Low birthweight is associated with lower glomerular filtration rate in middle-aged mainly healthy women.

BACKGROUND: Low birthweight (LBW) has been shown to increase the risk of severe kidney disease. Studies have also shown associations between LBW and lower estimated glomerular filtration rate (GFR) in young adults. In this study we investigated whether LBW associates with measured GFR (mGFR) in middle-aged mainly healthy adults. METHODS: We invited individuals with LBW (1100-2300 g) and individuals with normal BW (NBW; 3500-4000 g) ages 41-52 years. GFR was measured using plasma clearance of iohexol. BW and BW for gestational age (BWGA) were obtained from the Medical Birth Registry of Norway and tested as main predictors. GFR was the main outcome. RESULTS: We included 105 individuals (57 LBW and 48 NBW). The mean GFR was 95 ± 14 mL/min/1.73 m2 in the LBW group and 100 ± 13 mL/min/1.73 m2 in the NBW group (P = 0.04). There was a significant sex difference: in women the mean GFR was 90 ± 12 versus 101 ± 14 mL/min/1.73 m2 in the LBW and NBW groups, respectively (P = 0.006), whereas corresponding values for men were 101 ± 15 versus 100 ± 11 mL/min/1.73 m2 (P = 0.7). Using linear regression, we found the GFR was 4.5 mL/min/1.73 m2 higher per 1 kg higher BW for women (P = 0.02), with a non-significant 1.2 mL/min/1.73 m2 lower GFR for men (P = 0.6). In analyses of BWGA, there was also a significant association for women, but not for men. CONCLUSIONS: Middle-aged mainly healthy women with LBW had lower mGFR as compared with women with NBW. No such difference was found for men.

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.

Renal Functional Response-Association With Birth Weight and Kidney Volume.

Introduction: Renal functional response (RFR) is the acute increase in glomerular filtration rate (GFR) after a protein load. Low RFR is a marker of single nephron hyperfiltration. Low birth weight (LBW) is associated with reduced number of nephrons, lower kidney function, and smaller kidneys in adults. In the present study, we investigate the associations among LBW, kidney volume, and RFR. Methods: We studied adults aged 41 to 52 years born with either LBW (≤2300 g) or normal birth weight (NBW; 3500-4000 g). GFR was measured using plasma clearance of iohexol. A stimulated GFR (sGFR) was measured on a separate day after a protein load of 100 g using a commercially available protein powder, and RFR was calculated as delta GFR. Kidney volume was estimated from magnetic resonance imaging (MRI) images using the ellipsoid formula. Results: A total of 57 women and 48 men participated. The baseline mean ± SD GFR was 118 ± 17 ml/min for men and 98 ± 19 ml/min for women. The overall mean RFR was 8.2 ± 7.4 ml/min, with mean RFR of 8.3 ± 8.0 ml/min and 8.1 ± 6.9 ml/min in men and women, respectively (P = 0.5). No birth-related variables were associated with RFR. Larger kidney volume was associated with higher RFR, 1.9 ml/min per SD higher kidney volume (P = 0.009). Higher GFR per kidney volume was associated with a lower RFR, -3.3ml/min per SD (P < 0.001). Conclusion: Larger kidney size and lower GFR per kidney volume were associated with higher RFR. Birth weight was not shown to associate with RFR in mainly healthy middle-aged men and women.

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.

Birth Weight Is Associated With Kidney Size in Middle-Aged Women.

INTRODUCTION: Low birth weight (LBW) is associated with increased risk of kidney disease due to lower nephron endowment leading to hyperfiltration and subsequent nephron loss. Kidney size is commonly used as a proxy for nephron number. We compared kidney volume measured by magnetic resonance imaging (MRI) with measured glomerular filtration rate (mGFR) in adults with either normal birth weight (NBW) or low birth weight (LBW). METHODS: Healthy individuals aged 42 to 52 years with LBW (1100-2300 g) and NBW (3500 -4000 g) were invited to participate. The GFR was measured using plasma clearance of iohexol. Kidney volume was measured on magnetic resonance images using axial T2 images and coronal T1 images with fat saturation without contrast enhancement; calculations were performed according to the ellipsoid formula π/6 × length × width × depth. RESULTS: We included 102 individuals (54 LBW and 48 NBW). Total kidney volume was 302 ± 51 ml for female NBW vs 258 ± 48 ml for female LBW individuals (P = 0.002). For male individuals, total kidney volume was 347 ± 51 ml vs. 340 ± 65 ml (P = 0.7). The mGFR was significantly associated with kidney volume, with r = 0.52 (P < 0.001) for women and r = 0.39 (P = 0.007) for men. A mediation analysis showed that the association between birth weight and mGFR (significant in total sample and women) was mediated by kidney volume. CONCLUSION: Healthy female individuals born with LBW have smaller kidneys than healthy females born with NBW. The previously shown associations between LBW and lower mGFR in adult women might be explained by smaller kidney volume.