The burden of kidney disease in many African countries is unknown. Equations used to estimate kidney function from serum creatinine have limited regional validation. We sought to determine the most accurate way to measure kidney function and thus estimate the prevalence of impaired kidney function in African populations. We measured serum creatinine, cystatin C, and glomerular filtration rate (GFR) using the slope-intercept method for iohexol plasma clearance (mGFR) in population cohorts from Malawi, Uganda, and South Africa. We compared performance of creatinine and cystatin C-based estimating equations to mGFR, modelled and validated a new creatinine-based equation, and developed a multiple imputation model trained on the mGFR sample using age, sex, and creatinine as the variables to predict the population prevalence of impaired kidney function in west, east, and southern Africa. Of 3025 people who underwent measured GFR testing (Malawi n=1020, South Africa n=986, and Uganda n=1019), we analysed data for 2578 participants who had complete data and adequate quality measurements. Among 2578 included participants, creatinine-based equations overestimated kidney function compared with mGFR, worsened by use of ethnicity coefficients. The greatest bias occurred at low kidney function, such that the proportion with GFR of less than 60 mL/min per 1·73 m either directly measured or estimated by cystatin C was more than double that estimated from creatinine. A new creatinine-based equation did not outperform existing equations, and no equation, including the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 race-neutral equation, estimated GFR within plus or minus 30% of mGFR for 75% or more of the participants. Using a model to impute kidney function based on mGFR, the estimated prevalence of impaired kidney function was more than two-times higher than creatinine-based estimates in populations across six countries in Africa. Estimating GFR using serum creatinine substantially underestimates the individual and population-level burden of impaired kidney function in Africa with implications for understanding disease progression and complications, clinical care, and service provision. Scalable and affordable ways to accurately identify impaired kidney function in Africa are urgently needed. The GSK Africa Non-Communicable Disease Open Lab. For the Luganda, Chichewa and Xitsonga translations of the abstract see Supplementary Materials section.

中文翻译：

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马拉维、南非和乌干达肾功能的测量：一项多中心队列研究

许多非洲国家的肾脏疾病负担尚不清楚。用于根据血清肌酐估计肾功能的方程的区域验证有限。我们试图确定测量肾功能的最准确方法，从而估计非洲人群肾功能受损的患病率。我们在马拉维、乌干达和南非的人群中使用碘海醇血浆清除率 (mGFR) 的斜率截距法测量了血清肌酐、胱抑素 C 和肾小球滤过率 (GFR)。我们将基于肌酐和胱抑素 C 的估计方程与 mGFR 的性能进行了比较，建模并验证了一个新的基于肌酐的方程，并开发了一个在 mGFR 样本上训练的多重插补模型，使用年龄、性别和肌酐作为预测人群的变量西非、东非和南部非洲肾功能受损的患病率。在接受测量 GFR 测试的 3025 人中（马拉维 n=1020、南非 n=986 和乌干达 n=1019），我们分析了 2578 名拥有完整数据和充分质量测量的参与者的数据。在 2578 名参与者中，与 mGFR 相比，基于肌酐的方程高估了肾功能，而使用种族系数则使情况变得更糟。最大的偏差发生在低肾功能时，直接测量或通过胱抑素 C 估计的 GFR 低于 60 mL/min 每 1·73 m 的比例是根据肌酐估计的两倍多。基于肌酐的新方程并未优于现有方程，并且没有方程，包括慢性肾病流行病学合作组织 (CKD-EPI) 2021 种族中性方程，估计 GFR 在 mGFR 的正负 30% 范围内，其中 75% 或更多参与者们。使用基于 mGFR 的模型估算肾功能，在非洲六个国家的人群中，肾功能受损的患病率估计值比基于肌酐的估计值高出两倍多。使用血清肌酐估算 GFR 大大低估了非洲肾功能受损的个体和人群水平负担，这对于了解疾病进展和并发症、临床护理和服务提供具有重要意义。非洲迫切需要可扩展且负担得起的方法来准确识别肾功能受损。葛兰素史克非洲非传染性疾病开放实验室。有关摘要的卢干达语、奇切瓦语和西松加语翻译，请参阅补充材料部分。