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Background Guidelines recommend estimation of glomerular filtration rate (eGFR) prior to iodine contrast media (CM) examinations. It is also recommended that absolute eGFR in mL/min, not commonly used relative GFR (adjusted to body surface area; mL/min/1.73 m2), should be preferred when dosing and evaluating toxicity of renally excreted drugs. Purpose To validate the absolute Lund-Malmö equation (LM-ABS) in comparison with the absolute Cockcroft-Gault (CG) equation and the relative equations, revised Lund-Malmö (LM-REV), MDRD, and CKD-EPI, after converting relative estimates to absolute values, and to analyze change in eGFR classification when absolute instead of relative eGFR was used. Material and Methods A total of 3495 plasma clearance of iohexol to measure GFR (mGFR) served as reference test. Bias, precision, and accuracy (percentage of estimates ±30% of mGFR; P30) were compared overall and after stratification for various mGFR, eGFR, age, and BMI subgroups. Results The overall P30 results of CG/LM-ABS/LM-REV/MDRD/CKD-EPI were 62.8%/84.9%/83.7%/75.3%/75.6%, respectively. LM-ABS was the most stable equations across subgroups and the only equation that did not exhibit marked overestimation in underweight patients. For patients with relative eGFR 30-44 and 45-59 mL/min/1.73 m2, 36% and 58% of men, respectively, and 24% and 32% of women, respectively, will have absolute eGFR values outside these relative eGFR intervals. Conclusion Choosing one equation to estimate GFR prior to contrast medium examinations, LM-ABS may be preferable. Unless absolute instead of relative eGFR are used, systematic inaccuracies in assessment of renal function may occur in daily routine and research on CM nephrotoxicity may be flawed. [ABSTRACT FROM AUTHOR]

Objective: The NH(2)-terminal portion of the precursor of brain natriuretic peptide (Nt-proBNP) has been reported to be elevated in left ventricular dysfunction. This peptide is a split product from the proBNP molecule, and its level in the circulation is not, as the mature BNP peptide, dependent on the peripheral number of BNP receptors. We aimed to test the hypothesis that asymptomatic left ventricular dysfunction (ALVD), as estimated by Nt-proBNP, would be more prevalent in patients with type 2 diabetes without overt cardiovascular disease in comparison with matched control subjects.Research Design and Methods: The study population consisted of 253 patients with type 2 diabetes and 230 matched control subjects aged 40-70 years without any overt heart disease from primary care centers in Western Finland and Southern Sweden. Nt-proBNP was measured in plasma by competitive enzyme immunosorbent assay.Results: Patients with type 2 diabetes were shown to have higher Nt-proBNP values (360.9 pmol/l [262.6-467.9]) than control subjects (302.7 pmol/l [215.4-419.2]) (P < 0.001). Nt-proBNP levels were independently related to diabetes after adjustment for age, sex, systolic and diastolic blood pressure, BMI, heart rate, drug treatment, serum creatinine, and cystatin C.Conclusions: Our data suggest that the secretion of Nt-proBNP is increased in type 2 diabetic patients with no overt heart disease, suggesting that type 2 diabetes is associated with a higher prevalence of ALVD than hitherto thought. Nt-proBNP may thus serve as a screening instrument to select patients with type 2 diabetes who could benefit from an echocardiographical examination. [ABSTRACT FROM AUTHOR]

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.)., (Copyright © 2023 Massachusetts Medical Society.)

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.

Shrunken pore syndrome (SPS) is defined by a cystatin C-based estimation of glomerular filtration rate (eGFR CYS ) being less than 60% or 70% of a creatinine-based GFR estimation (eGFR CR ) in the absence of extrarenal influences on cystatin C or creatinine concentrations. SPS has been associated with a substantial increase in mortality or morbidity in all investigated populations. However, in these studies, neither the diagnoses, nor causes of death were described, and only estimated GFR was available. The present study concerns 2781 individuals with measured GFR (mGFR), known diagnoses, and known causes of death during 5.6 years in median. Cox multivariate proportional hazards regression model was used to estimate hazard ratios (HR) for all-cause and cancer, cardiovascular, diabetes or chronic kidney disease (CKD) as cause-specific mortality among patients with SPS. At an eGFR CYS /eGFR CR -ratio <0.70, the adjusted SPS death risk in the total cohort (HR 3.0, 95% CI 2.4-3.7) was clearly higher than that for the other diagnosis groups. In a sub-cohort of 1300 persons with or without diagnosis, but with normal mGFR, the all-cause mortality of SPS was markedly increased (HR 4.1, 95% CI 2.6-6.5). In a sub-cohort of 567 persons with normal mGFR and no diagnosis, the all-cause mortality of SPS was even more increased (HR 7.3, 95% CI 2.3-23). The prevalence of SPS in the total cohort was 23% and in the sub-cohorts 17 and 12%, respectively. As SPS is associated with a high mortality, occurs in the absence of reduced mGFR and albuminuria, it expands the spectrum of kidney disorders.

Background: The recently established international cystatin C calibrator makes it possible to develop non-laboratory specific glomerular filtration rate (GFR) estimating (eGFR) equations. This study compares the performance of the arithmetic mean of the revised Lund-Malmö creatinine and CAPA cystatin C equations (MEANLM-REV+CAPA), the arithmetic mean of the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) creatinine and cystatin C equations (MEANCKD-EPI), and the composite CKD-EPI equation (CKD-EPICREA+CYSC) with the corresponding single marker equations using internationally standardized calibrators for both cystatin C and creatinine., Methods: The study included 1200 examinations in 1112 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 51 mL/min/1.73 m2). Bias, precision (interquartile range, IQR) and accuracy (percentage of estimates ±30% of mGFR; P30) were compared., Results: Combined marker equations were unbiased and had higher precision and accuracy than single marker equations. Overall results of MEANLM-REV+CAPA/MEANCKD-EPI/CKD-EPICREA+CYSC were: median bias -2.2%/-0.5%/-1.6%, IQR 9.2/9.2/8.8 mL/min/1.73 m2, and P30 91.3%/91.0%/91.1%. The P30 figures were about 7-14 percentage points higher than the single marker equations. The combined equations also had a more stable performance across mGFR, age and BMI intervals, generally with P30 ≥90% and never <80%. Combined equations reached P30 of 95% when the difference between eGFRCREA and eGFRCYSC was <10% but decreased to 82% at a difference of ≥40%., Conclusions: Combining cystatin C and creatinine assays improves GFR estimations with P30 ≥90% in adults. Reporting estimates of both single and combined marker equations in clinical settings makes it possible to assess the validity of the combined equation based on the agreement between the single marker equations.

Background: The performance of creatinine-based glomerular filtration rate (GFR) estimating equations may vary in subgroups defined by GFR, age and body mass index (BMI). This study compares the performance of the Modification of Diet in Renal Disease (MDRD) study and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations with the revised Lund-Malmö equation (LM Revised), a new equation that can be expected to handle changes in GFR across the life span more accurately., Methods: The study included 3495 examinations in 2847 adult Swedish patients referred for measurement of GFR (mGFR) 2008-2010 by plasma clearance of iohexol (median 52 mL/min/1.73 m²). Bias, precision [interquartile range (IQR)] and accuracy [percentage of estimates ±10% (P₁₀) and ±30% (P₃₀) of mGFR] were compared., Results: The overall results of LM Revised/MDRD/CKD-EPI were: median bias 2%/8%/11%, IQR 12/14/14 mL/min/1.73 m², P₁₀ 40%/35%/35% and P₃₀ 84%/75%/76%. LM Revised was the most stable equation in terms of bias, precision and accuracy across mGFR, age and BMI intervals irrespective of gender. MDRD and CKD-EPI overestimated mGFR in patients with decreased kidney function, young adults and elderly. All three equations overestimated mGFR and had low accuracy in patients with BMI <20 kg/m², most pronounced among men., Conclusions: In settings similar to the investigated cohort LM Revised should be preferred to MDRD and CKD-EPI due to its higher accuracy and more stable performance across GFR, age and BMI intervals.

Objective: To compare the recently developed CKD-EPI equation to estimate GFR in adult Swedish-Caucasians with the MDRD equation., Material and Methods: Swedish-Caucasians (N = 850, 376 females; median age 60, range 5-95 years) referred for plasma iohexol-clearance (median 55, range 5-223 mL/min/1.73 m²) constituted the Lund-Malmö Study cohort. Bias, precision (interquartile range, IQR, of the differences between estimated and measured GFR), accuracy expressed as percentage of estimates ±10% (P₁₀) and ±30% (P₃₀) of measured GFR, and classification ability for five GFR stages <15, 15-29, 30-59, 60-89 and ≥90 mL/min/1.73 m² were compared., Results: Overall there were no important differences between the equations; CKD-EPI/MDRD median values of bias +5.4%/+3.4%, IQR both 14 mL/min/1.73 m², P₁₀ 36%/34%, P₃₀ both 80%, and correctly classified GFR stages 68%/67%. P₃₀ for the CKD-EPI equation was substantially higher than for MDRD at GFR ≥90 mL/min/1.73 m² (93% versus 79%). The MDRD equation performed better in the GFR interval 30-89 mL/min/1.73 m², while accuracy was limited for both equations at GFR <30 mL/min/1.73 m² (P(30) <75% in both females and males). The CKD-EPI/MDRD equations caused a +22%/+14% bias in the 18-39 year interval and the MDRD equation a +18% bias ≥80 years. Both equations performed poorly in males with BMI <20 kg/m² (CKD-EPI/MDRD median bias +36%/46%)., Conclusion: Overall the recently developed CKD-EPI equation performed well but was not superior to the MDRD equation. The CKD-EPI equation may be preferred in screenings of general populations and in the elderly. None of the equations appeared reliable among patients with markedly decreased GFR, young adults and underweight males.

Objective: To demonstrate how patients' probability of having chronic kidney disease (CKD) stage 3-5 (measured GFR <60 mL/min/1.73 m(2)) can be predicted from a specific value of estimated glomerular filtration rate (eGFR)., Material and Methods: The probability of CKD stage 3-5 was predicted from a logistic regression model (n = 850) using three different eGFR prediction equations: Lund-Malmö, MDRD and CKD-EPI. Population weighting was used to illustrate how this probability varies in three different populations: original sample (55% true prevalence of CKD stage 3-5), a screening (6.7% prevalence) and a CKD population (84% prevalence)., Results: All three eGFR-equations had high classification ability (area under the receiver-operating-characteristic curve = 97%). The probability of CKD stage 3-5 increased with decreasing eGFR, varied substantially among the populations studied and to some extent between the eGFR-equations. Using the Lund-Malmö equation as illustration, the probability of CKD stage 3-5 is > 90% only when eGFR is <38 mL/min/1.73 m(2) in a screening population, whereas it is > 90% already when eGFR is <51 mL/min/1.73 m(2) in a CKD population. Conversely, the probability of CKD stage 3-5 is <10% if eGFR > 59 mL/min/1.73 m(2) in a screening population, whereas it is <10% only when eGFR is > 88 mL/min/1.73 m(2) in a CKD population., Conclusion: Instead of reporting diagnostic accuracy as sensitivity, specificity, and predictive values, actual eGFR supplemented with the probability that it represents a true GFR <60 mL/min/1.73 m(2) may be more valuable for physicians. Clinical (pre-test) probability in the population must be considered when predicting this probability.

Objective: Diagnostic accuracy of a quantitative diagnostic test at a given numeric cutoff is dependent on the type of population (e.g., chronic, referrals, or screening) under investigation. Simple weighted averages calculated from a single study sample may be used to assess variability in accuracy in different types of populations., Study Design and Setting: We evaluated the accuracy of the 4-variable Modification of Diet in Renal Disease (MDRD) Study equation as a diagnostic test to separate stage 1 and 2 chronic kidney disease (>or=60 mL/min per 1.73 m(2)) from stage 3-5 (<60 mL/min per 1.73 m(2) requiring treatment to prevent progression) in a sample of 850 patients referred for determination of glomerular filtration rate (GFR). Using population weighting, we also estimated the accuracy of the MDRD equation when the GFR distribution typically found in screening situations was mimicked., Results: Estimated diagnostic accuracy of the MDRD equation varied substantially for different population types (sensitivity range 82%-97%, specificity 67%-93%; figures include the original MDRD study)., Conclusions: Reports of diagnostic accuracy should include estimates of the variability of diagnostic accuracy, using different real or tentative population distributions. Population weighting is a useful tool for this purpose.