S. K. Venuthurupalli

Biomarkers in chronic kidney disease: a review

Chronic kidney disease (CKD) is a major public health problem. The classification of CKD by KDOQI and KDIGO and the routine eGFR reporting have resulted in increased identification of CKD. It is important to be able to identify those at high risk of CKD progression and its associated cardiovascular disease (CVD). Proteinuria is the most sensitive marker of CKD progression in clinical practice, especially when combined with eGFR, but these have limitations. Hence, early, more sensitive, biomarkers are required. Recently, promising biomarkers have been identified for CKD progression and its associated CVD morbidity and mortality. These may be more sensitive biomarkers of kidney function, the underlying pathophysiological processes, and/or cardiovascular risk. Although there are some common pathways to CKD progression, there are many primary causes, each with its own specific pathophysiological mechanism. Hence, a panel measuring multiple biomarkers including disease-specific biomarkers may be required. Large, longitudinal observational studies are needed to validate candidate biomarkers in a broad range of populations prior to implementation into routine CKD management. Recent renal biomarkers discovered include neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, and liver-type fatty acid-binding protein. Although none are ready for use in clinical practice, it is timely to review the role of such biomarkers in predicting CKD progression and/or CVD risk in CKD.

Taming the chronic kidney disease epidemic: a global view of surveillance efforts

Chronic kidney disease is now recognized to be a worldwide problem associated with significant morbidity and mortality and there is a steep increase in the number of patients reaching end-stage renal disease. In many parts of the world, the disease affects younger people without diabetes or hypertension. The costs to family and society can be enormous. Early recognition of CKD may help prevent disease progression and the subsequent decline in health and longevity. Surveillance programs for early CKD detection are beginning to be implemented in a few countries. In this article, we will focus on the challenges and successes of these programs with the hope that their eventual and widespread use will reduce the complications, deaths, disabilities, and economic burdens associated with CKD worldwide.

CKD.QLD: chronic kidney disease surveillance and research in Queensland, Australia

Background Chronic kidney disease (CKD) is recognized as a major public health problem in Australia with significant mortality, morbidity and economic burden. However, there is no comprehensive surveillance programme to collect, collate and analyse data on CKD in a systematic way. Methods We describe an initiative called CKD Queensland (CKD.QLD), which was established in 2009 to address this deficiency, and outline the processes and progress made to date. The foundation is a CKD Registry of all CKD patients attending public health renal services in Queensland, and patient recruitment and data capture have started. Results We have established through early work of CKD.QLD that there are over 11 500 CKD patients attending public renal services in Queensland, and these are the target population for our registry. Progress so far includes conducting two CKD clinic site surveys, consenting over 3000 patients into the registry and initiation of baseline data analysis of the first 600 patients enrolled at the Royal Brisbane and Womens Hospital (RBWH) site. In addition, research studies in dietary intake and CKD outcomes and in models of care in CKD patient management are underway. Conclusions Through the CKD Registry, we will define the distribution of CKD patients referred to renal practices in the public system in Queensland by region, remoteness, age, gender, ethnicity and socioeconomic status. We will define the clinical characteristics of those patients, and the CKD associations, stages, co-morbidities and current management. We will follow the course and outcomes in individuals over time, as well as group trends over time. Through our activities and outcomes, we are aiming to provide a nidus for other states in Australia to join in a national CKD registry and network.

CKD.QLD: establishment of a chronic kidney disease [CKD] registry in Queensland, Australia

BackgroundChronic kidney disease [CKD] is recognised as a global public health problem. Until recently, the majority of information informing on CKD has been generated from renal registries reporting on patients with end-stage kidney disease [ESKD] and on renal replacement therapy [RRT]. There has been a paucity of information on pre-dialysis CKD cohorts, and many issues related to these poorly described populations are unresolved. To this end, international organizations have called for CKD surveillance systems across all countries.DescriptionIn Australia, we have responded by developing the Chronic Kidney Disease in Queensland [CKD.QLD] with three main platforms consisting of CKD Registry, clinical trials and development of biobank. This registry which is the core component of CKD surveillance was conceptualized specifically for the pre-dialysis population in the public health system in Queensland, Australia. Recruitment started in May 2011, and to date the Registry has evolved as one of the largest CKD cohorts in the world with recruitment close to 7000 patients. The Registry has had many outcomes, including being the nidus for Australia’s first National Health and Medical Research Council [NHMRC] CKD Centre of Research Excellence [CKD.CRE].ConclusionsThe Registry, with its linkage to Queensland Health datasets, is reporting, and is expected to continue generating, significant information on multiple aspects of CKD, its trajectory, management and patient outcomes. Intent of the CKD.CRE is to facilitate an expanded Registry network that has representation from health services, both public and private, across Australia.

Chronic Kidney Disease, Queensland (CKD.QLD) Registry: Management of CKD With Telenephrology

Introduction Enabled by the Chronic Kidney Disease, Queensland (CKD.QLD) Registry, we aim to outline the structure, implementation, and outcomes of telenephrology clinics for the management of patients with chronic kidney disease (CKD) in rural, regional, and remote areas of the Darling Downs region in Queensland, Australia. Methods This is an observational registry–based study involving adult patients with CKD, attending specialist clinics, and residing ≥50 km away from Toowoomba Hospital. The telenephrology cohort (TC) included those who had their follow-up appointments via videoconference at local Queensland Health facilities, and the standard care cohort (SCC) included those who continue to have their follow-up in Toowoomba Hospital. Results A total of 234 patients with CKD were seen via videoconference clinics between September 1, 2011 and December 31, 2016, representing 22.2% of the CKD registry cohort from Toowoomba Hospital. The baseline characteristics and comorbid profiles of both groups were similar. The Aboriginal population was overrepresented in the TC (22.2% vs. 5.9%). As a group for each visit, the TC traveled 100,000 km less (both ways) to see a specialist physically. During follow-up, 5.1% of patients in the TC were initiated on dialysis whereas 9.9% were initiated on dialysis in the SCC (P = 0.02). There was lower mortality in the TC (11.1% vs. 18.2%; P = 0.02). Conclusion Telenephrology clinics were safe, economical, and efficient for the delivery of specialist care for patients with CKD living at a distance from the main referral hospital. Such care was comparable to standard care delivered at the main hospital but with clear benefits to the patients in terms of reduced travel distance, more independence, and similar outcomes.

CKD Screening and Surveillance in Australia: Past, Present, and Future

Chronic kidney disease (CKD) was largely a hidden health problem until the publication of an internationally agreed approach to its identification, monitoring, and treatment. The 2002 National Kidney Foundation CKD classification and the subsequent 2006 Kidney Disease Improving Global Outcomes (KDIGO) recommendations are powerful tools for translating thinking about CKD into clinical practice. These guidelines were strongly endorsed by the international community, including Australia, and were incorporated into CKD practice guidelines. In the past, CKD research studies in Australia focused on screening the general population, and more specifically, individuals at risk for CKD. Information from these studies led to the recognition that the CKD burden in Australia is a public health problem and contributed to the development of national health policies and priorities. At present, apart from the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA) that reports on CKD patients undergoing renal replacement therapy (RRT), long-term surveillance to describe the natural history of the CKD population not on RRT has only recently started. Entities such as CKD. Queensland and the Western Australian Nephrology Database are able to fill the gap and provide opportunities for collaborative research of CKD in Australia. Establishment of a National Health and Medical Research Centre−funded CKD Centre of Excellence in 2015 and the Better Evidence and Translation–Chronic Kidney Disease in 2016 are likely to change the future of CKD surveillance and research in Australia.

CKD.QLD: Effect of bariatric procedures on renal and non-renal parameters in obese CKD patients

Background: Obesity has an adverse impact on metabolic parameters including CKD. Bariatric procedures produce significant weight loss compared to non-surgical means and have a positive effect on renal and non-renal parameters. The present study retrospectively evaluated the effect of bariatric procedures and weight loss on renal function, proteinuria, hypertension, lipid profile and diabetic status in chronic kidney disease (CKD) patients in Queensland, Australia. Methods: Of the 880 patients who consented to the CKD Registry, data of patients who underwent bariatric procedures were analysed. Changes in anthropometric measures, renal functions, lipid profile, glycosylated haemoglobin A1c (HbA1c) (%), proteinuria and requirement for blood pressure medications and insulin dose were noted during follow-up. Results: Eight patients (1%) (mean age 48 years: there were 5 men) underwent bariatric procedures (gastric banding - four, gastric sleeve - three and gastric bypass - one). Mean follow-up duration was 10 years. During follow-up a trend towards reduction was noted in weight (kg) (163 - 115 p = 0.01), proteinuria (g/mol) (381 - 65 p = 0.302), HbA1c (%) (8.1 to 6.7 p = 0.03) and total cholesterol (mmol/L) (4.7 to 4.0 p = 0.33). The estimated glomerular filtration rate (eGFR) (mL/min/1.73m2) did not change significantly (58.1 - 54.1 p = 0.426). Reductions of anti-hypertensive medications (1.8 - 0.75, p = 0.08) and insulin dose (IU) (61.3 - 25 p = 0.37) were also noted. One patient developed complications requiring removal of the gastric band. One patient progressed to end-stage renal disease. Conclusions: There was significant weight loss leading to improvement in multiple metabolic parameters. There was a trend towards a slow progression of CKD post-bariatric surgery during the follow-up. Although the numbers are small bariatric procedures appears to have a significant role in the management of obesity associated with CKD and related metabolic conditions.

Risk Factors of Starting Renal Replacement Therapy and Mortality in Ckd.Qld Patients

Aim: To investigatenongenomic effects of aldosteroneon renal protein expressions of sodium hydrogen exchanger 1 and 3 (NHE1and3), andproteinkinaseCbeta 1 and2 (PKCβ 1 and2) Introduction: Wehave previously demonstrated that aldosterone rapidly elevates epidermal growth factor receptor (EGFR) phosphorylation and increases extracellular signal-related kinase1and2(ERK1⁄2)inratkidney.ERK1⁄2inducedbyaldosterone activates NHE (1 and 3) in renal tubular cells. In vitro studies showed that aldosterone nongenomically stimulates PKCβ. PKCβ1alsomediatedstimulationofNHEactivity.Therearenoreports ofproteinexpressionsofNHE(1and3)andPKCβ (1and2) simultaneously in ratkidney regarding these circumstances. Methods: Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150mg/kg BW). After 30minutes, abundances and localizations of NHE (1 and 3) and PKCβ (1 and 2) proteins were determined by Western blot analysis and immunohistochemistry, respectively. Results: ByWestern blot analysis, aldosterone increased renal protein abundances of NHE1 andNHE3 to be 152%and 134%, respectively (P< 0.05). Aldosterone significantly enhanced protein abundances of PKCβ1 by 30%, whereas PKCβ2 protein trended to decline. Aldosterone increasedmore protein expressions of NHE1 and NHE3 in the medulla than cortex. Protein expression PKCβ1 was enhanced in the glomeruli, renal vasculatures and thin limb of Henles loop by aldosterone. However, PKCβ2 was declined in the medulla. Conclusion: This in vivo study is the first to demonstrate simultaneously that aldosterone rapidly elevates PKCβ1 and NHE (1 and 3) protein abundances in rat kidney. The stimulation of NHE protein expressions by aldosterone, per se, may occur through PKCβ1 activation. 002 KEY ROLE OFAPOPTOSIS INHIBITOR OF MACROPHAGE IN PHLOGOGENIC ACTION OF GLOMERULAR NEPHRITOGENIC IGA IN IGA NEPHROPATHY TAKAHATA A, KITADA K, NOGI C, ARAI S, MAKITA Y, SUZUKI H, NAKATA J, HORIKOSHI S, MIYAZAKI T, SUZUKI Y Division of Nephrology, Department of Internal Medicine Juntendo University School of Medicine, Bunkyo-ku, Japan, Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Japan

Ckd.Qld: Effect of Bariatric Procedures On Renal and Non Renal Parameters in Obese Ckd Patients

Aim: To investigatenongenomic effects of aldosteroneon renal protein expressions of sodium hydrogen exchanger 1 and 3 (NHE1and3), andproteinkinaseCbeta 1 and2 (PKCβ 1 and2) Introduction: Wehave previously demonstrated that aldosterone rapidly elevates epidermal growth factor receptor (EGFR) phosphorylation and increases extracellular signal-related kinase1and2(ERK1⁄2)inratkidney.ERK1⁄2inducedbyaldosterone activates NHE (1 and 3) in renal tubular cells. In vitro studies showed that aldosterone nongenomically stimulates PKCβ. PKCβ1alsomediatedstimulationofNHEactivity.Therearenoreports ofproteinexpressionsofNHE(1and3)andPKCβ (1and2) simultaneously in ratkidney regarding these circumstances. Methods: Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150mg/kg BW). After 30minutes, abundances and localizations of NHE (1 and 3) and PKCβ (1 and 2) proteins were determined by Western blot analysis and immunohistochemistry, respectively. Results: ByWestern blot analysis, aldosterone increased renal protein abundances of NHE1 andNHE3 to be 152%and 134%, respectively (P< 0.05). Aldosterone significantly enhanced protein abundances of PKCβ1 by 30%, whereas PKCβ2 protein trended to decline. Aldosterone increasedmore protein expressions of NHE1 and NHE3 in the medulla than cortex. Protein expression PKCβ1 was enhanced in the glomeruli, renal vasculatures and thin limb of Henles loop by aldosterone. However, PKCβ2 was declined in the medulla. Conclusion: This in vivo study is the first to demonstrate simultaneously that aldosterone rapidly elevates PKCβ1 and NHE (1 and 3) protein abundances in rat kidney. The stimulation of NHE protein expressions by aldosterone, per se, may occur through PKCβ1 activation. 002 KEY ROLE OFAPOPTOSIS INHIBITOR OF MACROPHAGE IN PHLOGOGENIC ACTION OF GLOMERULAR NEPHRITOGENIC IGA IN IGA NEPHROPATHY TAKAHATA A, KITADA K, NOGI C, ARAI S, MAKITA Y, SUZUKI H, NAKATA J, HORIKOSHI S, MIYAZAKI T, SUZUKI Y Division of Nephrology, Department of Internal Medicine Juntendo University School of Medicine, Bunkyo-ku, Japan, Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Japan

Membranoproliferative Glomerular Nephritis (Mpgn) in a Patient with Hepatitis C, Cryoglbulinaemia and Falsely-Positive Anti-Gbm Antibodies

Aim: To investigatenongenomic effects of aldosteroneon renal protein expressions of sodium hydrogen exchanger 1 and 3 (NHE1and3), andproteinkinaseCbeta 1 and2 (PKCβ 1 and2) Introduction: Wehave previously demonstrated that aldosterone rapidly elevates epidermal growth factor receptor (EGFR) phosphorylation and increases extracellular signal-related kinase1and2(ERK1⁄2)inratkidney.ERK1⁄2inducedbyaldosterone activates NHE (1 and 3) in renal tubular cells. In vitro studies showed that aldosterone nongenomically stimulates PKCβ. PKCβ1alsomediatedstimulationofNHEactivity.Therearenoreports ofproteinexpressionsofNHE(1and3)andPKCβ (1and2) simultaneously in ratkidney regarding these circumstances. Methods: Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (150mg/kg BW). After 30minutes, abundances and localizations of NHE (1 and 3) and PKCβ (1 and 2) proteins were determined by Western blot analysis and immunohistochemistry, respectively. Results: ByWestern blot analysis, aldosterone increased renal protein abundances of NHE1 andNHE3 to be 152%and 134%, respectively (P< 0.05). Aldosterone significantly enhanced protein abundances of PKCβ1 by 30%, whereas PKCβ2 protein trended to decline. Aldosterone increasedmore protein expressions of NHE1 and NHE3 in the medulla than cortex. Protein expression PKCβ1 was enhanced in the glomeruli, renal vasculatures and thin limb of Henles loop by aldosterone. However, PKCβ2 was declined in the medulla. Conclusion: This in vivo study is the first to demonstrate simultaneously that aldosterone rapidly elevates PKCβ1 and NHE (1 and 3) protein abundances in rat kidney. The stimulation of NHE protein expressions by aldosterone, per se, may occur through PKCβ1 activation. 002 KEY ROLE OFAPOPTOSIS INHIBITOR OF MACROPHAGE IN PHLOGOGENIC ACTION OF GLOMERULAR NEPHRITOGENIC IGA IN IGA NEPHROPATHY TAKAHATA A, KITADA K, NOGI C, ARAI S, MAKITA Y, SUZUKI H, NAKATA J, HORIKOSHI S, MIYAZAKI T, SUZUKI Y Division of Nephrology, Department of Internal Medicine Juntendo University School of Medicine, Bunkyo-ku, Japan, Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Japan