FC 059EARLY LIFE FACTORS AND ADULT KIDNEY FUNCTION ESTIMATED BY CYSTATIN C AND CREATININE GLOMERULAR FILTRATION RATE EQUATIONS AND ALBUMINURIA: A SWEDISH COHORT STUDY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Agne Laucyte-Cibulskiene ◽  
Shantanu Sharma ◽  
Peter M Nilsson ◽  
Anders Christensson

Abstract Background and Aims Renal functional capacity is influenced by factors acting early in life, such as intrauterine environment, maturity, birth weight, length at birth, placental weight etc. Early life factors are responsible for the number of nephrons a person starts life with, and the consequence of a low nephron number is earlier kidney ageing and chronic kidney disease (CKD). Notably, most reports addressing early life factors in the context of adult kidney function use creatinine-based eGFR equations and/or albuminuria and lack longer follow-up (<30 years). Therefore, we aimed to identify early life factors associated with kidney function, determined by different creatinine and cystatin C equations and urinary albumin-to-creatinine ratio (UACR), more than 40 years later. Method 94 women and 494 men, born 1923-50, who participated in The Malmo Diet and Cancer (MDC) study were analyzed. Perinatal data records including birth weight (BW), birth length, head circumference, gestational age, placenta weight (PW) and mother related risk factors were collected from hospital and regional state archives. After a follow-up of 46 to 67 years study subjects underwent physical examination, blood pressure measurements and estimation of glomerular filtration rate (eGFR) using 4 different equations: Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2012 creatinine and cystatin C formula (CKD-EPI_creatinine, CKD-EPI_cystatin C), cystatin C eGFR equation based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised creatinine based eGFR equation (LM_rev). Urinary albumin-to-creatinine ratio (UACR) was measured in morning urine samples, albuminuria was defined as UACR ⩾3 mg/mmol. Birth weight z-scores (gender specific BWz and combined BWz) acquired by using the equation as reported by Marsal et al.(1996). Four growth mismatch phenotypes defined by combining low or high BW z-score (lowBWz or hiBWz respectively) with lower or higher body mass index at 20 years of age (lowBMI20 ir hiBMI20 respectively). Results Linear regression analysis of early life factors indicated that in females birth weight was positively associated with kidney function measured by both CAPA and CKD-EPI_cystatin C. In the whole population, birth weight adjusted for gestational age and sex, together with prematurity were independently associated to CKD-EPI_cystatin C, while BW/PW ratio was related to LM_rev. Logistic regression analysis showed that only gender specific BWz and combined BWz shared the same odds ratios for age and pulse pressure adjusted albuminuria in males (OR 0,75 (95%CI [0,58; 0,96]). While analyzing postnatal growth mismatch we found that females with hiBWz/lowBMI20 phenotype had significantly worse kidney function acquired by both cystatin C equations compared to those with lowBWz/lowBMI20 phenotype (p=0.044 for CAPA, p=0.040 for CKD-EPI_cystatin C). The logistic regression analysis revealed that hiBWz/hiBMI20 phenotype was related to lower risk of age and pulse pressure adjusted albuminuria (OR 0,35 (95%CI[0,12;0,93]) Conclusion Here we report that lower birth weight in females is associated with worse kidney function determined by cystatin C eGFR equations, while in males lower birth weight z-score is a risk factor for albuminuria in adulthood. Postnatal growth catch-up is not related to worse kidney function. We identified the protective phenotype (hiBWz/hiBMI20) for albuminuria in males and the unfavorable phenotype (hiBWz/lowBMI20) for kidney function in females. This suggests that lower birth weight and postnatal growth curve have a potential sex specific effect to kidney function and development of CKD in middle-aged Swedish subjects. Further studies are warranted to address early life factor prognostic accuracy in kidney function and outcomes prediction later in the lifetime.

Author(s):  
Agne Laucyte-Cibulskiene ◽  
Shantanu Sharma ◽  
Anders Christensson ◽  
Peter M. Nilsson

Abstract Background Early life factors influence the number of nephrons a person starts life with and a consequence of that is believed to be premature kidney ageing. Thus, we aimed to identify early life factors associated with cystatin C and creatinine-based estimated glomerular filtration (eGFR) rate equations and urine -albumin-to-creatinine ratio after a follow-up of 46–67 years. Methods The study included 593 Swedish subjects without diabetes mellitus from the Malmo Diet Cancer Cohort. Perinatal data records including birth weight, gestational age, placenta weight and maternal related risk factors were analysed. eGFR was determined by Chronic Kidney Disease Epidemiology (CKD-EPI), the Lund-Malmö revised and Caucasian, Asian, Paediatric, and Adult (CAPA) equations. Postnatal growth phenotypes were defined as low (≤ 0) or high (> 0) birth weight z-score, or low (≤ median) or high (> median) body mass index at 20 years of age. Results In women, lower birth weight was associated with lower eGFR (CAPA; CKD-EPI cystatin C). Birth weight z-score predicted adult albuminuria specifically in men (OR 0.75, 95% CI [0.58; 0.96]). Women with high birth weight z-score and low BMI at 20 years had lower eGFR (CAPA; CKD-EPI cystatin C; p = 0.04). Men with high birth weight z-score and high BMI at 20 years had lower risk for albuminuria (OR 0.35, 95% CI [0.12; 0.93]). Conclusions Lower birth weight, prematurity and postnatal growth curve have a potential sex- specific effect of early exposure to an adverse environment on lower cystatin C-based eGFR and albuminuria later in life. Cystatin C compared to creatinine -eGFR equations shows a higher ability to detect these findings. Graphic abstract


2008 ◽  
Vol 40 (4) ◽  
pp. 563-575 ◽  
Author(s):  
MWENZA BLELL ◽  
TESSA M. POLLARD ◽  
MARK S. PEARCE

SummarySeveral studies have found relationships between early life factors (birth weight, length of gestation, height, weight, duration of breast-feeding, maternal age, social class, periods of infection, presence of adverse life events, and quality of housing conditions in childhood) and age at menarche but none has considered all of these factors in the same study. The follow-up study of the Newcastle Thousand Families birth cohort, established in 1947, provided age at menarche data collected retrospectively at age 50 from 276 women who returned self-completion questionnaires in 1997. Three main independent associations were observed: girls who experienced a shorter gestation, girls whose mothers were younger when they were born, and girls who were heavier at age 9 had earlier menarche. Birth weight, standardized for gestational age, was found to have different relationships with age at menarche depending upon how heavy or light a girl was at age 9. The results of this study support the hypotheses that conditions in fetal and early life are associated with the timing of menarche and that greater childhood growth is associated with earlier menarche. It is suggested that future work should focus on illuminating the mechanisms underlying these statistical relationships.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Mark Shipeng Yu ◽  
Alan H Matsumoto ◽  
Karol Pencina ◽  
Katherine Tuttle ◽  
Wencan He ◽  
...  

Introduction: Ischemic nephropathy due to atherosclerotic renal artery stenosis (ARAS) is associated with poor event free survival. However, previous studies suggest that stenosis severity has a poor relation to kidney function. We sought to test the interactions of stenosis severity, and revascularization, on kidney function in people with ARAS. Hypothesis: Stenosis severity is associated with poor renal function in people with ARAS. Methods: The Cardiovascular Outcomes in Renal Atherosclerotic Lesions (CORAL) clinical trial is a prospective trial of individuals with atherosclerotic renal-artery stenosis. Patients were followed to a maximum of 8 years. Angiographic images were measured at a single core lab (University of Virginia) using quantitative computer-assisted angiography. Estimated glomerular filtration rate (eGFR) was measured using creatinine and cystatin-C, performed at a single core lab (University of Minnesota), and calculated using the CKD-EPI Creatinine-Cystatin C formula. The analyses are controlled by age and gender. Results: At baseline CKD-EPI eGFR was strongly and negatively correlated with percent stenosis (-0.2472, p<0.0001) and positively correlated with minimal luminal diameter (0.2974, p<0.0001). Interestingly, peak systolic pressure gradient and mean pressure gradients were not (p=ns for both). At three years follow-up baseline percent stenosis remained significant by univariate analysis (0.1380, p=0.01), however, it was not significant by multivariate analysis. Conclusions: Stenosis severity is strongly related to kidney function at the time of presentation in patients with atherosclerotic renal artery stenosis. However, by three years follow-up, this relationship appears to be lost.


Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Alex R CHANG ◽  
G. C Wood ◽  
Adam Cook ◽  
Xin Chu ◽  
Morgan Grams

Background: Persons with morbid obesity are at increased risk for end-stage kidney disease, and prior studies have shown an association between bariatric surgery and improvements in creatinine-based estimated glomerular filtration rate (eGFR cr ). However, eGFR cr could be biased by loss of muscle mass after surgery, and creatinine-cystatin C estimated glomerular filtration rate (eGFR cr-cyc ) has been shown to be more accurate in this setting. Methods: We matched 144 patients who underwent bariatric surgery on pre-surgery age, sex, race, body mass index (BMI), and eGFR cr with 144 morbidly obese non-surgery patients at Geisinger with serial biobanked serum samples. We measured filtration markers (creatinine, cystatin C, beta-2 microglobulin [B2M] and beta-trace protein [BTP], and calculated eGFR cr-cyc using the CKD-EPI combined equation. Using mixed effects models with random intercepts, we compared changes in filtration markers and eGFR cr-cyc between surgery and non-surgery groups. Results: Mean (SD) values for age, BMI, and eGFR cr were 48.2 (10.4) years, 45.2 (6.3) kg/m 2 , and 91.7 (17.5) ml/min/1.73m 2 ; 87.5% were female, 0.7% were black, 50.3% had hypertension, and 41.0% had type 2 diabetes. Mean eGFR cr-cyc slope in the surgery group was -0.41 ml/min/1.73m 2 /yr (95% CI: -0.74, -0.08) over a mean follow-up of 9.2 (1.4) years, compared to -1.43 ml/min/1.73m 2 /yr in the non-surgery group over a mean follow-up of 8.2 (1.1) years. Bariatric surgery was associated with a 1.02 ml/min/1.73m 2 /yr slower decline in eGFR cr-cyc , and smaller increase in all 4 filtration markers (p< 0.02 for all comparisons). Conclusions: Bariatric surgery is associated with slower decline in kidney function, as assessed by eGFR cr-cyc , B2M and BTP.


2014 ◽  
Vol 5 (3) ◽  
pp. 189-196 ◽  
Author(s):  
P. Khandelwal ◽  
V. Jain ◽  
A. K. Gupta ◽  
M. Kalaivani ◽  
V. K. Paul

Growth acceleration or catch-up growth (CUG) in early infancy is a plausible risk factor for later obesity and cardiovascular disease. We postulate that this risk may be mediated by an adverse programming of body composition by CUG in early infancy. The study was aimed at evaluating the association between the pattern of gain in weight and length of term low birth weight (LBW) infants from birth to 6 months, with fat mass percent (FM%) at 6 months. Term healthy singleton LBW infants were enrolled. Baby’s weight and length z-scores were measured at birth and three follow-up visits. Body composition was measured by dual-energy absorptiometry at last visit. A total of 54 babies (28 boys) were enrolled. The mean birth weight and gestation were 2175±180 g and 37.6±0.6 weeks. Follow-up visits were at 1.4±0.0, 3.0±0.3 and 7.2±0.8 months. The proportion of babies who showed CUG [increase in weight for age z-score (∆WAZ)>0.67] from birth to 1.4, 3.0 and 7.2 months was 29.6, 26.4 and 48.5%, respectively. The mean FM% at 7.2 months was 16.6±7.8%. Infants with greater ∆WAZ from birth to 3 and 7.2 months had significantly greater FM% at 7.2 months after adjusting for current age, size and gender. Infants with early CUG (<1.4 months) had higher FM% than infants with no CUG. We conclude that earlier and greater increment in WAZ is positively associated with FM%.


2019 ◽  
Vol 374 (1770) ◽  
pp. 20180123 ◽  
Author(s):  
Caroline H. D. Fall ◽  
Kalyanaraman Kumaran

An association of low birth weight with an increased risk of adult cardiovascular disease and diabetes led to the developmental origins of health and disease (DOHaD) hypothesis, which proposes that undernutrition during early development permanently ‘programmes’ organ structure and metabolism, leading to vulnerability to later cardio-metabolic disease. High birth weight caused by maternal gestational diabetes is also associated with later diabetes, suggesting that fetal over-nutrition also has programming effects. Post-natal factors (excess weight gain/obesity, smoking, poor diets and physical inactivity) interact with fetal exposures to increase disease risk. Animal studies have shown permanent metabolic effects in offspring after alterations to maternal or early post-natal diets but evidence in humans is largely limited to observational and quasi-experimental situations such as maternal famine exposure. Randomized trials of maternal nutritional interventions during pregnancy have so far had limited follow-up of the offspring. Moreover, interventions usually started after the first trimester and therefore missed key peri-conceptional or early pregnancy events such as epigenetic changes, placentation and fetal organogenesis. Recent and ongoing trials intervening pre-conceptionally and powered for long-term offspring follow-up will address these issues. While current preventive strategies for cardio-metabolic disease focus on high-risk individuals in mid-life, DOHaD concepts offer a ‘primordial’ preventive strategy to reduce disease in future generations by improving fetal and infant development. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.


2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Juliana Nyasordzi ◽  
Katharina Penczynski ◽  
Thomas Remer ◽  
Anette Buyken

AbstractIntroductionEarly life factors may predispose an offspring to cardiovascular risk factors in later life. It is plausible a range of exposures in early life may be involved in this predisposition, which may extend to “healthy” populations in Western populations.We examined the association between a number of early life factors with the carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis, in early adulthood of a healthy German population.MethodsWe studied term participants (n = 265) of the DONALD Study, with a bilateral sonographic measurement of the IMT in young adulthood (18–40 years) and data on early life factors (maternal and paternal age at child birth, birth weight (including appropriateness of birth weight- for gestational age), gestational weight gain and full breastfeeding (breastfeeding > 17weeks). Sonographic IMT measurements were performed on the left and right common carotid artery using a minimum of 4 measurements. Mean IMT values were obtained averaging the measurements from both sides, an overall average obtained from 8 and 16 measurement of both sides was used for this analysis. Information on gestation and birth were abstracted from the “Mutterpass”, maternal and paternal age at birth were inquired at study entry and breastfeeding information was assessed prospectively. Prospective association between early life factors and IMT were analyzed using multivariable linear regression models, considering age at IMT measurement, physician taking the measurement, in addition: birth year, first born status, maternal and paternal educational status, maternal overweight, presence of smokers in the household tested for potential confounding.ResultsMean adult IMT was 0.56mm ± 0.03, range: 0.41mm-0.78 mm. Maternal age at child birth was of prospective relevance for IMT in young adulthood, however, this association was sex specific: Increased maternal age at child birth was independently associated with an increased IMT among female offspring during young adulthood (β 0.029, SE 0.009) mm/decade, P = 0.003) only, this was not mediated by adult waist circumference. None of the remaining early life factors showed relevance for adult IMT levels among males and females in early adulthood.ConclusionThis study suggests that advanced maternal age at child birth is of prospective relevance for IMT levels in younger adulthood in a healthy Western population. This association appears to be sex specific, with maternal age at child birth positively associated with IMT in females in early adulthood only.


2008 ◽  
Vol 61 (9) ◽  
pp. 958-963 ◽  
Author(s):  
Merete Osler ◽  
Margit Kriegbaum ◽  
Ulla Christensen ◽  
Rikke Lund ◽  
Anne-Marie Nybo Andersen

Author(s):  
Mike Wenzel ◽  
Hang Yu ◽  
Annemarie Uhlig ◽  
Christoph Würnschimmel ◽  
Manuel Wallbach ◽  
...  

Abstract Purpose To test the value of preoperative and postoperative cystatin C (CysC) as a predictor on kidney function after partial (PN) or radical nephrectomy (RN) in renal cell carcinoma (RCC) patients with normal preoperative renal function. Methods From 01/2011 to 12/2014, 195 consecutive RCC patients with a preoperative estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73m2 underwent surgical RCC treatment with either PN or RN. Logistic and linear regression models tested for the effect of CysC as a predictor of new-onset chronic kidney disease in follow-up (eGFR < 60 ml/min/1.73m2). Moreover, postoperative CysC and creatinine values were compared for kidney function estimation. Results Of 195 patients, 129 (66.2%) underwent PN. In postoperative and in follow-up setting (median 14 months, IQR 10–20), rates of eGFR < 60 ml/min/1.73m2 were 55.9 and 30.2%. In multivariable logistic regression models, preoperative CysC [odds ratio (OR): 18.3] and RN (OR: 13.5) were independent predictors for a reduced eGFR < 60 ml/min/1.73m2 in follow-up (both p < 0.01), while creatinine was not. In multivariable linear regression models, a difference of the preoperative CysC level of 0.1 mg/dl estimated an eGFR decline in follow-up of about 5.8 ml/min/1.73m2. Finally, we observed a plateau of postoperative creatinine values in the range of 1.2–1.3 mg/dl, when graphically depicted vs. postoperative CysC values (‘creatinine blind area’). Conclusion Preoperative CysC predicts renal function impairment following RCC surgery. Furthermore, CysC might be superior to creatinine for renal function monitoring in the early postoperative setting.


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