CardioExchange Archive

Recently the Kidney Disease Improving Global Outcomes (KDIGO) Lipid Management in Patients with Chronic Kidney Disease Guideline was published in Kidney International. Now a synopsis has appeared in the Annals of Internal Medicine. Harlan Krumholz spoke with the co-chairman of the guideline, Marcello Tonelli.

Krumholz: Like the new US Guidelines, the KDIGO Guideline abandons targets. Were you aware of the US Guidelines or did your group come to that conclusion independently?

Tonelli: Our guideline was published on November 1. We had been anticipating the release of the US guidelines but had no idea what they would say, as we had no contact with the US guidelines panels. As an individual, I don’t agree with all aspects of the US guidelines — but as the KDIGO co-chair, it is nice to see that they abandon LDL-C targets, which will facilitate implementation of our guideline in kidney patients.

Krumholz: Many people outside the kidney community may not be familiar with KDIGO. Can you tell me about this organization?

Tonelli: KDIGO has been producing international practice guidelines about the care of people with kidney disease or kidney failure since 2003. KDIGO makes guidelines on multiple topics relevant to kidney patients, including anemia, bone disease, hypertension, and CKD care. This is the first lipid guideline. Any funds from industry must support KDIGO’s overall mission, and cannot be used to support specific guidelines. In addition to industry support, KDIGO receives financial and/or in-kind support from several (independent) national nephrology societies, which in my view adds an additional layer of credibility. KDIGO has an international board of directors and two co-chairs who at present are from the UK and the US. The board, executive committee and co-chairs select topics based on stakeholder input, and then select workgroup co-chairs (in this case, Dr. Wanner and myself). The workgroup co-chairs then propose workgroup members who in turn are approved by the KDIGO co-chairs. Further details on KDIGO are available at the KDIGO website.

Krumholz: Unlike the US Guidelines, you state that the statin/ezetimibe combination or statins are acceptable for patients with chronic kidney disease. The US FDA declined to grant Merck, the producer of ezetimibe, an indication, so in the US you are making an off-label recommendation. What was your thinking in deciding to include the combination?

Tonelli: KDIGO makes guidelines for an international audience, and so although we’re certainly interested in US regulatory decisions, they’re not directly relevant to the majority of our users. I can’t comment on the rationale for the US guideline panel’s decision, but here is our thinking: SHARP was the largest randomized controlled trial (RCT) ever done in CKD patients and the only one to show a convincing benefit of lipid lowering in people with advanced CKD. It compared simvastatin/ezetimibe versus placebo and found a clinically relevant benefit. Unlike the situation in the general population, there are no RCTs showing benefit of statin monotherapy in advanced CKD. It doesn’t seem rational to recommend a statin alone in patients with advanced CKD even though it was combination therapy that showed benefit in the best available trial. But of course, the available data from post hoc analyses of trials in moderate CKD plus the tremendous body of clinical and experimental evidence suggests that statin monotherapy would be beneficial too. So we recommended for either statin monotherapy or combination therapy in advanced CKD, which seems most consistent with the evidence. You will note that in less advanced CKD (the patients who were not included in SHARP) we recommended for statin monotherapy and not combination therapy. The rationale for all of these judgments is presented in more detail in the full guideline.

Krumholz: When I first read the recommendation I had concerns about whether Merck had a role in the Guideline. I wrote you and I want to give you an opportunity to share with readers what you told me. So let me ask you directly, did Merck have a role and what did you do to protect your guideline process from potential conflicts of interest.

Tonelli: Evaluating the quality of guideline processes is difficult — but our guideline achieves high scores using the AGREE-2 tool, which is the accepted criterion for judging rigor of guideline development. Regarding commercial bias — KDIGO is funded by a basket of sponsors (listed below). The list does not include Merck. Although BMS is a sponsor they had nothing to do with this guideline — they obviously made a financial contribution to KDIGO but it was not tied to any specific guideline or topic. I didn’t realize that BMS had provided funds as I had never carefully read the sponsors list until you emailed to ask — it has simply not been relevant to our work on this guideline. From an administrative perspective, KDIGO paid for the travel of the guideline panel and all costs related to guideline production and guideline meetings. Neither we nor the independent evidence review team had any dealings with anyone from industry during guideline development.

The Annals synopsis includes COI information that can be found by clicking on the “Article and author information” link and describes the COI for the panel members. This information is also available on the KDIGO website. You will note that Dr. Wanner and I have both done work for Merck. I donated these honoraria (like all of the honoraria that I receive from industry) to charity, and if possible I ask the company to pay the charity directly– although this is much harder than it used to be. I accept that both my honoraria and Dr. Wanner’s are potential conflicts of interest that should be considered when reading our guideline.

Here are the published disclosures:

Financial Support: KDIGO is supported by a consortium of sponsors and no funding is accepted for the development of specific guidelines. KDIGO’s founding sponsor is the National Kidney Foundation. Support for KDIGO is also provided by Abbott, Amgen, Bayer Schering Pharma, Belo Foundation, Bristol-Myers Squibb, Chugai Pharmaceutical, Coca-Cola Company, Dole Food Company, Fresenius Medical Care, Genzyme, Hoffmann-LaRoche, International Society of Nephrology, JC Penney, Kyowa Hakko Kirin, NATCO—The Organization for Transplant Professionals, National Kidney Foundation (NKF)-Board of Directors, Novartis, Pharmacosmos, PUMC Pharmaceutical, Robert and Jane Cizik Foundation, Shire, Takeda Pharmaceutical, Transwestern Commercial Services, Vifor Pharma, and Wyeth.

Grant Support: Dr. Tonelli was supported by an AHFMR Population Health Scholar award and a Government of Canada Research Chair in the optimal care of persons with chronic kidney disease.

Potential Conflicts of Interest: Dr. Tonelli reports provision of technical and administrative assistance from KDIGO, and consultancy/speaker honoraria from Merck that were donated to charity. Dr. Wanner reports speaker honoria from Astellas-Pfizer (Japan), Merck, and Merck Sharp & Dohme.