Rescaling creatinine makes GFR estimation equations generally applicable across populations - validation results for the Lund-Malmö equation in a French cohort of sub-Saharan ancestry.

OBJECTIVES: To make glomerular filtration rate (GFR) estimating equations applicable across populations with different creatinine generation by using rescaled serum creatinine (sCr/Q) where sCr represents the individual creatinine level and Q the average creatinine value in healthy persons of the same population. METHODS: GFR measurements (mGFR, plasma clearance of 51Cr-EDTA) were conducted in 964 adult Black Europeans. We established the re-expressed Lund-Malmö revised equation (r-LMR) by replacing serum creatinine (sCr) with rescaled creatinine sCr/Q. We evaluated the r-LMR equation based on Q-values of White Europeans (r-LMRQ-white; Q-values females: 62 µmol/L, males: 80 µmol/L) and Black Europeans (r-LMRQ-Black; Q-values females: 65 µmol/L, males: 90 µmol/L), and the European Kidney Function Consortium equation (EKFCQ-White and EKFCQ-Black) regarding bias, precision (interquartile range, IQR) and accuracy (percentage of estimates within ±10 % [P10] and ±30 % [P30] of mGFR). RESULTS: Median bias of r-LMRQ-White/r-LMRQ-Black/EKFCQ-White/EKFCQ-Black were -9.1/-4.5/-6.3/-0.9 mL/min/1.73 m2, IQR 14.7/14.5/14.5/15.6 mL/min/1.73 m2, P10 25.1 %/34.8 %/30.3 %/37.2 % and P30 74.2 %/84.1 %/80.6 %/83.6 %. The improvement of bias and accuracy when using proper Q-values was most pronounced in men. Similar improvements were obtained above and below mGFR 60 mL/min/1.73 m2 and at various age and BMI intervals, except for BMI<20 kg/m2 where bias increased, and accuracy decreased. CONCLUSIONS: GFR estimating equations may be re-expressed to include rescaled creatinine (sCr/Q) and used across populations with different creatinine generation if population-specific average creatinine concentrations (Q-values) for healthy persons are established.

Absolute and relative GFR and contrast medium dose/GFR ratio: cornerstones when predicting the risk of acute kidney injury.

Glomerular filtration rate (GFR) is considered the best overall index of kidney function in health and disease and its use is recommended to evaluate the risk of iodine contrast medium-induced acute kidney injury (CI-AKI) either as a single parameter or as a ratio between the total contrast medium dose (gram iodine) and GFR. GFR may be expressed in absolute terms (mL/min) or adjusted/indexed to body surface area, relative GFR (mL/min/1.73 m2). Absolute and relative GFR have been used interchangeably to evaluate the risk of CI-AKI, which may be confusing and a potential source of errors. Relative GFR should be used to assess the GFR category of renal function as a sign of the degree of kidney damage and sensitivity for CI-AKI. Absolute GFR represents the excretion capacity of the individual and may be used to calculate the gram-iodine/absolute GFR ratio, an index of systemic drug exposure (amount of contrast medium in the body) that relates to toxicity. It has been found to be an independent predictor of AKI following percutaneous coronary angiography and interventions but has not yet been fully validated for computed tomography (CT). Prospective studies are warranted to evaluate the optimal gram-iodine/absolute GFR ratio to predict AKI at various stages of renal function at CT. Only GFR estimation (eGFR) equations based on standardized creatinine and/or cystatin C assays should be used. eGFRcystatin C/eGFRcreatinine ratio < 0.6 indicating selective glomerular hypofiltration syndrome may have a stronger predictive power for postcontrast AKI than creatinine-based eGFR. CLINICAL RELEVANCE STATEMENT: Once the degree of kidney damage is established by estimating relative GFR (mL/min/1.73 m2), contrast dose in relation to renal excretion capacity [gram-iodine/absolute GFR (mL/min)] may be the best index to evaluate the risk of contrast-induced kidney injury. KEY POINTS: • Relative glomerular filtration rate (GFR; mL/min/1.73 m2) should be used to assess the GFR category as a sign of the degree of kidney damage and sensitivity to contrast medium-induced acute kidney injury (CI-AKI). • Absolute GFR (mL/min) is the individual's actual excretion capacity and the contrast-dose/absolute GFR ratio is a measure of systemic exposure (amount of contrast medium in the body), relates to toxicity and should be expressed in gram-iodine/absolute GFR (mL/min). • Prospective studies are warranted to evaluate the optimal contrast medium dose/GFR ratio predicting the risk of CI-AKI at CT and intra-arterial examinations.

Extending the cystatin C based EKFC-equation to children - validation results from Europe.

BACKGROUND: A new cystatin C based European Kidney Function Consortium (EKFCCysC) equation was recently developed for adults, using the same mathematical form as the previously published full age spectrum creatinine based EKFC-equation (EKFCCrea). In the present study the cystatin C based EKFC-equation is extended to children, by defining the appropriate cystatin C rescaling factor QCysC. METHODS: Rescaling factor QCysC for cystatin C was defined as: a) 0.83 mg/L, exactly as it was defined for young adults in the adult equation, and b) a more complex QCysC-age relationship based on 4th degree cystatin C-age polynomials after evaluation of data from Uppsala, Stockholm and Canada and aggregated data from Germany. The EKFCCysC equation was then validated in an independent dataset in European children (n = 2,293) with measured GFR, creatinine, cystatin C, age, height and sex available. RESULTS: The EKFCCysC with the simple QCysC-value of 0.83 had a bias of -7.6 [95%CI -8.4;-6.5] mL/min/1.73 m2 and a P30-value of 85.8% [95%CI 84.4;87.3] equal to the EKFCCysC with the more complex 4th degree QCysC-value. The arithmetic mean of the EKFCCrea and EKFCCysC with the simple QCysC of 0.83 had a bias of -4.0 [95%CI -4.5;-3.1] mL/min/1.73 m2 and P30 of 90.4% [95%CI 89.2;91.6] similar to using the more complex 4th degree QCysC-polynomial. CONCLUSION: Using exactly the same QCysC of 0.83 mg/L, the adult EKFCCysC can easily be extended to children, with some bias but acceptable P30-values. The arithmetic mean of EKFCCrea and EKFCCysC results in bias closer to zero and P30 slightly over 90%.

Performance of the European Kidney Function Consortium (EKFC) creatinine-based equation in United States cohorts.

Estimating glomerular filtration rate (GFR) is important in daily practice to assess kidney function and adapting the best clinical care of patients with and without chronic kidney disease. The new creatinine-based European Kidney Function Consortium (EKFC) equation is used to estimate GFR. This equation was developed and validated mainly in European individuals and based on a rescaled creatinine, with the rescaling factor (Q-value) defined as the median normal value of serum creatinine in a given population. The validation was limited in Non-Black Americans and absent in Black Americans. Here, our cross-sectional analysis included 12,854 participants from nine studies encompassing large numbers of both non-Black and Black Americans with measured GFR by clearance of an exogenous marker (reference method), serum creatinine, age, sex, and self-reported race available. Two strategies were considered with population-specific Q-values in Black and non-Black men and women (EKFCPS) or a race-free Q-value (EKFCRF). In the whole population, only the EKFCPS equation showed no statistical median bias (0.14, 95% confidence interval [-0.07; 0.35] mL/min/1.73m2), and the bias for the EKFCRF (0.74, [0.51; 0.94] mL/min/1.73m2) was closer to zero than that for the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI2021) equation (1.22, [0.99; 1.47]) mL/min/1.73m2]. The percentage of estimated GFR within 30% of measured GFR was similar for CKD-EPI2021 (79.2% [78.5%; 79.9%]) and EKFCRF (80.1% [79.4%; 80.7%]), but improved for the EKFCPS equation (81.1% [80.5%; 81.8%]). Thus, our EKFC equations can be used to estimate GFR in the United States incorporating either self-reported race or unknown race at the patient's discretion per hospital registration records.

Revised Swedish guidelines on intravenous iodine contrast medium-induced acute kidney injury 2022: A summary.

The Swedish Society of Uroradiology has revised their computed tomography (CT) guidelines regarding iodine contrast media-induced acute kidney injury (CI-AKI). They are more cautious compared to the European Society of Urogenital Radiology and the American College of Radiology since the actual risk of CI-AKI remains uncertain in patients with moderate to severe kidney damage due to a lack of prospective controlled studies and mainly based on retrospective propensity score-matched studies with low-grade evidence. Another source of uncertainty is the imprecision of glomerular filtration rate (GFR) estimating equations. However, randomized hydration studies indictae an upper limit risk of CI-AKI of about 5% for outpatients with a GFR in the range of 30-44 or 45-59 mL/min/1.73m2 combined with multiple risk factors. Apart from GFR limits, the guideline also includes limits for systemic contrast medium exposure expressed in gram-iodine/GFR ratio.

Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex.

BACKGROUND: The accuracy of estimation of kidney function with the use of routine metabolic tests, such as measurement of the serum creatinine level, has been controversial. The European Kidney Function Consortium (EKFC) developed a creatinine-based equation (EKFC eGFRcr) to estimate the glomerular filtration rate (GFR) with a rescaled serum creatinine level (i.e., the serum creatinine level is divided by the median serum creatinine level among healthy persons to control for variation related to differences in age, sex, or race). Whether a cystatin C-based EKFC equation would increase the accuracy of estimated GFR is unknown. METHODS: We used data from patients in Sweden to estimate the rescaling factor for the cystatin C level in adults. We then replaced rescaled serum creatinine in the EKFC eGFRcr equation with rescaled cystatin C, and we validated the resulting EKFC eGFRcys equation in cohorts of White patients and Black patients in Europe, the United States, and Africa, according to measured GFR, levels of serum creatinine and cystatin C, age, and sex. RESULTS: On the basis of data from 227,643 patients in Sweden, the rescaling factor for cystatin C was estimated at 0.83 for men and women younger than 50 years of age and 0.83 + 0.005 × (age - 50) for those 50 years of age or older. The EKFC eGFRcys equation was unbiased, had accuracy that was similar to that of the EKFC eGFRcr equation in both White patients and Black patients (11,231 patients from Europe, 1093 from the United States, and 508 from Africa), and was more accurate than the Chronic Kidney Disease Epidemiology Collaboration eGFRcys equation recommended by Kidney Disease: Improving Global Outcomes. The arithmetic mean of EKFC eGFRcr and EKFC eGFRcys further improved the accuracy of estimated GFR over estimates from either biomarker equation alone. CONCLUSIONS: The EKFC eGFRcys equation had the same mathematical form as the EKFC eGFRcr equation, but it had a scaling factor for cystatin C that did not differ according to race or sex. In cohorts from Europe, the United States, and Africa, this equation improved the accuracy of GFR assessment over that of commonly used equations. (Funded by the Swedish Research Council.).

Estimated glomerular filtration rates are higher when creatinine-based equations are compared with a cystatin C-based equation in coronavirus disease 2019.

OBJECTIVES: Estimations of glomerular filtration rate (eGFR) are based on analyses of creatinine and cystatin C, respectively. Coronavirus disease 2019 (COVID-19) patients in the intensive care unit (ICU) often have acute kidney injury (AKI) and are at increased risk of drug-induced kidney injury. The aim of this study was to compare creatinine-based eGFR equations to cystatin C-based eGFR in ICU patients with COVID-19. METHODS: After informed consent, we included 370 adult ICU patients with COVID-19. Creatinine and cystatin C were analyzed at admission to the ICU as part of the routine care. Creatinine-based eGFR (ml/min) was calculated using the following equations, developed in chronological order; the Cockcroft-Gault (C-G), Modified Diet in Renal Disease (MDRD)1999, MDRD 2006, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), and Lund-Malmö revised (LMR) equations, which were compared with eGFR calculated using the cystatin C-based Caucasian Asian Pediatric Adult (CAPA) equation. RESULTS: The median eGFR when determined by C-G was 99 ml/min and interquartile range (IQR: 67 ml/min). Corresponding estimations for MDRD1999 were 90 ml/min (IQR: 54); MDRD2006: 85 ml/min (IQR: 51); CKD-EPI: 91 ml/min (IQR: 47); and for LMR 83 ml/min (IQR: 41). eGFR was calculated using cystatin C and the CAPA equation value was 70 ml/min (IQR: 38). All differences between creatinine-based eGFR versus cystatin C-based eGFR were significant (p < .00001). CONCLUSIONS: Estimation of GFR based on various analyses of creatinine are higher when compared with a cystatin C-based equation. The C-G equation had the worst performance and should not be used in combination with modern creatinine analysis methods for determination of drug dosage in COVID-19 patients.

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.

Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil and Africa.

BACKGROUND: A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.

Standardization of serum creatinine is essential for accurate use of unbiased estimated GFR equations: evidence from three cohorts matched on renal function.

Background: Differences in the performance of estimated glomerular filtration rate (eGFR) equations have been attributed to the mathematical form of the equations and to differences between patient demographics and measurement methods. We evaluated differences in serum creatinine (SCr) and eGFR in cohorts matched for age, sex, body mass index (BMI) and measured GFR (mGFR). Methods: White North Americans from Minnesota (n = 1093) and the Chronic Renal Insufficiency Cohort (CRIC) (n = 1548) and White subjects from the European Kidney Function Consortium (EKFC) cohort (n = 7727) were matched for demographic patient characteristics (sex, age ± 3 years, BMI ± 2.5 kg/m2) and renal function (mGFR ± 3 ml/min/1.73 m2). SCr was measured with isotope dilution mass spectrometry (IDMS)-traceable assays in the Minnesota and EKFC cohorts and with non-standardized SCr assays recalculated to IDMS in the CRIC. The Minnesota cohort and CRIC shared a common method to measure GFR (renal clearance of iothalamate), while the EKFC cohort used a variety of exogenous markers and methods, all with recognized sufficient accuracy. We compared the SCr levels and eGFR predictions [for Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and EKFC equations] of patients fulfilling these matching criteria. Results: For 305 matched individuals, mean SCr (mg/dL) was not different between the Minnesota and EKFC cohorts (females 0.83 ± 0.20 versus 0.86 ± 0.23, males 1.06 ± 0.23 versus 1.12 ± 0.37; P > .05) but significantly different from the CRIC [females 1.13 ± 0.23 (P < .0001), males 1.42 ± 0.31 (P < .0001)]. The CKD-EPI equations performed better than the EKFC equation in the CRIC, while the opposite was true in the Minnesota and EKFC cohorts. Conclusion: Significant differences in SCr concentrations between the Minnesota and EKFC cohorts versus CRIC were observed in subjects with the same level of mGFR and equal demographic characteristics and can be explained by the difference in SCr calibration.

Differential Bias for Creatinine- and Cystatin C- Derived Estimated Glomerular Filtration Rate in Critical COVID-19.

COVID-19 is a systemic disease, frequently affecting kidney function. Dexamethasone is standard treatment in severe COVID-19 cases, and is considered to increase plasma levels of cystatin C. However, this has not been studied in COVID-19. Glomerular filtration rate (GFR) is a clinically important indicator of renal function, but often estimated using equations (eGFR) based on filtered metabolites. This study focuses on sources of bias for eGFRs (mL/min) using a creatinine-based equation (eGFRLMR) and a cystatin C-based equation (eGFRCAPA) in intensive-care-treated patients with COVID-19. This study was performed on 351 patients aged 18 years old or above with severe COVID-19 infections, admitted to the intensive care unit (ICU) in Uppsala University Hospital, a tertiary care hospital in Uppsala, Sweden, between 14 March 2020 and 10 March 2021. Dexamethasone treatment (6 mg for up to 10 days) was introduced 22 June 2020 (n = 232). Values are presented as medians (IQR). eGFRCAPA in dexamethasone-treated patients was 69 (37), and 74 (46) in patients not given dexamethasone (p = 0.01). eGFRLMR was not affected by dexamethasone. eGFRLMR in females was 94 (20), and 75 (38) in males (p = 0.00001). Age and maximal CRP correlated negatively to eGFRCAPA and eGFRLMR, whereas both eGFR equations correlated positively to BMI. In ICU patients with COVID-19, dexamethasone treatment was associated with reduced eGFRCAPA. This finding may be explained by corticosteroid-induced increases in plasma cystatin C. This observation is important from a clinical perspective since adequate interpretation of laboratory results is crucial.

Regarding Iodixanol for Pediatric CTA. Comment on Pop, M. Cardiothoracic CTA in Infants Referred for Aortic Arch Evaluation-Retrospective Comparison of Iomeprol 350, Ioversol 350, Iopromide 370 and Iodixanol 320. Children 2021, 8, 949.

With interest, we read the publication 'Cardiothoracic CTA in Infants Referred for Aortic Arch Evaluation-Retrospective Comparison of Iomeprol 350, Ioversol 350, Iopromide 370 and Iodixanol 320' by Pop [...].

Evaluation of the creatinine-based chronic kidney disease in children (under 25 years) equation in healthy children and adolescents.

BACKGROUND: The Chronic Kidney Disease in children (CKiD) equation to estimate glomerular filtration rate eGFR = k × Ht / SCr (Ht = height in cm, SCr = serum creatinine in mg/dL), with fixed k = 0.413, has recently been optimized by introducing age/sex dependent k-values valid for young children up to young adults (the CKiD Under 25 years (CKiDU25) equation). Although the CKiD equation was designed for children with chronic kidney disease (CKD), this equation found common use both clinically and in research, and also in children without CKD. This report aims to evaluate properties of CKiD and CKiDU25 in healthy children and adolescents. METHOD: Sex-specific metadata (height and creatinine) for healthy children were obtained from national growth curves and creatinine versus age curves. These data were used to calculate average CKiD and CKiDU25 values for each year of age and compare them against age-independent measured GFR of 107 mL/min/1.73 m2. RESULTS: The CKiD estimations show a steep decline with age (1.5 mL/min/1.73 m2/year in females and 2.0 mL/min/1.73 m2/year in males) over the entire age range (2-20 years) and large differences between adolescent males and females. Due to the age/sex specific k-values, the CKiDU25 equation solves this age-decline artifact of the CKiD equation. However, CKiDU25 still shows a systematic higher estimation of about 10% in healthy males compared to females over the entire age range. CONCLUSION: Although the CKiDU25 shows major improvements compared to the CKiD equation, as the unexpected age decline has been removed, a systematic difference is still observed between healthy males and females.

Performance of creatinine-based equations to estimate glomerular filtration rate with a methodology adapted to the context of drug dosage adjustment.

AIM: The Cockcroft-Gault (CG) creatinine-based equation is still used to estimate glomerular filtration rate (eGFR) for drug dosage adjustment. Incorrect eGFR may lead to hazardous over- or underdosing. METHODS: In a cross-sectional analysis, CG was validated against measured GFR (mGFR) in 14 804 participants and compared with the Modification-of-Diet-in-Renal-Diseases (MDRD), Chronic-Kidney-Disease-Epidemiology (CKD-EPI), Lund-Malmö-Revised (LMR) and European-Kidney-Function-Consortium (EKFC) equations. Validation focused on bias, imprecision and accuracy (percentage of estimates within ±30% of mGFR, P30), overall and stratified for mGFR, age and body mass index at mGFR <60 mL/min, as well as classification in mGFR stages. RESULTS: The CG equation performed worse than the other equations, overall and in mGFR, age and BMI subgroups in terms of bias (systematic overestimation), imprecision and accuracy except for patients ≥65 years where bias and P30 were similar to MDRD and CKD-EPI, but worse than LMR and EKFC. In subjects with mGFR <60 mL/min and at BMI 18.5-25 kg/m2 , all equations performed similarly, and for BMI < 18.5 kg/m2 CG and LMR had the best results though all equations had poor P30-accuracy. At BMI ≥ 25 kg/m2 the bias of the CG increased with increasing BMI (+17.2 mL/min at BMI ≥ 40 kg/m2 ). The four more recent equations also classified mGFR stages better than CG. CONCLUSIONS: The CG equation showed poor ability to estimate GFR overall and in analyses stratified for mGFR, age and BMI. CG was inferior to correctly classify the patients in the mGFR staging compared to more recent creatinine-based equations.

[GFR estimation in children - age-adjusted creatinine makes the adult Lund-Malmö equation applicable in children and facilitates automatic GFR reporting from the clinical laboratory]. / Så kan formel för vuxna skatta glomerulär filtration hos barn.

Age-adjustment of creatinine, i.e. recalculation of childhood levels of creatinine to corresponding levels at 18 years of age and applied in the adult revised Lund-Malmö GFR equation led to markedly improved accuracy in Swedish children (n=1 718) at measured GFR <75 mL/min/1.73 m2 (n=318) and preserved high accuracy at ≥75 mL/min/1.73 m2 (n=1 400). The adjusted LMR equation performed as well as dedicated paediatric equations based on height. The proposed adjustment strategy has four strengths: (i) the original coefficients of the adult GFR equation can be used, (ii) the same equation can be used across the entire lifespan without artificial changes in estimated GFR when switching from paediatric to adult care, (iii) the lack of height factor makes it easier to automatically report estimated GFR by the laboratories and (iv) age-adjusted creatinine values imply that well-established creatinine reference intervals for adults can also be used for children.

Minimal risk of contrast-induced kidney injury in a randomly selected cohort with mildly reduced GFR.

OBJECTIVES: Previous large studies of contrast-induced or post-contrast acute kidney injury (CI-AKI/PC-AKI) have been observational, and mostly retrospective, often with patients undergoing non-enhanced CT as controls. This carries risk of inclusion bias that makes the true incidence of PC-AKI hard to interpret. Our aim was to determine the incidence of PC-AKI in a large, randomly selected cohort, comparing the serum creatinine (Scr) changes after contrast medium exposure with the normal intraindividual fluctuation in Scr. METHODS: In this prospective study of 1009 participants (age 50-65 years, 48% females) in the Swedish CArdioPulmonary bioImage Study (SCAPIS), with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min, all received standard dose intravenous iohexol at coronary CT angiography (CCTA). Two separate pre-CCTA Scr samples and a follow-up sample 2-4 days post-CCTA were obtained. Change in Scr was statistically analyzed and stratification was used in the search of possible risk factors. RESULTS: Median increase of Scr post-CCTA was 0-2 µmol/L. PC-AKI was observed in 12/1009 individuals (1.2%) according to the old ESUR criteria (> 25% or > 44 µmol/L Scr increase) and 2 individuals (0.2%) when using the updated ESUR criteria (≥ 50% or ≥ 27 µmol/L Scr increase). Possible risk factors (e.g., diabetes, age, eGFR, NSAID use) did not show increased risk of developing PC-AKI. The mean effect of contrast media on Scr did not exceed the intraindividual Scr fluctuation. CONCLUSIONS: Iohexol administration to a randomly selected cohort with mildly reduced eGFR is safe, and PC-AKI is very rare, occurring in only 0.2% when applying the updated ESUR criteria. KEY POINTS: • Iohexol administration to a randomly selected cohort, 50-65 years old with mildly reduced eGFR, is safe and PC-AKI is very rare. • Applying the updated ESUR PC-AKI criteria resulted in fewer cases, 0.2% compared to 1.2% using the old ESUR criteria in this cohort with predominantly mild reduction of renal function. • The mean effect of CM on Scr did not exceed the intraindividual background fluctuation of Scr, regardless of potential risk factors, such as diabetes or NSAID use in our cohort of 1009 individuals.