A collaborative, individual-level analysis compared longitudinal outcomes across the International Network of Chronic Kidney Disease (iNETCKD) cohorts

Abstract

Rates of chronic kidney disease (CKD) progression, end stage kidney disease (ESKD), all-cause mortality, and cardiovascular (CVD) events among individuals with CKD vary widely across countries. Well-characterized demographic, comorbidity, and laboratory markers captured for prospective cohorts may explain, in part, such differences. To investigate whether core characteristics of individuals with CKD explain differences in rates of outcomes, we conducted an individual-level analysis of eight studies that are part of iNET-CKD, an international network of CKD cohort studies. Overall, the rate of CKD progression was 40 events/1000 person-year (95% confidence interval 39-41), 28 (27-29) for ESKD, 41 (40-42) for death, and 29 (28-30) for CVD events. However, standardized rates were highly heterogeneous across studies (over 92.5%). Interactions by study group on the association between baseline characteristics and outcomes were then identified. For example, the adjusted hazard ratio for CKD progression was 0.44 (95% confidence interval 0.35-0.56) for women vs. men among the Japanese (CKD-JAC), while it was 0.66 (0.59-0.75) among the Uruguayan (NRHP). The adjusted hazard ratio for ESKD was 2.02 (95% CI 1.88-2.17) per 10 units lower baseline eGFR among Americans (CRIC), while it was 3.01 (2.57-3.53) among Canadians (CanPREDDICT) (significant interaction for comparisons across all studies). The risks of CKD progression, ESKD, death, and CVD vary across countries even after accounting for the distributions of age, sex, comorbidities, and laboratory markers. Thus, our findings support the need for a better understanding of specific factors in different populations that explain this variation.

Worldwide Disparity in the Relation Between CKD Prevalence and Kidney Failure Risk

“…( independently associated with KRT incidence. (3,4,10,13,25) It also showed that in more developed countries, the private for-profit share of hemodialysis facilities was also associated with higher KRT incidence, This study and ours raise the issue of overtreatment related to early-start dialysis in countries with extremely high KRT incidence. In France, eGFR level at dialysis start explained a substantial part of the variations in KRT incidence between regions.…”

“…(12, 13) These variations in CKD progression, however, persisted despite adjustment for baseline eGFR, age, sex, albuminuria, comorbidities, and use of renin-angiotensin system inhibitors. The international network of CKD cohorts (iNET-CKD) hasalso observed different baseline profiles and highly heterogeneous risks of CKD progression, KRT incidence, and mortality among individuals with CKD participating in eight cohort studies around the globe (12,13). This study also observed that adjustment for several patient characteristics and laboratory markers did not substantially attenuate the differences in outcomes.…”

“…(11) Since then, two studies have investigated potential explanatory factors for differences in CKD progression across countries. (12,13) Nevertheless, no overview is available of the gaps in KRT incidence between countries with their links to CKD prevalence within and across world regions, although it would help in understanding the possible sources of variations.…”

Burden of Chronic Kidney Disease by KDIGO Categories of Glomerular Filtration Rate and Albuminuria: A Systematic Review

“…Since this systematic review was conducted, two further articles have been published reporting the prevalence of the KDIGO 2012 albuminuria categories from the UK, Germany, France and USA [41,42] (Table S6). The cohorts included patients with CKD, with a higher proportion of moderately and severely increased albuminuria compared with the general population cohorts included in this systematic review.…”

The Global Kidney Health Atlas: Burden and Opportunities to Improve Kidney Health Worldwide

“…Within the context of research and improved understanding of CKD and its causes, consequences, and cures, there are several international collaborative research efforts facilitated by the ISN with its partners. ISN-ACT (Advancing Clinical Trials) aims to connect the global kidney clinical trial community to increase capacity and quality of trials answering important questions; iNET CKD (International Network of CKD Cohorts) has established a collaborative research network with individuallevel data and bio-samples to examine variation in outcomes and biological parameters around the world and to leverage that information to inform clinical trials as needed [13][14][15]. The Hydration for Kidney Health initiative (ISN-H4KH), a partnership between Danone and ISN, has established research projects and supported investigators who are interested in improving the understanding of the role of hydration in specific environments and specific kidney disease populations.…”