Automated laboratory reporting of estimated glomerular filtration rate: is it good for the health of patients and their doctors?

Koncentracija kreatinina u serumu je nepouzdan i neosjetljiv biljeg kronične bolesti bubrega (engl. chronic kidney disease, CKD). Kako bi poboljšali otkrivanje CKD mnogi europski i sjevernoamerički laboratoriji te svi australoazijski laboratoriji izračunavaju i u nalazu ispisuju procijenjenu brzinu glomerularne filtracije (engl. estimated glomerular filtration rate, eGFR) primjenjujući formulu MDRD (engl. Modification ofDiet in Renal Disease, MDRD) kod svakog zahtjeva za određivanje koncentracije kreatinina u serumu. Cilj ovog rada je pružanje pravovremene informacije kliničkim kemičarima o snazi, slabostima te dostupnim dokazima o ulozi automatiziranih laboratorijskih nalaza eGFR u otkrivanju CKD. Točnost i preciznost eGFR su prihvatljivi za većinu odraslih osoba kod kojih su izračunane vrijednosti 60 mL/min/1,73 m2 te kod djece). U ovom se radu također raspravlja o odlukama koje su povezane eGFR, a tiču se kliničkih postupaka, indikacija za upućivanje nef rologu, važnosti standardizacije određivanja kreatinina, te uloge eGFR u odluci o doziranju lijeka. Zaključno, automatizirani laboratorijski nalazi eGFR povećati će rano otkrivanje CKD te omogućiti pravovremeno određivanje odgovarajućih renalno- i kardioprotektivnih terapija, kao i pružiti bolje informacije kod odlučivanja o propisivanju lijekova koji se izlučuju bubregom.Serum creatinine concentration is an unreliable and insensitive marker of chronic kidney disease (CKD). To improve CKD detection, many European and North American laboratories and all Australasian laboratories calculate and report an estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) formula with every request for serum creatinine concentration. The aim of this paper is to provide timely information to Clinical Chemists about the strengths, weaknesses and available evidence for the role of automated laboratory reporting of eGFR in CKD detection. The accu-racy and precision of eGFRs is reasonable in most adults in whom calculated values are 60 mL/min/1.73 m2 and children). This paper also discusses eGFR-related decision points for clinical actions, the indications for nephrologist referral, the importance of creatinine assay standardisation and the role of eGFR in drug dose decision-making. In conclusion, automatic laboratory reporting of eGFR will enhance early detection of CKD, allow the timely institution of appropriate reno- and cardioprotective therapies, and better inform decisions regarding the pres-cription of renally excreted medications

Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial)

Background: The main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin (R) ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet (R))

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Data quality of the Australia and New Zealand dialysis and transplant registry: A pilot audit

Aim: Most clinical registries in Australia, including the Australia and New Zealand Dialysis and Transplant Registry (ANZDATA), do not audit submitted data. Inaccurate data can bias registry analysis. This study aimed to audit data submitted to ANZDATA from a single region. Methods: A retrospective audit of individual haemodialysis patient data recorded by ANZDATA at 31 December 2009 was completed by nephrologists in a blinded fashion. Original data were recorded by nursing staff. Patients received treatment at a public hospital, two affiliated satellite haemodialysis units, and three private haemodialysis units. Results: Fifty-one audits were completed of a total 175 patients (29.1%) undertaking haemodialysis in 2009. Primary renal disease was correct in 86.3% (95%CI: 74.3-93.2), although errors in type of glomerulonephritis were common. Date of first dialysis (± 1-month error margin) was correct for 93.6%. Creatinine at first dialysis (± 10% error margin) was correct in 74.4%. Baseline comorbidity accuracy included: peripheral vascular disease (sensitivity 36.4% (95%CI: 24.6-50.1), specificity 82.8% (95%CI: 70.2-90.7)), ischaemic heart disease (sensitivity 69.2% (95%CI: 55.6-80.2), specificity 88.0% (95%CI: 76.3-94.3)), chronic lung disease (sensitivity 25.0% (95%CI: 15.2-38.3), specificity 93.6% (95%CI: 83.4-97.7)), diabetes (sensitivity 86.4% (95%CI: 74.4-93.2), specificity 96.6% (95%CI: 87.5-99.1)), cerebrovascular disease (sensitivity 75.0% (95%CI: 61.7-84.8), specificity 95.3% (95%CI: 85.8-98.6)), and ever smoked (sensitivity 83.3% (95%CI: 70.3-91.4), specificity 71.4% (95%CI: 57.3-82.3)). Non-melanoma skin cancer was under-reported and inaccurate. Conclusion: Data accuracy was favourable compared with other renal registry validation studies. Data accuracy may be improved by education and training of collectors. A larger audit is necessary to validate ANZDATA

Urine and serum midkine levels in an Australian chronic kidney disease clinic population: an observational study

Background and objectives The cytokine midkine (MK) is pathologically implicated in progressive chronic kidney disease (CKD) and its systemic consequences and has potential as both a biomarker and therapeutic target. To date, there are no published data on MK levels in patients with different stages of CKD. This study aims to quantify MK levels in patients with CKD and to identify any correlation with CKD stage, cause, progression, comorbid disease or prescribed medication