Abstract：
UNASSIGNED: Due to its potential nephrotoxicity, screening for pre-existing renal function disorders has become a routine clinical assessment for initiating Tenofovir diphosphate fumarate (TDF)-containing antiretroviral treatment (ART) or pre-exposure prophylaxis (PrEP) in pregnant and non-pregnant adults. We aimed to establish reference values for commonly used markers of renal function in healthy pregnant women of African origin.
UNASSIGNED: Pregnant women ≥18 years, not living with HIV, and at 14-28 weeks gestation were enrolled in a PrEP clinical trial in Durban, South Africa between September 2017 and December 2019. Women were monitored 4-weekly during pregnancy until six months postpartum. We measured maternal weight and serum creatinine (sCr) at each visit and calculated creatinine clearance (CrCl) rates using the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Reference ranges for sCr and CrCl by CG and MDRD calculations were derived from the mean ± 2SD of values for pregnancy and postdelivery.
UNASSIGNED: Between 14--and 40 weeks gestation, 249 African women not exposed to TDF-PrEP contributed a total of 1193 renal function values. Postdelivery, 207 of these women contributed to 800 renal function values. The normal reference range for sCr was 30-57 and 32-60 umol/l in the 2nd and 3rd trimesters of pregnancy. Normal reference ranges for CrCl using the MDRD calculation were 129-282 and 119-267 ml/min/1.73m2 for the 2nd and 3rd trimesters, respectively. Using the CG method of calculation, normal reference ranges for CrCl were 120-304 and 123-309 ml/min/1.73m2 for the 2nd and 3rd trimesters respectively. In comparison, the normal reference range for sCr, CrCl by MDRD and CG calculations postpartum was 40-77 umol/l, 92-201, and 90-238 ml/min/1.73m2, respectively.
UNASSIGNED: In African women, the Upper Limit of Normal (ULN) for sCr in pregnancy is approximately 20% lower than 6 months postnatally. Inversely, the Lower Limit of Normal (LLN) for CrCl using either MDRD or CG equation is approximately 35% higher than 6 months postnatally. We provide normal reference ranges for sCr and CrCl for both methods of calculation and appropriate for the 2nd and 3rd trimesters of pregnancy in African women.
Screening for pre-existing renal function disorders has become a routine clinical assessment for initiating TDF-containing antiretroviral treatment or pre-exposure prophylaxis in adults including pregnant women. Pregnancy inherently increases renal function, hence normal reference standards for non-pregnant adults cannot be used for pregnant women. In a secondary analysis of data from a healthy pregnant population not living with HIV who participated in a PrEP clinical trial, we established reference intervals for serum creatinine (sCr) concentration and creatinine clearance (CrCl) during pregnancy and postpartum in an African population. Using sCr and CrCl values for 249 healthy pregnant African women, we can confirm that the upper limit of normal for sCr in pregnancy is 20% lower than that for the 6-month postnatal period and recommend an upper limit of 57 umol/l and 60 umol/l in the second and third trimesters respectively to determine normal renal function in pregnant African women.We further determined the lower limit of normal for creatinine clearance using two methods of calculation, which was 35% higher than that of the postnatal period. Using the modification of diet in renal disease calculation, we recommend a lower limit of 129 and 119 ml/min/1.73m2 for the second and third trimesters respectively. Using the Cockcroft–Gault calculation, we recommend a lower limit of 120 and 123 ml/min/1.73m2 for the second and third trimesters respectively. Using current standard cut-off values estimated for adults may lead to underreporting of abnormal renal function in African pregnant women.
UNASSIGNED: Pregnant women ≥18 years, not living with HIV, and at 14-28 weeks gestation were enrolled in a PrEP clinical trial in Durban, South Africa between September 2017 and December 2019. Women were monitored 4-weekly during pregnancy until six months postpartum. We measured maternal weight and serum creatinine (sCr) at each visit and calculated creatinine clearance (CrCl) rates using the Cockcroft-Gault (CG) and Modification of Diet in Renal Disease (MDRD) formulae. Reference ranges for sCr and CrCl by CG and MDRD calculations were derived from the mean ± 2SD of values for pregnancy and postdelivery.
UNASSIGNED: Between 14--and 40 weeks gestation, 249 African women not exposed to TDF-PrEP contributed a total of 1193 renal function values. Postdelivery, 207 of these women contributed to 800 renal function values. The normal reference range for sCr was 30-57 and 32-60 umol/l in the 2nd and 3rd trimesters of pregnancy. Normal reference ranges for CrCl using the MDRD calculation were 129-282 and 119-267 ml/min/1.73m2 for the 2nd and 3rd trimesters, respectively. Using the CG method of calculation, normal reference ranges for CrCl were 120-304 and 123-309 ml/min/1.73m2 for the 2nd and 3rd trimesters respectively. In comparison, the normal reference range for sCr, CrCl by MDRD and CG calculations postpartum was 40-77 umol/l, 92-201, and 90-238 ml/min/1.73m2, respectively.
UNASSIGNED: In African women, the Upper Limit of Normal (ULN) for sCr in pregnancy is approximately 20% lower than 6 months postnatally. Inversely, the Lower Limit of Normal (LLN) for CrCl using either MDRD or CG equation is approximately 35% higher than 6 months postnatally. We provide normal reference ranges for sCr and CrCl for both methods of calculation and appropriate for the 2nd and 3rd trimesters of pregnancy in African women.
Screening for pre-existing renal function disorders has become a routine clinical assessment for initiating TDF-containing antiretroviral treatment or pre-exposure prophylaxis in adults including pregnant women. Pregnancy inherently increases renal function, hence normal reference standards for non-pregnant adults cannot be used for pregnant women. In a secondary analysis of data from a healthy pregnant population not living with HIV who participated in a PrEP clinical trial, we established reference intervals for serum creatinine (sCr) concentration and creatinine clearance (CrCl) during pregnancy and postpartum in an African population. Using sCr and CrCl values for 249 healthy pregnant African women, we can confirm that the upper limit of normal for sCr in pregnancy is 20% lower than that for the 6-month postnatal period and recommend an upper limit of 57 umol/l and 60 umol/l in the second and third trimesters respectively to determine normal renal function in pregnant African women.We further determined the lower limit of normal for creatinine clearance using two methods of calculation, which was 35% higher than that of the postnatal period. Using the modification of diet in renal disease calculation, we recommend a lower limit of 129 and 119 ml/min/1.73m2 for the second and third trimesters respectively. Using the Cockcroft–Gault calculation, we recommend a lower limit of 120 and 123 ml/min/1.73m2 for the second and third trimesters respectively. Using current standard cut-off values estimated for adults may lead to underreporting of abnormal renal function in African pregnant women.
摘要：
■由于其潜在的肾毒性，筛查预先存在的肾功能障碍已成为在孕妇和非孕妇中启动含有富马酸二磷酸替诺福韦（TDF）的抗逆转录病毒治疗（ART）或暴露前预防（PrEP）的常规临床评估。我们旨在为非洲裔健康孕妇的常用肾功能标志物建立参考值。
■孕妇≥18岁，没有感染艾滋病毒，在怀孕14-28周时，他们参加了德班的PrEP临床试验，2017年9月至2019年12月之间的南非。妇女在怀孕期间每周监测4次，直到产后6个月。我们在每次就诊时测量了母体体重和血清肌酐（sCr），并使用Cockcroft-Gault（CG）和肾脏疾病饮食改良（MDRD）公式计算了肌酐清除率（CrCl）。通过CG和MDRD计算得出的sCr和CrCl的参考范围是从妊娠和分娩后的平均值±2SD得出的。
■在妊娠14到40周之间，249名未暴露于TDF-PrEP的非洲女性贡献了总共1193个肾功能值。交货后,这些女性中有207人贡献了800项肾功能值。在妊娠的第2和第3个月，sCr的正常参考范围为30-57和32-60umol/l。使用MDRD计算的CrCl的正常参考范围为第2和第3个月的129-282和119-267ml/min/1.73m2。分别。使用CG计算方法，第2和第3个月CrCl的正常参考范围分别为120-304和123-309ml/min/1.73m2。相比之下,sCr的正常参考范围，经MDRD和CG计算，产后CrCl为40-77umol/l，92-201和90-238ml/min/1.73m2。
■在非洲女性中，妊娠期sCr的正常上限(ULN)比出生后6个月低约20%。相反，使用MDRD或CG方程的CrCl的正常下限（LLN）比出生后6个月高出约35％。我们为两种计算方法提供了sCr和CrCl的正常参考范围，并适用于非洲妇女的妊娠第二和第三三个月。
筛查预先存在的肾功能障碍已成为启动含TDF的抗逆转录病毒治疗或暴露前预防包括孕妇在内的成人的常规临床评估。怀孕本身会增加肾功能，因此，非孕妇成人的正常参考标准不能用于孕妇。在对参与PrEP临床试验的未感染HIV的健康孕妇的数据进行的二次分析中，我们建立了非洲人群妊娠和产后血清肌酐(sCr)浓度和肌酐清除率(CrCl)的参考区间.使用249名健康怀孕非洲妇女的sCr和CrCl值，我们可以确认妊娠中sCr的正常值上限比产后6个月低20％，并建议在第二和第三三个月中分别使用57umol/l和60umol/l的上限来确定妊娠非洲妇女的正常肾功能。我们使用两种计算方法进一步确定肌酐清除率的正常值下限，比产后高35%。在肾脏疾病计算中使用饮食的修改，我们建议第二和第三个三个月的下限分别为129和119ml/min/1.73m2。使用Cockcroft-Gault计算，我们建议第二和第三个三个月的下限分别为120和123ml/min/1.73m2。使用目前为成年人估计的标准临界值可能会导致非洲孕妇的肾功能异常报告不足。
■孕妇≥18岁，没有感染艾滋病毒，在怀孕14-28周时，他们参加了德班的PrEP临床试验，2017年9月至2019年12月之间的南非。妇女在怀孕期间每周监测4次，直到产后6个月。我们在每次就诊时测量了母体体重和血清肌酐（sCr），并使用Cockcroft-Gault（CG）和肾脏疾病饮食改良（MDRD）公式计算了肌酐清除率（CrCl）。通过CG和MDRD计算得出的sCr和CrCl的参考范围是从妊娠和分娩后的平均值±2SD得出的。
■在妊娠14到40周之间，249名未暴露于TDF-PrEP的非洲女性贡献了总共1193个肾功能值。交货后,这些女性中有207人贡献了800项肾功能值。在妊娠的第2和第3个月，sCr的正常参考范围为30-57和32-60umol/l。使用MDRD计算的CrCl的正常参考范围为第2和第3个月的129-282和119-267ml/min/1.73m2。分别。使用CG计算方法，第2和第3个月CrCl的正常参考范围分别为120-304和123-309ml/min/1.73m2。相比之下,sCr的正常参考范围，经MDRD和CG计算，产后CrCl为40-77umol/l，92-201和90-238ml/min/1.73m2。
■在非洲女性中，妊娠期sCr的正常上限(ULN)比出生后6个月低约20%。相反，使用MDRD或CG方程的CrCl的正常下限（LLN）比出生后6个月高出约35％。我们为两种计算方法提供了sCr和CrCl的正常参考范围，并适用于非洲妇女的妊娠第二和第三三个月。
筛查预先存在的肾功能障碍已成为启动含TDF的抗逆转录病毒治疗或暴露前预防包括孕妇在内的成人的常规临床评估。怀孕本身会增加肾功能，因此，非孕妇成人的正常参考标准不能用于孕妇。在对参与PrEP临床试验的未感染HIV的健康孕妇的数据进行的二次分析中，我们建立了非洲人群妊娠和产后血清肌酐(sCr)浓度和肌酐清除率(CrCl)的参考区间.使用249名健康怀孕非洲妇女的sCr和CrCl值，我们可以确认妊娠中sCr的正常值上限比产后6个月低20％，并建议在第二和第三三个月中分别使用57umol/l和60umol/l的上限来确定妊娠非洲妇女的正常肾功能。我们使用两种计算方法进一步确定肌酐清除率的正常值下限，比产后高35%。在肾脏疾病计算中使用饮食的修改，我们建议第二和第三个三个月的下限分别为129和119ml/min/1.73m2。使用Cockcroft-Gault计算，我们建议第二和第三个三个月的下限分别为120和123ml/min/1.73m2。使用目前为成年人估计的标准临界值可能会导致非洲孕妇的肾功能异常报告不足。
