IWG newsletter

   
Dear Friends,

In this fourth newsletter of Immunonephrology Working Group (IWG), you will find updates from the recently published articles and late-breaking clinical trials on the immune-mediated renal diseases. Moreover, we would like to inform you of the upcoming joint meetings and CME courses of IWG which will be held in Berlin, Tours and Vienna, respectively.

We hope that you will find the newsletter of value.

We are looking forward to meeting you during our CME courses. We would also like to invite you to kindly encourage your colleagues interested in research, teaching, communication and education in the field of immuno-mediated renal diseases to become an IWG Member.

With kind regards,

Vladimir Tesar,  Chairman of Immunonephrology Working Group
Mårten Segelmark, Secretary of the Immunonephrology Working Group

Immunonephrology Working Group Newsletter, No. 4, December 2015
   
1. Updates from recent publications

Let us start with the fourth VALIGA paper entitled “Tonsillectomy in a European Cohort of 1.147 Patients with IgA Nephropathy” very recently e-published in Nephron, 2015 November. In the large VALIGA cohort of European subjects with IgA Nephropathy (IgAN), no significant correlation was found between tonsillectomy and renal function decline, even using a propensity score statistical method on patients having had tonsillectomy after renal biopsy matched with patients with similar clinical and renal biopsy MEST features. These results fit with another study from VALIGA cohort, “Can tonsillectomy modify the innate and adaptive immunity pathways involved in IgA nephropathy?” published in J Nephrol 2015 February. In this study, the activation of innate immunity via toll-like receptors (TLR) and ubiquitin-proteasome pathways and the pro-oxidative milieu were not affected by tonsillectomy. In tonsillectomized patients, the levels of aberrantly galactosylated IgA1, originally thought to be lower in patients with IgAN who had tonsillectomy, were still significantly higher than controls. On the opposite, the activation of TLR4 and oxidative stress were even more enhanced in patients with tonsillectomy, suggesting the persistent mucosal associated lymphoid tissue (MALT) activation, likely originated from the intestinal mucosal barrier exposed to bacterial LPS, the natural ligand of TLR4.
The area of intestine-renal connection in IgAN has been further stressed by the recently published paper from Renato Monteiro’s groupGluten exacerbates IgA nephropathy in humanized mice through gliadin-CD89 interaction” in Kidney Int. 2015 August.
Another important IgAN study is “Novel lectin-independent approach to detect galactose-deficient IgA1 in IgA nephropathy” by Yasutake et al reported in Nephrol Dial Transplant. They were able to establish a novel lectin-independent galactose-deficient IgA1 (Gd-IgA1) ELISA that can detect serum Gd-IgA1 in patients with IgAN.
Next, there are two important papers published recently about diabetic nephropathy, all very relevant to nephrologists. The first one, a randomised trial by de Zeeuw et al in Lancet Diabetes Endocrinol, is entitled "The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial". In this randomised, double-blind, placebo-controlled clinical trial, their results suggest that CCR2 inhibition with CCX140-B has renoprotective effects on top of current standard of care in patients with type 2 diabetes and nephropathy. The second one is a review paper published in J Clin Med by Perez-Gomez et al and entitled “Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade”. Perez-Gomez et al reviewed the most likely therapeutic candidates for diabetic nephropathy which will be in the market by 2020, based on currently ongoing or recently completed clinical trials.
Finally, Sethi et al published a consensus report “Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN" in J Am Soc Nephrol, which emphasized a pathogenesis-based classification of GN and provided guidelines for the standardized reporting of GN.

2. Updates from late-breaking clinical trials

Furthermore we would like to draw your attention to the results of two high-impact clinical trials that could affect kidney-related medical care presented at ASN Kidney Week 2015, November 3-8 at the San Diego Convention Center in San Diego, CA.

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STOP-IgAN Trial “Corticosteroid Monotherapy versus Combined Immunosuppression in IgA Nephropathy: Insights from the STOP-IgAN Trial” by Jürgen Floege et al. The trial was very recently published in NEJM.
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The NEFIGAN Trial: NEFECON, a Novel Targeted Release Formulation of Budesonide, Reduces Proteinuria and Stabilizes eGFR in IgA Nephropathy Patients at Risk of ESRD” by Bengt C. Fellstrom et al.

Although the results of STOP-IgAN raised a major question-mark for immunosuppression in IgAN, NEFIGAN trial showed the beneficial effects of oral modified-release capsule of budesonide in IgAN. We will comment on both trials in detail in our next newsletter

3. Upcoming joint meetings and CME courses

ISN’s Nexus Symposium, Berlin, Germany on April 14-17, 2016
It is our pleasure to invite you to attend the joint IWG symposium within the ISN’s Nexus Symposium 2016 taking place in Berlin, Germany on April 14-17, 2016. This meeting is set to cover translational immunology in kidney disease and new therapies for renal immunopathology. Final symposium program will be communicated to all IWG Members in the future.

Symposium on IgA Nephropathy, Tours, France on September 15-17, 2016
The focus of this 14th International Symposium on IgA Nephropathy will be “Pathogenesis, Biomarkers and Therapeutic Innovation”. The symposium is organized through the IgA Nephropathy Network and IWG Board Members. Final symposium program will be announced to all IWG Members soon.

IWG CME course, 53rd ERA-EDTA Congress, Vienna, Austria on May 21, 2016
This course will focus namely on “News in the diagnostics and treatment of glomerular diseases”. We sincerely hope that you will participate in this meeting and already looking forward to seeing you in Vienna.

  • Feehally J, Coppo R, Troyanov S et al: VALIGA study of the ERA-EDTA Immunonephrology Working Group. Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy. Nephron  2015 Nov 20.
  • Vergano L, Loiacono E, Albera R et al. Can tonsillectomy modify the innate and adaptive immunity pathways involved in IgA nephropathy? J Nephrol. 2015 Feb; 28(1): 51-8.
  • Papista C, Lechner S, Ben Mkaddem S et al. Gluten exacerbates IgA nephropathy in humanized mice through gliadin-CD89 interaction. Kidney Int. 2015; 88(2): 276-85.
  • Yasutake J, Suzuki Y, Suzuki H et al. Novel lectin-independent approach to detect galactose-deficient IgA1 in IgA nephropathy. Nephrol Dial Transplant. 2015; 30(8): 1315-21.
  • de Zeeuw D, Bekker P, Henkel E et al: CCX140-B Diabetic Nephropathy Study Group. The effect of CCR2 inhibitor CCX140-B on residual albuminuria in patients with type 2 diabetes and nephropathy: a randomised trial. Lancet Diabetes Endocrinol. 2015; 3(9): 687-96.
  • Perez-Gomez MV, Sanchez-Niño MD, Sanz AB et al. Horizon 2020 in Diabetic Kidney Disease: The Clinical Trial Pipeline for Add-On Therapies on Top of Renin Angiotensin System Blockade. J Clin Med. 2015; 4(6): 1325-47.
  • Sethi S, Haas M, Markowitz GS et al. Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN. J Am Soc Nephrol. 2015 Nov 13.
  • Floege J, Rauen T, Eitner F, Fitzner C, Hilgers RD. Corticosteroid Monotherapy versus Combined Immunosuppression inIgA Nephropathy: Insights from the STOP-IgAN Trial. Late-Breaking Clinical Trial Posters. SA-PO1097.  Saturday, November 7 9:30 a.m. - 4:30 p.m. ASN Kidney Week 2015, November 3-8 at the San Diego Convention Center in San Diego, CA.
  • Rauen T, Eitner F, Fitzner C et al; STOP-IgAN Investigators. Intensive Supportive Care plus Immunosuppression in IgA Nephropathy. N Engl J Med  2015; 373(23): 2225-36.
  • Fellstrom BC, Coppo R, Feehally J et al. The NEFIGAN Trial: NEFECON, a Novel Targeted Release Formulation of Budesonide, Reduces Proteinuria and Stabilizes eGFR in IgA Nephropathy Patients at Risk of ESRD.High-Impact Clinical Trials. Saturday, November 7, ASN Kidney Week 2015, November 3-8 at the San Diego Convention Center in San Diego, CA.

Report prepared by Yasar Caliskan, Co-editor of IWG Newsletter