Long-term ambient air pollution exposure and renal function and biomarkers of renal disease.

BACKGROUND: Despite accumulating evidence of an association between air pollution and renal disease, studies on the association between long-term exposure to air pollution and renal function are still contradictory. This study aimed to investigate this association in a large population with relatively low exposure and with improved estimation of renal function as well as renal injury biomarkers. METHODS: We performed a cross-sectional analysis in the middle-aged general population participating in the Swedish CardioPulmonary bioImaging Study (SCAPIS; n = 30 154). Individual 10-year exposure to total and locally emitted fine particulate matter (PM2.5), inhalable particulate matter (PM10), and nitrogen oxides (NOx) were modelled using high-resolution dispersion models. Linear regression models were used to estimate associations between exposures and estimated glomerular filtration rate (eGFR, combined creatinine and cystatin C) and serum levels of renal injury biomarkers (KIM-1, MCP-1, IL-6, IL-18, MMP-2, MMP-7, MMP-9, FGF-23, and uric acid), with consideration of potential confounders. RESULTS: Median long-term PM2.5 exposure was 6.2 µg/m3. Almost all participants had a normal renal function and median eGFR was 99.2 mL/min/1.73 m2. PM2.5 exposure was associated with 1.3% (95% CI 0.6, 2.0) higher eGFR per 2.03 µg/m3 (interquartile range, IQR). PM2.5 exposure was also associated with elevated serum matrix metalloproteinase 2 (MMP-2) concentration, with 7.2% (95% CI 1.9, 12.8) higher MMP-2 per 2.03 µg/m3. There was a tendency towards an association between PM10 and higher levels of uric acid, but no associations were found with the other biomarkers. Associations with other air pollutants were null or inconsistent. CONCLUSION: In this large general population sample at low exposure levels, we found a surprising association between PM2.5 exposure and a higher renal filtration. It seems unlikely that particle function would improve renal function. However, increased filtration is an early sign of renal injury and may be related to the relatively healthy population at comparatively low exposure levels. Furthermore, PM2.5 exposure was associated with higher serum concentrations of MMP-2, an early indicator of renal and cardiovascular pathology.

Iohexol plasma clearance measurement protocol standardization for adults: a consensus paper of the European Kidney Function Consortium.

International consensus supports the development of standardized protocols for measured glomerular filtration rate (mGFR) to facilitate the integration of mGFR testing in both clinical and research settings. To this end, the European Kidney Function Consortium convened an international group of experts with relevant experience in mGFR. The working group performed an extensive literature search to inform the development of recommendations for mGFR determination using 1-compartment plasma clearance models and iohexol as the exogenous filtration marker. Iohexol was selected as it is non-radio labeled, inexpensive, and safe, can be assayed at a central laboratory, and the other commonly used non-radio-labeled tracers have been (inulin) or are soon to be (iothalamate) discontinued. A plasma clearance model was selected over urine clearance as it requires no urine collection. A 1 compartment was preferred to 2 compartments as it requires fewer samples. The recommendations are based on published evidence complemented by expert opinion. The consensus paper covers practical advice for patients and health professionals, preparation, administration, and safety aspects of iohexol, laboratory analysis, blood sample collection and sampling times using both multiple and single-sample protocols, description of the mGFR mathematical calculations, as well as implementation strategies. Supplementary materials include patient and provider information sheets, standard operating procedures, a study protocol template, and support for mGFR calculation.

Diabetic status and the performances of creatinine- and cystatin C-based eGFR equations.

BACKGROUND AND HYPOTHESIS: The estimation of glomerular filtration rate (GFR) is one main tool to detect renal disease. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equation is the most validated in Europe. More recently, cystatin C, has been proposed. We studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status. METHODS: Four cohorts from the EKFC dataset were retrospectively considered in which the diabetic status was available. GFR was measured by plasma clearances (mGFR) (iohexol or 51Cr-EDTA). The performance of the equations was assessed by calculating bias, precision (IQR) and P30 (percentage of eGFR-values within ± 30% of mGFR). RESULTS: In the whole population (n = 6 158), median [IQR] age was 61 [47;72] years, with 45.8% women. Mean mGFR was 60 [39;82] mL/min/1.73m². Compared to non-diabetic individuals (n = 5 124), diabetic patients (n = 1 034) were older, more frequently male, heavier, and had lower mGFR. The performance of the EKFCcys equation was similar to EKFCcrea, but the EKFCcrea+cys had better P30 than the single-biomarker equations. P30 values were substantially lower in diabetic patients than in non-diabetic but, according to a matched analysis, this is mainly explained by the difference in GFR levels between the two populations, not by diabetic status. CONCLUSION: We showed that equation combining creatinine and cystatin C present a better performance. If accuracy of equations seems better in non-diabetic than in diabetic individuals, it is more due to differences in GFR levels than to the diabetic status.

Occupational particle exposure and chronic kidney disease: a cohort study in Swedish construction workers.

OBJECTIVES: Increasing epidemiological and experimental evidence suggests that particle exposure is an environmental risk factor for chronic kidney disease (CKD). However, only a few case-control studies have investigated this association in an occupational setting. Hence, our objective was to investigate associations between particle exposure and CKD in a large cohort of Swedish construction workers. METHODS: We performed a retrospective cohort study in the Swedish Construction Workers' Cohort, recruited 1971-1993 (n=286 089). A job-exposure matrix was used to identify workers exposed to nine different particulate exposures, which were combined into three main categories (inorganic dust and fumes, wood dust and fibres). Incident CKD and start of renal replacement therapy (RRT) were obtained from validated national registries until 2021 and analysed using adjusted Cox proportional hazards models. RESULTS: Exposure to inorganic dust and fumes was associated with an increased risk of CKD and RRT during working age (adjusted HR for CKD at age <65 years 1.15, 95% CI 1.05 to 1.26). The elevated risk did not persist after retirement age. Exposure to cement dust, concrete dust and diesel exhaust was associated with CKD. Elevated HRs were also found for quartz dust and welding fumes. CONCLUSIONS: Workers exposed to inorganic particles seem to be at elevated risk of CKD and RRT. Our results are in line with previous evidence of renal effects of ambient air pollution and warrant further efforts to reduce occupational and ambient particle exposure.

A study of size-selective renal elimination using a novel human model.

The recently discovered selective glomerular hypofiltration syndromes have increased interest in the actual elimination of molecules in the human kidney. In the present study, a novel human model was introduced to directly measure the single-pass renal elimination of molecules of increasing size. Plasma concentrations of urea, creatinine, C-peptide, insulin, pro-BNP, ß2-microglobulin, cystatin C, troponin-T, orosomucoid, albumin, and IgG were analysed in arterial and renal venous blood from 45 patients undergoing Transcatheter Aortic Valve Implantation (TAVI). The renal elimination ratio (RER) was calculated as the arteriovenous concentration difference divided by the arterial concentration. Estimated glomerular filtration rate (eGFR) was calculated by the CKD-EPI equations for both creatinine and cystatin C. Creatinine (0.11 kDa) showed the highest RER (21.0 ± 6.3%). With increasing molecular size, the RER gradually decreased, where the RER of cystatin C (13 kDa) was 14.4 ± 5.3% and troponin-T (36 kDa) was 11.3 ± 4.6%. The renal elimination threshold was found between 36 and 44 kDa as the RER of orosomucoid (44 kDa) was -0.2 ± 4.7%. The RER of creatinine and cystatin C showed a significant and moderate positive linear relationship with eGFR (r = 0.48 and 0.40). In conclusion, a novel human model was employed to demonstrate a decline in renal elimination with increasing molecular size. Moreover, RERs of creatinine and cystatin C were found to correlate with eGFR, suggesting the potential of this model to study selective glomerular hypofiltration syndromes.

Prevalence of impaired renal function among childless men as compared to fathers: a population-based study.

Male reproductive impairment has been linked with an increased risk of numerous non-communicable diseases. Yet, epidemiological data on renal disease among subfertile men is scarce. Therefore, by using male childlessness as a proxy for male infertility, we aimed to investigate its association with renal function. Data was sourced from a population-based cohort including 22,444 men. After exclusion of men aged < 45 years (n = 10,842), the remaining men were divided into two groups: these being childless (n = 5494) and fathers (n = 6108). Logistic regression was applied to explore the association between male childlessness and renal impairment. Childless men as compared to fathers, were more likely to have an estimated-glomerular filtration rate < 60 ml/min/1.73m2 (OR 1.36, 95 CI 1.08-1.70; p = 0.008). After adjustment for age, marital status, smoking habits, diabetes, hypertension and other components of metabolic syndrome, childless men were also more likely to have dipstick proteinuria (OR 1.85, 95 CI 1.16-2.95; p = 0.01). With the growing panorama of disease associated with male reproductive impairment, men with fertility issues may constitute a target population with potential benefit from closer follow-up of their renal function.

Associations between birth weight and adult apolipoproteins: The LifeGene cohort.

BACKGROUND: Early life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with apolipoproteins, which are linked to CVD. The study objective was to assess the associations between birth variables and adult apolipoproteins (apoA1 and apoB, and their ratio) in a population-based cohort. METHODS: The LifeGene Study is a prospective cohort comprising index participants randomly sampled from the general population. Blood samples were collected between 2009 and 2016. In this sub-study, we used birth variables, obtained from a national registry for all participants born 1973 or later, including birth weight and gestational age, while adult CVD risk factors included age, sex, body mass index (BMI), lipids, and smoking history. We employed univariate and multivariate general linear regression to explore associations between birth variables, lipid levels and other adult CVD risk factors. The outcomes included non-fasting apoA1 and apoB and their ratio, as well as total cholesterol and triglycerides. A total of 10,093 participants with both birth information and lipoprotein levels at screening were included. Of these, nearly 42.5% were men (n = 4292) and 57.5% were women (n = 5801). RESULTS: The mean (standard deviation) age of men was 30.2 (5.7) years, and for women 28.9 (5.8) years. There was an increase of 0.022 g/L in apoA1 levels per 1 kg increase in birth weight (p = 0.005) after adjusting for age, sex, BMI, gestational age, and smoking history. Similarly, there was a decrease of 0.023 g/L in apoB levels per 1 kg increase in birth weight (p<0.001) after adjusting for the same variables. There were inverse associations of birth weight with the apoB/apoA1 ratio. No independent association was found with total cholesterol, but with triglyceride levels (ẞ-coefficient (95% Confidence Interval); -0.067 (-0.114, -0.021); p-value 0.005). CONCLUSIONS: Lower birth weight was associated with an adverse adult apolipoprotein pattern, i.e., a higher apoB/apoA1 ratio, indicating increased risk of future CVD manifestations. The study highlights the need of preconception care and pregnancy interventions that aim at improving maternal and child outcomes with long-term impacts for prevention of cardiovascular disease by influencing lipid levels.

Aortic Stiffness Can be Predicted From Different eGFR Formulas With Long Follow-Up in the Malmö Diet Cancer Study.

We studied the impact of estimated glomerular filtration rate (eGFR) based on either creatinine or cystatin C, or in combination, on vascular aging (aortic stiffness) and central hemodynamics (central systolic blood pressure) in a Swedish urban population with median 17 years of follow-up. Participants (n = 5049) from the population-based Malmö Diet and Cancer Study that underwent baseline examination and later participated in the prospective cardiovascular arm were selected. Of these, 2064 with measured carotid-femoral pulse wave velocity (cfPWV) and central blood pressure at follow-up were enrolled. eGFR was calculated using cystatin C (eGFRCYS) and creatinine (eGFRCR) equations: Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised (LMrev), and the European Kidney Function Consortium (EKFC) equations. Lower adjusted eGFRCR, but not eGFRCYS, were independently associated with higher cfPWV (P < .001, respectively). eGFR <60 mL/min/1.73 m2 determined higher cfPWV except when using the EKFC equation. Conversely, CAPA/LMrev and CAPA/EKFC ratios were not associated with aortic stiffness. Lower eGFRCR is associated with higher future aortic stiffness independently of age, sex, heart rate, mean blood pressure, body mass index, and antihypertensive treatment. The ratio of eGFRCYS and eGFRCR equations could not predict aortic stiffness at all.

Active Vitamin D Use and Fractures in Hemodialysis Patients: Results from the International DOPPS.

Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independently of its ability to suppress parathyroid hormone (PTH). We analyzed the association between the prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in-center hemodialysis patients from 21 countries in phases 3 to 6 (2005 to 2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per-protocol approach to censor patients at treatment switch during follow-up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient-year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed versus not prescribed active vitamin D was 1.02 (0.90 to 1.17) for any fracture and 1.00 (0.81 to 1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher versus lower active vitamin D prescriptions. Thus, our results do not suggest a PTH-independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. © 2023 American Society for Bone and Mineral Research (ASBMR).

Associations between birth parameters and skin autofluorescence advanced glycation end products and ankle-brachial index in young adulthood: the Malmö Offspring Study.

BACKGROUND: Low birth weight (LBW), advanced glycation end-products (AGE), and ankle-brachial index (ABI) have all been independently associated with risk of cardiovascular disease. Evidence is lacking on the effect of LBW on adult AGE, a marker of glucose metabolism, and ABI, a marker of peripheral atherosclerosis. The objective was to study these associations in a population-based cohort. METHODS: Data from the Malmö Offspring Study, Sweden, were used for 2012 participants (958 men, 1054 women) born between 1973 and 2000, linked to the Medical Birth Register. General linear regression analysis (with ß coefficients and 95% confidence intervals) was applied for associations between birth weight and skin auto-fluorescence (sf)AGE as well as mean ABI (right/left), before and after adjusting for gestational age, sex, glucose, lipids, smoking, BMI and SBP. RESULTS: The mean (SD) age of men was 29.3 (7.3) and of women 28.6 (7.3) years. There was an average 0.054 decrease in sfAGE value per 1 kg increase in birth weight (adjusted for gestational age and sex). Similarly, 1 kg increase in birth weight (adjusted for gestational age and confounders) was associated with an average 0.016 decrease in mean ABI. CONCLUSION: Birth weight, adjusted for gestational age and other confounding variables, is inversely associated with ABI in young adulthood, an age range when ABI may represent hemodynamic changes more than atherosclerosis, but for sfAGE, the association was attenuated upon further adjustment. These risk markers may, therefore, represent mediating pathways for early life factors affecting cardiovascular risk later in life.

The complexity of kidney disease and diagnosing it - cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.

Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.

Dialysis as a Novel Adjuvant Treatment for Malignant Cancers.

Cancer metabolism is characterized by an increased utilization of fermentable fuels, such as glucose and glutamine, which support cancer cell survival by increasing resistance to both oxidative stress and the inherent immune system in humans. Dialysis has the power to shift the patient from a state dependent on glucose and glutamine to a ketogenic condition (KC) combined with low glutamine levels-thereby forcing ATP production through the Krebs cycle. By the force of dialysis, the cancer cells will be deprived of their preferred fermentable fuels, disrupting major metabolic pathways important for the ability of the cancer cells to survive. Dialysis has the potential to reduce glucose levels below physiological levels, concurrently increase blood ketone body levels and reduce glutamine levels, which may further reinforce the impact of the KC. Importantly, ketones also induce epigenetic changes imposed by histone deacetylates (HDAC) activity (Class I and Class IIa) known to play an important role in cancer metabolism. Thus, dialysis could be an impactful and safe adjuvant treatment, sensitizing cancer cells to traditional cancer treatments (TCTs), potentially making these significantly more efficient.

Increased fat mass index is associated with decreased glomerular filtration rate estimated from cystatin C. Data from Malmö Diet and Cancer cohort.

BACKGROUND: This study aims to describe associations of obesity and CKD in a Swedish urban population. The impact of fat mass, from bioimpedance analysis, on eGFR based on cystatin C and/or creatinine is studied. METHODS: 5049 participants from Malmö Diet and Cancer Study the cardiovascular arm (MDCS-CV) with available body mass composition (single frequency bioimpedance analysis) and cystatin C measured at baseline were selected. Body mass index (kg/m2) was used to define overweight/obesity. eGFR was calculated using cystatin C (eGFRCYS) and creatinine (eGFRCR) equations: Chronic Kidney Disease Epidemiology Collaboration 2012 (CKD-EPICR, CKD-EPICYS, CKD-EPICR-CYS), eGFRCYS based on Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised equation (LMrev), and Modified Full Age Spectrum creatinine-based equation (EKFCCR). Two different fat mass index (FMI) z-scores were calculated: FMI z-scoreLarsson and FMI z-scoreLee. RESULTS: Lower eGFRCYS and eGFRCR-CYS following multiple adjustments were prevalent in overweight/obese subjects. Increase in FMI z-scoreLarsson or FMI z-scoreLee was related to decrease in predicted CAPA, CKD-EPICYS, CKD-EPICR-CYS and CAPA-LMrev equation. CONCLUSION: eGFRCYS, in contrast to combined eGFRCR-CYS and eGFRCR, demonstrate the strongest association between FMI and kidney function.

Associations between long-term exposure to low-level air pollution and risk of chronic kidney disease-findings from the Malmö Diet and Cancer cohort.

BACKGROUND: Associations between air pollution and chronic kidney disease (CKD) have been reported, but studies at low exposure levels and relevant exposure time windows are still warranted. This study investigated clinical CKD at low air pollution levels in the Swedish Malmö Diet and Cancer Cohort in different exposure time windows. METHODS: This study included 30,396 individuals, aged 45-74 at enrollment 1991-1996. Individual annual average residential outdoor PM2.5, PM10, nitrogen oxides (NOx), and black carbon (BC) were assigned using dispersion models from enrollment to 2016. Diagnoses of incident CKD were retrieved from national registries. Cox proportional hazards models were used to obtain hazard ratios (HRs) for CKD in relation to three time-dependent exposure time windows: exposure at concurrent year (lag 0), mean exposure in the 1-5 or 6-10 preceding years (lag 1-5 and lag 6-10), and baseline exposure. RESULTS: During the study period, the average annual residential exposures were 16 µg/m3 for PM10, 11 µg/m3 for PM2.5, 26 µg/m3 for NOx, and 0.97 µg/m3 for BC. For lag 1-5 and lag 6-10 exposure, significantly elevated HRs for incident CKD were found for total PM10:1.13 (95% CI: 1.01-1.26) and 1.22 (1.06-1.41); NOx: 1.19 (1.07-1.33) and 1.13 (1.02-1.25) and BC: 1.12 (1.03-1.22) and 1.11 (1.02-1.21) per interquartile range increase in exposure. For total PM2.5 the positive associations of 1.12 (0.97-1.31) and 1.16 (0.98-1.36) were not significant. For baseline or lag 0 exposure there were significant associations only for NOx and BC, not for PM. CONCLUSION: Residential exposure to outdoor air pollution was associated with increased risk of incident CKD at relatively low exposure levels. Average long-term exposure was more clearly associated with CKD than current exposure or exposure at recruitment. Our findings imply that the health effects of low-level air pollution on CKD are considerable.

Impaired selective renal filtration captured by eGFRcysC/eGFRcrea ratio is associated with mortality in a population based cohort of older women.

Deranged renal filtration of mid-sized (5-30 kDa) compared to smaller molecules (< 0.9 kDa) results in increased plasma levels of cystatin C (cysC) compared to creatinine resulting in a low eGFRcysC/eGFRcrea ratio. A ratio below 0.6 or 0.7, is termed shrunken pore syndrome (SPS), which in patient based studies is associated with mortality. Reference values for eGFRcysC/eGFRcrea ratio, the prevalence of SPS and the consequence of low eGFRcysC/eGFRcrea ratio in the general, elderly population are unknown. 75-yr old women (n = 849) from the population-based OPRA cohort, followed for 10-years had eGFR calculated with CKD-EPI study equation, and eGFRcysC/eGFRcrea ratio calculated. Mortality risk (HR [95% CI]) was estimated. Women with sarcopenia or on glucocorticoids were excluded. Almost 1 in 10 women (9%) had eGFRcysC/eGFRcrea ratio < 0.6 at age 75 and this did not increase appreciably with age. Women with ratio < 0.6 had higher 10-yr mortality risk compared with ratios > 0.9 (HRadj 1.6 [95% CI 1.1-2.5]). In elderly women eGFRcysC/eGFRcrea ratio < 0.6 is common and associated with increased mortality. Our results confirm patient-based findings, suggesting that identifying individuals with SPS may be clinically relevant to assessing mortality risk in the elderly.

[Use cystatin C-based GFR-estimating equations]. / Använd ekvationer utan ¼ras«-termer för att bestämma GFR.

Glomerular filtration rate (GFR) is estimated by creatinine or cystatin C-based GFR-estimating equations. Those based upon creatinine, but not those based upon cystatin C, use "race" terms due to that different populations differ in average muscular mass, influencing the creatinine, but not the cystatin C, level. "Race" is not a biological, but a sociological term, determined by self-assesment. New international studies therefore strongly recommend use of cystatin C-based GFR-estimating equations.

Early life factors in relation to albuminuria and estimated glomerular filtration rate based on cystatin C and creatinine in adults from a Swedish population-based cohort study.

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.

The risk of chronic kidney disease in relation to anthropometric measures of obesity: A Swedish cohort study.

BACKGROUND: It has been shown that individuals with obesity have a higher risk for chronic kidney disease (CKD). However, it is unclear which measure of obesity is most useful for prediction of CKD in the general population. The aim of this large prospective study was to explore the association between several anthropometric measures of obesity, i. e., body mass index (BMI), waist circumference (WC), waist circumference to height ratio (WHtR), waist-to-hip ratio (WHR), percentage of body fat (BF%), weight, height and incidence of hospitalizations due to CKD, in a population-based cohort study. METHODS: The 'Malmö Diet and Cancer Study (MDCS)' cohort in Sweden was examined during 1991 to 1996. A total of 28,449 subjects underwent measurement of anthropometric measures and blood pressure and filled out a questionnaire. Incidence of in- and outpatient hospital visits for CKD was monitored from the baseline examination over a mean follow-up of 18 years. Cox proportional hazards regression was used to explore the association between anthropometric measures and incidence of CKD, with adjustments for risk factors. RESULTS: The final study population included 26,723 subjects, 45-73 years old at baseline. Higher values of BMI, WC, WHR, WHtR and weight were associated with an increased risk of developing CKD in both men and women. Only in women, higher values of BF% was associated with higher risk of CKD. Comparing the 4th vs 1st quartile of the obesity measure, the highest hazard ratio (HR) for CKD in men was observed for BMI, HR 1.51 (95% CI: 1.18-1.94) and weight (HR 1.52 (95% CI: 1.19-1.94). For women the highest HR for CKD was observed for BF%, HR 2.01 (95% CI: 1.45-2.78). CONCLUSIONS: In this large prospective study, all anthropometric measures of obesity were associated with a substantially increased incidence of CKD, except for BF% in men. Some measures were slightly more predictive for the risk of CKD than others such as BMI and weight in men and BF% in women. In clinical daily practice use of all anthropometric measures of obesity might be equally useful to assess the risk of developing CKD. This study supports the strong evidence for an association between obesity and CKD.