapy of the histologic variants. , 2004, Journal of the American Society of Nephrology : JASN.

[38]  L. Moreland,et al.  A multicentre, double blind, randomised, placebo controlled trial of anakinra (Kineret), a recombinant interleukin 1 receptor antagonist, in patients with rheumatoid arthritis treated with background methotrexate , 2004, Annals of the rheumatic diseases.

[39]  Jonathan C Craig,et al.  The number, quality, and coverage of randomized controlled trials in nephrology. , 2004, Journal of the American Society of Nephrology : JASN.

[40]  G. Filler,et al.  Is there really an increase in non-minimal change nephrotic syndrome in children? , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[41]  T. Chan,et al.  Idiopathic minimal change nephrotic syndrome in older adults: steroid responsiveness and pattern of relapses. , 2003, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[42]  R. Portman,et al.  Changing patterns in the histopathology of idiopathic nephrotic syndrome in children. , 1999, Kidney international.

[43]  J. Grimshaw,et al.  Potential benefits, limitations, and harms of clinical guidelines , 1999, BMJ.

[44]  R. Doherty Long term follow up , 1999, BMJ.

[45]  D. Cattran,et al.  Long-term outcome in children and adults with classic focal segmental glomerulosclerosis. , 1998, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[46]  M. Haas,et al.  Changing etiologies of unexplained adult nephrotic syndrome: a comparison of renal biopsy findings from 1976-1979 and 1995-1997. , 1997, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[47]  S. Mak,et al.  Long-term outcome of adult-onset minimal-change nephropathy , 1996 .

[48]  M. Schwartz,et al.  The racial prevalence of glomerular lesions in nephrotic adults. , 1996, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[49]  M. Schwartz,et al.  Focal segmental glomerular sclerosis in adults: presentation, course, and response to treatment. , 1995, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[50]  E. Lewis,et al.  Primary focal segmental glomerulosclerosis: clinical course and response to therapy. , 1994, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[51]  C. Ponticelli,et al.  The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults. A collaborative retrospective study. , 1991, Clinical nephrology.

[52]  J. Cameron,et al.  Adult-onset minimal change nephrotic syndrome: a long-term follow-up. , 1986, Kidney international.

[53]  C. Chantler,et al.  The long-term prognosis of patients with focal segmental glomerulosclerosis. , 1978, Clinical nephrology.

[54]  M. Rotondi,et al.  Heterogeneous genetic alterations in sporadic nephrotic syndrome associate with resistance to immunosuppression. , 2015, Journal of the American Society of Nephrology : JASN.

[55]  A. Sinha,et al.  Extending initial prednisolone treatment in a randomized control trial from 3 to 6 months did not significantly influence the course of illness in children with steroid-sensitive nephrotic syndrome. , 2015, Kidney international.

[56]  A. Sinha,et al.  Efficacy and safety of rituximab in children with difficult-to-treat nephrotic syndrome. , 2015, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[57]  W. Hop,et al.  Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome. , 2013, Journal of the American Society of Nephrology : JASN.

[58]  M. Brittberg,et al.  A Long-term Follow-up , 2013 .

[59]  D. Molony,et al.  Randomized controlled trials in nephrology: state of the evidence and critiquing the evidence. , 2012, Advances in chronic kidney disease.

[60]  T. Mochizuki,et al.  Rituximab treatment for adult patients with focal segmental glomerulosclerosis. , 2012, Internal medicine.

[61]  E. Morales,et al.  Absence of hypoalbuminemia despite massive proteinuria in focal segmental glomerulosclerosis secondary to hyperfiltration. , 1999, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[62]  Primary nephrotic syndrome in children: clinical significance of histopathologic variants of minimal change and of diffuse mesangial hypercellularity. A Report of the International Study of Kidney Disease in Children. , 1981, Kidney international.