Data driven approach to characterize rapid decline in autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic kidney disease with high phenotypic variability. Furthering insights into patients' ADPKD progression could lead to earlier detection, management, and alter the course to end stage kidney disease (ESKD). We sought to identify patients with rapid decline (RD) in kidney function and to determine clinical factors associated with RD using a data-driven approach. A retrospective cohort study was performed among patients with incident ADPKD (1/1/2002-12/31/2018). Latent class mixed models were used to identify RD patients using differences in eGFR trajectories over time. Predictors of RD were selected based on agreements among feature selection methods, including logistic, regularized, and random forest modeling. The final model was built on the selected predictors and clinically relevant covariates. Among 1,744 patients with incident ADPKD, 125 (7%) were identified as RD. Feature selection included 42 clinical measurements for adaptation with multiple imputations; mean (SD) eGFR was 85.2 (47.3) and 72.9 (34.4) in the RD and non-RD groups, respectively. Multiple imputed datasets identified variables as important features to distinguish RD and non-RD groups with the final prediction model determined as a balance between area under the curve (AUC) and clinical relevance which included 6 predictors: age, sex, hypertension, cerebrovascular disease, hemoglobin, and proteinuria. Results showed 72%-sensitivity, 70%-specificity, 70%-accuracy, and 0.77-AUC in identifying RD. 5-year ESKD rates were 38% and 7% among RD and non-RD groups, respectively. Using real-world routine clinical data among patients with incident ADPKD, we observed that six variables highly predicted RD in kidney function.

Representation of Real-World Adults With Chronic Kidney Disease in Clinical Trials Supporting Blood Pressure Treatment Targets.

BACKGROUND: Little is known about how well trial participants with chronic kidney disease (CKD) represent real-world adults with CKD. We assessed the population representativeness of clinical trials supporting the 2021 Kidney Disease: Improving Global Outcomes blood pressure (BP) guidelines in real-world adults with CKD. METHODS AND RESULTS: Using a cross-sectional analysis, we identified patients with CKD who met the guideline definition of hypertension based on use of antihypertensive medications or sustained systolic BP ≥120 mm Hg in 2019 in the Veterans Affairs and Kaiser Permanente of Southern California. We applied the eligibility criteria from 3 BP target trials, SPRINT (Systolic Pressure Intervention Trial), ACCORD (Action to Control Cardiovascular Risk in Diabetes), and AASK (African American Study of Kidney Disease), to estimate the proportion of adults with a systolic BP above the guideline-recommended target and the proportion who met eligibility criteria for ≥1 trial. We identified 503 480 adults in the Veterans Affairs and 73 412 adults in Kaiser Permanente of Southern California with CKD and hypertension in 2019. We estimated 79.7% in the Veterans Affairs and 87.3% in the Kaiser Permanente of Southern California populations had a systolic BP ≥120 mm Hg; only 23.8% [23.7%-24.0%] in the Veterans Affairs and 20.8% [20.5%-21.1%] in Kaiser Permanente of Southern California were trial-eligible. Among trial-ineligible patients, >50% met >1 exclusion criteria. CONCLUSIONS: Major BP target trials were representative of fewer than 1 in 4 real-world adults with CKD and hypertension. A large proportion of adults who are at risk for cardiovascular morbidity from hypertension and susceptible to adverse treatment effects lack relevant treatment information.

Impact of Thyroid Status on Incident Kidney Dysfunction and Chronic Kidney Disease Progression in a Nationally Representative Cohort.

OBJECTIVE: To examine the relationship between thyroid status and incident kidney dysfunction/chronic kidney disease (CKD) progression. PATIENTS AND METHODS: We examined incident thyroid status, ascertained by serum thyrotropin (TSH) levels measured from January 1, 2007, through December 31, 2018, among 4,152,830 patients from the Optum Labs Data Warehouse, containing deidentified retrospective administrative claims data from a large national health insurance plan and electronic health record data from a nationwide network of provider groups. Associations of thyroid status, categorized as hypothyroidism, euthyroidism, or hyperthyroidism (TSH levels >5.0, 0.5-5.0, and <0.5 mIU/L, respectively), with the composite end point of incident kidney dysfunction in patients without baseline kidney dysfunction and CKD progression in those with baseline CKD were examined using Cox models. RESULTS: Patients with hypothyroidism and hyperthyroidism had higher risk of incident kidney dysfunction/CKD progression in expanded case-mix analyses (reference: euthyroidism): adjusted hazard ratios (aHRs) (95% CIs) were 1.37 (1.34 to 1.40) and 1.42 (1.39 to 1.45), respectively. Incrementally higher TSH levels in the upper reference range and TSH ranges for subclinical, mild overt, and overt hypothyroidism (≥3.0-5.0, >5.0-10.0, >10.0-20.0, and >20.0 mIU/L, respectively) were associated with increasingly higher risk of the composite end point (reference: TSH level, 0.5 to <3.0 mIU/L): aHRs (95% CIs) were 1.10 (1.09 to 1.11), 1.37 (1.34 to 1.40), 1.70 (1.59 to 1.83), and 1.70 (1.50 to 1.93), respectively. Incrementally lower TSH levels in the subclinical (<0.5 mIU/L) and overt (<0.1 mIU/L) hyperthyroid ranges were also associated with the composite end point: aHRs (95% CIs) were 1.44 (1.41 to 1.47) and 1.48 (1.39 to 1.59), respectively. CONCLUSION: In a national cohort, TSH levels in the upper reference range or higher (≥3.0 mIU/L) and below the reference range (<0.5 mIU/L) were associated with incident kidney dysfunction/CKD progression.

Hyperaldosteronism Screening and Findings From a Large Diverse Population With Resistant Hypertension Within an Integrated Health System.

INTRODUCTION: Hyperaldosteronism (HA) is a common cause of secondary hypertension and may contribute to resistant hypertension (RH). The authors sought to determine and characterize HA screening, positivity rates, and mineralocorticoid receptor antagonist (MRA) use among patients with RH. METHODS: A cross-sectional study was performed within Kaiser Permanente Southern California (7/1/2012-6/30/2017). Using contemporary criteria, RH was defined as blood pressure uncontrolled (≥ 130/80) on ≥ 3 medications or requiring ≥ 4 antihypertensive medications. The primary outcome was screening rate for HA defined as any aldosterone and plasma renin activity measurement. Secondary outcomes were HA screen positive rates and MRA use among all patients with RH. Multivariable logistic regression analysis was used to estimate odds ratio (with 95% confidence intervals) for factors associated with HA screening and for patients that screened positive. RESULTS: Among 102,480 patients identified as RH, 1977 (1.9%) were screened for HA and 727 (36.8%) screened positive for HA. MRA use was 6.5% among all patients with RH (22.5% among screened, 31.2% among screened positive). Black race, potassium < 4, bicarbonate > 29, chronic kidney disease, obstructive sleep apnea, and systolic blood pressure were associated with HA screening, but only Black race (1.55 [1.20-2.01]), potassium (1.82 [1.48-2.24]), bicarbonate levels (1.39 [1.10-1.75]), and diastolic blood pressure (1.15 [1.03-1.29]) were associated with positive screenings. CONCLUSION: The authors' findings demonstrate low screening rates for HA among patients with difficult-to-control hypertension yet a high positivity rate among those screened. Factors associated with screening did not always correlate with screening positive. Screening and targeted use of MRA may lead to improved blood pressure control and outcomes among patients with RH.

Treatment and Control of Hypertension Among Adults With Chronic Kidney Disease, 2011 to 2019.

BACKGROUND: Hypertension frequently accompanies chronic kidney disease (CKD) as etiology and sequela. We examined contemporary trends in hypertension treatment and control in a national sample of adults with CKD. METHODS: We evaluated 5% cross-sectional samples of adults with CKD between 2011 and 2019 in the Veterans Health Administration. We defined CKD as a sustained estimated glomerular filtration rate value <60 mL/min per 1.73 m2 or a urine albumin-to-creatinine ratio ≥30 mg/g. The main outcomes were blood pressure (BP) control, defined as a systolic BP <140 mm Hg and a diastolic BP <90 mm Hg based on the mean of monthly BP measurements, and prescriptions for antihypertensive medications. RESULTS: The annual samples ranged between n=22 110 and n=33 039 individuals, with a mean age of 72 years, 96% of whom were men. Between 2011 and 2014, the age-adjusted proportion of adults with controlled BP declined from 78.0% to 72.2% (P value for linear trend, <0.001), reached a nadir of 71.0% in 2015, and then increased to 72.9% by 2019 (P value for linear trend, <0.001). Among adults with BP above goal, the age-adjusted proportion who did not receive antihypertensive treatment increased throughout the decade from 18.8% to 21.6%, and the age-adjusted proportion who received ≥3 antihypertensive medications decreased from 41.8% to 36.3%. Prescriptions for first-line antihypertensive agents also decreased. CONCLUSIONS: Among adults with CKD treated in the Veterans Health Administration, the proportion with controlled BP declined between 2011 and 2015 followed by a modest increase, coinciding with fewer prescriptions for antihypertensive medications.

Development and Validation of a Prediction Model for Incident Hypothyroidism in a National Chronic Kidney Disease Cohort.

CONTEXT: Hypothyroidism is a common yet under-recognized condition in patients with chronic kidney disease (CKD), which may lead to end-organ complications if left untreated. OBJECTIVE: We developed a prediction tool to identify CKD patients at risk for incident hypothyroidism. METHODS: Among 15 642 patients with stages 4 to 5 CKD without evidence of pre-existing thyroid disease, we developed and validated a risk prediction tool for the development of incident hypothyroidism (defined as thyrotropin [TSH] > 5.0 mIU/L) using the Optum Labs Data Warehouse, which contains de-identified administrative claims, including medical and pharmacy claims and enrollment records for commercial and Medicare Advantage enrollees as well as electronic health record data. Patients were divided into a two-thirds development set and a one-third validation set. Prediction models were developed using Cox models to estimate probability of incident hypothyroidism. RESULTS: There were 1650 (11%) cases of incident hypothyroidism during a median follow-up of 3.4 years. Characteristics associated with hypothyroidism included older age, White race, higher body mass index, low serum albumin, higher baseline TSH, hypertension, congestive heart failure, exposure to iodinated contrast via angiogram or computed tomography scan, and amiodarone use. Model discrimination was good with similar C-statistics in the development and validation datasets: 0.77 (95% CI 0.75-0.78) and 0.76 (95% CI 0.74-0.78), respectively. Model goodness-of-fit tests showed adequate fit in the overall cohort (P = .47) as well as in a subcohort of patients with stage 5 CKD (P = .33). CONCLUSION: In a national cohort of CKD patients, we developed a clinical prediction tool identifying those at risk for incident hypothyroidism to inform prioritized screening, monitoring, and treatment in this population.

Discontinuation of Renin-Angiotensin-Aldosterone System Inhibitors Secondary to Hyperkalemia Translates into Higher Cardiorenal Outcomes.

INTRODUCTION: Discontinuation of renin-angiotensin-aldosterone system inhibitor (RAASi) is common after hyperkalemia. We evaluated the risk of kidney and mortality outcomes associated with RAASi discontinuation among patients with chronic kidney disease (CKD) and hyperkalemia. METHODS: We identified adult patients with CKD (eGFR <60 mL/min/1.73 m2) who experienced new-onset hyperkalemia (potassium ≥5.0 mEq/L) between 2016 and 2017 from Kaiser Permanente Southern California and followed them through 2019. We defined treatment discontinuation as having ≥90-day gap in refills of all RAASi within 3 months after hyperkalemia. We used multivariable Cox proportional hazards models to evaluate the association between RAASi discontinuation and the primary composite outcome of kidney (≥40% eGFR decline, dialysis, kidney transplant) or all-cause mortality. We evaluated cardiovascular events and recurrence of hyperkalemia as secondary outcomes. RESULTS: Among 5,728 patients (mean age 76 years), 13.5% discontinued RAASi within 3 months after new-onset hyperkalemia. During the median 2 years of follow-up, 29.7% had the primary composite outcome (15.5% with ≥40% eGFR decline, 2.8% dialysis or kidney transplant, 18.4% all-cause mortality). Patients who discontinued RAASi had a higher all-cause mortality compared with those who continued RAASi (26.7% vs. 17.1%) but had no differences in kidney outcomes, cardiovascular events, and recurrence of hyperkalemia. RAASi discontinuation was associated with a higher risk of kidney or all-cause mortality composite outcome (adjusted hazard ratio [aHR] 1.21, 95% CI: 1.06, 1.37) mainly driven by all-cause mortality (aHR: 1.34, 95% CI: 1.14, 1.56). CONCLUSION: RAASi discontinuation after hyperkalemia was associated with worsened mortality, which may underscore the benefits of continuing RAASi among patients with CKD.

All-Cause and Cardiovascular-Related Mortality in CKD Patients With and Without Heart Failure: A Population-Based Cohort Study in Kaiser Permanente Southern California.

Rationale & Objective: Heart failure and chronic kidney disease (CKD) frequently coexist reflective of the strong interplay between these organ systems. A better understanding of the prevalence of different types of heart failure (preserved and reduced ejection fraction) and their subsequent mortality risks among advanced CKD patients would provide important epidemiologic insights and may pave the way for more focused and proactive management strategies. Study Design: Retrospective cohort study. Setting & Population: Patients aged ≥18 years with incident CKD (estimated glomerular filtration rate ≤45 mL/min/1.73 m2) with and without heart failure in a large integrated health care system in Southern California. Exposure: Heart failure, heart failure with preserved ejection fraction (HFpEF), heart failure with reduced ejection fraction (HFrEF). Outcomes: All-cause and cardiovascular-related mortality within one year of CKD identification. Analytical Approach: HRs were estimated using Cox proportional-hazards model for risk of all-cause mortality and Fine-Gray subdistribution hazard model for risk of cardiovascular-related mortality within 1 year. Results: The study cohort included 76,688 patients with incident CKD between 2007 and 2017, of which 14,249 (18.6%) had prevalent heart failure. Among these patients, 8,436 (59.2%) had HFpEF and 3,328 (23.3%) had HFrEF. Compared with patients without heart failure, the HR for 1-year all-cause mortality was 1.70 (95% CI, 1.60-1.80) among patients with heart failure. The HRs were 1.59 (95% CI, 1.48-1.70) for patients with HFpEF and 2.43 (95% CI, 2.23-2.65) for patients with HFrEF. Compared with patients without heart failure, the 1-year cardiovascular-related mortality HR for patients with heart failure was 6.69 (95% CI, 5.93-7.54). Cardiovascular-related mortality HR was even higher among those with HFrEF (HR, 11.47; 95% CI, 9.90-13.28). Limitations: Retrospective design with a short 1-year follow-up period. Additional variables including medication adherence, medication changes, and time-varying variables were not accounted for in this intention-to-treat analysis. Conclusions: Among patients with incident CKD, heart failure was highly prevalent with HFpEF accounting for over 70% among patients with known ejection fraction. Although the presence of heart failure was associated with higher 1-year all-cause and cardiovascular-related mortality, patients with HFrEF were the most vulnerable.

Comparison of Blood Pressure Measurements from Clinical Practice and a Research Study At Kaiser Permanente Southern California.

BACKGROUND: Accurate blood pressure (BP) measurement is essential to identify and manage hypertension. Prior studies have reported a difference between BP measured in routine patient care and in research studies. We aimed to investigate the agreement between BP measured in routine care and research-grade BP in Kaiser Permanente Southern California, a large, integrated healthcare system with initiatives to standardize BP measurements during routine patient care visits. METHODS: We included adults ≥65 years old with hypertension, taking antihypertensive medication, and participating in the Ambulatory Blood Pressure in Older Adults (AMBROSIA) study in 2019-2021. Clinic BP from routine care visits was extracted from the electronic health record. Research-grade BP was obtained by trained AMBROSIA study staff via an automatic oscillometric device. The mean difference between routine care and research-grade BP, limits of agreement, and correlation were assessed. RESULTS: We included 309 participants (mean age 75 years; 54% female; 49% non-Hispanic white). Compared with measurements from routine care, mean research-grade systolic BP (SBP) was 0.1 mm Hg higher (95% CI: -1.5 to 1.8) and diastolic BP (DBP) was 0.4 mm Hg lower (95% CI: -1.6 to 0.7). Limits of agreement were -29 to 30 mm Hg for SBP and -21 to 20 mm Hg for DBP. The intraclass correlation coefficient was 0.42 (95% CI: 0.33 to 0.51) for SBP and 0.43 (95% CI: 0.34 to 0.52) for DBP. CONCLUSIONS: High within-person variation and moderate correlation were present between BP measured in routine care and following a research protocol suggesting the importance of standardized measurements.

Health Disparities in Kidney Failure Among Patients With Autosomal Dominant Polycystic Kidney Disease: A Cross-Sectional Study.

Rationale & Objective: Understanding potential differences in patterns of kidney failure among patients with autosomal dominant polycystic kidney disease (ADPKD) may provide insights into improving disease management. We sought to characterize patients with ADPKD and kidney failure across different race/ethnicities. Study Design: Cross-sectional study. Setting & Participants: Kaiser Permanente Southern California members diagnosed with ADPKD between January1, 2002, and December 31, 2018. Exposure: ADPKD. Outcome: Kidney failure, dialysis, or receipt of kidney transplant. Analytical Approach: Differences in characteristics by race/ethnicity were assessed using analysis of variance F test and χ2 test. To compare the range and distribution of the average age at onset of kidney failure by race/ethnicity and sex, we used box plots and confidence intervals. Multivariable logistic regression was used to estimate OR for kidney transplant. Results: Among 3,677 ADPKD patients, 1,027 (27.3%) had kidney failure. The kidney failure cohort was comprised of Black (n=138; 30.7%), White (n=496; 30.6%), Hispanic (n=306; 24.7%), and Asian (n=87; 23.6%) patients. Hispanic patients had the youngest mean age of kidney failure onset (50 years) compared to Black (56 years) and White (57 years) patients. Black (44.2%; OR, 0.72) and Hispanic (49.7%; OR, 0.65) patients had lower rates of kidney transplantation compared to White (53.8%) patients. Preemptive kidney transplantations occurred in 15.0% of patients. Limitations: Retrospective study design and possible misclassification of ADPKD cases. Kidney function calculations were based on equations incorporating race, potentially overestimating kidney function in African Americans. The study was conducted within a single, integrated health care system in 1 geographic region and may not be generalizable to all ADPKD patients. Conclusions: Among a large diverse ADPKD population, we observed racial/ethnic differences in rates of kidney failure, age of kidney failure onset, and rates of kidney transplantation. Our real-world ADPKD cohort provides insight into racial/ethnic variation in clinical features of disease and potential disparities in care, which may affect ADPKD outcomes.

Comparison of safety and outcomes related to remdesivir treatment among dialysis patients hospitalized with COVID-19.

Background: Patients with end-stage kidney disease (ESKD) are highly susceptible to coronavirus disease 2019 (COVID-19) infection and its complications. Remdesivir has improved outcomes in COVID-19 patients but its use has been limited among ESKD patients due to insufficient data regarding safety outcomes. We sought to evaluate the safety of remdesivir among dialysis patients hospitalized with COVID-19. Methods: This retrospective cohort study was conducted among patients age ≥18 years on maintenance dialysis and hospitalized with COVID-19 between 1 May 2020 and 31 January 2021 within an integrated health system who were treated or not treated with remdesivir. The primary outcome was 30-day all-cause mortality. Secondary outcomes were intensive care unit (ICU) stay, and transaminitis (AST/ALT >5× normal). Pseudo-populations were created using inverse probability of treatment weights with propensity scoring to balance patient characteristics among the two groups. Multivariable Poisson regression with robust error was performed to estimate 30-day mortality risk ratio. Results: A total of 486 (407 hemodialysis and 79 peritoneal dialysis) patients were hospitalized with COVID-19, among which 112 patients (23%) were treated with remdesivir [median treatment four days (interquartile range 2-5)]. The 30-day mortality rate was 24.1% among remdesivir-treated and 27.8% among non-treated patients. The estimated 30-day mortality rate was 0.74 (95% confidence interval 0.52-1.05) among remdesivir treated compared with non-treated patients. Liver injury and ICU admission rates were 1.8% and 14.3% among remdesivir-treated patients compared with 2.4% and 16% among non-treated patients. Conclusion: Among dialysis patients hospitalized with COVID-19, remdesivir was not associated with higher rates of liver injury or ICU admissions, and demonstrated a trend toward lower 30-day mortality.

Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems.

BACKGROUND AND OBJECTIVES: More intensive BP goals have been recommended for patients with CKD. We estimated the prevalence of apparent treatment-resistant hypertension among patients with CKD according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA; BP goal <130/80 mm Hg) and 2021 Kidney Disease Improving Global Outcomes (KDIGO; systolic BP <120 mm Hg) guidelines in two US health care systems. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We included adults with CKD (an eGFR <60 ml/min per 1.73 m2) and treated hypertension from Kaiser Permanente Southern California and the Veterans Health Administration. Using electronic health records, we identified apparent treatment-resistant hypertension on the basis of (1) BP above the goal while prescribed three or more classes of antihypertensive medications or (2) prescribed four or more classes of antihypertensive medications regardless of BP. In a sensitivity analysis, we required diuretic use to be classified as apparent treatment-resistant hypertension. We estimated the prevalence of apparent treatment-resistant hypertension per clinical guideline and by CKD stage. RESULTS: Among 44,543 Kaiser Permanente Southern California and 241,465 Veterans Health Administration patients with CKD and treated hypertension, the prevalence rates of apparent treatment-resistant hypertension were 39% (Kaiser Permanente Southern California) and 35% (Veterans Health Administration) per the 2017 ACC/AHA guideline and 48% (Kaiser Permanente Southern California) and 55% (Veterans Health Administration) per the 2021 KDIGO guideline. By requiring a diuretic as a criterion for apparent treatment-resistant hypertension, the prevalence rates of apparent treatment-resistant hypertension were lowered to 31% (Kaiser Permanente Southern California) and 23% (Veterans Health Administration) per the 2017 ACC/AHA guideline. The prevalence rates of apparent treatment-resistant hypertension were progressively higher at more advanced stages of CKD (34%/33%, 42%/36%, 52%/41%, and 60%/37% for Kaiser Permanente Southern California/Veterans Health Administration eGFR 45-59, 30-44, 15-29, and <15 ml/min per 1.73 m2, respectively) per the 2017 ACC/AHA guideline. CONCLUSIONS: Depending on the CKD stage, up to a half of patients with CKD met apparent treatment-resistant hypertension criteria.

Real-world use patterns of angiotensin receptor-neprilysin inhibitor (sacubitril/valsartan) among patients with heart failure within a large integrated health system.

BACKGROUND: Sacubitril/valsartan is a first-in-class angiotensin receptor-neprilysin inhibitor (ARNI) that is now preferred in guidelines over angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) for patients with heart failure with reduced ejection fraction (HFrEF). However, it has not been broadly adopted in clinical practice. OBJECTIVE: To characterize ARNI use within a large diverse real-world population and assess for any racial disparities. METHODS: We conducted a cross-sectional study within Kaiser Permanente Southern California. Adult patients with HFrEF who received ARNIs, ACEIs, or ARBs between January 1, 2014, and November 30, 2020, were identified. The prevalence of ARNI use among the cohort and patient characteristics by ARNIs vs ACEIs/ARBs use were described. Multivariable regression was performed to estimate odds ratios and 95% CIs of receiving ARNI by race and ethnicity. RESULTS: Among 12,250 patients with HFrEF receiving ACEIs, ARBs, or ARNIs, 556 (4.54%) patients received ARNIs. ARNI use among this cohort increased from 0.02% in 2015 to 7.48% in 2020. Patients receiving ARNIs were younger (aged 62 vs 69 years) and had a lower median ejection fraction (27% vs 32%) compared with patients receiving ACEIs/ARBs. They also had higher use of mineralocorticoid antagonists (24.1% vs 19.8%) and automatic implantable cardioverterdefibrillators (17.4% vs 13.3%). There were no significant differences in rate of ARNI use by race and ethnicity. CONCLUSIONS: Within a large diverse integrated health system in Southern California, the rate of ARNI use has risen over time. Patients given ARNIs were younger with fewer comorbidities, while having worse ejection fraction. Racial minorities were no less likely to receive ARNIs compared with White patients. DISCLOSURES: Dr Huang had stock ownership in Gilead and Pfizer. Dr Liang received support for article processing and medical writing.

Outcomes Among Hospitalized Patients With COVID-19 and Acute Kidney Injury Requiring Renal Replacement Therapy.

IntroductionAcute kidney injury (AKI) occurs in up to 10%-30% of coronavirus disease 2019 (COVID-19) patients. AKI patients who require renal replacement therapy (RRT) often have concurrent respiratory failure and represent a high-mortality-risk population. The authors sought to describe outcomes in hospitalized COVID-19 patients with AKI requiring RRT and determine factors associated with poor outcomes. MethodsA retrospective cohort study of hospitalized COVID-19 patients with AKI requiring RRT during the period from March 14, 2020, to September 30, 2020, was performed at Kaiser Permanente Southern California. RRT was defined as conventional hemodialysis and/or continuous renal replacement therapy. The primary outcome was hospitalization mortality, and secondary outcomes were mechanical ventilation, vasopressor support, and dialysis dependence among discharged patients. Hospitalization mortality risk ratios were estimated up to 30 days from RRT initiation. ResultsA total of 167 hospitalized COVID-19 patients were identified with AKI requiring RRT. The study population had a mean age of 60.7 years and included 71.3% male patients and 60.5% Hispanic patients. Overall, 114 (68.3%) patients died during their hospitalization. Among patients with baseline estimated glomerular filtration rate (eGFR) values of ≥ 60, 30-59, and < 30 mL/min, the mortality rates were 76.8%, 78.1%, and 50.0%, respectively. Among the 53 patients who survived to hospital discharge, 29 (54.7%) continued to require RRT. Compared to patients with eGFR < 30 mL/min, the adjusted 30-day hospitalization mortality risk ratios (95% CI) were 1.38 (0.90-2.12) and 1.54 (1.06-2.25) for eGFR values of 30-59 and ≥ 60, respectively. ConclusionAmong a diverse cohort of hospitalized COVID-19 patients with AKI requiring RRT, survival to discharge was low. Greater mortality was observed among patients with higher baseline kidney function. Most of the patients discharged alive continued to be dialysis-dependent.

Statin Use and Mortality among Patients Hospitalized with Sepsis: A Retrospective Cohort Study within Southern California, 2008-2018.

Background: Despite early goal-directed therapy, sepsis mortality remains high. Statins exhibit pleiotropic effects. Objective: We sought to compare mortality outcomes among statin users versus nonusers who were hospitalized with sepsis. Methods: Retrospective cohort study of patients (age ≥18 years) during 1/1/2008-9/30/2018. Mortality was compared between statin users and nonusers and within statin users (hydrophilic versus lipophilic, fungal versus synthetic derivation, and individual statins head-to-head). Multivariable Cox regression models were used to estimate hazard ratios (HR) for 30-day and 90-day mortality. Inverse probability treatment weighting (IPTW) analysis was performed to account for indication bias. Results: Among 128,161 sepsis patients, 34,088 (26.6%) were prescribed statin drugs prior to admission. Statin users compared to nonusers had a 30-day and 90-day mortality HR (95% CI) of 0.80 (0.77-0.83) and 0.79 (0.77-0.81), respectively. Synthetic derived statin users compared to fungal derived users had a 30- and 90-day mortality HR (95% CI) of 0.86 (0.81-0.91) and 0.85 (0.81-0.89), respectively. Hydrophilic statin users compared to lipophilic users had a 30-day and 90-day mortality HR (95% CI) of 0.90 (0.81-1.01) and 0.86 (0.78-0.94), respectively. Compared to simvastatin, 30-day mortality HRs (95% CI) were 0.85 (0.66-1.10), 0.87 (0.82-0.92), 0.87 (0.76-0.98), and 1.22 (1.10-1.36) for rosuvastatin, atorvastatin, pravastatin, and lovastatin, respectively. Conclusion: Statin use was associated with lower mortality in patients hospitalized with sepsis. Hydrophilic and synthetic statins were associated with better outcomes than lipophilic and fungal-based preparations.

Antibiotic practice patterns with procalcitonin levels in patients with acute lower respiratory tract infection.

OBJECTIVES: Procalcitonin (PCT) testing is FDA approved to guide antibiotic therapy in patients with lower respiratory tract infection (LRTI). However, its utilization and impact on real-world antibiotic prescribing behavior are unknown. We investigated the rate of PCT testing to evaluate an association between initial PCT level and antibiotic prescription patterns for patients with suspected LRTI within a large integrated health system. STUDY DESIGN: Retrospective cohort study. METHODS: A retrospective cohort study (January 1, 2016, through December 31, 2017) was performed in patients 18 years and older who were hospitalized with LRTI and had a PCT measurement. Antibiotic changes were noted before and 36 hours after initial PCT results. Antibiotic concordance was determined using a PCT cutoff value of 0.25 mcg/L. Concordance was defined as (1) patients received antibiotics after a PCT of at least 0.25 mcg/L resulted or (2) antibiotics were withheld after a PCT less than 0.25 mcg/L resulted. RESULTS: PCT testing occurred in 18% of hospitalized patients with LRTI. Among 1606 patients, antibiotic concordance with PCT results was 55%. Among the discordant population, 77% of patients received antibiotics in the setting of a low PCT level compared with 23% who did not receive antibiotics at a high PCT level. There were no statistical differences between LRTI types between patients with PCT-discordant and PCT-concordant care. CONCLUSIONS: Within a real-world environment of patients hospitalized with LRTI, PCT testing was low and the PCT levels did not appear to influence antibiotic prescribing behavior. Our findings suggest that clinicians continue to prioritize clinical judgment over initial PCT levels when prescribing antibiotics for suspected LRTIs.

Potentially Harmful Medication Dispenses After a Fall or Hip Fracture: A Mixed Methods Study of a Commonly Used Quality Measure.

BACKGROUND: High-risk medication dispenses to patients with a prior fall or hip fracture represent a potentially dangerous disease-drug interaction among older adults. The research team quantified the prevalence, identified risk factors, and generated patient and provider insights into high-risk medication dispenses in a large, community-based integrated health system using a commonly used quality measure. METHODS: This was a mixed methods study with a convergent design combining a retrospective cohort study using electronic health record (EHR) data, individual interviews of primary care physicians, and a focus group of patient advisors. RESULTS: Of 113,809 patients ≥ 65 years with a fall/fracture in 2009-2015, 35.4% had a potentially harmful medication dispensed after their fall/fracture. Most medications were prescribed by primary care providers. Older age, male gender, and race/ethnicity other than non-Hispanic White were associated with a reduced risk of high-risk medication dispenses. Patients with a pre-fall/fracture medication dispense were substantially more likely to have a post-fall/fracture medication dispense (hazard ratio [HR] = 13.26, 95% confidence interval [CI] = 12.91-13.61). Both patients and providers noted that providers may be unaware of patient falls due to inconsistent assessments and patient reluctance to disclose falls. Providers also noted the lack of a standard location to document falls and limited decision support alerts within the EHR. CONCLUSION: High-risk medication dispenses are common among older patients with a history of falls/fractures. Future interventions should explore improved assessment and documentation of falls, decision support, clinician training strategies, patient educational resources, building trusting patient-clinician relationships to facilitate long-term medication discontinuation among persistent medication users, and a focus on fall prevention.

Causes of Death in End-Stage Kidney Disease: Comparison between the United States Renal Data System and a Large Integrated Health Care System.

INTRODUCTION: Using a large diverse population of incident end-stage kidney disease (ESKD) patients from an integrated health system, we sought to evaluate the concordance of causes of death (CODs) between the underlying COD from the United States Renal Data System (USRDS) registry and CODs obtained from Kaiser Permanente Southern California (KPSC). METHODS: A retrospective cohort study was performed among incident ESKD patients who had mortality records and CODs reported in both KPSC and USRDS databases between January 1, 2007, and December 31, 2016. Underlying CODs reported by the KPSC were compared to the CODs reported by USRDS. Overall and subcategory-specific COD agreements were assessed using Cohen's weighted kappa statistic (95% CI). Proportions of positive and negative agreement were also determined. RESULTS: Among 4,188 ESKD patient deaths, 4,118 patients had CODs recorded in both KPSC and USRDS. The most common KPSC CODs were circulatory system diseases (35.7%), endocrine/nutritional/metabolic diseases (24.2%), genitourinary diseases (12.9%), and neoplasms (9.6%). Most common USRDS CODs were cardiac disease (46.9%), withdrawal from dialysis (12.6%), and infection (10.1%). Of 2,593 records with causes listed NOT as "Other," 453 (17.4%) had no agreement in CODs between the USRDS and the underlying, secondary, tertiary, or quaternary causes recorded by KPSC. In comparing CODs recorded within KPSC to the USRDS, Cohen's weighted kappa (95% CI) was 0.20 (0.18-0.22) with overall agreement of 36.4%. CONCLUSION: Among an incident ESKD population with mortality records, we found that there was only fair or slight agreement between CODs reported between the USRDS registry and KPSC, a large integrated health care system.