Low birth weight, intrauterine growth restriction and risk of chronic kidney disease in adult age

Background and aims: Studies have shown that adults with low birth weight (LBW) face an increased risk for chronic kidney disease (CKD), high blood pressure and cardiovascular disease (CVD). Previous Norwegian studies have shown that individuals with LBW more often develop kidney failure; however, there is a need for more knowledge regarding risk of more moderate kidney disease, such as chronic kidney disease (CKD). Methods: This thesis consists of three studies that were conducted as retrospective registry-based cohort studies. Datasets were obtained through linkage of the Medical Birth Registry of Norway (MBR), Norwegian Population Registry (NPoR), Norwegian Renal Registry (NRR) and the Norwegian Patient Registry (NPR) (data available for 2008-2016 for the latter). We included all individuals born in Norway since 1967. For Paper I, we investigated the risk of kidney failure as registered in the NRR, and for Papers II and III, we investigated the risk of diverse forms of kidney disease as registered in the NPR. Relative risk (RR) estimates were obtained by Cox-regression or logistic regression statistics. Results: In our studies, we were able to include about 2.6 million individuals. In Paper I, 1126 individuals developed kidney failure and individuals with LBW had a RR of 1.61 (95% CI 1.38-1.98) for kidney failure, and individuals with small for gestational age (SGA) had a RR of 1.44 (1.22-1.70). In Papers II and III, 4495 individuals had been diagnosed with CKD and 12,818 with other groups of kidney disease. LBW was associated with a RR of 1.72 (1.60-1.90) for CKD and SGA with a RR of 1.79 (1.65-194). These birth-related factors were more strongly associated with CKD than with other forms of kidney disease. In Paper III, we found that as compared the individuals who did not have LBW and who did not have a sibling with LBW, individuals who did not have LBW but who had a sibling with LBW had a RR of 1.33 (1.19-1.49), individuals with LBW but no siblings with LBW had a RR of 1.74 (1.55-1.95) and individuals with LBW and a sibling with LBW had a RR of 1.77 (1.54-2.04) for CKD. Conclusion: In our cohort studies with a follow-up of 50 years, low birth weight and intrauterine growth restriction were found to be associated with an increased risk for both kidney failure and CKD. Taken together, our results support the hypothesis that intrauterine growth restriction (IUGR) increases the risk of CKD in adult life.Doktorgradsavhandlin

Intrauterine growth restriction and risk of diverse forms of kidney disease during the first 50 years of life

Background and objectives: Previous studies have shown that individuals with low birth weight (LBW) or small for gestational age (SGA) have higher risk of kidney failure. This study investigates birth-related exposures and risk of CKD and other kidney diagnoses. Design, setting, participant, & measurements: The Medical Birth Registry of Norway has registered extensive medical data on all births in Norway since 1967. The Norwegian Patient Registry has registered diagnostic codes for all admissions and outpatient visits to Norwegian hospitals since 2008. Data from these registries were linked, and risk of CKD and other groups of kidney disease were analyzed using logistic regression statistics. LBW (below the tenth percentile), SGA (birth weight below the tenth percentile for gestational age), and preterm birth (<37 weeks) were analyzed as exposures. Results: A total of 2,663,010 individuals were included. After a mean follow-up of 26 years (maximum 50 years), 4495 had been diagnosed with CKD and 12,818 had been diagnosed with other groups of kidney disease. LBW was associated with an odds ratio (OR) for CKD of 1.72 (95% confidence interval [95% CI], 1.60 to 1.90), SGA with an OR of 1.79 (95% CI, 1.65 to 1.94), and preterm birth with an OR of 1.48 (95% CI, 1.33 to 1.66). Analyses using diagnosis of CKD at stages 3–5 as end point showed similar results. Results were similar for men and women. We analyzed adjusted ORs for other groups of kidney disease and found that LBW was associated with an adjusted OR of 1.44 (95% CI, 1.33 to 1.56) for acute kidney disease, 1.24 (95% CI, 1.14 to 1.36) for GN, 1.35 (95% CI, 1.17 to 1.56) for cystic kidney disease, and 1.15 (95% CI, 1.06 to 1.25) for kidney disease resulting from kidney or urinary tract malformations. Conclusions: LBW, SGA, and preterm birth are associated with higher risk of CKD in the first 50 years of life. Risk of other groups of kidney disease was less pronounced.acceptedVersio

Measurement of renal functional response using iohexol clearance—a study of different outpatient procedures

Background: Glomerular filtration rate (GFR) increases after a heavy protein load; an increase termed renal functional response (RFR). Decreased RFR could be a marker of early kidney damage, but published methods are cumbersome in the outpatient setting. The present study investigates the use of iohexol clearance to measure RFR in outpatients using both one- and two-sample methods. Methods: Fourteen healthy volunteers with a mean ± SD age of 42 ± 12 years were included (six males and eight females). GFR was measured using plasma iohexol clearance with one- and two-sample methodologies. Four measurements in each individual were performed: one baseline test and three protein loading tests containing 80 g protein (commercially available protein supplementations from Myo Nutrition and Proteinfabrikken and 350 g chicken breast). RFR was calculated as percentage increase in GFR from the baseline test. Results: Mean RFR was 11.4 ± 5.4% and 12.1 ± 6.4% using one- and two-sample methods, respectively. The three different protein loads resulted in similar mean RFR but there was considerable intra-individual variability. One- and two-sample methods for measurement of RFR showed similar results with near-identical means, but there was some intra-individual variation that was similar for different protein loads. The overall 95% limit of agreement between one- and two-sample methods for calculating RFR was −8.7 to 7.3. Conclusions: RFR can be investigated using plasma iohexol clearance in an outpatient setting. Protocols using commercially available protein supplementation showed a mean RFR of about 12%. One- and two-sample methods for measuring RFR yield similar results.publishedVersio

Intrauterine growth restriction, preterm birth and risk of end-stage renal disease during the first 50 years of life

Background: Low birth weight (LBW) is associated with a higher risk of end-stage renal disease (ESRD). The relative impacts of absolute birth weight, birth weight in relation to gestational age and preterm birth are, however, uncertain. Methods: The Medical Birth Registry of Norway has since 1967 recorded data on all births. All patients with ESRD since 1980 have been registered in the Norwegian Renal Registry. Data from these registries were linked. All individuals registered in the Medical Birth Registry were included and the development of ESRD was used as endpoint in Cox regression statistics. LBW and LBW for gestational age [small for gestational age (SGA)] according to the 10th percentiles were used as the main predictor variables. Results: Of the 2 679 967 included subjects, 1181 developed ESRD. Compared with subjects without LBW, subjects with LBW had an adjusted hazard ratio (aHR) for ESRD of 1.61 (1.38–1.98). SGA had an aHR of 1.44 (1.22– 1.70). Further analyses showed that as compared with subjects who had none of the risk factors LBW, SGA and preterm birth, subjects with one risk factor had an aHR of 1.05 (0.84–1.31), subjects with two risk factors had an aHR of 1.67 (1.40–1.98) and subjects with three risk factors had an aHR of 2.96 (1.84–4.76). Conclusions: We conclude that LBW was associated with increased risk for ESRD during the first 50 years. Our analyses add to previous knowledge showing that only subjects with at least two of the risk factors LBW, SGA or preterm birth have increased risk.publishedVersio

Digital phenotyping of individual feed intake in Atlantic salmon (Salmo salar) with the X-ray method and image analysis

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Applying genetic technologies to combat infectious diseases in aquaculture

Disease and parasitism cause major welfare, environmental and economic concerns for global aquaculture. In this review, we examine the status and potential of technologies that exploit genetic variation in host resistance to tackle this problem. We argue that there is an urgent need to improve understanding of the genetic mechanisms involved, leading to the development of tools that can be applied to boost host resistance and reduce the disease burden. We draw on two pressing global disease problems as case studies—sea lice infestations in salmonids and white spot syndrome in shrimp. We review how the latest genetic technologies can be capitalised upon to determine the mechanisms underlying inter- and intra-species variation in pathogen/ parasite resistance, and how the derived knowledge could be applied to boost disease resistance using selective breeding, gene editing and/or with targeted feed treatments and vaccines. Gene editing brings novel opportunities, but also implementation and dissemination challenges, and necessitates new protocols to integrate the technology into aquaculture breeding programmes. There is also an ongoing need to minimise risks of disease agents evolving to overcome genetic improvements to host resistance, and insights from epidemiological and evolutionary models of pathogen infestation in wild and cultured host populations are explored. Ethical issues around the different approaches for achieving genetic resistance are discussed. Application of genetic technologies and approaches has potential to improve fundamental knowledge of mechanisms affecting genetic resistance and provide effective pathways for implementation that could lead to more resistant aquaculture stocks, transforming global aquaculture.publishedVersio

Assessment of scientific gaps related to the effective environmental management of deep-seabed mining

A comprehensive understanding of the deep-sea environment and mining’s likely impacts is necessary to assess whether and under what conditions deep-seabed mining operations comply with the International Seabed Authority’s obligations to prevent ‘serious harm’ and ensure the ‘effective protection of the marine environment from harmful effects’ in accordance with the United Nations Convention on the Law of the Sea. A synthesis of the peer-reviewed literature and consultations with deep-seabed mining stakeholders revealed that, despite an increase in deep-sea research, there are few categories of publicly available scientific knowledge comprehensive enough to enable evidence-based decision-making regarding environmental management, including whether to proceed with mining in regions where exploration contracts have been granted by the International Seabed Authority. Further information on deep-sea environmental baselines and mining impacts is critical for this emerging industry. Closing the scientific gaps related to deep-seabed mining is a monumental task that is essential to fulfilling the overarching obligation to prevent serious harm and ensure effective protection, and will require clear direction, substantial resources, and robust coordination and collaboration. Based on the information gathered, we propose a potential high-level road map of activities that could stimulate a much-needed discussion on the steps that should be taken to close key scientific gaps before any exploitation is considered. These steps include the definition of environmental goals and objectives, the establishment of an international research agenda to generate new deep-sea environmental, biological, and ecological information, and the synthesis of data that already exist

A blueprint for an inclusive, global deep-sea Ocean Decade field programme

The ocean plays a crucial role in the functioning of the Earth System and in the provision of vital goods and services. The United Nations (UN) declared 2021–2030 as the UN Decade of Ocean Science for Sustainable Development. The Roadmap for the Ocean Decade aims to achieve six critical societal outcomes (SOs) by 2030, through the pursuit of four objectives (Os). It specifically recognizes the scarcity of biological data for deep-sea biomes, and challenges the global scientific community to conduct research to advance understanding of deep-sea ecosystems to inform sustainable management. In this paper, we map four key scientific questions identified by the academic community to the Ocean Decade SOs: (i) What is the diversity of life in the deep ocean? (ii) How are populations and habitats connected? (iii) What is the role of living organisms in ecosystem function and service provision? and (iv) How do species, communities, and ecosystems respond to disturbance? We then consider the design of a global-scale program to address these questions by reviewing key drivers of ecological pattern and process. We recommend using the following criteria to stratify a global survey design: biogeographic region, depth, horizontal distance, substrate type, high and low climate hazard, fished/unfished, near/far from sources of pollution, licensed/protected from industry activities. We consider both spatial and temporal surveys, and emphasize new biological data collection that prioritizes southern and polar latitudes, deeper (&gt; 2000 m) depths, and midwater environments. We provide guidance on observational, experimental, and monitoring needs for different benthic and pelagic ecosystems. We then review recent efforts to standardize biological data and specimen collection and archiving, making “sampling design to knowledge application” recommendations in the context of a new global program. We also review and comment on needs, and recommend actions, to develop capacity in deep-sea research; and the role of inclusivity - from accessing indigenous and local knowledge to the sharing of technologies - as part of such a global program. We discuss the concept of a new global deep-sea biological research program ‘Challenger 150,’ highlighting what it could deliver for the Ocean Decade and UN Sustainable Development Goal 14