The Number of Episodes of Subtherapeutic Tacrolimus Blood Level Is Independently Associated With Reduced Kidney Graft Survival.

BACKGROUND: Tacrolimus blood level variability is associated with reduced graft survival among kidney transplant recipients. To date, no practical approach for reducing variability has been validated. We defined specific tacrolimus blood level patterns correlated with variability and evaluated their independent association with reduced graft survival. METHODS: In this single-center retrospective study, we predefined 12 patterns that exhibited correlation with high tacrolimus blood level variability. Subsequently, we utilized a multivariate Cox proportional hazard model, in conjunction with the Akaike information criteria, to evaluate the association between the predefined patterns and decreased graft survival. RESULTS: Our cohort included 1305 kidney transplant recipients. The primary outcome of this trial was graft loss, defined as the initiation of chronic dialysis or the need for retransplantation. The secondary outcome was the combination of death-censored graft loss and death with a functioning graft. During the study's follow-up period, there were 131 events of graft loss. The number of episodes of subtherapeutic tacrolimus level during the first-year posttransplantation was significantly associated with graft loss (HR 1.208 per episode, 95% CI 1.075-1.356, p = 0.001) and significantly improved the relative likelihood of the model compared to the multivariate model as demonstrated by the delta AIC value (8.256, p = 0.016). CONCLUSION: In addition to increased tacrolimus blood level variability, the number of episodes of subtherapeutic tacrolimus levels is independently associated with decreased graft survival among kidney transplant recipients.

Acute Kidney Injury and Hair-Straightening Products: A Case Series.

RATIONALE & OBJECTIVE: Keratin-based hair-straightening treatment is a popular hair-styling method. The majority of keratin-based hair-straightening products in Israel contain glycolic acid derivatives, which are considered safe when used topically. Systemic absorption of these products is possible, and anecdotal reports have described kidney toxicity associated with their use. We report a series of cases of severe acute kidney injury (AKI) following use of hair-straightening treatment in Israel during the past several years. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: We retrospectively identified 26 patients from 14 medical centers in Israel who experienced severe AKI and reported prior treatment with hair-straightening products in 2019-2022. FINDINGS: The 26 patients described had a median age of 28.5 (range, 14-58) years and experienced severe AKI following a hair-straightening procedure. The most common symptoms at presentation were nausea, vomiting, and abdominal pain. Scalp rash was noted in 10 (38%) patients. Two patients experienced a recurrent episode of AKI following a repeat hair-straightening treatment. Seven patients underwent kidney biopsies, which demonstrated intratubular calcium oxalate deposition in 6 and microcalcification in tubular cells in 1. In all biopsies, signs of acute tubular injury were present, and an interstitial infiltrate was noted in 4 cases. Three patients required temporary dialysis. LIMITATIONS: Retrospective uncontrolled study, small number of kidney biopsies. CONCLUSIONS: This series describes cases of AKI with prior exposure to hair-straightening treatments. Acute oxalate nephropathy was the dominant finding on kidney biopsies, which may be related to absorption of glycolic acid derivatives and their metabolism to oxalate. This case series suggests a potential underrecognized cause of AKI in the young healthy population. Further studies are needed to confirm this association and to assess the extent of this phenomenon as well as its pathogenesis.

Absence of hemoglobin increase is associated with reduced graft survival after kidney transplantation.

BACKGROUND: Anemia is prevalent following kidney transplantation and is associated with reduced graft survival. The association between temporal changes in hemoglobin (Hb) level at the early post-transplant period and graft survival is unknown. PATIENTS AND METHODS: The study cohort included consecutive patients included in a single center transplantation registry between January 2002 and December 2016. Temporal changes in Hb values during the first 90 days after the transplantation were evaluated by piecewise linear regression model. Significant Hb increase rate was defined as an increase of .5 gram/deciliter/month. Patients were divided into groups according to the presence of significant Hb increase. The primary outcome was death-censored graft failure. RESULTS: Of 946 patients included in the study cohort, 831 (87.8%) had at least one interval of Hb increase, and 115 (12.2%) had no Hb increase. The absence of Hb increase was associated with an elevated risk of death censored graft failure by univariate (HR 2.9, 95% CI 1.88-4.49, P < .001) and multivariate (HR 2.47, 95% CI 1.48-4.12, P = .001) analyses. The timing and rate of Hb increase had no association with the main outcome. CONCLUSIONS: Lack of Hb increase during the early post-transplant period is associated with an increased risk of graft loss.

Alarming increase in ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes during the first wave of the COVID-19 pandemic in Israel.

OBJECTIVE: To evaluate the incidence and severity of ketoacidosis (DKA) at type 1 diabetes diagnosis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic in Israel. RESEARCH DESIGN AND METHODS: A population-based study the product of a national collaboration of Israeli pediatric diabetes centers investigated the presentation of childhood-onset type 1 diabetes. The frequencies of DKA and severe DKA observed during the COVID-19 period from March 15, 2020 (commencement of the first nationwide lockdown) until June 30, 2020 were compared with the same periods in 2019, 2018, and 2017 using multivariable logistic regression, adjusting for age, sex, and socioeconomic position. RESULTS: During the COVID-19 period, DKA incidence was 58.2%, significantly higher than in 2019 (adjusted OR [aOR] 2.18 [95% CI, 1.31-3.60], P = 0.003); 2018 (aOR 2.05 [95% CI, 1.26-3.34], P = 0.004); and 2017 (aOR, 1.79 [95% CI, 1.09-2.93], P = 0.022). The incidence of severe DKA was 19.9%, significantly higher than in 2018 (aOR, 2.49 [95% CI, 1.20-5.19], P = 0.015) and 2017 (aOR, 2.73 [95% CI, 1.28-5.82], P = 0.009). In 2020, admissions and duration of stay in the intensive care unit were higher than in previous years (P = 0.001). During the COVID-19 pandemic, children aged 6-11 years had higher incidences of DKA (61.3% vs. 34.0%, 40.6%, and 45.1%, respectively, P = 0.012), and severe DKA (29.3% vs. 15.1%, 10.9%, and 5.9%, respectively, P = 0.002). CONCLUSIONS: The dramatic increase in DKA at presentation of childhood-onset type 1 diabetes during the COVID-19 pandemic mandates targeted measures to raise public and physician awareness.

Risk Factors and Outcome of Polymicrobial Bacteremia: A Retrospective Cohort Study.

BACKGROUND: Recent data regarding polymicrobial bacteremia (PMB) are lacking. OBJECTIVES: To characterize risk factors as well as clinical, microbiological, and prognostic patterns of patients with PMB in a modern hospital setting. METHODS: A single center retrospective study including all patients diagnosed with PMB during 2013 was conducted. PMB was defined as two or more organisms cultured from the blood of the same patient within 72 hours. Patients with monomicrobial infections served as controls. RESULTS: There were 135 episodes (2% of all bacteremia episodes) of true PMB among 123 patients during the study period. Recent invasive procedures (odds ratio [OR] 3.59, 95% confidence interval [95%CI] 1.41-9.12, P = 0.006) and foreign bodies (OR 1.88, 95%CI 1.06-3.33, P = 0.04) were risk factors for PMB when compared with 79 patients with monomicrobial bacteremia. Central-line-associated infections were the most common infection source among patients with PMB (n=34, 28%). Enterobacteriaceae were the most commonly implicated pathogen (n=95, 77%). Non-fermenting Gram-negative bacilli were significantly more common than previously reported (n=55, 45%). Although crude 30-day mortality was higher (48% vs. 33%) in PMB patients, adjusted mortality was comparable in the two groups. CONCLUSIONS: PMB rate in our cohort was considerably lower than in previous reports. Central-line-associated infections were more common than classic PMB sources. Mortality remained high. Strategies for early identification and better care for these patients should be pursued.

Acute Kidney Injury and Long-Term Risk for Cardiovascular Events in Patients after Kidney Transplantation.

BACKGROUND: Acute kidney injury (AKI) was found to be associated with an increased risk of major adverse cardiovascular events (MACE) in the general population. Patients after kidney transplantation are prone to AKI events and are also at an increased risk of cardiovascular (CV) disease. The association between AKI and MACE in kidney transplant patients is yet to be studied. METHODS: This retrospective single-center cohort study reviewed 416 adult renal allograft recipients transplanted between 2005 and 2010. AKI events were recorded starting 2 weeks after transplantation, or following discharge with a functioning graft. AKI was defined, according to the KDIGO criteria. The primary outcome was the composite of MACE starting 6 months after transplantation and all-cause mortality. For survival analysis, we used univariate and multivariate time varying Cox proportional hazard model. RESULTS: One hundred and twenty-four patients (29.8%) had at least one episode of AKI. During the median follow-up time of 7.2 years (interquartile range 4.3-9.1), 144 outcome events occurred. By time varying Cox regression analysis, AKI was associated with an increased rate of CV outcomes or death (hazard ratio [HR] 1.96, 95% CI 1.36-2.81, p < 0.001), and the association remained significant by multivariate adjusted model (HR 1.76, 95% CI 1.18-2.63, p = 0.005). As for the different components of MACE, all-cause mortality and CV mortality were the only outcomes that were significantly associated with AKI. No interaction between AKI timing and MACE was found. CONCLUSION: AKI in kidney transplant recipient is associated with an increased risk of CV disease.

Two-year follow-up of the effectiveness of a multifaceted intervention to improve adherence to annual colorectal cancer screening in community health centers.

PURPOSE: We previously found that a multifaceted outreach intervention achieved 82 % annual adherence to colorectal cancer (CRC) screening with fecal occult blood testing (FOBT). This study assessed adherence to FOBT after a second outreach. METHODS: We followed 225 patients in community health centers in Chicago, Illinois, who were randomized to the intervention group. Our primary analysis focused on 124 patients who completed FOBT during the first outreach and were due again for annual FOBT; 90% were Latino, 87% preferred to speak Spanish, and 77% were uninsured. Second outreach consisted of (1) a mailed reminder letter, a free fecal immunochemical test (FIT) with postage-paid return envelope, (2) automated phone and text messages, (3) automated reminders 2 weeks later if the FIT was not returned, and (4) a telephone call after 3 months. Our main outcome was completion of FIT within 6 months of the due date. We also analyzed the proportion of the original 225 patients who were fully screened for CRC over the 2-year study period. RESULTS: A total of 88.7% of patients completed a FIT within 6 months of their second outreach. Over the 2 years since the first outreach, 71.6% of the 225 patients assigned to the intervention group were fully up to date on CRC screening, another 11.1% had been screened suboptimally, and 17.3% were inadequately screened or not screened. CONCLUSIONS: It is possible to achieve high rates of CRC screening over a 2-year period for vulnerable populations using outreach with FIT as a primary strategy.

Comparative Effectiveness of Multifaceted Outreach to Initiate Colorectal Cancer Screening in Community Health Centers: A Randomized Controlled Trial.

INTRODUCTION: Colorectal cancer (CRC) screening rates are low among vulnerable populations. Fecal immunochemical tests (FITs) are one screening modality with few barriers. Studies have shown that outreach can improve CRC screening, but little is known about its effectiveness among individuals with no CRC screening history. We sought to determine whether outreach increases FIT uptake among patients with no CRC screening history compared to usual care. METHODS: This study was a patient-level randomized controlled trial, including 420 patients who had never completed CRC screening and were eligible for FIT; 66% were female, 62.1% were Latino, and 70.7% were uninsured. The main outcome measure was FIT completion within 6 months of the randomization date. We assessed FIT completion at different time points corresponding to receipt of outreach components. All analyses were re-run with 12-month data. RESULTS: Patients who received outreach were more likely to complete FIT than those in usual care (36.7% vs. 14.8%; p < 0.001). FIT completion was more common among patients with increased clinic visits. The difference in FIT completion between the outreach and usual care groups decreased over time. DISCUSSION: The intervention improved FIT uptake among patients with no CRC screening history. However, the intervention was less effective than in a previous trial targeting patients due for repeat screening. Additional research is needed to determine the best methods for improving CRC screening among this hard-to-reach group.

The effect of implementing a dialysis start unit on modality decision among patients with unplanned start kidney replacement therapy.

INTRODUCTION: Many individuals start dialysis in an acute setting with suboptimal pre-dialysis education. These individuals are often treated with central venous catheter insertion and initiation of in-center hemodialysis and only a minority will transfer to a home-based therapy. The dialysis start unit is a program performing in-center hemodialysis in a separate space while providing support and education on chronic kidney disease and treatment options in the initial weeks of kidney replacement therapy. We aimed to assess the uptake of home dialysis therapies between 2013 and 2021 among patients who started acute inpatient hemodialysis at University Health Network, Toronto and underwent dialysis at the dialysis start unit. METHODS: This is a retrospective observational cohort study based on prospectively collected data. Patients' demographics were obtained from electronic charts. In the dialysis start unit, all patients received dialysis modality education by a nurse educator, dedicated home dialysis nurses, and the allied health care team. FINDINGS: During 2013-2021, 122 patients were dialyzed in the dialysis start unit and included in the study. Among those patients, 68 patients ultimately chose home dialysis (57 peritoneal dialysis and 11 home hemodialysis). Fifty-four patients continued in-center hemodialysis. Patients adopting home dialysis were less likely to have diabetes and hypertension as the etiology of kidney failure and more likely to have glomerulonephritis or vasculitis. DISCUSSION: Dialysis modality education is implementable in advanced chronic kidney disease. Individualized education and care after unplanned start dialysis can potentially enhance home dialysis choice and utilization.

Design of a randomized controlled trial to assess the comparative effectiveness of a multifaceted intervention to improve adherence to colorectal cancer screening among patients cared for in a community health center.

BACKGROUND: Colorectal cancer (CRC) is common and leads to significant morbidity and mortality. Although screening with fecal occult blood testing (FOBT) or endoscopy has been shown to decrease CRC mortality, screening rates remain suboptimal. Screening rates are particularly low for people with low incomes and members of underrepresented minority groups. FOBT should be done annually to detect CRC early and to reduce CRC mortality, but this often does not occur. This paper describes the design of a multifaceted intervention to increase long-term adherence to FOBT among poor, predominantly Latino patients, and the design of a randomized controlled trial (RCT) to test the efficacy of this intervention compared to usual care. METHODS: In this RCT, patients who are due for repeat FOBT are identified in the electronic health record (EHR) and randomized to receive either usual care or a multifaceted intervention. The usual care group includes multiple point-of-care interventions (e.g., standing orders, EHR reminders), performance measurement, and financial incentives to improve CRC screening rates. The intervention augments usual care through mailed CRC screening test kits, low literacy patient education materials, automated phone and text message reminders, in-person follow up calls from a CRC Screening Coordinator, and communication of results to patients along with a reminder card highlighting when the patient is next due for screening. The primary outcome is completion of FOBT within 6 months of becoming due. DISCUSSION: The main goal of the study is to determine the comparative effectiveness of the intervention compared to usual care. Additionally, we want to assess whether or not it is possible to achieve high rates of adherence to CRC screening with annual FOBT, which is necessary for reducing CRC mortality. The intervention relies on technology that is increasingly widespread and declining in cost, including EHR systems, automated phone and text messaging, and FOBTs for CRC screening. We took this approach to ensure generalizability and allow us to rapidly disseminate the intervention through networks of community health centers (CHCs) if the RCT shows the intervention to be superior to usual care. TRIAL REGISTRATION: ClinicalTrials.gov NCT01453894.

Plasma porphyrins among end stage renal disease patients and cutaneous symptoms- is there still an association?

Introduction: Several abnormalities of porphyrin metabolism leading to Porphyria Cutanea Tarda (PCT) have been described in early studies of End Stage Renal Disease (ESRD) patients, with a reported prevalence of 5-18%. We aimed to evaluate porphyrin levels and correlation to skin manifestations in modern dialysis era. Methods: The study cohort included adult hemodialysis patients from a single center tertiary medical center. All patients underwent a full skin examination, completed the Dermatology Life Quality Index questioner, and provided a blood sample for porphyrin levels assessment. Results: A total of 94 adult hemodialysis patients were recruited to the study. No clinical PCT was diagnosed. Porphyrin levels did not correlate with any clinical or dialysis quality parameters. Conclusions: In modern hemodialysis era, possibly due to improved porphyrins' metabolism and dialysis removal, PCT is much less prevalent among hemodialysis patients than previously reported in the past.

Change in Kidney Function and 2-Year Mortality After Transcatheter Aortic Valve Replacement.

Importance: Chronic kidney disease (CKD) is prevalent in the population of patients undergoing transcatheter aortic valve replacement (TAVR). Data on the association of TAVR with kidney function are scarce, as are data on the relationship between changes in kidney function after TAVR and mortality. Objective: To describe the changes in kidney function (both periprocedural and at steady state) after TAVR and to explore the association of TAVR with midterm mortality. Design, Setting, and Participants: This single-center, retrospective cohort study was conducted at a public, tertiary academic medical center, which serves as a regional referral center for valvular heart interventions. Consecutive cases of patients undergoing TAVR from November 5, 2008, to December 31, 2019, were included in the study, with available baseline and post-TAVR data on kidney function. Exposures: Steady state (1 month) change in kidney function after TAVR. Significant improvement or deterioration in renal function was defined as a greater than or equal to 10% change in estimated glomerular filtration rate (eGFR). Main Outcomes and Measures: Overall mortality at 2-year follow-up. Results: A total of 894 patients (mean [SD] age, 82.2 [7.1] years; 452 women ([51.2%]) were evaluated. A total of 362 patients (40.5%) were treated from 2017 to 2019, 348 patients (38.9%) were treated from 2013 to 2016, and 184 patients (20.5%) were treated from 2008 and 2012. Patients had a mean (SD) Society of Thoracic Surgeons (STS) score of 5.2% (4.0%) and a mean (SD) eGFR of 65.1 (23.1) mL/min/1.73 m2. Acute kidney injury occurred in 115 (11.1%) patients by 48 hours, of whom 73 (63.5%) resolved by discharge. One month after TAVR, eGFR improved by at least 10% in 329 patients (36.8%) and deteriorated by at least 10% in 233 patients (26.1%). Overall, CKD stage remained stable or improved in 720 patients (80.6%), and only 5 patients (0.97%) progressed to stage 5 CKD 1 month after TAVR. A deterioration of 10% or greater in eGFR 1 month after TAVR was associated with a hazard ratio of 2.16 (95% CI, 1.24-5.24; P = .04) at 2-year mortality. Patients who showed CKD status resolution (eGFR improvement to >60 mL/min/1.73 m2 after TAVR) had a similar 2-year mortality to those with baseline eGFR greater than 60 mL/min/1.73 m2 and vice versa. Factors associated with steady state CKD status resolution after TAVR included lower STS score, higher left ventricular ejection fraction, higher baseline eGFR, no acute kidney injury at discharge from the TAVR admission, and lower contrast-eGFR ratio. Conclusions and Relevance: In this cohort study, kidney outcomes after TAVR were reassuring; greater than 80% of patients showed stable or improved kidney function 1 month after the procedure. Improvement in kidney function was associated with a lower 2-year mortality, whereas deterioration in kidney function was associated with increased mortality. Our data suggest that cardiorenal syndrome was a possible cause of CKD in patients in need of TAVR and that there was potential for improvement in both renal and cardiac function after this procedure.