Nephron numbers and hyperfiltration as drivers of progression

Author(s):  
Valerie A. Luyckx

The relationship between low birth weight (LBW) and subsequent increased risk of hypertension and renal disease in humans is now well established. The initial hypothesis suggested that an adverse intrauterine environment, reflected by LBW, would impact renal development, resulting in a low nephron number and predisposition to hypertension and renal disease. Studies in various populations have shown a direct correlation between birth weight and nephron number, and in infants, nephron numbers are reduced in those of LBW. Among Caucasian and Australian Aboriginal adults, lower nephron numbers are associated with higher blood pressure, whereas higher nephron numbers appear to protect against hypertension. LBW is currently the best clinical surrogate for low nephron number and has been independently associated with higher blood pressure from infancy through to adulthood in many populations, as well as an increased risk of proteinuria, reduced glomerular filtration rate, chronic kidney disease, and end-stage renal disease in later life. The pathophysiology is analogous to that in other chronic kidney diseases where surviving nephrons are subject to hyperfiltration early on, resulting in glomerular hypertrophy, proteinuria, and eventually, especially in the setting of other renal disease risk factors, glomerulosclerosis, and loss of renal function. Mean nephron number varies by up to 13-fold in certain populations, however, therefore nephron number is unlikely the sole developmentally programmed risk factor for renal disease in later life, but may be a first ‘hit’ impacting an individual’s susceptibility to or resistance to superimposed renal injury. Augmentation of nephron number perinatally has only been addressed in experimental settings. In humans, therefore optimization of nephron number is likely best achieved through good perinatal care and adequate postnatal nutrition. Cardiovascular disease and diabetes are also developmentally programmed and therefore likely coexist in subjects with LBW and low nephron numbers. Awareness of an individual’s birth weight should serve to highlight the possibility of low nephron number and potential risk for future hypertension and renal disease, which may be attenuated by optimization of early nutrition, lifestyle choices, and management of other risk factors for renal disease.

2008 ◽  
Vol 149 (15) ◽  
pp. 691-696
Author(s):  
Dániel Bereczki

Chronic kidney diseases and cardiovascular diseases have several common risk factors like hypertension and diabetes. In chronic renal disease stroke risk is several times higher than in the average population. The combination of classical risk factors and those characteristic of chronic kidney disease might explain this increased risk. Among acute cerebrovascular diseases intracerebral hemorrhages are more frequent than in those with normal kidney function. The outcome of stroke is worse in chronic kidney disease. The treatment of stroke (thrombolysis, antiplatelet and anticoagulant treatment, statins, etc.) is an area of clinical research in this patient group. There are no reliable data on the application of thrombolysis in acute stroke in patients with chronic renal disease. Aspirin might be administered. Carefulness, individual considerations and lower doses might be appropriate when using other treatments. The condition of the kidney as well as other associated diseases should be considered during administration of antihypertensive and lipid lowering medications.


2019 ◽  
Vol 11 (1) ◽  
pp. 86-95
Author(s):  
Amna Umer ◽  
Candice Hamilton ◽  
Lesley Cottrell ◽  
Peter Giacobbi ◽  
Kim Innes ◽  
...  

AbstractThe reported associations between birth weight and childhood cardiovascular disease (CVD) risk factors have been inconsistent. In this study, we investigated the relationship between birth weight and CVD risk factors at 11 years of age. This study used longitudinally linked data from three cross-sectional datasets (N = 22,136) in West Virginia; analysis was restricted to children born full-term (N = 19,583). The outcome variables included resting blood pressure [systolic blood pressure (SBP), diastolic blood pressure (DBP)] and lipid profile [total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, non-HDL, and triglycerides (TG)]. Multiple regression analyses were performed, adjusting for child’s body mass index (BMI), sociodemographics, and lifestyle characteristics. Unadjusted analyses showed a statistically significant association between birth weight and SBP, DBP, HDL, and TG. When adjusted for the child’s BMI, the association between birth weight and HDL [b = 0.14 (95% CI: 0.11, 0.18) mg/dl per 1000 g increase] and between birth weight and TG [b = –0.007 (–0.008, –0.005) mg/dl per 1000 g increase] remained statistically significant. In the fully adjusted model, low birth weight was associated with higher LDL, non-HDL, and TGs, and lower HDL levels. The child’s current BMI at 11 years of age partially (for HDL, non-HDL, and TG) and fully mediated (for SBP and DBP) the relationship between birth weight and select CVD risk factors. While effects were modest, these risk factors may persist and amplify with age, leading to potentially unfavorable consequences in later adulthood.


Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Laura S Latham ◽  
Adam S Woodson ◽  
Deborah S Minor ◽  
Lynda M Richards ◽  
Gail G Sweat ◽  
...  

Introduction: Health fair-type screenings are one of the most recognizable forms of community-based health promotion. Though these screenings offer benefits in theory, little evidence supports their value. Through REAP, Mississippi Kidney Foundation routinely provides screenings for cardiovascular and renal disease risk factors. At each screening, participants obtain blood pressure, height, weight, laboratory assessments (metabolic/renal blood chemistries, complete blood count, total cholesterol, urinalysis) and complete a questionnaire regarding risk factors and disease history. Participants also receive written information about values/goals and consultation with a healthcare provider. Without a systematic evaluation, the overall value of this program is unknown. The purpose of this study was to review the impact and results of REAP and identify any changes that could improve outreach and patient care. Methods: We reviewed demographics and prevalence of cardiovascular and renal disease risk factors among participants over the previous 4 years (2010-2013). Screening sites were classified as urban or rural, according to census data. Risk factors were defined as elevated blood pressure (SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg), cholesterol (total > 200 mg/dL), or blood glucose (fasting ≥ 100 mg/dL); reduced kidney function (elevated BUN/Cr and/or eGFR < 60 ml/min); and proteinuria (≥ 30 mg/dL). Results: Over the review period, 57 screenings were performed at 34 sites, 15 classified as rural. Of the 5,545 participants, 4,299 were at urban and 1,246 at rural sites. Overall, 1,760 (32%) had elevated blood pressure (36% vs 31%, rural vs urban, respectively), 2,013 (36%, 40% vs 35%) elevated cholesterol and 1,046 (19%, 23% vs 18%) elevated glucose. Reduced kidney function was identified in 762 (14%, 15% vs 13%) participants, while 1,423 (26%, 29% vs 25%) had proteinuria. Among those reporting ethnicity (n=1,948) and gender (n=3,164), 614 (32%) were Caucasian, 1,290 (66%) African-American, and 2,270 (72%) female. Conclusions: Through this review, we determined that though REAP appears to target at risk populations, further efforts are needed to improve participation of males and those in rural areas. Elevated risk factors were more prevalent in rural areas; however, this may reflect differences in treatment rates, not absolute values. To better assess the impact of REAP, define risk factors, and influence patient care, we identified that more rigorous tracking, review of disease and treatment history, and further assessments are needed (i.e. full lipid panel). A graded system targeting patient follow-up is necessary, particularly among those at greatest risk. Based on these findings, these changes will be implemented, along with a post-screening evaluation of participants’ perceived benefits and result utilization.


2016 ◽  
Vol 7 (2) ◽  
pp. 132-143 ◽  
Author(s):  
M. G. Musa ◽  
J. Kagura ◽  
P. T. Pisa ◽  
S. A. Norris

Low birth weight and a rapid weight gain in early childhood may lead to an increased risk for developing cardiovascular disease later in life, such as hypertension and dyslipidaemia. In this study, we examined the associations between size at birth, relative weight gain in infancy and childhood with specific cardiovascular disease risk factors in early adulthood. Adolescents (n=1935) from the Birth to Twenty plus (BT20+) cohort were included in the analysis. The following were treated as exposure variables: weight at birth, and relative conditional weight gain (CW), independent of height, between ages 0–24 months and 24–48 months. Outcomes were serum lipids and body composition variables at age 18 years. After adjusting for sex and other confounders, early life exposures were not associated with adolescent lipid profile. Following adjustment for sex and height (body size), birth weight [β=0.704 (0.40, 1.01)], CW 0–24 [β=1.918 (1.56, 2.28)] and CW24–48 [β=1.485 (1.14, 1.82)] accounted for 48% of the variance in fat mass. However, birth weight [β=0.773 (0.54, 1.01)], CW 0–24 [β=1.523 (1.24, 1.80)] and CW24–48 [β=1.226 (0.97, 1.49)] were also positively predicted and accounted for 71% of the variance in fat mass in adolescence (P<0.05). Our data suggests that birth weight and weight gain during infancy and early childhood independent of linear growth are related to adolescent body composition but not blood lipid profiles in an urban African population.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Piddock ◽  
F Britton ◽  
V Goode ◽  
E White ◽  
A Greenstein ◽  
...  

Abstract Background Cardiotoxic therapy causes significant morbidity and mortality in patients (pts) treated for Hodgkin lymphoma (HL). Cardiovascular (CVS) risk calculators do not include cancer therapy despite epidemiological data demonstrating increased risk. We have assessed modifiable CVS risk factors and predicted risk of CVS disease in a cohort of HL survivors. Hypothesis Cardiovascular risk calculators will not identify high risk in young HL survivors. Methods Pts now aged ≤50 treated with doxorubicin and/or radiotherapy (RT) to cardiac tissue for HL >5 years ago were identified. Telephone review of CVS risk factors was offered to pts taking statins or already diagnosed with cerebrovascular or CVS disease. Remaining pts were offered clinical review to assess BMI, blood pressure, cholesterol and HbA1c. Carotid-radial pulse wave velocity (PWV) was measured if available. CVS risk was predicted using international risk calculators (European SCORE, QRISK3, Framingham). Results 160 eligible pts were identified. Median age was 43 years (26–50) and 52% were female. Median time since treatment was 182 months (61–367). Pts received doxorubicin (n=150), with RT (n=97) or RT alone (n=10). Pts were excluded from study due to severe medical condition (n=8), recurrence (n=1), relocation (n=3) or death (n=1). Data were gathered at clinical review (n=70) or telephone review (n=26). Existing cardiovascular diagnoses included hypertension (n=5), transient ischaemic attack (n=2), valvular disease (n=3), heart failure (n=1), atrial fibrillation (n=2), complete heart block (n=1) and coronary artery disease (n=1). At clinical review 51% pts had 3 or more modifiable risk factors with a median of 3 (0–5) per pt. Total cholesterol was >5.0 mmol/L in 58% of patients with a median of 5.2 mmol/L (3.2–8.6). Median systolic blood pressure was 125.5 mmHg (103–164). Median body mass index was 26.3 kg/m-2 (18.6–56.1) with 60% of patients classed as overweight or obese.Advice was offered to all smokers (9%), pts that drank alcohol above UK recommended levels (20%) or exercised below the recommended amount (60%). Risk calculators classified 1.4% (QRISK3) and 10% (Framingham) of pts at high risk of CVS disease and 0% (European SCORE) at high risk of CVS mortality. Pulse wave velocity measured in 34 pts was elevated (>8 m/s) in 76% of cases with a median 10.2 m/s (2.3–16.8). Conclusions Numerous modifiable CVS risk factors were identified in an HL survivor population known from epidemiological studies to be at high risk of CVS morbidity/mortality. None of the CVS risk calculators identified this high risk. Intriguing data indicate PWV may represent an accessible early indicator of CVS dysfunction. These data prompt comprehensive assessment and management of CVS risk factors in cancer survivors and review of the use of risk calculators in this population. Acknowledgement/Funding The Christie NHS Foundation Trust


2016 ◽  
Vol 113 (10) ◽  
pp. E1402-E1411 ◽  
Author(s):  
Christopher J. Morris ◽  
Taylor E. Purvis ◽  
Kun Hu ◽  
Frank A. J. L. Scheer

Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk.


2021 ◽  
Vol 84 (4) ◽  
pp. 431-441
Author(s):  
Kinga Michnik ◽  
Maciej Mularczyk ◽  
Marta Stępień-Słodkowska

Abstract The Polish national program for the prevention of cardiovascular disease (CHUK) uses the Systematic Coronary Risk Evaluation (SCORE) index which evaluates the upcoming risk of death from cardiovascular causes for a 10 year period, based on information such as age, systolic blood pressure, cholesterol levels, smoking and gender. The aim of this study was to determine health indicators in the population enrolled in the program and identify the relationships between the cardiovascular risk factors. The data was collected from 303 participating individuals; 172 women (aged 35 to 58 years) and 131 men (aged 31 to 60 years). The SCORE index showed a statistically significant positive relationship between CVD and the male gender. The higher frequency of 3–4% and 5–9% for SCORE index in men indicates that they were at a higher risk of cardiovascular incidents. The increased risk of a cardiovascular incidence in men was associated with a higher mean arm circumference, waist circumference, BMI, systolic blood pressure, diastolic blood pressure, total cholesterol, LDL cholesterol, triglyceride and fasting glucose. HDL cholesterol and heart rate were statistically significantly higher in women. Among the study subjects, the most common parameters above the normal range were elevated LDL cholesterol and total cholesterol. The highest correlation with the SCORE index was observed for the age of the subjects, total cholesterol and LDL cholesterol, regardless of gender. The results showed that biochemical parameters and blood pressure were above normal values in almost all subjects. Men had significantly less favorable parameters compared to women of similar age range. According to the SCORE index, total cholesterol and LDL cholesterol significantly increased the risk of cardiovascular incident regardless of gender. Women were characterized by a lower risk of cardiovascular incident according to the SCORE index.


2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Thorsten Braun ◽  
Vivien Filleböck ◽  
Boris Metze ◽  
Christoph Bührer ◽  
Andreas Plagemann ◽  
...  

AbstractObjectivesTo compare the long-term effects of antenatal betamethasone (ANS, ≤16 mg, =24 mg and >24 mg) in twins on infant and childhood growth.MethodsA retrospective cohort follow up study among 198 twins after ANS including three time points: U1 first neonatal examination after birth and in the neonatal period; U7 examination from the 21st to the 24th month of life and U9 examination from the 60th to the 64th month of life using data from copies of the children’s examination booklets. Inclusion criteria are twin pregnancies with preterm labor, cervical shortening, preterm premature rupture of membranes, or vaginal bleeding, and exposure to ANS between 23+5 and 33+6 weeks. Outcome measures are dosage-dependent and sex-specific effects of ANS on growth (body weight, body length, head circumference, body mass index and ponderal index) up to 5.3 years.ResultsOverall, 99 live-born twin pairs were included. Negative effects of ANS on fetal growth persisted beyond birth, altered infant and childhood growth, independent of possible confounding factors. Overall weight percentile significantly decreased between infancy and early childhood by 18.8%. Birth weight percentiles significantly changed in a dose dependent and sex specific manner, most obviously in female-female and mixed pairs. The ponderal index significantly decreased up to 42.9%, BMI index increased by up to 33.8%.ConclusionsANS results in long-term alterations in infant and childhood growth. Changes between infancy and early childhood in ponderal mass index and BMI, independent of dose or twin pair structure, might indicate an ANS associated increased risk for later life disease.SynopsisFirst-time report on long-term ANS administration growth effects in twin pregnancies, showing persisting alterations beyond birth in infant and childhood growth up to 5.3 years as potential indicator of later life disease risk.


2006 ◽  
Vol 154 (1) ◽  
pp. 131-139 ◽  
Author(s):  
Lenora M Camarate S M Leão ◽  
Mônica Peres C Duarte ◽  
Dalva Margareth B Silva ◽  
Paulo Roberto V Bahia ◽  
Cláudia Medina Coeli ◽  
...  

Background: There has been a growing interest in treating postmenopausal women with androgens. However, hyperandrogenemia in females has been associated with increased risk of cardiovascular disease. Objective: We aimed to assess the effects of androgen replacement on cardiovascular risk factors. Design: Thirty-seven postmenopausal women aged 42–62 years that had undergone hysterectomy were prospectively enrolled in a double-blind protocol to receive, for 12 months, percutaneous estradiol (E2) (1 mg/day) combined with either methyltestosterone (MT) (1.25 mg/day) or placebo. Methods: Along with treatment, we evaluated serum E2, testosterone, sex hormone-binding globulin (SHBG), free androgen index, lipids, fibrinogen, and C-reactive protein; glucose tolerance; insulin resistance; blood pressure; body-mass index; and visceral and subcutaneous abdominal fat mass as assessed by computed tomography. Results: A significant reduction in SHBG (P < 0.001) and increase in free testosterone index (P < 0.05; Repeated measures analysis of variance) were seen in the MT group. Total cholesterol, triglycerides, fibrinogen, and systolic and diastolic blood pressure were significantly lowered to a similar extent by both regimens, but high-density lipoprotein cholesterol decreased only in the androgen group. MT-treated women showed a modest rise in body weight and gained visceral fat mass relative to the other group (P < 0.05), but there were no significant detrimental effects on fasting insulin levels and insulin resistance. Conclusion: This study suggests that the combination of low-dose oral MT and percutaneous E2, for 1 year, does not result in expressive increase of cardiovascular risk factors. This regimen can be recommended for symptomatic postmenopausal women, although it seems prudent to perform baseline and follow-up lipid profile and assessment of body composition, especially in those at high risk of cardiovascular disease.


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