scholarly journals Relationship between birth weight and chronic kidney disease: evidence from systematics review and two-sample Mendelian randomization analysis

2020 ◽  
Vol 29 (13) ◽  
pp. 2261-2274 ◽  
Author(s):  
Xinghao Yu ◽  
Zhongshang Yuan ◽  
Haojie Lu ◽  
Yixin Gao ◽  
Haimiao Chen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Birth Weight ◽  
Kidney Disease ◽  
Low Birth Weight ◽  
Kidney Function ◽  
Large Scale ◽  
Mendelian Randomization ◽  
Negative Relationship ◽  
Sensitivity Analyses ◽  
Inverse Association

Abstract Observational studies showed an inverse association between birth weight and chronic kidney disease (CKD) in adulthood existed. However, whether such an association is causal remains fully elusive. Moreover, none of prior studies distinguished the direct fetal effect from the indirect maternal effect. Herein, we aimed to investigate the causal relationship between birth weight and CKD and to understand the relative fetal and maternal contributions. Meta-analysis (n = ~22 million) showed that low birth weight led to ~83% (95% confidence interval [CI] 37–146%) higher risk of CKD in late life. With summary statistics from large scale GWASs (n = ~300 000 for birth weight and ~481 000 for CKD), linkage disequilibrium score regression demonstrated birth weight had a negative maternal, but not fetal, genetic correlation with CKD and several other kidney-function related phenotypes. Furthermore, with multiple instruments of birth weight, Mendelian randomization showed there existed a negative fetal casual association (OR = 1.10, 95% CI 1.01–1.16) between birth weight and CKD; a negative but non-significant maternal casual association (OR = 1.09, 95% CI 0.98–1.21) was also identified. Those associations were robust against various sensitivity analyses. However, no maternal/fetal casual effects of birth weight were significant for other kidney-function related phenotypes. Overall, our study confirmed the inverse association between birth weight and CKD observed in prior studies, and further revealed the shared maternal genetic foundation between low birth weight and CKD, and the direct fetal and indirect maternal causal effects of birth weight may commonly drive this negative relationship.

scholarly journals Relationship between birth weight and chronic kidney disease: an integrative analysis of observational studies and causal inference through genetic approaches

2019 ◽  
Author(s):  
Xinghao Yu ◽  
Zhongshang Yuan ◽  
Haimiao Chen ◽  
Jiaji Yang ◽  
Yixin Gao ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Birth Weight ◽  
Kidney Disease ◽  
Instrumental Variables ◽  
Observational Studies ◽  
Large Scale ◽  
Causal Effect ◽  
Meta Analysis ◽  
Likelihood Method ◽  
Inverse Association

ABSTRACTObjectiveAlthough many observational studies have shown that there was an inverse association between birth weight and chronic kidney disease (CKD) in adults, whether such association is causal remains largely unclear.MethodsWe first conducted a systematic review and meta-analysis to investigate the association between birth weight and CKD. Then using a set of valid instrumental variables for birth weight, we performed a two-sample Mendelian randomization (MR) to evaluate its causal effect on CKD based on summary association statistics available from large scale genome-wide association study (GWAS) (up to 143,677 individuals for birth weight and 118,147 individuals for CKD). We further validated the MR results with extensive sensitive analyses.ResultsThe results of meta-analysis showed that individuals with low birth weight have about 76% (95% CI 36∼126%) higher risk of CKD in late life compared with those with normal birth weight. Depending on 26 instrumental variables, the inverse variance weighted MR showed that the odds ratio per one SD increase of birth weight on CKD was estimated to be 0.91 (95% CI 0.72∼1.14, p=0.396). The similar null association between birth weight and CKD is also observed using the weighted median method and maximum likelihood method as well as the Egger regression. Such non-significant association is robust against potential instrumental outliers and pleiotropic effects.ConclusionOur study identifies an inverse association between birth weight and adult CKD in observational studies, while it is not supportive of the causal role of birth weight on CKD based on our MR analysis.

scholarly journals SP279THE LINK BETWEEN LOW BIRTH WEIGHT AND CHRONIC KIDNEY DISEASE

2018 ◽  
Vol 33 (suppl_1) ◽  
pp. i437-i437
Author(s):  
Altynay Balmukhanova ◽  
Kairat Kabulbayev
Keyword(s):  
Chronic Kidney Disease ◽  
Birth Weight ◽  
Kidney Disease ◽  
Low Birth Weight

scholarly journals Causal Effects of Life Course Adiposity on Chronic Kidney Disease: A Mendelian Randomization Study

2021 ◽  
Author(s):  
Wanchun Yang ◽  
Hongchun Chen ◽  
Qiuyun Yuan ◽  
Yang Zou
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Life Course ◽  
Causal Relationship ◽  
Mendelian Randomization ◽  
Causal Effect ◽  
Sensitivity Analyses ◽  
Body Fat Percentage ◽  
Fat Percentage ◽  
Hip Circumference

Abstract Background Obesity is reported to be tightly correlated the development of chronic kidney disease (CKD). However, whether there exists causation is unknown, and it remains controversial about the role of obesity in CKD is protective or destructive. In this study, we try to infer the causal relationship between life course adiposity and CKD, to provide a rationale for obesity management in CKD patients.Methods A two-sample Mendelian randomization (MR) analysis was conducted to explore the causal relationship of life course adiposity traits including including body mass index (BMI), childhood BMI, body fat percentage (BF), birth weight (BW), waist circumference, hip circumference and waist-to-hip ratio (WHR) to CKD. Significant single nucleotide polymorphisms from genome-wide association study on human adiposity traits were utilized as exposure instruments, and summary statistics of CKD as outcome. The causal relationship was evaluated by inverse variance weighted, MR Egger regression and weighted median methods, and further verified by extensive sensitivity analyses.Results Genetically determined one standard deviation increase in adult BMI was associated with higher risk of CKD in all four MR methods. And other indexes including childhood BMI, body fat percentage, and waist/hip circumference also have a causal effect on the risk of CKD. The results were robust under all sensitivity analyses.Conclusions There exist causal effect of life course adiposity on the risk of CKD. A genetic predisposition to higher adult BMI may increase the risk of CKD.

scholarly journals Perinatal factors contributing to chronic kidney disease in a cohort of Japanese children with very low birth weight

2020 ◽  
Author(s):  
Osamu Uemura ◽  
Kenji Ishikura ◽  
Tetsuji Kaneko ◽  
Daishi Hirano ◽  
Yuko Hamasaki ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Birth Weight ◽  
Kidney Disease ◽  
Low Birth Weight ◽  
Very Low Birth Weight ◽  
Neonatal Period ◽  
Late Onset ◽  
Growth Restriction ◽  
Circulatory Collapse ◽  
Kidney Dysfunction

Abstract Background Developmental programming of chronic kidney disease (CKD) in young adults is linked to preterm birth and intrauterine growth restriction (IUGR). Which confers a higher risk of progression to chronic kidney damage in children with very low birth weight (VLBW; born weighing < 1500 g): prematurity or IUGR? Methods This is a national historical cohort study of children with VLBW cared for in perinatal medical centers in Japan. Predictive factors included three latent variables (prematurity, IUGR, stress during neonatal period) and eight observed variables (gestational age, birth weight Z-score, maternal age, duration of treatment with antibiotics and diuretics, maternal smoking, late-onset circulatory collapse, kidney dysfunction) during the perinatal period. The primary endpoint was estimated glomerular filtration rate (eGFR) at age ≥ 3 years. A structural equation model was used to examine the pathologic constitution. Results The 446 children with VLBW included 253 boys and 193 girls, of mean age 5.8 ± 2.6 years and mean eGFR 111.7 ml/min/1.73 m2 at last encounter. Pathway analyses showed intrauterine malnutrition (β = 0.85) contributed more to chronic kidney damage than stress during the neonatal period (β = − 0.19) and prematurity (β = 0.12), and kidney dysfunction and late-onset circulatory collapse were important observed variables in stress during the neonatal period. Conclusions IUGR was more harmful to future kidneys of VLBW neonates. Neonatal kidney dysfunction and late-onset circulatory collapse were important risk factors for subsequent CKD development. This emphasizes the need for obstetricians to monitor for fetal growth restriction and neonatologists to minimize neonatal stress to prevent CKD in later life.

scholarly journals P0192RELATIONSHIP BETWEEN SERUM HEPCIDIN AND THE PROGRESSION OF CHRONIC KIDNEY DISEASE: KOREAN COHORT STUDY FOR OUTCOME IN PATIENTS WITH CHRONIC KIDNEY DISEASE (KNOW-CKD)

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Su Ah Sung ◽  
Kum Hyun Han ◽  
Jien Lee ◽  
Taehee Lee
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Large Scale ◽  
Hemoglobin Level ◽  
Renal Diseases ◽  
Hepcidin Level ◽  
Replacement Treatment ◽  
Serum Hepcidin ◽  
The Relationship

Abstract Background and Aims Hepcidin plays a central role in iron metabolism. However, few studies have evaluated the relationship between serum hepcidin and the progression of chronic kidney disease (CKD). This study aimed to determine the relationship between serum hepcidin levels and the progression of renal diseases in patients with CKD. Method We reviewed data of 2,016 patients from a large-scale multicenter, prospective study enrolled between 2011 and 2016, who had data regarding the serum hepcidin level, hemoglobin level, iron indices, usage of erythopoiesis-stimulating agents (ESA) or iron, and follow-up of renal events. Renal events were defined as a &gt;50% decrease in kidney function from the baseline values, doubling of the serum creatinine level, or initiation of renal-replacement treatment. Results During a mean 3.6 years, 556 patients developed renal events (27.6%). In multivariate Cox proportional hazard regression analysis adjusted for confounders including kidney function, the hemoglobin level, conventional iron indices, usage of ESA or iron, and other chronic diseases, the hazard of serum hepcidin for renal events was evident in the comparison between only the first and fourth quartiles (hazard ratio 1.603, 95% confidence interval, 1.187-2.163, P = 0.002). In the multivariate penalized spline curve analysis, the relationship between serum hepcidin and renal events was J-shaped, and the renal hazard was particularly evident at a serum hepcidin level ≥60 ng/ml. Conclusion Increased serum hepcidin levels independently predict the progression of CKD in non-dialysis patients with CKD. The potential direct renal hazard of serum hepcidin needs to be confirmed in future randomized controlled trials.

New Insights into Acute-on-Chronic Kidney Disease in Nephrology Patients: The CKD-REIN Study

2021 ◽  
Author(s):  
Aghilès Hamroun ◽  
Luc Frimat ◽  
Maurice Laville ◽  
Marie Metzger ◽  
Christian Combe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Birth Weight ◽  
Kidney Disease ◽  
Low Birth Weight ◽  
Hospital Discharge ◽  
Incidence Rates ◽  
High Rate ◽  
Cox Models ◽  
Ckd Stage

Abstract Background Acute-on-chronic kidney disease (ACKD) is poorly understood and often overlooked. We studied its incidence, circumstances, determinants, and outcomes in patients with CKD. Methods We used the Kidney Disease Improving Global Outcomes criteria to identify all-stage acute kidney injury (AKI) events in 3033 nephrology outpatients with CKD stage 3-5 participating in the CKD-REIN cohort study (2013-2020), and cause-specific Cox models to estimate hazard ratios (HR, 95% confidence intervals [CI]) of AKI-associated risk factors. Results At baseline, 22% of the patients (mean age 67 years, 65% men, mean eGFR 32 ml/min/1.73m2) had a history of AKI. Over a 3-year follow-up, 443 had at least one AKI event: 27% were stage 2 or 3, and 11% required dialysis; 74% involved hospitalization including 47% acquired as hospital inpatients; a third were not reported in hospital discharge reports. Incidence rates were 10.1 and 4.8 per 100 person-years in patients with and without an AKI history, respectively. In 2375 patients without this history, male sex, diabetes, cardiovascular disease, cirrhosis, several drugs, low eGFR, and serum albumin levels were significantly associated with a higher risk of AKI, as were low birth weight (&lt;2500 g) (adjusted HR, 1.98; 95%CI, 1.35 to 2.91) and hemoglobin level (HR 1.21; 1.12 to 1.32 per 1 g/dl decrease). Within one year, only 63% of the patients had recovered their previous kidney function, 13.7% had started kidney replacement therapy, and 12.7% had died. Conclusions The study highlights the high rate of hospital-acquired AKI events in patients with CKD, and their underreporting at hospital discharge. It also reveals low birth weight and anemia as possible new risk factors in CKD patients.

scholarly journals Thyroid function, renal events and mortality in chronic kidney disease patients: the German Chronic Kidney Disease study

2020 ◽  
Author(s):  
Ulla T Schultheiss ◽  
Inga Steinbrenner ◽  
Matthias Nauck ◽  
Markus P Schneider ◽  
Fruzsina Kotsis ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Thyroid Function ◽  
Positive Association ◽  
Inverse Association ◽  
All Cause Mortality ◽  
Disease Study ◽  
Reduced Kidney Function

Abstract Background Hypothyroidism and low free triiodothyronine (FT3) syndrome [low FT3 levels with normal thyroid-stimulating hormone (TSH)] have been associated with reduced kidney function cross-sectionally in chronic kidney disease (CKD) patients with severely reduced estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD). Results on the prospective effects of impaired thyroid function on renal events and mortality for patients with severely reduced eGFR or from population-based cohorts are conflicting. Here we evaluated the association between thyroid and kidney function with eGFR (cross-sectionally) as well as renal events and mortality (prospectively) in a large, prospective cohort of CKD patients with mild to moderately reduced kidney function. Methods Thyroid markers were measured among CKD patients from the German Chronic Kidney Disease study. Incident renal endpoints (combined ESKD, acute kidney injury and renal death) and all-cause mortality were abstracted from hospital records and death certificates. Time to first event analysis of complete data from baseline to the 4-year follow-up (median follow-up time 4.04 years) of 4600 patients was conducted. Multivariable linear regression and Cox proportional hazards models were fitted for single and combined continuous thyroid markers [TSH, free thyroxine (FT4), FT3] and thyroid status. Results Cross-sectionally, the presence of low-FT3 syndrome showed a significant inverse association with eGFR and continuous FT3 levels alone showed a significant positive association with eGFR; in combination with FT4 and TSH, FT3 levels also showed a positive association and FT4 levels showed a negative association with eGFR. Prospectively, higher FT4 and lower FT3 levels were significantly associated with a higher risk of all-cause mortality (Nevents = 297). Per picomole per litre higher FT3 levels the risk of reaching the composite renal endpoint was 0.73-fold lower (95% confidence interval 0.65–0.82; Nevents = 615). Compared with euthyroid patients, patients with low-FT3 syndrome had a 2.2-fold higher risk and patients with hypothyroidism had a 1.6-fold higher risk of experiencing the composite renal endpoint. Conclusions Patients with mild to moderate CKD suffering from thyroid function abnormalities are at an increased risk of adverse renal events and all-cause mortality over time.

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