Impacts of center and clinical factors in antihypertensive medication use after kidney transplantation

Hypertension guidelines recommend calcium channel blockers (CCBs), thiazide diuretics, and angiotensin‐converting‐enzyme inhibitors/angiotensin receptor blockers (ACEi/ARBs) as first‐line agents to treat hypertension. Hypertension is common among kidney transplant (KTx) recipients, but data are limited regarding patterns of antihypertensive medication (AHM) use in this population. We examined a novel database that links national registry data for adult KTx recipients (age > 18 years) with AHM fill records from a pharmaceutical claims warehouse (2007‐2016) to describe use and correlates of AHM use during months 7‐12 post‐transplant. For patients filling AHMs, individual agents used included: dihydropyridine (DHP) CCBs, 55.6%; beta‐blockers (BBs), 52.8%; diuretics, 30.0%; ACEi/ARBs, 21.1%; non‐DHP CCBs, 3.0%; and others, 20.1%. Both BB and ACEi/ARB use were significantly lower in the time period following the 2014 Eighth Joint National Committee (JNC‐8) guidelines (2014‐2016), compared with an earlier period (2007‐2013). The median odds ratios generated from case‐factor adjusted models supported variation in use of ACEi/ARBs (1.51) and BBs (1.55) across transplant centers. Contrary to hypertension guidelines for the general population, KTx recipients are prescribed relatively more BBs and fewer ACEi/ARBs. The clinical impact of this AHM prescribing pattern warrants further study.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154651/1/ctr13803.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154651/2/ctr13803_am.pd

Associations of obesity with antidiabetic medication use after living kidney donation: An analysis of linked national registry and pharmacy fill records

We examined a novel linkage of national US donor registry data with records from a pharmacy claims warehouse (2007‐2016) to examine associations (adjusted hazard ratio, LCLaHRUCL) of post‐donation fills of antidiabetic medications (ADM, insulin or non‐insulin agents) with body mass index (BMI) at donation and other demographic and clinical factors. In 28 515 living kidney donors (LKDs), incidence of ADM use at 9 years rose in a graded manner with higher baseline BMI: underweight, 0.9%; normal weight, 2.1%; overweight, 3.5%; obese, 8.5%. Obesity was associated with higher risk of ADM use compared with normal BMI (aHR, 3.364.596.27). Metformin was the most commonly used ADM and was filled more often by obese than by normal weight donors (9‐year incidence, 6.87% vs 1.85%, aHR, 3.555.007.04). Insulin use was uncommon and did not differ significantly by BMI. Among a subgroup with BMI data at the 1‐year post‐donation anniversary (n = 19 528), compared with stable BMI, BMI increase >0.5 kg/m2 by year 1 was associated with increased risk of subsequent ADM use (aHR, 1.031.482.14, P = .04). While this study did not assess the impact of donation on the development of obesity, these data support that among LKD, obesity is a strong correlate of ADM use.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152001/1/ctr13696_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152001/2/ctr13696.pd

Characterizing Long COVID: Deep Phenotype of a Complex Condition.

BACKGROUND: Numerous publications describe the clinical manifestations of post-acute sequelae of SARS-CoV-2 (PASC or long COVID ), but they are difficult to integrate because of heterogeneous methods and the lack of a standard for denoting the many phenotypic manifestations. Patient-led studies are of particular importance for understanding the natural history of COVID-19, but integration is hampered because they often use different terms to describe the same symptom or condition. This significant disparity in patient versus clinical characterization motivated the proposed ontological approach to specifying manifestations, which will improve capture and integration of future long COVID studies. METHODS: The Human Phenotype Ontology (HPO) is a widely used standard for exchange and analysis of phenotypic abnormalities in human disease but has not yet been applied to the analysis of COVID-19. FINDINGS: We identified 303 articles published before April 29, 2021, curated 59 relevant manuscripts that described clinical manifestations in 81 cohorts three weeks or more following acute COVID-19, and mapped 287 unique clinical findings to HPO terms. We present layperson synonyms and definitions that can be used to link patient self-report questionnaires to standard medical terminology. Long COVID clinical manifestations are not assessed consistently across studies, and most manifestations have been reported with a wide range of synonyms by different authors. Across at least 10 cohorts, authors reported 31 unique clinical features corresponding to HPO terms; the most commonly reported feature was Fatigue (median 45.1%) and the least commonly reported was Nausea (median 3.9%), but the reported percentages varied widely between studies. INTERPRETATION: Translating long COVID manifestations into computable HPO terms will improve analysis, data capture, and classification of long COVID patients. If researchers, clinicians, and patients share a common language, then studies can be compared/pooled more effectively. Furthermore, mapping lay terminology to HPO will help patients assist clinicians and researchers in creating phenotypic characterizations that are computationally accessible, thereby improving the stratification, diagnosis, and treatment of long COVID. FUNDING: U24TR002306; UL1TR001439; P30AG024832; GBMF4552; R01HG010067; UL1TR002535; K23HL128909; UL1TR002389; K99GM145411

Minimal change disease associated with balsalazide therapy for ulcerative colitis

Introduction: 5-aminosalicylic acid (5-ASA) compounds have been used in the management of ulcerative colitis for decades. Nephrotoxicity has been previously described in patients treated with 5-ASA compounds and usually manifests as interstitial nephritis, however a few cases of nephrotic syndrome have been reported. Balsalazide is a pro-drug composed of 5-ASA linked to an inert carrier. Case Presentation: Here we report the case of a 74-year-old man with a history of ulcerative proctosigmoiditis treated with balsalazide who presented to our clinic with bilateral lower extremity edema three months after initiation of balsalazide. Laboratory workup showed nephrotic range proteinuria without an apparent secondary etiology. Given worsening proteinuria and renal function despite cessation of balsalazide, the patient underwent renal biopsy that revealed minimal change disease. High dose steroids were started and complete remission of proteinuria was achieved one month into therapy which was slowly tapered over the next five months. Eventual resolution of edema and return of creatinine back to patient’s baseline level was achieved. Conclusion: To our knowledge, this is the first report of nephrotic syndrome manifesting soon after initiation of balsalazide therapy. Our work highlights the importance of maintaining a high clinical suspicion for nephrotoxicity when using balsalazide

"Association of Severity of Posttraumatic Stress Disorder With Inflammation: Using Total White Blood Cell Count as a Marker".

Inflammation is known to be associated with posttraumatic stress disorder (PTSD). It is not known if total white blood cell (WBC) count, a routinely checked inflammatory marker, is associated with PTSD symptom trajectories using medical record data. We used latent class growth analysis to identify three-year PTSD symptom trajectories using PTSD Checklist (PCL) scores. The outcome for each patient was maximum WBC count from index PTSD diagnosis to last PCL. Using linear regression analysis, we then calculated and compared the average WBC count for each trajectory before and after controlling for age, gender, race, obesity, smoking, diabetes, hypertension, cardiovascular disease, depression and other co-morbid inflammatory conditions. Patients were 40.2 (SD±13.5) years of age, 83.7% male and 67.9% white. We identified three PCL trajectory groups based on symptom severity over time: 'moderate-large decrease', 'moderate severe-slight decrease', and 'severe-persistent'. In adjusted analyses, 'severe-persistent' vs. 'moderate-large decrease' had significantly higher WBC count (B=0.64; 95%CI=0.18, 1.09; p=.006). Although non-significant, 'moderate severe-slight decrease' vs. 'moderate-large decrease' also had a higher WBC count (B=0.42; 95% CI: -0.02, 0.86; p=.061). Persistently severe PTSD is associated with a higher WBC count than improving PTSD. WBC appears to have utility for measuring the association between psychiatric disorders and inflammation in retrospective cohort studies involving large administrative medical record data bases

"Association of Severity of Posttraumatic Stress Disorder With Inflammation: Using Total White Blood Cell Count as a Marker".

Background:Inflammation is known to be associated with posttraumatic stress disorder (PTSD). It is not known if total white blood cell (WBC) count, a routinely checked inflammatory marker, is associated with PTSD symptom trajectories using medical record data. Methods:We used latent class growth analysis to identify three-year PTSD symptom trajectories using PTSD Checklist (PCL) scores. The outcome for each patient was maximum WBC count from index PTSD diagnosis to last PCL. Using linear regression analysis, we then calculated and compared the average WBC count for each trajectory before and after controlling for age, gender, race, obesity, smoking, diabetes, hypertension, cardiovascular disease, depression and other co-morbid inflammatory conditions. Results:Patients were 40.2 (SD±13.5) years of age, 83.7% male and 67.9% white. We identified three PCL trajectory groups based on symptom severity over time: 'moderate-large decrease', 'moderate severe-slight decrease', and 'severe-persistent'. In adjusted analyses, 'severe-persistent' vs. 'moderate-large decrease' had significantly higher WBC count (B=0.64; 95%CI=0.18, 1.09; p=.006). Although non-significant, 'moderate severe-slight decrease' vs. 'moderate-large decrease' also had a higher WBC count (B=0.42; 95% CI: -0.02, 0.86; p=.061). Conclusion:Persistently severe PTSD is associated with a higher WBC count than improving PTSD. WBC appears to have utility for measuring the association between psychiatric disorders and inflammation in retrospective cohort studies involving large administrative medical record data bases

Safety, tolerability, and outcomes of losartan use in patients hospitalized with SARS-CoV-2 infection: A feasibility study

BACKGROUND: Retrospective studies on the use of Renin-Angiotensin-Aldosterone System blockade in patients with Coronavirus Disease 2019 (COVID-19) have been informative but conflicting, and prospective studies are required to demonstrate the safety, tolerability, and outcomes of initiating these agents in hospitalized patients with COVID-19 and hypertension. METHODS AND FINDINGS: This is a single center feasibility study encompassing two cohorts: (1) prospective cohort (April 21, 2020 to May 29, 2020) and (2) retrospective cohort (March 7, 2020 to April 1, 2020) of hospitalized patients with real-time polymerase chain reaction (PCR) positive SARS-CoV-2 by nasopharyngeal swab. Key inclusion criteria include BP > 130/80 and a requirement of supplemental oxygen with FiO2 of 25% or higher to maintain SpO2 > 92%. Key exclusion criteria included hyperkalemia and acute kidney injury (AKI) at the time of enrollment. Prospective cohort consisted of de novo initiation of losartan and continuation for a minimum of 7 days and assessed for adverse events (AKI, hyperkalemia, transaminitis, hypotension) and clinical outcomes (change in SpO2/FiO2 and inflammatory markers, need for ICU admission and mechanical ventilation). Retrospective cohort consisted of continuation of losartan (prior-to-hospitalization) and assessment of similar outcomes. In the prospective cohort, a total of 250 hospitalized patients were screened and inclusion/exclusion criteria were met in 16/250 patients and in the retrospective cohort, a total of 317 hospitalized patients were screened and inclusion/exclusion criteria were met in 14/317 patients. Most common adverse event was hypotension, leading to discontinuation in 3/16 (19%) and 2/14 (14%) patients in the prospective and retrospective cohort. No patients developed AKI in the prospective cohort as compared to 1/14 (7%) patients in the retrospective cohort, requiring discontinuation of losartan. Hyperkalemia occurred in 1/16 (6%) and 0/14 patients in the prospective and retrospective cohorts, respectively. In the prospective cohort, 3/16 (19%) and 2/16 (13%) patients required ICU admission and mechanical ventilation. In comparison, 3/14 (21%) required ICU admission and mechanical ventilation in the retrospective cohort. A majority of patients in both cohorts (14/16 (88%) and 13/14 (93%) patients from the prospective and retrospective cohort) were discharged alive from the hospital. A total of 9/16 (prospective) and 5/14 (retrospective) patients completed a minimum 7 days of losartan. In these 9 patients in the prospective cohort, a significant improvement in SpO2/FiO2 ratio was observed from day 1 to 7. No significant changes in inflammatory markers (initiation, peak, and day 7) were observed in either cohort. CONCLUSION: In this pilot study we demonstrate that losartan was well-tolerated among hospitalized patients with COVID-19 and hypertension. We also demonstrate the feasibility of patient recruitment and the appropriate parameters to assess the outcomes and safety of losartan initiation or continuation, which provides a framework for future randomized clinical trials

The Association of Posttraumatic Stress Disorder With Longitudinal Change in Glomerular Filtration Rate in World Trade Center Responders

ObjectiveHigh levels of psychological distress increase the risk of a wide range of medical diseases. In this study, we investigated the association between posttraumatic stress disorder (PTSD) and kidney disease.MethodsWorld Trade Center (WTC) responders were included if they had two or more measures of estimated glomerular filtration rate (eGFR). The PTSD Checklist (PCL) was used to define no PTSD (PCL < 40), "mild" PTSD (40 ≤ PCL <50), and "severe" PTSD (PCL ≥50). Subtypes of PTSD by symptom clusters were analyzed. Multinomial logistic regression was used to estimate the association of PTSD with two GFR change outcomes (decline or increase) compared with the stable GFR outcome.ResultsIn 2266 participants, the mean age was 53.1 years, 8.2% were female, and 89.1% were White. Individuals with PTSD (n = 373; 16.5%) did not differ in mean baseline GFR from individuals without PTSD (89.73 versus 90.56 mL min-1 1.73 m-2; p = .29). During a 2.01-year mean follow-up, a mean GFR decline of -1.51 mL min-1 1.73 m-2 per year was noted. In multivariable-adjusted models, PTSD was associated with GFR decline (adjusted relative risk [aRR] = 1.74 [1.32-2.30], p < .001) compared with stable GFR, with "hyperarousal" symptoms showing the strongest association (aRR =2.11 [1.40-3.19]; p < .001). Dose-response effects were evident when comparing mild with severe PTSD and comparing PTSD with versus without depression. PTSD was also associated with GFR rise (aRR = 1.47 [1.10-1.97], p < .009). The association between PTSD and GFR change was stronger in participants older than 50 years.ConclusionsPTSD may be a novel risk factor for exaggerated longitudinal GFR change in young, healthy adults. These findings need to be validated in other cohorts