Estimating Analytical Errors of Glomerular Filtration Rate Measurement.

BACKGROUND: Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated. METHODS: We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements. RESULTS: GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 2.6-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software. CONCLUSIONS: We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty.

Long-term Transplant Function After Thrombolytic Treatment Ex Vivo of Donated Kidneys Retrieved 4 to 5 H After Circulatory Death.

BACKGROUND: Using a novel thrombolytic technique, we present long-term transplant function, measured by creatinine and iohexol clearance, after utilizing kidneys from porcine donors with uncontrolled donation after circulatory deaths, with 4.5-5 h of warm ischemia. METHODS: Pigs in the study group were subjected to simulated circulatory death. After 2 h, ice slush was inserted into the abdomen and 4.5 h after death, the kidneys were retrieved. Lys-plasminogen, antithrombin-III, and alteplase were injected through the renal arteries on the back table. Subsequent ex vivo perfusion was continued for 3 h at 15°C, followed by 3 h with red blood cells at 32°C, and then transplanted into pigs as an autologous graft as only renal support. Living-donor recipient pigs that did not receive ex vivo perfusion, and unilateral nephrectomized pigs served as the controls. RESULTS: Pigs in the study group (n = 13), surviving 10 d or more were included, of which 7 survived for 3 mo. Four animals in the living-donor group (n = 6) and all 5 nephrectomized animals survived for 3 mo. Creatinine levels in the plasma and urine, neutrophil gelatinase-associated lipocalin levels, Kidney Injury Marker-1 expression, and iohexol clearance at 3 mo did not differ significantly between the study and living-donor groups. Histology and transmission electron microscopy after 3 mo showed negligible fibrosis and no other damage. CONCLUSIONS: The present method salvages kidneys from extended unontrolled donation after circulatory death using thrombolytic treatment while preserving histology and enabling transplantation after ex vivo reconditioning, with clinically acceptable late function after 3 mo, as measured by creatinine and iohexol clearance.

Cardiac troponin T concentrations and patient-specific risk of myocardial infarction using the novel PALfx parameter.

BACKGROUND: Myocardial infarction (MI) is more likely if the heart damage biomarker cardiac troponin T (cTnT) is elevated in a blood sample from a patient with chest pain. There is no conventional method to estimate the risk of MI at a specific cTnT concentration. The purpose of this study was to evaluate the performance of a novel method that converts cTnT concentrations to patient-specific risks of MI. METHODS: Admission cTnT measurements in 15,425 ED patients from three hospitals with a primary complaint of chest pain, with or without a clinical diagnosis of MI, were Box-Cox-transformed to normality density functions to calculate the percentage with MI among patients with a given cTnT concentration, the parametric predictive value among lookalikes (PALfx). The ability of the PALfx to generate stable risk estimates of MI was examined by bootstrapping and expressed as the coefficient of variation (CV). RESULTS: Four age and sex-specific subgroups above or below 60 years of age with distinct cTnT distributions were identified among patients without MI. The cTnT distributions across subgroups with MI were similar, allowing us to use all admissions with MI to calculate the PALfx in the four subgroups. For instance, at a baseline cTnT concentration of 7 ng/L, a female patient <60 years would have a 0.5% risk of MI whereas a male patient >60 years would have a 1.9% risk of MI. To assess the stability of the PALfx method we bootstrapped smaller and smaller subsets of the 15,422 ED visits. We found that 1950 patients without MI and 50 patients with MI were sufficient to limit the variation of the PALfx with a CV of 0.8-5.4%, close to the CV using the entire dataset. The MI risk estimates were similar when data from the three hospitals were used separately to derive the PALfx equations. CONCLUSIONS: The PALfx can be used to estimate the risk of MI at patient-specific cTnT concentrations with acceptable margins of error. The patient-specific risk of disease using the PALfx could complement decision limits.