National Kidney Foundation Laboratory Engagement Working Group Recommendations for Implementing the CKD-EPI 2021 Race-Free Equations for Estimated Glomerular Filtration Rate: Practical Guidance for Clinical Laboratories.

Recognizing that race is a social and not a biological construct, healthcare professionals and the public have called for removal of race in clinical algorithms. In response, the National Kidney Foundation and the American Society of Nephrology created the Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Diseases to examine the issue and provide recommendations. The final report from the Task Force recommends calculating estimated glomerular filtration rate (eGFR) without a race coefficient using the recently published CKD-EPI 2021 creatinine (cr) and creatinine-cystatin C (cr-cys) equations. The Task Force recommends immediately replacing older eGFRcr equations (MDRD Study and CKD-EPI 2009) with the new CKD-EPI 2021 equation. In a 2019 survey by the College of American Pathologists, 23% of 6200 laboratories reporting eGFRcr used an incorrect equation that is not suitable for use with standardized creatinine measurements, 34% used the CKD-EPI 2009 equation and 43% used the MDRD Study 2006 equation re-expressed for standardized creatinine measurement. Rapid transition to using the CKD-EPI 2021 equation is an opportunity for laboratories to standardize to a single equation to eliminate differences in eGFRcr due to different equations used by different laboratories, and to report eGFR without use of race. We provide guidance to laboratories for implementing the CKD-EPI 2021 equations for both eGFRcr and eGFRcr-cys.

The Relationship Between Circulating Acetaminophen-Protein Adduct Concentrations and Alanine Aminotransferase Activities in Patients With and Without Acetaminophen Overdose and Toxicity.

INTRODUCTION: Measurement of serum acetaminophen-protein adducts (APAP-CYS) has been suggested to support or refute a diagnosis of acetaminophen (APAP)-induced hepatotoxicity when ingestion histories are unreliable or unavailable and when circulating APAP concentrations are low or undetectable. Non-APAP overdose patients commonly have used APAP products in non-toxic quantities and, thus, will have measurable APAP-CYS concentrations, even when hepatic injury results from other causes, such as ischemic hepatitis. The relationship between alanine aminotransferase (ALT) activity and APAP-CYS concentration might assist in distinguishing between toxic and non-toxic APAP doses in patients suspected of drug overdose. METHODS: We measured serial levels of serum APAP-CYS and ALT activities in 500 overdose patients in whom APAP toxicity was suspected on inpatient admission, but who were then classified at time of discharge and before results of APAP-CYS concentrations were available into three groups: 1) definite APAP group; 2) definitely not APAP group; and 3) indeterminate group. Subjects in the definite and definitely not APAP groups were selected in whom a plasma ALT activity was measured within ± 4 h of a serum APAP-CYS concentration. Regressions with correlation coefficients between APAP-CYS and ALT were calculated for repeat measures in the 335 subjects (908 blood samples) in the definite APAP group and 79 subjects (231 samples) in the definitely not APAP group, with an emphasis on APAP-CYS concentrations and calculation of 95% prediction intervals when ALT was ≥ 1000 IU/L. RESULTS: A strong correlation was found between APAP-CYS and ALT in the definite APAP group over all ALT activities (r = 0.93, p < 0.001; N = 335), and when ALT was > 1000 IU/L (r = 0.82, p < 0.001, N = 144). In the 79 definitely not APAP subjects, no significant correlation was found when ALT exceeded 1000 IU/L (r = 0.04; p = 0.84, N = 32). All subjects in the definitely not APAP group displayed APAP-CYS concentrations < 3 µM. In definitely not APAP subjects, the great majority of APAP-CYS levels were below the 95% prediction interval for APAP-CYS concentrations in definite APAP group subjects when ALT was ≥ 1000 IU/L. However, some definitely not APAP group subjects who had ingested non-toxic doses of APAP displayed APAP-CYS concentrations as high as 2.8 µM in the face of ALT elevation from ischemic hepatitis. CONCLUSION: The interpretation of serum APAP-CYS concentrations must always be made in light of detailed clinical information and the population being tested, especially because of some overlap in APAP-CYS levels in subjects with and without APAP toxicity.

Legal Blood Alcohol Testing in the U.S. Military.

OBJECTIVE: To retrospectively analyze multiple years of legal blood alcohol test (LBAT) results as part of a laboratory process improvement plan. METHODS: We analyzed the LBAT requests received by the Brooke Army Medical Center during calendar years 2013 and 2014. RESULTS: We received 365 samples from 11 installations; 351 were tested and 14 were rejected. Nearly one-third of the tested samples had negligible ethanol levels. One installation was responsible for submitting 10 rejected samples which prompted laboratory intervention. CONCLUSION: The ability to perform timely LBATs is invaluable to the Department of Defense as the results are more readily accepted in a court of law than routine clinical ethanol test results.

An unexpected emergency request for glucose-6-phosphate dehydrogenase testing in a 9-year-old African American boy.

PATIENT: 9-year-old African American male. CHIEF COMPLAINT: Recently diagnosed with acute lymphoblastic leukemia (ALL) after investigation into a large anterior mediastinal mass causing airway compression. HISTORY OF PRESENT ILLNESS: The day before the unexpected urgent glucose-6-phosphate dehydrogenase (G6PD) request, the patient was diagnosed with an aggressive form of leukemia and a significant tumor mass causing airway compression. A computed tomography (CT) scan indicated potential renal involvement. Based on this information and the size of the mass, the patient was referred for immediate chemotherapy. However, there was a concern that he could develop tumor lysis syndrome (TLS) during treatment. To avoid this condition, the pediatric intensive care unit (ICU) sought to pretreat the child with rasburicase, which led to the emergency G6PD request. PREVIOUS MEDICAL HISTORY: Unknown. FAMILY HISTORY: Largely unknown, but no apparent chronic diseases. PHYSICAL EXAMINATION FINDINGS: Three weeks of progressively worsening lymphadenopathy, coughing, night sweats, mild hepatosplenomegaly, and breathing difficulty when supine. The patient arrived at the medical center for airway management and had a temperature of 36.1°C; blood pressure, 120/87 mmHg; pulse, 115 bpm; respiratory rate, 22 breaths per minute, with labored breathing but normal O(2) saturation while upright and awake, in room air. PRINCIPLE LABORATORY FINDINGS: Table 1.

Effects of atrazine on sexual maturation in female Japanese quail induced by photostimulation or exogenous gonadotropin.

The herbicide atrazine has gained recent attention for its reported effects on reproduction in amphibians. The present study examined the putative effects of atrazine during sexual maturation in the photostimulated female Japanese quail. Furthermore, the effects of atrazine on birds administered exogenous gonadotropin (pregnant mare serum gonadotropin [PMSG]) were investigated. Atrazine was administered up to 1,000 ppm in the diet to female quail undergoing photoperiodically induced sexual maturation. At high dietary concentrations, atrazine exhibits signs of overt toxicity with reductions in growth, feed intake, and liver weights, but these effects were dependent on the timing of treatment administration. Atrazine did not influence the weights of reproductive tissues (ovary and oviduct) or circulating concentrations of luteinizing hormone (LH). However, high concentrations of atrazine depressed circulating concentrations of estradiol. Treatment with atrazine for four weeks during sexual maturation inhibited growth but did not affect any other parameter assessed (feed intake, liver, ovary, or oviduct weights or the circulating concentrations of LH and estradiol). In birds receiving daily injections of PMSG, atrazine reduced growth, feed intake, and liver weights. However, PMSG-induced gonadal and oviduct growth was not affected by atrazine. The present results suggest that dietary atrazine exhibits limited reproductive toxicity in female quail during sexual maturation and only at concentrations above ecological relevance.

Atrazine and the hypothalamo-pituitary-gonadal axis in sexually maturing precocial birds: studies in male Japanese quail.

The herbicide atrazine is a putative endocrine disruptor. The present studies investigated the effects of atrazine in male Japanese quail during sexual maturation. Atrazine was administered for two weeks in the diet or systemically to birds under long photoperiods. Atrazine had no effect on mortality but depressed both feed intake and growth (average daily gain [ADG] in g/day) at dietary concentrations of 1000 ppm. Atrazine in the diet at 10 ppm, but at no other concentrations, increased testes weight and gonadal-somatic-index and decreased the seminiferous tubule diameter-to-testis weight ratio. However, there were no effects on absolute tubule diameter, relative stage of testicular development, or the presence of a lumen. Atrazine in the diet at 1000 ppm increased circulating concentrations of testosterone but this effect was not observed consistently in all studies. Dietary atrazine at 10 ppm increased circulating concentrations of estradiol. Moreover, in one study, atrazine at 1000 ppm in the diet decreased circulating concentrations of luteinizing hormone. Atrazine administered systemically exerted no effect on indices of growth or reproduction. Atrazine did not mimic the effects of either estradiol or tamoxifen in male quail; thus, atrazine did not exhibit overt estrogenic or anti-estrogenic activity. Conversely, atrazine augmented the effects of testosterone and estradiol on testis regression, presumably by increasing the negative-feedback effects of these sex-steroids on follicle stimulating hormone secretion. It is concluded that atrazine up to 1000 ppm in the diet may exert some effects on reproductive development in sexually maturing male birds, but these are inconsistent and modest.