Improved care for kidney disease patients at core of research program

Clinician-researcher, Professor David Johnson, is championing patient-centred kidney disease research. His work over the past two decades has led to several changes in clinical guidelines as well as the creation of The University of Queensland Centre for Kidney Disease Research (CKDR) and the Australasian Kidney Trials Network (AKTN). With both the CKDR and the AKTN headquartered at the Translational Research Institute (TRI), we spoke to Professor Johnson about his research and its impact on patient care.

In addition to being the CKDR Director, Professor Johnson is the Medical Director-Queensland Kidney Transplant Service at the Princess Alexandra Hospital.

TRI:  As a highly successful kidney specialist, why is it important for you to be involved in research?

DJ: Research is the best way I can try to improve patient care for the one in 10 Australians who have chronic kidney disease. These patients have a higher risk of cardiovascular disease and cancer, and a higher likelihood of an early death. The disease also has a negative impact on people's lifestyles and relationships. Research is the only way you can inform the best practice patient care, and how you improve patient outcomes. I’m very driven to do high-quality research, which is relevant and important to patients. For me, it’s important that I prioritise my research on what’s meaningful to patients. Plus if it’s high-quality work, and involves as many renal units as possible in Australia and New Zealand, then it’s likely to result in meaningful outcomes, which will be published in top journals and then taken up in clinical practice guidelines around the world.

TRI: When and why did you establish the Centre for Kidney Disease Research?

DJ: I launched the Centre for Kidney Disease Research in 1998, not long after I started at the Princess Alexandra Hospital. I was very interested in being involved in research, but at the time there was very little happening in the Hospital’s Renal Department. The Centre was an important development because it allowed us to do basic scientific research. We began with a $40,000 grant from the PA Foundation and a collaboration with [University of Queensland molecular biologist and CKDR Research Director, Associate Professor] Glenda Gobe. Together, we started looking at laboratory models of kidney disease to identify novel ways to prevent kidney cancer. Today, the Centre is involved in more than 80 active projects and its mission is to improve the kidney health of adults and children through scientific research and education of the highest international standard in the field of nephrology.

TRI:  Your first major project with the CKDR led to an international change in patient care for kidney disease patients, can you tell us more about it?

DJ: Yes, the ‘Initiating Dialysis Early and Late’ or IDEAL trial ran from 2000 to 2008. I was the Principal Investigator on this landmark study, which led to a paper in the New England Journal of Medicine, and international changes in clinical practice guidelines providing recommendations to clinicians on dialysis initiation decision-making for chronic kidney disease patients. IDEAL was a large project. It involved 828 adults with progressive, advanced chronic kidney disease, who were recruited from 32 centres in Australia and New Zealand. Our results were significant because we found that in asymptomatic patients with advanced chronic kidney disease, dialysis could be safely postponed until symptoms appeared. In Australia, the finding meant a saving of $18,000 per patient and six months less of unnecessary dialysis.

TRI:  You helped launch the Australasian Kidney Trials Network in 2004, how did this come about?

DJ: The IDEAL study was a big learning curve for us, and we realised partway through the project that we didn’t want to lose the knowledge base or momentum it had created among so many collaborators in Australia, New Zealand and beyond. Fortunately, the need for a clinical trials network was also recognised by both the Australian and New Zealand Society of Nephrology Council and Kidney Health Australia. In late 2003, they asked for expressions of interest to form a network and in 2004 the Australasian Kidney Trials Network, involving our group as a Brisbane-based Operations Secretariat, was launched. (We really were the underdogs in winning the tender to operate the group.)

Today, the Network is a ‘one-stop-shop’ for running clinical trials, taking suggestions for research projects from both patients and clinicians. Our team develops research ideas into projects, writes grant applications, helps the investigators through the ethics and governance processes, administers the clinical trial and then supports data management and the implementation of research outcomes. We’re very pragmatic in our approach. We want to minimise the research costs while increasing the outcomes. It took years to find our feet and get to this point, but we are now highly successful in securing grants – our success has really escalated – and our work is being published in the leading peer-review journals. We’ve had five publications so far in the New England Journal of Medicine, which is the Mt Everest of medical journals.

TRI:  How many research projects has the Network run and have any of these changed clinical practice?

DJ: Through the AKTN, we’ve completed eleven trials with more in development. Several of these trials have led to a change in clinical practice, but I suspect our most recent study, the CDK-FIX trial, will have a major impact internationally on clinical guidelines. In this large study, we showed the drug, allopurinol, was ineffective in slowing the progress of kidney disease. This drug is prescribed for about 20 per cent of patients with chronic kidney disease. Similarly, in the IMPROVE-CKD trial we found the commonly prescribed lanthanum carbonate, did not reduce kidney patients’ risk of cardiovascular disease.

The results from our HONEYPOT trial led to changes almost overnight in clinical practice. We found antibiotics were superior to antibacterial honey, which was very popular with renal units, to prevent catheter-associated infections in peritoneal dialysis patients. Likewise, the FAVOURED trial led to a lot of clinicians abandoning the use of fish oils or aspirin to prevent catheter failure after we showed the common practice was ineffective. Following the HERO trial, we were able to recommend the use of Oxypentifylline as a treatment option for patients with erythropoiesis-stimulating agent-resistant anaemia—a condition affecting about 10 per cent of chronic kidney disease patients.

To read more about completed AKTN trials visit: https://aktn.org.au/trials/completed-trials/

TRI:  What is your next big area of research?

DJ: We’re looking at ways to improve peritoneal or home dialysis for end-stage kidney disease patients. Home dialysis really is an important issue that we need to address. It can be performed easily in rural areas and it makes it much easier to manage care for patients during pandemics and natural disasters. Most patients would prefer to do dialysis at home. My group is part of the global SONG Initiative for Peritoneal Dialysis, involving 3000 centres across nine countries. The idea is to develop a suite of interventions that make home dialysis a viable option for patients.

Our TEACH-PD study is a big project. We have several grants, including a Medical Research Future Fund (MRFF) grant, for this research. In collaboration with the Home Network, we have developed online training for trainers and patients, which we hope will improve the outcomes from home dialysis. Patients have to be taught how to do home-based dialysis, but there is no standardised program for teaching patient and there’s currently a huge variation between renal units. Home dialysis is easier for patients and much cheaper for the healthcare system, but infection is a huge risk. This risk varies 10-fold depending on the renal centre, and we think training is driving this outcome. We have 31 hospitals signed up to take part in our trial.

In 2020, I also received an NHMRC Investigator grant to look at how we can improve the availability, accessibility and affordability of home dialysis to patients.

TRI:  How does being based at TRI help your research?

DJ: Being based at TRI means our clinicians get to interact with other researchers. We also find we get great support from TRI, especially with helping us disseminate knowledge, which is important if we are going to impact practice.

About Professor David Johnson

Professor David Johnson is the full-time Director of the Metro South Integrated Nephrology and Transplant Service (MINTS) and Medical Director of the Queensland Kidney Transplant Service at Princess Alexandra Hospital, Brisbane, Australia; Professor of Medicine and Professor of Population Health at University of Queensland, and Director of the Centre for Kidney Disease Research, Brisbane, Australia.

He has a number of international leadership responsibilities, including President of the International Society for Peritoneal Dialysis, Councillor of the International Society of Nephrology (ISN), Co-Chair of the ISN Global Kidney Health Atlas, Co-Chair of the Global PDOPPS Steering Committee and Chair of SONG-PD. He is currently a chair or member of 10 national and six international guideline groups and has influenced policy and practice through his leadership as Deputy Chair of the Australian NHMRC Better Evidence And Translation in Chronic Kidney Disease (BEAT-CKD) program, Deputy Chair of the Australasian Kidney Trials Network (AKTN), Chair of the Primary Healthcare Education Advisory Committee to Kidney Health Australia (PEAK), Co-Chair of the Australasian Creatinine and eGFR Consensus Working Party, Co-Chair of the Australasian Proteinuria Consensus Working Party, Member and Past-Chair of the ANZDATA Registry Peritoneal Dialysis Working Group, and Past-Chair of the Queensland Statewide Renal Clinical Network.

Having published over 930 original manuscripts in peer-reviewed journals and presented more than 500 abstracts at national and international scientific meetings, he brings critical expertise in designing and conducting multi-centre, multi-national randomised controlled trials (RCT), developing national and international registries, and using innovative research methodologies (such as registry-based randomised controlled trials). He has held lead roles in more than 40 clinical studies, including high-impact, large, multi-centre RCTs that have informed global clinical practice, including IDEAL, balANZ, HONEYPOT, TESTING, HERO, IMPENDIA and CKD-FIX. He is principal investigator of the TEACH-PD trial.

Professor Johnson has won numerous awards for both his basic science and clinical research science studies, including the Australian and New Zealand Society of Nephrology TJ Neale Award for “outstanding contributions to nephrologic science” (2005), the US National Kidney Foundation International Distinguished Medal (2014) and the Canadian Society of Nephrology Dimitrios Oreopoulos Award (2017). He was a Queensland finalist in the Australian of the Year Awards in 2009 and was awarded a Public Service Medal by the Governor-General of Australia in 2011 for outstanding public service, particularly research into the early detection and management of kidney disease.

Recent journal publications (selected)

• Badve, Sunil V., Pascoe, Elaine M., Tiku, Anushree, Boudville, Neil, Brown, Fiona G., Cass, Alan, Clarke, Philip, Dalbeth, Nicola, Day, Richard O., de Zoysa, Janak R., Douglas, Bettina, Faull, Randall, Harris, David C., Hawley, Carmel M., Jones, Graham R. D., Kanellis, John, Palmer, Suetonia C., Perkovic, Vlado, Rangan, Gopala K., Reidlinger, Donna, Robison, Laura, Walker, Robert J., Walters, Giles, Johnson, David W. and CKD-FIX Study Investigators (2020). Effects of allopurinol on the progression of chronic kidney disease. The New England Journal of Medicine, 382 (26), 2504-2513. doi: 10.1056/nejmoa1915833
• Bello AK, Levin A, Lunney M, Osman MA, Ye F, Ashuntanang G, Bellorin-Font E, Gharbi MB, Davison S, Ghnaimat M, Harden P, Htay H, Jha V, Kalantar-Zadeh, Kerr PG, Klarenbach S, Kovesdy CP, Luyckx V, Neuen B, O’Donoghue D, Ossareh S, Perl J, Rashid HU, Rondeau E, See E, Syed S, Sola L, Tchokonelidze I, Tesar V, Tungsanga K, Kazancioglu R, Wang AYM, Wiebe N, Yang CW, Zemchenkov A, Zhao MH, Jager KJ, Caskey F, Perkovic V, Jindal KK, Okpechi IG, Tonelli M, Fehally J, Harris DC, Johnson DW. Current status of end-stage kidney disease care in world countries and regions: An international survey. British Medical Journal 367:l5873, 2019.
• Lalji R, Francis A, Johnson DW, McCulloch M. Health disparities in access to kidney replacement therapy amongst children and adolescents with end stage kidney disease in low- and lower-middle income countries. Kidney International 97:463-5, 2020
• Perl, Jeffrey, Fuller, Douglas S., Bieber, Brian A., Boudville, Neil, Kanjanabuch, Talerngsak, Ito, Yasuhiko, Nessim, Sharon J., Piraino, Beth M., Pisoni, Ronald L., Robinson, Bruce M., Schaubel, Douglas E., Schreiber, Martin J., Teitelbaum, Isaac, Woodrow, Graham, Zhao, Junhui and Johnson, David W. (2020). Peritoneal Dialysis–Related Infection Rates and Outcomes: Results From the Peritoneal Dialysis Outcomes and Practice Patterns Study (PDOPPS). American Journal of Kidney Diseases, 76 (1), 42-53. doi: 10.1053/j.ajkd.2019.09.016
• Manera KE, Johnson DW, Craig JC, Shen JI, Gutman T, Cho Y, Wang AYM, Brown E, Brunier G, Dong J, Dunning T, Mehrotra R, Naicker S, Pecoits-Filho R, Perl J, Wilkie M, Tong A. Establishing a Core Outcome Set for Peritoneal Dialysis: Report of the Standardized Outcomes in Nephrology – Peritoneal Dialysis (SONG-PD) Consensus Workshop. American Journal of Kidney Diseases. 75(3):404-12, 2020.
• Htay H, Bello AK, Levin A, Lunney M, Osman MA, Ye F, Ashuntanang G, Bellorin-Font E, Gharbi MB, Davison S, Ghnaimat M, Harden P, Jha V, Kalantar-Zadeh, Kerr PG, Klarenbach S, Kovesdy CP, Luyckx V, Neuen B, O’Donoghue D, Ossareh S, Perl J, Rashid HU, Rondeau E, See E, Syed S, Sola L, Tchokonelidze I, Tesar V, Tungsanga K, Kazancioglu R, Wang AYM, Yang CW, Zemchenkov A, Zhao MH, Jager KJ, Caskey F, Perkovic V, Jindal KK, Okpechi IG, Tonelli M, Fehally J, Harris DC, Johnson DW. Haemodialysis Use and Practice Patterns: An International Survey Study. American Journal of Kidney Disease. Published August 12, 2020. DOI:https://doi.org/10.1053/j.ajkd.2020.05.030.
• Palamuthusingam, Dharmenaan, Nadarajah, Arun, Pascoe, Elaine M., Craig, Jonathan, Johnson, David W., Hawley, Carmel M. and Fahim, Magid (2020). Postoperative mortality in patients on chronic dialysis following elective surgery: a systematic review and meta-analysis. PLoS One, 15 (6) e0234402, e0234402. doi: 10.1371/journal.pone.0234402
• Xu, Ying, Zhang, Yuhui, Yang, Bin, Luo, Suping, Yang, Zhikai, Johnson, David W. and Dong, Jie (2020). Prevention of peritoneal dialysis-related peritonitis by regular patient retraining via technique inspection or oral education: A randomized controlled trial. Nephrology Dialysis Transplantation, 35 (4), 676-686. doi: 10.1093/ndt/gfz238
• Pecoits-Filho, Roberto, Okpechi, Ikechi G., Donner, Jo-Ann, Harris, David C.H., Aljubori, Harith M., Bello, Aminu K., Bellorin-Font, Ezequiel, Caskey, Fergus J., Collins, Allan, Cueto-Manzano, Alfonso M., Feehally, John, Goh, Bak Leong, Jager, Kitty J., Nangaku, Masaomi, Rahman, Muhibur, Sahay, Manisha, Saleh, Abdulkarim, Sola, Laura, Turan Kazancioglu, Rumeyza, Walker, Rachael C., Walker, Robert, Yao, Qiang, Yu, Xueqing, Zhao, Ming-Hui and Johnson, David W. (2020). Capturing and monitoring global differences in untreated and treated end-stage kidney disease, kidney replacement therapy modality, and outcomes. Kidney International Supplements, 10 (1), e3-e9. doi: 10.1016/j.kisu.2019.11.001
• Chan S, Ng S, Chan HP, Pascoe E, Playford EG, Wong G, Chapman JR, Lim WH, Francis RS, Isbel NM, Campbell SB, Hawley CM, Johnson DW. Perioperative antibiotics for preventing post-surgical site infections in solid organ transplant recipients (Review). Cochrane Database of Systematic Reviews 2020, Issue 8. Art. No.: CD013209. DOI: 10.1002/14651858.CD013209.pub2
• Rangaswamy, Dharshan, Guddattu, Vasudeva, Webster, Angela C., Borlace, Monique, Boudville, Neil, Clayton, Philip, Badve, Sunil, Johnson, David W. and Sud, Kamal (2020). Icodextrin use for peritoneal dialysis in Australia: A cohort study using Australia and New Zealand Dialysis and Transplant Registry. Peritoneal Dialysis International, 40 (2), 209-219. doi: 10.1177/0896860819894058
• Sahlawi, Muthana Al, Wilson, Gregory, Stallard, Belinda, Manera, Karine E., Tong, Allison, Pisoni, Ronald L., Fuller, Douglas S., Cho, Yeoungjee, Johnson, David W., Piraino, Beth, Schreiber, Martin J., Boudville, Neil C., Teitelbaum, Isaac and Perl, Jeffrey (2020). Peritoneal dialysis-associated peritonitis outcomes reported in trials and observational studies: A systematic review. Peritoneal Dialysis International, 40 (2), 132-140. doi: 10.1177/0896860819893810
• Chow, Josephine S.F., Adams, Kelly, Cho, Yeoungjee, Choi, Peter, Equinox, Keri-Lu, Figueiredo, Ana E., Hawley, Carmel M., Howard, Kirsten, Johnson, David W., Jose, Matthew D., Lee, Anna, Longergan, Maureen, Manera, Karine E., Moodie, Jo-Anne, Paul-Brent, Peta-Anne, Pascoe, Elaine M., Reidlinger, Donna, Steiner, Genevieve Z., Tomlins, Melinda, Tong, Allison, Voss, David and Boudville, Neil C (2020). Targeted Education ApproaCH to improve Peritoneal Dialysis Outcomes (TEACH-PD): A feasibility study. Peritoneal Dialysis International, 40 (2), 153-163. doi: 10.1177/0896860819887283
• Kelly, Jaimon T., Conley, Marguerite, Hoffmann, Tammy, Craig, Jonathan C., Tong, Allison, Reidlinger, Dianne P., Reeves, Marina M., Howard, Kirsten, Krishnasamy, Rathika, Kurtkoti, Jagadeesh, Palmer, Suetonia C., Johnson, David W. and Campbell, Katrina L. (2020). A coaching program to improve dietary intake of patients with CKD: ENTICE-CKD. Clinical Journal of the American Society of Nephrology, 15 (3), 330-340. doi: 10.2215/cjn.12341019
• Krishnasamy, Rathika, Hawley, Carmel M., Jardine, Meg J., Roberts, Matthew A., Cho, Yeoungjee, Wong, Muhgeot, Heath, Anne, Nelson, Craig L., Sen, Shaundeep, Mount, Peter F., Pascoe, Elaine M., Vergara, Liza A., Paul-Brent, Peta-Anne, Toussaint, Nigel D., Johnson, David W. and Hutchison, Colin A. (2020). A tRial evaluating mid cut-off value membrane clearance of albumin and light chains in HemoDialysis patients: a safety device study. Blood Purification, 49 (4), 1-11. doi: 10.1159/000505567
• Mac, Kathy, Hedley, James, Kelly, Patrick J., Lee, Vincent W, Agar, John W. M., Hawley, Carmel M., Johnson, David W., See, Emily J., Polkinghorne, Kevan R., Rabindranath, Kannaiyan S., Sud, Kamal and Webster, Angela C. (2020). Effect of centre- and patient-related factors on uptake of haemodiafiltration in Australia and New Zealand: a cohort study using ANZDATA. Nephrology, 25 (1) nep.13574, 63-72. doi: 10.1111/nep.13574
• Htay, Htay, Cho, Yeoungjee, Pascoe, Elaine M., Hawley, Carmel, Clayton, Philip A., Borlace, Monique, Badve, Sunil V., Sud, Kamal, Boudville, Neil, Chen, Jenny H. C., Sypek, Matthew and Johnson, David W. (2020). Multicentre registry data analysis comparing outcomes of culture-negative peritonitis and different subtypes of culture-positive peritonitis in peritoneal dialysis patients. Peritoneal Dialysis International, 40 (1), 47-56. doi: 10.1177/0896860819879891

Follow Professor Johnson Twitter: @DWJohnsonNeph