Effect of Changing Estimated Glomerular Filtration Rate Formula on Sugammadex Use and Pulmonary Complications for African American and non-African American Patients.

BACKGROUND: Sugammadex is associated with fewer postoperative pulmonary complications than is neostigmine reversal of neuromuscular blockade. However, the Food and Drug Administration-approved package insert states that its use is "not recommended" in severe renal impairment, separately defined as creatinine clearance <30 mL/min. Recently, the formula for estimating glomerular filtration rate (GFR) was updated to remove the race variable. Compared to the prior formula, the new consensus equation lowers the estimated GFR for African American patients and raises it for everyone else. We sought to determine how this change could differently impact the use of sugammadex, and thus the rate of pulmonary complications, for both African American and non-African American patients. METHODS: We used Monte Carlo simulation models to estimate the difference in pulmonary complications that would be suffered by patients when the change in creatine clearance calculated from the estimated GFR (using the old race-based and new race-neutral Chronic Kidney Disease Epidemiology Collaboration formulas) crossed the 30 mL/min threshold, which would require a change in sugammadex or neostigmine use. RESULTS: We found that 0.22% (95% confidence interval 0.14%-0.36%) of African American patients' creatinine clearance would drop from above to below 30 mL/min making sugammadex not recommended and 0.19% (0.16%-0.22%) of non-African American patients would have creatinine clearance increase to >30 mL/min making sugammadex now recommended. Based on our model, we estimate that African American patients would suffer (count [95% confidence interval]) 3 [0.4-6] more pulmonary complications per 100,000 African American patients who received rocuronium or vecuronium through the change from sugammadex to neostigmine reversal to comply with labeling recommendations. Conversely, the same change in formulas would reduce the number of non-African American patients suffering pulmonary complications by 3 [2-4] per 100,000. CONCLUSIONS: The recent change in GFR formulas may potentially be associated with an increase in postoperative pulmonary complications in African American patients and a decrease in postoperative pulmonary complications in non-African American patients through GFR-driven changes in sugammadex use.

CCL14 Predicts Oliguria and Dialysis Requirement in Patients with Moderate to Severe Acute Kidney Injury.

INTRODUCTION: AKI is a frequent complication of critical illness and portends poor outcome. CCL14 is a validated predictor of persistent severe AKI in critically ill patients. We examined the association of CCL14 with urine output within 48 h. METHODS: In pooled data from 2 studies of critically ill patients with KDIGO stage 2-3 AKI, CCL14 was measured by NEPHROCLEAR™ CCL14 Test on the Astute 140® Meter (low, intermediate, and high categories [1.3 and 13 ng/mL]). Average hourly urine output over 48 h, stage 3 AKI per urine output criterion on day 2, and composite of dialysis or death within 7 days were examined using multivariable mixed and logistic regression models. RESULTS: Of the 497 subjects with median age of 65 (56-74) years, 49% (242/497) were on diuretics. CCL14 concentration was low in 219 (44%), intermediate in 217 (44%), and high in 61 (12%) patients. In mixed regression analysis, hourly urine output over time was different within each CCL14 risk category based on diuretic use due to significant three-way interaction (p < 0.001). In logistic regression analysis, CCL14 risk category was independently associated with low urine output on day 2 per KDIGO stage 3 (adjusted for diuretic use and baseline clinical variables), and composite of dialysis or death within 7 days (adjusted for urine output within 48 h of CCL14 measurement). CONCLUSIONS: CCL14 measured in patients with moderate to severe AKI is associated with urine output trajectory within 48 h, oliguria on day 2, and dialysis within 7 days.

The Association of Oxygen Delivery and Transfusion on Cardiopulmonary Bypass with Acute Kidney Injury.

OBJECTIVES: To estimate whether the association of transfusion and acute kidney injury (AKI) has a threshold of oxygen delivery below which transfusion is beneficial but above which it is harmful. DESIGN: Retrospective study SETTING: Cardiovascular operating room and intensive care unit PARTICIPANTS: Patients undergoing cardiac surgery with continuous oxygen delivery monitoring during cardiopulmonary bypass INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Logistic regression was used to estimate the associations between oxygen delivery (mean, cumulative deficit, and bands of oxygen delivery), transfusion, and their interaction and AKI. A subgroup analysis of transfused and nontransfused patients with exact matching on cumulative oxygen deficit and time on bypass with adjustment for propensity to receive a transfusion using logistic regression. Nine hundred ninety-one of 4,203 patients developed AKI within 7 days. After adjustment for confounders, lower mean oxygen delivery (odds ratio [OR], 0.968; 95% confidence interval [CI], 0.949-0.988; p = 0.002) and transfusions (OR, 1.442; 95% CI, 1.077, 1.932; p = 0.014) were associated with increased odds of AKI by 7 days. As oxygen delivery decreased, the risk of AKI increased, with the slope of the OR steeper at <160 mL/m2/min. In the subgroup analysis, matched transfused patients were more likely than matched nontransfused patients to develop AKI (45% [n = 145] v 31% [n = 101]; p < 0.001). However, after propensity score adjustment, the difference was nonsignificant (OR, 1.181; 95% CI, 0.796-1.752; p = 0.406). CONCLUSIONS: We found a nonlinear relationship between oxygen delivery and AKI. We found no level of oxygen delivery at which transfusion was associated with a decreased risk of AKI.

Continuous Renal Replacement Therapy among Patients with COVID-19 and Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: Acute kidney injury (AKI) is a common complication among patients with COVID-19 and acute respiratory distress syndrome. Reports suggest that COVID-19 confers a pro-thrombotic state, which presents challenges in maintaining hemofilter patency and delivering continuous renal replacement therapy (CRRT). We present our initial experience with CRRT in critically ill patients with COVID-19, emphasizing circuit patency and the association between fluid balance during CRRT and respiratory parameters. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Retrospective chart review of 32 consecutive patients with COVID-19 and AKI managed with continuous venovenous hemodiafiltration with regional citrate anticoagulation (CVVHDF-RCA) according to the University of Michigan protocol. Primary outcome was mean CRRT circuit life per patient during the first 7 days of CRRT. We used simple linear regression to assess the relationship between patient characteristics and filter life. We also explored the relationship between fluid balance on CRRT and respiratory parameters using repeated measures modeling. RESULTS: Patients' mean age was 54.8 years and majority were Black (75%). Comorbidities included hypertension (90.6%), obesity (70.9%) diabetes (56.2%), and chronic kidney disease (40.6%). Median CRRT circuit life was 53.5 [interquartile range 39.1-77.6] hours. There was no association between circuit life and inflammatory or pro-thrombotic laboratory values (ferritin p = 0.92, C-reactive protein p = 0.29, D-dimer p = 0.24), or with systemic anticoagulation (p = 0.37). Net daily fluid removal during the first 7 days of CRRT was not associated with daily (closest recorded values to 20:00) PaO2/FIO2 ratio (p = 0.21) or positive end-expiratory pressure requirements (p = 0.47). CONCLUSIONS: We achieved adequate CRRT circuit life in COVID-19 patients using an established CVVHDF-RCA protocol. During the first 7 days of CRRT therapy, cumulative fluid balance was not associated with improvements in respiratory parameters, even after accounting for baseline fluid balance.

Limited clinical utility for GWAS or polygenic risk score for postoperative acute kidney injury in non-cardiac surgery in European-ancestry patients.

BACKGROUND: Prior studies support a genetic basis for postoperative acute kidney injury (AKI). We conducted a genome-wide association study (GWAS), assessed the clinical utility of a polygenic risk score (PRS), and estimated the heritable component of AKI in patients who underwent noncardiac surgery. METHODS: We performed a retrospective large-scale genome-wide association study followed by a meta-analysis of patients who underwent noncardiac surgery at the Vanderbilt University Medical Center ("Vanderbilt" cohort) or Michigan Medicine, the academic medical center of the University of Michigan ("Michigan" cohort). In the Vanderbilt cohort, the relationship between polygenic risk score for estimated glomerular filtration rate and postoperative AKI was also tested to explore the predictive power of aggregating multiple common genetic variants associated with AKI risk. Similarly, in the Vanderbilt cohort genome-wide complex trait analysis was used to estimate the heritable component of AKI due to common genetic variants. RESULTS: The study population included 8248 adults in the Vanderbilt cohort (mean [SD] 58.05 [15.23] years, 50.2% men) and 5998 adults in Michigan cohort (56.24 [14.76] years, 49% men). Incident postoperative AKI events occurred in 959 patients (11.6%) and in 277 patients (4.6%), respectively. No loci met genome-wide significance in the GWAS and meta-analysis. PRS for estimated glomerular filtration rate explained a very small percentage of variance in rates of postoperative AKI and was not significantly associated with AKI (odds ratio 1.050 per 1 SD increase in polygenic risk score [95% CI, 0.971-1.134]). The estimated heritability among common variants for AKI was 4.5% (SE = 4.5%) suggesting low heritability. CONCLUSION: The findings of this study indicate that common genetic variation minimally contributes to postoperative AKI after noncardiac surgery, and likely has little clinical utility for identifying high-risk patients.

Telavancin pharmacokinetics in patients with chronic kidney disease receiving haemodialysis.

BACKGROUND: Telavancin is a lipoglycopeptide antibiotic with limited pharmacokinetic data to guide drug dosing in patients receiving haemodialysis. OBJECTIVES: This study characterized telavancin pharmacokinetics in patients receiving haemodialysis. PATIENTS AND METHODS: This was a Phase IV, prospective, open-label, single-centre, crossover pharmacokinetic study (ClinicalTrials.gov: NCT02392208). Eight subjects with end-stage kidney disease requiring maintenance haemodialysis (mean ±â€ŠSD: 47 ±â€Š20 years, 69.5 ±â€Š17.1 kg) received 5 mg/kg telavancin IV 3 h before starting a 3.5 hour haemodialysis treatment with a high-permeability haemodialyser (haemodialysis period). After a 14 day washout period, a second 5 mg/kg dose was administered post-haemodialysis (control period). Telavancin plasma concentrations were measured over a 2 day period after each dose and non-compartmental pharmacokinetic analyses were performed. RESULTS: The geometric mean (GM) of telavancin overall clearance was 11.2 mL/h/kg (intrinsic clearance and dialytic clearance) in the haemodialysis period and 5.9 mL/h/kg (off-haemodialysis clearance) in the control period [GM ratio (GMR) = 1.89; 90% CI: 1.70-2.10; P < 0.01]. The GM t½ was 13.1 h when haemodialysis occurred 3 h post-dosing in the haemodialysis period but extended to 20.9 h with post-haemodialysis dosing in the control period (GMR = 0.63; 90% CI: 0.54-0.73; P < 0.01). The GM of telavancin plasma concentrations removed by haemodialysis was 27.7%. The GMR of peak plasma concentration and volume of distribution of the haemodialysis period and the control period were 0.88 (90% CI: 0.79-0.98; P = 0.08) and 1.17 (90% CI: 1.05-1.30; P = 0.048), respectively. CONCLUSIONS: Haemodialysis with high-permeability haemodialysers removes telavancin considerably (∼⅓ of body load). Telavancin 5 mg/kg every 48 h post-haemodialysis dosing is recommended, but dose adjustments may be warranted if haemodialysis starts within 3 h of telavancin administration.

Burden and Cost of Caring for US Veterans With CKD: Initial Findings From the VA Renal Information System (VA-REINS).

Kidney disease is a common, complex, costly, and life-limiting condition. Most kidney disease registries or information systems have been limited to single institutions or regions. A national US Department of Veterans Affairs (VA) Renal Information System (VA-REINS) was recently developed. We describe its creation and present key initial findings related to chronic kidney disease (CKD) without kidney replacement therapy (KRT). Data from the VA's Corporate Data Warehouse were processed and linked with national Medicare data for patients with CKD receiving KRT. Operational definitions for VA user, CKD, acute kidney injury, and kidney failure were developed. Among 7 million VA users in fiscal year 2014, CKD was identified using either a strict or liberal operational definition in 1.1 million (16.4%) and 2.5 million (36.3%) veterans, respectively. Most were identified using an estimated glomerular filtration rate laboratory phenotype, some through proteinuria assessment, and very few through International Classification of Diseases, Ninth Revision coding. The VA spent ∼$18 billion for the care of patients with CKD without KRT, most of which was for CKD stage 3, with higher per-patient costs by CKD stage. VA-REINS can be leveraged for disease surveillance, population health management, and improving the quality and value of care, thereby enhancing VA's capacity as a patient-centered learning health system for US veterans.

Deployment of a New CRRT/PIRRT Device during the COVID-19 Pandemic Emergency: Organizational Challenges and Implementation Results.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic led to increased demand nationwide for dialysis equipment, including supplies and machines. To meet the demand in our institution, our surge plan included rapid mobilization of a novel continuous renal replacement treatment (CRRT) machine named SAMI. The SAMI is a push-pull filtration enhanced dialysis machine that can conjugate extremely high single-pass solute removal efficiency with very precise fluid balance control. MATERIAL AND METHODS: Machine assembly was conducted on-site by local biomedical engineers with remote assistance by the vendor. One 3-h virtual training session of 3 dialysis nurses was conducted before SAMI deployment. The SAMI was deployed in prolonged intermittent replacement therapy (PIRRT) mode to maximize patients covered per machine per day. Live on-demand vendor support was provided to troubleshoot any issues for the first few cases. After 4 weeks of the SAMI implementation, data on treatments with the SAMI were collected, and a questionnaire was provided to the nurse trainees to assess device usability. RESULTS: On-site installation of the SAMI was accomplished with remote assistance. Delivery of remote training was successfully achieved. 23 PIRRT treatments were conducted in 10 patients. 7/10 of patients had CO-VID-19. The median PIRRT dose was 50 mL/kg/h (IQR [interquartile range] 44 - 62 mL/kg/h), and duration of the treatment was 8 h (IQR 6.3 - 8 h). Solute control was adequate. The user response was favorable to the set of usability questions involving user interface, on-screen instructions, machine setup, troubleshooting, and the ease of moving the machine. CONCLUSION: Assembly of the SAMI and training of nurses remotely are possible when access to vendor employees is restricted during states of emergency. The successful deployment of the SAMI in our institution during the pandemic with only 3-h virtual training supports that operating the SAMI is simple and safe.

Predictors of kidney function recovery among incident ESRD patients.

BACKGROUND: ESRD is considered an irreversible loss of renal function, yet some patients will recover kidney function sufficiently to come off dialysis. Potentially modifiable predictors of kidney recovery, such as dialysis prescription, have not been fully examined. METHODS: Retrospective cohort study using United States Renal Data System (USRDS) data to identify incident hemodialysis (HD) patients between 2012 and 2016, the first 4 years for which dialysis treatment data is available. The primary outcome was kidney recovery within 1 year of ESRD and HD initiation, defined by a specific recovery code and survival off dialysis for at least 30 days. Patient and treatment characteristics were compared between those that recovered versus those that remained dialysis-dependent. A time-dependent survival model was used to identify independent predictors of kidney recovery. RESULTS: During the study period, there were 372,387 incident HD patients with available data, among whom 16,930 (4.5%) recovered to dialysis-independence. Compared to non-recovery, a higher proportion of patients with kidney recovery were of white race, and non-Hispanic ethnicity. Both groups had a similar age distribution. Patients with an acute kidney injury diagnosis as primary cause of ESRD were most likely to recover, but the most common ESRD diagnosis among recovering patients was type 2 diabetes (29.8% of recovery cases). Higher eGFR and lower albumin at ESRD initiation were associated with increased likelihood of recovery. When examining HD ultrafiltration rate (UFR), each quintile above the first quintile was associated with a progressively lower likelihood of recovery (HR 0.45, 95% CI 0.43-0.48 for highest versus lowest quintile, p < 0.001). CONCLUSIONS: We identified non-modifiable and potentially modifiable factors associated with kidney recovery which may assist clinicians in counseling and monitoring incident ESRD patients with a greater chance to gain dialysis-independence. Clinical trials are warranted to examine the impact of dialysis prescription on subsequent kidney function recovery.

Severe secondary hyperkalemia and arrhythmia from drug interactions between calcium-channel blocker and voriconazole: a case presentation.

BACKGROUND: Patients with kidney disease may have concurrent hypertension and infection. Dihydropyridine calcium-channel blockers (CCB) are the most popular class of antihypertensive drugs used in clinical settings and can be metabolized by cytochrome P450 isoenzyme 3A4 (CYP3A4). Voriconazole is a commonly used antifungal treatment and a CYP3A4-inhibitor. Insufficient attention to drug interactions from the concomitant use of CCB and voriconazole may result in serious adverse reactions. CASE PRESENTATION: Here, we report a patient with acute kidney injury on stable anti-neutrophil cytoplasm antibody associated vasculitis who developed hyperkalemia resulting in sinus arrest with junctional escape rhythm attributed to drug interactions of CCB with voriconazole. This is a very rarely reported case and may be an under-recognized complication. After continuous renal replacement therapy and changing the anti-hypertensive drugs, symptoms, and laboratory abnormalities of the patient fully recovered. CONCLUSIONS: This case warns us of severe consequences of drug interactions. Co-prescription of CYP3A4-inhibitors with calcium-channel blockers increases the risk of hypotension and acute kidney injury, which may further induce hyperkalemia and arrhythmia.

Regional citrate anticoagulation "non-shock" protocol with pre-calculated flow settings for patients with at least 6 L/hour liver citrate clearance.

BACKGROUND: Regional citrate anticoagulation (RCA) for the prevention of clotting of the extracorporeal blood circuit during continuous kidney replacement therapy (CKRT) has been employed in limited fashion because of the complexity and complications associated with certain protocols. Hypertonic citrate infusion to achieve circuit anticoagulation results in variable systemic citrate- and sodium load and increases the risk of citrate accumulation and hypernatremia. The practice of "single starting calcium infusion rate for all patients" puts patients at risk for clinically significant hypocalcemia if filter effluent calcium losses exceed replacement. A fixed citrate to blood flow ratio, personalized effluent and pre-calculated calcium infusion dosing based on tables derived through kinetic analysis enable providers to use continuous veno-venous hemo-diafiltration (CVVHDF)-RCA in patients with liver citrate clearance of at least 6 L/h. METHODS: This was a single-center prospective observational study conducted in intensive care unit patients triaged to be treated with the novel pre-calculated CVVHDF-RCA "Non-shock" protocol. RCA efficacy outcomes were time to first hemofilter loss and circuit ionized calcium (iCa) levels. Safety outcomes were surrogate of citrate accumulation (TCa/iCa ratio) and the incidence of acid-base and electrolyte complications. RESULTS: Of 53 patients included in the study, 31 (59%) had acute kidney injury and 12 (22.6%) had the diagnosis of cirrhosis at the start of CVVHDF-RCA. The median first hemofilter life censored for causes other than clotting exceeded 70 h. The cumulative incidence of hypernatremia (Na > 148 mM), metabolic alkalosis (HCO3- > 30 mM), hypocalcemia (iCa < 0.9 mM) and hypercalcemia (iCa > 1.5 mM) were 1/47 (1%), 0/50 (0%), 1/53 (2%), 1/53 (2%) respectively and were not clinically significant. The median (25th-75th percentile) of the highest TCa/iCa ratio for every 24-h interval on CKRT was 1.99 (1.91-2.13). CONCLUSIONS: The fixed citrate to blood flow ratio, as opposed to a titration approach, achieves adequate circuit iCa (< 0.4 mm/L) for any hematocrit level and plasma flow. The personalized dosing approach for calcium supplementation based on pre-calculated effluent calcium losses as opposed to the practice of "one starting dose for all" reduces the risk of clinically significant hypocalcemia. The fixed flow settings achieve clinically desirable steady state systemic electrolyte levels.

Obstetric Deliveries in US Women With ESKD: 2002-2015.

RATIONALE & OBJECTIVE: Women with end-stage kidney disease (ESKD) have decreased fertility and are at increased risk for pregnancy complications. This study examined secular trends and outcomes of obstetric deliveries in a US cohort of women with ESKD. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Women aged 18 to 44 years with ESKD and registered in the US Renal Data System from 2002 to 2015. EXPOSURE: ESKD modality (hemodialysis [HD], peritoneal dialysis, transplantation). OUTCOMES: Infant delivery, preterm delivery, cesarean delivery. ANALYTICAL APPROACH: Unadjusted delivery rates were expressed as number of delivering women per 1,000 patient-years among women aged 18 to 44 years within each year during the study period, stratified by ESKD modality. Logistic regression models were used to evaluate associations of delivery, preterm delivery, and cesarean delivery with patient characteristics. RESULTS: The delivery rate in women undergoing HD and women with a kidney transplant increased from 2.1 to 3.6 and 3.1 to 4.6 per 1,000 patient-years, respectively (P<0.001 for each). The delivery rate in patients undergoing peritoneal dialysis was lower and did not increase significantly (P=0.9). Women with a transplant were less likely to deliver preterm compared with women undergoing HD (OR, 0.92; 95% CI, 0.84-1.00), though more likely have a cesarean delivery (OR, 1.18; 95% CI, 1.06-1.31). For deliveries occurring in the 2012 to 2015 period, 75% of women treated with HD were prescribed 4 or fewer outpatient HD treatments per week and 25% were prescribed 5-plus treatments per week in the 30 days before delivery. LIMITATIONS: Ascertainment of outcomes and comorbid conditions using administrative claims data. CONCLUSIONS: The delivery rate in women of reproductive age with ESKD increased from 2002 to 2015 among those treated with transplantation or HD. Women with a functioning transplant were less likely to deliver preterm, but more likely to have a cesarean delivery. Prescriptions for outpatient intensified HD for pregnant women with ESKD were infrequent in 2012 to 2015.

Preoperative Risk and the Association between Hypotension and Postoperative Acute Kidney Injury.

BACKGROUND: Despite the significant healthcare impact of acute kidney injury, little is known regarding prevention. Single-center data have implicated hypotension in developing postoperative acute kidney injury. The generalizability of this finding and the interaction between hypotension and baseline patient disease burden remain unknown. The authors sought to determine whether the association between intraoperative hypotension and acute kidney injury varies by preoperative risk. METHODS: Major noncardiac surgical procedures performed on adult patients across eight hospitals between 2008 and 2015 were reviewed. Derivation and validation cohorts were used, and cases were stratified into preoperative risk quartiles based upon comorbidities and surgical procedure. After preoperative risk stratification, associations between intraoperative hypotension and acute kidney injury were analyzed. Hypotension was defined as the lowest mean arterial pressure range achieved for more than 10 min; ranges were defined as absolute (mmHg) or relative (percentage of decrease from baseline). RESULTS: Among 138,021 cases reviewed, 12,431 (9.0%) developed postoperative acute kidney injury. Major risk factors included anemia, estimated glomerular filtration rate, surgery type, American Society of Anesthesiologists Physical Status, and expected anesthesia duration. Using such factors and others for risk stratification, patients with low baseline risk demonstrated no associations between intraoperative hypotension and acute kidney injury. Patients with medium risk demonstrated associations between severe-range intraoperative hypotension (mean arterial pressure less than 50 mmHg) and acute kidney injury (adjusted odds ratio, 2.62; 95% CI, 1.65 to 4.16 in validation cohort). In patients with the highest risk, mild hypotension ranges (mean arterial pressure 55 to 59 mmHg) were associated with acute kidney injury (adjusted odds ratio, 1.34; 95% CI, 1.16 to 1.56). Compared with absolute hypotension, relative hypotension demonstrated weak associations with acute kidney injury not replicable in the validation cohort. CONCLUSIONS: Adult patients undergoing noncardiac surgery demonstrate varying associations with distinct levels of hypotension when stratified by preoperative risk factors. Specific levels of absolute hypotension, but not relative hypotension, are an important independent risk factor for acute kidney injury.

Exploring reasons for state-level variation in incidence of dialysis-requiring acute kidney injury (AKI-D) in the United States.

BACKGROUND: There is considerable state-level variation in the incidence of dialysis-requiring acute kidney injury (AKI-D). However, little is known about reasons for this geographic variation. METHODS: National cross-sectional state-level ecological study based on State Inpatient Databases (SID) and the Behavioral Risk Factor Surveillance System (BRFSS) in 2011. We analyzed 18 states and six chronic health conditions (diabetes mellitus [diabetes], hypertension, chronic kidney disease [CKD], arteriosclerotic heart disease [ASHD], cancer (excluding skin cancer), and chronic obstructive pulmonary disease [COPD]). Associations between each of the chronic health conditions and AKI-D incidence was assessed using Pearson correlation and multiple regression adjusting for mean age, the proportion of males, and the proportion of non-Hispanic whites in each state. RESULTS: The state-level AKI-D incidence ranged from 190 to 1139 per million population. State-level differences in rates of hospitalization with chronic health conditions (mostly < 3-fold difference in range) were larger than the state-level differences in prevalence for each chronic health condition (mostly < 2.5-fold difference in range). A significant correlation was shown between AKI-D incidence and prevalence of diabetes, ASHD, and COPD, as well as between AKI-D incidence and rate of hospitalization with hypertension. In regression models, after adjusting for age, sex, and race, AKI-D incidence was associated with prevalence of and rates of hospitalization with five chronic health conditions--diabetes, hypertension, CKD, ASHD and COPD--and rates of hospitalization with cancer. CONCLUSIONS: Results from this ecological analysis suggest that state-level variation in AKI-D incidence may be influenced by state-level variations in prevalence of and rates of hospitalization with several chronic health conditions. For most of the explored chronic conditions, AKI-D correlated stronger with rates of hospitalizations with the health conditions rather than with their prevalences, suggesting that better disease management strategies that prevent hospitalizations may translate into lower incidence of AKI-D.

Cramping, crashing, cannulating, and clotting: a qualitative study of patients' definitions of a "bad run" on hemodialysis.

BACKGROUND: Hemodialysis sessions frequently become unstable from complications such as intradialytic hypotension and untoward symptoms. Previous patient safety initiatives promote prevention of treatment complications; yet, they have placed little specific focus on avoidable session instability. A patient-centered definition of session instability grounded in patient experiences, and an understanding of patient perceptions of causes and solutions to instability, may enable such efforts. METHODS: Twenty-five participants participated in three focus groups and/or a survey. They were purposively sampled for variation in region of residence, and sensitivity to patient well-being. Focus group recordings were analyzed using descriptive coding, in vivo coding, and thematic analysis. RESULTS: Patients define unstable sessions ("bad runs") as those in which they experience severe discomfort or unanticipated events that interfere with their ability to receive therapy. Bad runs were characterized primarily by cramping, low blood pressure ("crashing"), cannulation-related difficulties ("bad sticks"), and clotting of the dialysis circuit or vascular access. Patients believed that cramping and crashing could be explained by both patient and clinician behavior: patient fluid consumption and providers' fluid removal goals. Patients felt that the responsibility for cannulation-related problems lay with dialysis staff, and they asked for different staff or self-cannulated as solutions. Clotting was viewed as an idiosyncratic issue with one's body, and perceived solutions were clinician-driven. Patients expressed concern about "bad runs" on their ability to achieve fluid balance. CONCLUSIONS: Findings point to novel priorities for efforts to enhance hemodialysis session stability, and areas in which patients can be supported to become involved in such efforts.

Identification of undocumented over-the-counter medications in an academic nephrology clinic.

OBJECTIVES: To explore how accurately over-the-counter (OTC) medications were documented in an academic nephrology clinic and the benefits of using a novel short questionnaire as part of medication reconciliation (MR). METHODS: We developed a 3-item tailored questionnaire with questions about use of aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs), and proton pump inhibitors (PPIs), which clinical leadership identified as medications of interest. Over the course of 20 days, medical assistants administered the questionnaire to clinic patients immediately after the standard MR. We summarized the rate of inaccurate medication documentation by individual drug and drug class, comparing the standard MR process with the questionnaire. We also calculated diagnostic performance characteristics of the questionnaire. We evaluated the severity of drug-drug interactions between OTC medications discovered using the OTC medication questionnaire and patients' other prescription medications. RESULTS: Nearly 30% (n = 133 of 450) of the participants had at least 1 inaccurately documented OTC medication after the standard MR. The sensitivity and specificity of the standard MR were 79.2% and 93.5%, respectively, for aspirin; 14.5% and 99.5% for NSAIDs; and 80.4% and 97.3% for PPIs. Medication omissions were resolved in the electronic health record approximately two-thirds of the time using the questionnaire. At least 1 drug-drug interaction (DDI) involving active use of an OTC medication was identified in 9.6% of the patients. Of the DDIs, the most common portended effects were increased nephrotoxicity (52.9%), increased bleeding risk (22.9%), and enhanced antiplatelet activity (7.1%). CONCLUSION: Despite the standard MR process, inaccurate documentation of commonly used OTC medications occurred in nearly one-third of outpatients in a nephrology clinic. A brief OTC medication questionnaire may be a scalable and effective strategy to address this problem.

Outpatient Dialysis for Acute Kidney Injury: Progress and Pitfalls.

Dialysis-requiring acute kidney injury (AKI) has increased markedly in the United States. At the same time, mortality rates have recently improved. As such, increasing numbers of patients with AKI are surviving to hospital discharge, including up to 30% who will continue to require outpatient dialysis. In recent years, policy changes have significantly affected the care of this high-risk population. Beginning in 2017, new legislation reversed a previous Centers for Medicare & Medicaid Services policy that prohibited dialysis for AKI at end-stage renal disease (ESRD) facilities. This has improved dialysis options for patients, but the impact on patient outcomes remains uncertain. Unfortunately, there is currently a lack of evidence basis to guide management of this vulnerable patient population. Moving forward, additional data reporting and analyses will be required, analogous to how the US Renal Data System has helped inform ESRD care. As the dialysis setting for patients with AKI shifts to the ESRD setting, it is incumbent on the nephrology community to identify best practices to promote kidney recovery, recognizing that these practices will differ from standard ESRD protocols.

The relation between dialysis-requiring acute kidney injury and recovery from end-stage renal disease: a national study.

BACKGROUND: Approximately 4-6% of incident end stage renal disease (ESRD) patients in the U.S. recover enough kidney function to discontinue dialysis but there is considerable geographic variation. We undertook this study to investigate whether state-level variations in renal recovery among incident ESRD patients correlated with state-level variations in incidence of acute kidney injury requiring dialysis (AKI-D). METHODS: We conducted a national cross-sectional ecological study at the state-level using data from State Inpatient Databases and U.S. Renal Data System. All hospital admissions and all ESRD patients in 18 US states (AZ, AR, CA, FL, IA, KY, MA, MD, MI, NJ, NM, NY, NV, OR, RI, SC, VT, and WA) were included. Correlation between AKI-D incidence and rate of renal recovery across states was determined using Pearson's r (overall and in subgroups). We also calculated partial correlations adjusted for sex and age. RESULTS: AKI-D incidence ranged from 99.0 per million population (pmp) in Vermont to 490.4 pmp in Nevada. Rate of renal recovery among incident ESRD patients ranged from 8.8 pmp in Massachusetts to 29.3 pmp in Florida. A positive correlation between AKI-D incidence and rate of renal recovery among incident ESRD patients at state level was found overall (unadjusted r = 0.67; p = 0.002) and in age, sex, and race subgroups. The overall correlation persisted after adjusting for age (adjusted r = 0.62; p < 0.001) and sex (adjusted r = 0.65; p < 0.001). CONCLUSION: Our findings suggest that AKI-D incidence is an important driver of renal recovery rates among incident ESRD patients.

Single dose oral ranolazine pharmacokinetics in patients receiving maintenance hemodialysis.

PURPOSE: Ranolazine is a novel anti-angina treatment approved in the United States for chronic stable angina. Ranolazine pharmacokinetics have not been studied previously in patients who receive maintenance hemodialysis. This study describes the pharmacokinetics of ranolazine and three major metabolites (CVT-2738, CVT-2512, CVT-2514) in patients receiving thrice weekly hemodialysis. METHODS: Eight participants receiving maintenance hemodialysis completed this prospective, open-label study (study identifier NCT01435174 at Clinicaltrials.gov). Three participants received a single tablet of ranolazine 500 mg (followed by an interim analysis), and five received 2 tablets of ranolazine 500 mg. Blood samples were collected over 65 h to determine the pharmacokinetic characteristics during and between hemodialysis sessions. Non-compartmental analysis was used to determine the individual pharmacokinetic parameters. RESULTS: Ranolazine off-hemodialysis elimination phase half-lives were 3.6 and 3.9 h for 500 mg and 1000 mg doses, respectively. The time to maximum concentration ranged from 2 to 18 hours and the average maximum concentration was 0.65 ± 0.27 mcg/mL and 1.18 ± 0.48 mcg/mL for ranolazine 500 mg and 1000 mg dose, respectively. The mean hemodialysis percent reduction ratio for the ranolazine 500 mg dose was 52.3 ± 8.1% and for the ranolazine 1000 mg dose was 69.2 ± 37.6%. CONCLUSIONS: Data on ranolazine dosing in patients receiving maintenance hemodialysis is almost non-existent. Given the extent of pharmacokinetic variability observed with the 500 mg and 1000 mg oral doses of ranolazine, neither can be recommended as a starting dose in patients receiving maintenance hemodialysis. Guided by the information gained form this study about the extent of hemodialytic drug clearance, further multi-dose clinical trials of ranolazine are needed to optimize therapeutic outcomes in this patient population.