Background: Chronic kidney disease (CKD) is a global health burden, yet it is still underrepresented within public health agendas in many countries. Studies focusing on the natural history of CKD are challenging to design and conduct, because of the long time-course of disease progression, a wide variation in etiologies, and a large amount of clinical variability among individuals with CKD. With the difference in health-related behaviors, healthcare delivery, genetics, and environmental exposures, this variability is greater across countries than within one locale and may not be captured effectively in a single study.

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.

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on behalf of the CRIC Study InvestigatorsRationale & Objective: Identification of novel risk factors for chronic kidney disease (CKD) progression may inform mechanistic investigations and improve identification of high-risk subgroups. The current study aimed to characterize CKD progression across levels of numerous risk factors and identify independent risk factors for CKD progression among those with and without diabetes.Study Design: The Chronic Renal Insufficiency Cohort (CRIC) Study is a prospective cohort study of adults with CKD conducted at 7 US clinical centers.Setting & Participants: Participants (N = 3,379) had up to 12.3 years of follow-up; 47% had diabetes.Predictors: 30 risk factors for CKD progression across sociodemographic, behavioral, clinical, and biochemical domains at baseline.Outcomes: Study outcomes were estimated glomerular filtration rate (eGFR) slope and the composite of halving of eGFR or initiation of kidney replacement therapy. Analytical Approach:Stepwise selection of independent risk factors was performed stratified by diabetes status using linear mixed-effects and Cox proportional hazards models.Results: Among those without and with diabetes, respectively, mean eGFR slope was −1.4 ± 3.3 and −2.7 ± 4.7 mL/min/1.73 m 2 per year. Among participants with diabetes, multivariable-adjusted hazard of the composite outcome was approximately 2-fold or greater with higher levels of the inflammatory chemokine CXCL12, the cardiac marker N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the kidney injury marker urinary neutrophil gelatinaseassociated lipocalin (NGAL). Among those without diabetes, low serum bicarbonate and higher high-sensitivity troponin T, NT-proBNP, and urinary NGAL levels were all significantly associated with a 1.5-fold or greater rate of the composite outcome. Limitations:The observational study design precludes causal inference.Conclusions: Strong associations for cardiac markers, plasma CXCL12, and urinary NGAL are comparable to that of systolic blood pressure ≥ 140 mm Hg, a well-established risk factor for CKD progression. This warrants further investigation into the potential mechanisms that these markers indicate and opportunities to use them to improve risk stratification.

A rterial hypertension is prevalent in chronic kidney disease (CKD) and contributes to its adverse outcomes. 1 The major benefits of lowering blood pressure (BP) for survival and cardiovascular outcomes are well established, as are those of inhibiting the renin angiotensinaldosterone system (RAAS) to slow CKD progression. 2-8 BP control and RAAS inhibitor use are therefore major goals in the management of patients with CKD, 9 although no consensus exists about the ideal BP level. Current guidelines