Acetazolamide causes renal [Formula: see text] wasting but inhibits ammoniagenesis and prevents the correction of metabolic acidosis by the kidney.

Carbonic anhydrase (CAII) binds to the electrogenic basolateral Na+-[Formula: see text] cotransporter (NBCe1) and facilitates [Formula: see text] reabsorption across the proximal tubule. However, whether the inhibition of CAII with acetazolamide (ACTZ) alters NBCe1 activity and interferes with the ammoniagenesis pathway remains elusive. To address this issue, we compared the renal adaptation of rats treated with ACTZ to NH4Cl loading for up to 2 wk. The results indicated that ACTZ-treated rats exhibited a sustained metabolic acidosis for up to 2 wk, whereas in NH4Cl-loaded rats, metabolic acidosis was corrected within 2 wk of treatment. [Formula: see text] excretion increased by 10-fold in NH4Cl-loaded rats but only slightly (1.7-fold) in ACTZ-treated rats during the first week despite a similar degree of acidosis. Immunoblot experiments showed that the protein abundance of glutaminase (4-fold), glutamate dehydrogenase (6-fold), and SN1 (8-fold) increased significantly in NH4Cl-loaded rats but remained unchanged in ACTZ-treated rats. Na+/H+ exchanger 3 and NBCe1 proteins were upregulated in response to NH4Cl loading but not ACTZ treatment and were rather sharply downregulated after 2 wk of ACTZ treatment. ACTZ causes renal [Formula: see text] wasting and induces metabolic acidosis but inhibits the upregulation of glutamine transporter and ammoniagenic enzymes and thus suppresses ammonia synthesis and secretion in the proximal tubule, which prevented the correction of acidosis. This effect is likely mediated through the inhibition of the CA-NBCe1 metabolon complex, which results in cell alkalinization. During chronic ACTZ treatment, the downregulation of both NBCe1 and Na+/H+ exchanger 3, along with the inhibition of ammoniagenesis and [Formula: see text] generation, contributes to the maintenance of metabolic acidosis.

Cost-effectiveness of Using Kidneys From HCV-Viremic Donors for Transplantation Into HCV-Uninfected Recipients.

RATIONALE & OBJECTIVE: Less than 4% of patients with kidney failure receive kidney transplants. Although discard rates of hepatitis C virus (HCV)-viremic kidneys are declining, ~39% of HCV-viremic kidneys donated between 2018 and 2019 were discarded. Highly effective antiviral agents are now available to treat chronic HCV infection. Thus, our objective was to examine the cost-effectiveness of transplanting kidneys from HCV-viremic donors into HCV-uninfected recipients. STUDY DESIGN: Markov state transition decision model. Data sources include Medline search results, bibliographies from relevant English language articles, Scientific Registry of Transplant Recipients, and the US Renal Data System. SETTING & POPULATION: US patients receiving maintenance hemodialysis who are on kidney transplant waiting lists. INTERVENTION(S): Transplantation with an HCV-unexposed kidney versus transplantation with an HCV-viremic kidney and HCV treatment. OUTCOMES: Effectiveness measured in quality-adjusted life-years and costs measured in 2018 US dollars. MODEL, PERSPECTIVE, AND TIMEFRAME: We used a health care system perspective with a lifelong time horizon. RESULTS: In the base-case analysis, transplantation with an HCV-viremic kidney was more effective and less costly than transplantation with an HCV-unexposed kidney because of the longer waiting times for HCV-unexposed kidneys, the substantial excess mortality risk while receiving dialysis, and the high efficacy of direct-acting antiviral agents for HCV infection. Transplantation with an HCV-viremic kidney was also preferred in sensitivity analyses of multiple model parameters. The strategy remained cost-effective unless waiting list time for an HCV-viremic kidney exceeded 3.1 years compared with the base-case value of 1.56 year. LIMITATIONS: Estimates of waiting times for patients willing to accept an HCV-viremic kidney were based on data for patients who received HCV-viremic kidney transplants. CONCLUSIONS: Transplanting kidneys from HCV-viremic donors into HCV-uninfected recipients increased quality-adjusted life expectancy and reduced costs compared with a strategy of transplanting kidneys from HCV-unexposed donors.

Pregnancy-Related Acute Kidney Injury in the United States: Clinical Outcomes and Health Care Utilization.

BACKGROUND: Acute kidney injury (AKI) during pregnancy is a public health problem and is associated with maternal and fetal morbidity and mortality. Clinical outcomes and health care utilization in pregnancy-related AKI, especially in women with diabetes, are not well studied. METHODS: Using data from the 2006 to 2015 Nationwide Inpatient Sample, we identified 42,190,790 pregnancy-related hospitalizations in women aged 15-49 years. We determined factors associated with AKI, including race/ethnicity, and associations between AKI and inpatient mortality, and between AKI and cardiovascular (CV) events, during pregnancy-related hospitalizations. We calculated health care expenditures from pregnancy-related AKI hospitalizations. RESULTS: Overall, the rate of AKI during pregnancy-related hospitalizations was 0.08%. In the adjusted regression analysis, a higher likelihood of AKI during pregnancy-related hospitalizations was seen in 2015 (OR 2.20; 95% CI 1.89-2.55) than in 2006; in older women aged 36-40 years (OR 1.49; 95% CI 1.36-1.64) and 41-49 years (OR 2.12; 95% CI 1.84-2.45) than in women aged 20-25 years; in blacks (OR 1.52; 95% CI 1.40-1.65) and Native Americans (OR 1.45; 95% CI 1.10-1.91) than in whites, and in diabetic women (OR 4.43; 95% CI 4.04-4.86) than in those without diabetes. Pregnancy-related hospitalizations with AKI were associated with a higher likelihood of inpatient mortality (OR 13.50; 95% CI 10.47-17.42) and CV events (OR 9.74; 95% CI 9.08-10.46) than were hospitalizations with no AKI. The median cost was higher for a delivery hospitalization with AKI than without AKI (USD 18,072 vs. 4,447). CONCLUSION: The rates of pregnancy-related AKI hospitalizations have increased during the last decade. Factors associated with a higher likelihood of AKI during pregnancy included older age, black and Native American race/ethnicity, and diabetes. Hospitalizations with pregnancy-related AKI have an increased risk of inpatient mortality and CV events, and a higher health care utilization than do those without AKI.

Racial Differences and Factors Associated with Pregnancy in ESKD Patients on Dialysis in the United States.

BACKGROUND: Pregnancy in women with ESKD undergoing dialysis is uncommon due to impaired fertility. Data on pregnancy in women on dialysis in the United States is scarce. METHODS: We evaluated a retrospective cohort of 47,555 women aged 15-44 years on dialysis between January 1, 2005 and December 31, 2013 using data from the United States Renal Data System with Medicare as primary payer. We calculated pregnancy rates and identified factors associated with pregnancy. RESULTS: In 47,555 women on dialysis, 2352 pregnancies were identified. Pregnancy rate was 17.8 per thousand person years (PTPY) with the highest rate in women aged 20-24 (40.9 PTPY). In the adjusted time-to-event analysis, a higher likelihood of pregnancy was seen in Native American (HR, 1.77; 95% CI, 1.33 to 2.36), Hispanic (HR, 1.51; 95% CI, 1.32 to 1.73), and black (HR, 1.33; 95% CI, 1.18 to 1.49) women than in white women. A higher rate of pregnancy was seen in women with ESKD due to malignancy (HR, 1.64; 95% CI, 1.27 to 2.12), GN (HR, 1.38; 95% CI, 1.21 to 1.58), hypertension (HR, 1.32; 95% CI, 1.16 to 1.51), and secondary GN/vasculitis (HR, 1.18; 95% CI, 1.02 to 1.37) than ESKD due to diabetes. A lower likelihood of pregnancy was seen among women on peritoneal dialysis than on hemodialysis (HR, 0.47; 95% CI, 0.41 to 0.55). CONCLUSIONS: The pregnancy rate is higher in women on dialysis than previous reports indicate. A higher likelihood of pregnancy was associated with race/ethnicity, ESKD cause, and dialysis modality.

Adenine acts in the kidney as a signaling factor and causes salt- and water-losing nephropathy: early mechanism of adenine-induced renal injury.

Chronic adenine feeding is extensively used to develop animal models of chronic renal failure with metabolic features resembling those observed in humans. However, the mechanism by which adenine induces renal failure is poorly understood. In this study, we examined the early effects of adenine on water metabolism and salt balance in rats placed in metabolic cages and fed control or adenine-containing diets for 7 days. Molecular and functional studies demonstrated that adenine-fed rats exhibited a significant reduction in food intake, polyuria, polydipsia, decreased urine osmolality, and increased salt wasting. These effects are independent of changes in food intake and result from a coordinated downregulation of water channel aquaporin-2 (AQP2) and salt transporter (Na+-K+-Cl- cotransporter 2; NKCC2) in the collecting duct and medullary thick ascending limb, respectively. As a result, adenine-fed rats exhibited massive volume depletion, as indicated by a significant body weight loss, increased blood urea nitrogen, and increased hematocrit and hemoglobin levels, all of which were significantly corrected with NaCl replacement. Adenine-induced urinary concentrating defect was not corrected by exogenous arginine vasopressin (AVP), and it correlated with reduced cAMP production in vivo and in vitro. In conclusion, adenine acts on renal tubules as a signaling molecule and causes nephrogenic diabetes insipidus with salt wasting, at least, by directly interfering with AVP V2 receptor signaling with subsequent downregulation of NKCC2 and AQP2 in the kidney. The combination of renal fluid loss and decreased food intake with subsequent massive volume depletion likely plays an important role in the development of early prerenal failure that progresses to chronic kidney disease in long-term adenine feeding.

Temporal Trends in Incident Mortality in Dialysis Patients: Focus on Sex and Racial Disparities.

BACKGROUND: Racial minorities and women constitute substantial portions of the incident and prevalent end-stage renal disease (ESRD) population in the United States. Although ESRD is characterized by high mortality, temporal trends, and race and sex differences in mortality have not been studied. METHODS: We evaluated 944,650 adult patients who initiated dialysis between January 1, 2005 and December 31, 2014, using the United States Renal Data System, for sex-related and race-related trends in mortality. Logistic regression models adjusted for pre-dialysis health status were used to examine associations among the predictors' sex, race, and year of incident dialysis, and the outcome all-cause mortality at 1-year post ESRD. RESULTS: The mean age was 65 ± 14 years. The 1-year crude mortality rates in incident ESRD patients decreased by 28% from 2004 to 2015. Risk-adjusted 1-year mortality decreased by 3% for each later year of incident ESRD (p < 0.001). In general, from 2005 to 2014, mortality rates decreased across both sexes, and all races. White patients experienced the lowest reduction in adjusted 1-year mortality rates (16%). While women experienced a survival advantage over men in 2005, by 2014 it was reversed to survival advantage for men. Combining all years, the adjusted risk of dying at 1-year after initiating dialysis was lower in women than men (OR 0.98; 95% CI 0.97-0.99), and as compared to whites, was lower in blacks (OR 0.73; 95% CI -0.72-0.74), Hispanics (OR 0.64; 95% CI 0.63-0.65), Asians (OR 0.55; 95% CI 0.53-0.56), and Native Americans (OR 0.67; 95% CI 0.63-0.71). CONCLUSION: The 1-year mortality rates among patients with ESRD have decreased steadily during a recent 10-year period across both men and women, and in all 5 races. Women have only a 2% lower risk of dying at 1-year after dialysis initiation than men. White patients had higher mortality as compared to other races. Our results suggest the need for sex, and race-specific treatment strategies in ESRD care.

Perceptions of nephrology among medical students and internal medicine residents: a national survey among institutions with nephrology exposure.

BACKGROUND: Fewer trainees are choosing to pursue nephrology. Only 60.1% of positions filled in the 2018 fellowship Match, which is concerning given the rising prevalence of end-stage kidney disease. Identifying factors influential in career choices is critical to inform focused approaches to recruit qualified applicants. METHODS: To understand perceptions of nephrology and assess factors influential in specialty choice among early career trainees, an anonymous survey was distributed to upper-level medical students and internal medicine residents at programs identified through the American Association of Medical Colleges (AAMC) and American Medical Association's Fellowship and Residency Electronic Interactive Database (FREIDA). RESULTS: Of 4199 recipients, 644 (15.3%) participants responded, including 315 upper-level medical students, 308 residents, and three chief residents from 30 institutions. An interest in the subject was the most critical factor in selecting a specialty (92%). Other key factors included a suitable work-life balance (73%), access to mentors (70%), and subject exposure (66%). Lack of interest was the most frequently-cited reason to forgo a nephrology fellowship (79%), followed by concerns regarding remuneration (43%), work-life balance (39%), and subject exposure (32%). In free-text responses, several participants described frustration with managing patients on hemodialysis and desired combined training with specialties such as critical care. Respondents who had considered nephrology at any point cited an interest in physiology or interface with a mentor as key driving factors. CONCLUSIONS: A lack of interest in and exposure to the subject, perceptions of poor earning potential and patient nonadherence, and concerns regarding work-life balance were influential in participants' decisions to forgo nephrology training. Incorporating novel educational tools and broadening the scope of the nephrology elective, highlighting ongoing areas of clinical and research innovation, expanding opportunities for interdisciplinary collaboration and procedural skills, and cultivating strategies to reduce burnout may be useful areas on which to focus future recruitment efforts.

Transplanting Hepatitis C Virus-Infected Versus Uninfected Kidneys Into Hepatitis C Virus-Infected Recipients: A Cost-Effectiveness Analysis.

Background: Direct-acting antiviral agents are now available to treat chronic hepatitis C virus (HCV) infection in patients with end-stage renal disease (ESRD). Objective: To examine whether it is more cost-effective to transplant HCV-infected or HCV-uninfected kidneys into HCV-infected patients. Design: Markov state-transition decision model. Data Sources: MEDLINE searches and bibliographies from relevant English-language articles. Target Population: HCV-infected patients with ESRD receiving hemodialysis in the United States. Time Horizon: Lifetime. Perspective: Health care system. Intervention: Transplant of an HCV-infected kidney followed by HCV treatment versus transplant of an HCV-uninfected kidney preceded by HCV treatment. Outcome Measures: Effectiveness, measured in quality-adjusted life-years (QALYs), and costs, measured in 2017 U.S. dollars. Results of Base-Case Analysis: Transplant of an HCV-infected kidney followed by HCV treatment was more effective and less costly than transplant of an HCV-uninfected kidney preceded by HCV treatment, largely because of longer wait times for uninfected kidneys. A typical 57.8-year-old patient receiving hemodialysis would gain an average of 0.50 QALY at a lifetime cost savings of $41 591. Results of Sensitivity Analysis: Transplant of an HCV-infected kidney followed by HCV treatment continued to be preferred in sensitivity analyses of many model parameters. Transplant of an HCV-uninfected kidney preceded by HCV treatment was not preferred unless the additional wait time for an uninfected kidney was less than 161 days. Limitation: The study did not consider the benefit of decreased HCV transmission from treating HCV-infected patients. Conclusion: Transplanting HCV-infected kidneys into HCV-infected patients increased quality-adjusted life expectancy and reduced costs compared with transplanting HCV-uninfected kidneys into HCV-infected patients. Primary Funding Source: Merck Sharp & Dohme and the National Center for Advancing Translational Sciences.

Gender and Racial Disparities in Initial Hemodialysis Access and Outcomes in Incident End-Stage Renal Disease Patients.

BACKGROUND: Arteriovenous (AV) access confers survival benefits over central venous catheters (CVC) in hemodialysis patients. Although chronic kidney disease disproportionately affects women and racial minorities, disparities in the -utilization of hemodialysis access across Asians, Native Americans, Hispanics, blacks, and whites among males and females after accounting for pre-dialysis health are not well studied. METHODS: We evaluated 885,699 patients with end-stage renal disease who initiated hemodialysis between January 1, 2004 and December 31, 2014 using the US Renal Data System. Multivariable logistic regression models -adjusted for pre-dialysis health were used to test the associations between gender and race on type of vascular access (AV access vs. CVC, and AV fistula vs. AV graft) at hemodialysis initiation as primary outcome, and on 1-year mortality as a secondary outcome. RESULTS: Mean age was 65 ± 14 years. Females were less likely to use AV access for hemodialysis initiation than were males (OR 0.85; 95% CI 0.84-0.86). Compared to whites, adjusted odds of AV access for hemodialysis initiation were higher in blacks (OR 1.08; 95% CI 1.07-1.70), Asians (OR 1.11; 95% CI 1.07-1.14); and lower in Hispanics (OR 0.89; 95% CI 0.87-0.90). There was no -significant difference in mortality between males and females. Compared to whites, 1-year adjusted mortality was lower in Asians (OR 0.55; 95% CI 0.53-0.56), blacks (OR 0.67; 95% CI 0.66-0.68), Hispanics (OR 0.62; 95% CI 0.61-0.63), and Native Americans (OR 0.62; 95% CI 0.58-0.66). CONCLUSION: Females had lower odds of using AV access than do males for hemodialysis initiation. As compared to whites, blacks and Asians were more likely, and Hispanics were less likely to use AV access for first outpatient hemodialysis. Further investigation of biological and process of care factors may help in developing ways to reduce these disparities.

Acute Kidney Injury before Dialysis Initiation Predicts Adverse Outcomes in Hemodialysis Patients.

BACKGROUND: Acute kidney injury (AKI) is associated with increased morbidity and mortality. Mortality in end-stage renal disease (ESRD) patients is highest during the first year of dialysis. The impact of pre-ESRD AKI events on long-term outcomes in incident ESRD patients remains unknown. METHODS: We evaluated a retrospective cohort of 47,341 incident hemodialysis patients from the United States Renal Data System with linked Medicare data for at least 2 years prior to hemodialysis initiation. We examined the impact of pre-ESRD AKI events in the 2-year pre-ESRD period on the type of vascular access used at hemodialysis initiation (central venous catheter (CVC) versus arteriovenous access), and 1-year all-cause mortality after initiating hemodialysis. RESULTS: The mean age was 72 ± 11 years. Of the study cohort, 18% initiated hemodialysis with arteriovenous access, and 54% of patients had at least one pre-ESRD AKI event. One-year, all-cause mortality was 32%. Compared to 75% for patients without a pre-ESRD AKI event, 89% of patients with a pre-ESRD AKI event initiated hemodialysis with CVC than arteriovenous access (p < 0.001). A pre-ESRD AKI event was associated with lower adjusted odds of starting hemodialysis with an arteriovenous access (OR 0.47; 95% CI 0.44-0.50, p < 0.001), and higher adjusted odds of 1-year mortality (OR 1.36; 95% CI 1.30-1.42, p < 0.001). CONCLUSION: An AKI event prior to initiating hemodialysis independently increases the risk of CVC use and predicts 1-year mortality. Improving processes of care after AKI events may improve dialysis outcomes in patients who progress to ESRD.

Functional status, pre-dialysis health and clinical outcomes among elderly dialysis patients.

BACKGROUND: Elderly patients comprise the fastest growing population initiating dialysis in United States. The impact of poor functional status and pre-dialysis health status on clinical outcomes in elderly dialysis patients is not well studied. METHODS: We studied a retrospective cohort of 49,645 incident end stage renal disease patients that initiated dialysis between January 1, 2008 and December 31, 2008 from the United States Renal Data System with linked Medicare data covering at least 2 years prior to dialysis initiation. Using logistic regression models adjusted for pre-dialysis health status and other cofounders, we examined the impact of poor functional status as defined from form 2728 on 1-year all-cause mortality as primary outcome, type of dialysis modality (hemodialysis vs. peritoneal dialysis), and type of initial vascular access (arteriovenous access vs. central venous catheter) among hemodialysis patients as secondary outcomes. RESULTS: Mean age was 72 ± 11 years. At dialysis initiation, 18.7% reported poor functional status, 88.9% had at least 1 pre-dialysis hospitalization, and 27.8% did not receive pre-dialysis nephrology care. In adjusted analyses, 1-year mortality was higher in patients with poor functional status (OR, 1.48; 95% CI, 1.40-1.57). Adjusted odds of being initiated on hemodialysis than peritoneal dialysis (odds ratio [OR], 1.39; 95% confidence interval [CI], 1.16-1.66) were higher in patients with poor functional status. Poor functional status decreased the adjusted odds of starting hemodialysis with arteriovenous access as compared to central venous catheter (OR, 0.79; 95% CI, 0.72-0.86). CONCLUSION: Poor functional status in elderly patients with end stage renal disease is associated with higher odds of initiating hemodialysis; increases the risk of central venous catheter use, and is an independent predictor of 1-year mortality.

Temporal trends of dialysis requiring acute kidney injury after orthotopic cardiac and liver transplant hospitalizations.

BACKGROUND: The epidemiology and outcomes of acute kidney injury (AKI) in prevalent non-renal solid organ transplant recipients is unknown. METHODS: We assessed the epidemiology of trends in acute kidney injury (AKI) in orthotopic cardiac and liver transplant recipients in the United States. We used the Nationwide Inpatient Sample to evaluate the yearly incidence trends (2002 to 2013) of the primary outcome, defined as AKI requiring dialysis (AKI-D) in hospitalizations after cardiac and liver transplantation. We also evaluated the trend and impact of AKI-D on hospital mortality and adverse discharge using adjusted odds ratios (aOR). RESULTS: The proportion of hospitalizations with AKI (9.7 to 32.7% in cardiac and 8.5 to 28.1% in liver transplant hospitalizations; ptrend<0.01) and AKI-D (1.63 to 2.33% in cardiac and 1.32 to 2.65% in liver transplant hospitalizations; ptrend<0.01) increased from 2002-2013. This increase in AKI-D was explained by changes in race and increase in age and comorbidity burden of transplant hospitalizations. AKI-D was associated with increased odds of in hospital mortality (aOR 2.85; 95% CI 2.11-3.80 in cardiac and aOR 2.00; 95% CI 1.55-2.59 in liver transplant hospitalizations) and adverse discharge [discharge other than home] (aOR 1.97; 95% CI 1.53-2.55 in cardiac and 1.91; 95% CI 1.57-2.30 in liver transplant hospitalizations). CONCLUSIONS: This study highlights the growing burden of AKI-D in non-renal solid organ transplant recipients and its devastating impact, and emphasizes the need to develop strategies to reduce the risk of AKI to improve health outcomes.

Dialysis Requiring Acute Kidney Injury in Acute Cerebrovascular Accident Hospitalizations.

BACKGROUND AND PURPOSE: The epidemiology of dialysis requiring acute kidney injury (AKI-D) in acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH) admissions is poorly understood with previous studies being from a single center or year. METHODS: We used the Nationwide Inpatient Sample to evaluate the yearly incidence trends of AKI-D in hospitalizations with AIS and ICH from 2002 to 2011. We also evaluated the trend of impact of AKI-D on in-hospital mortality and adverse discharge using adjusted odds ratios (aOR) after adjusting for demographics and comorbidity indices. RESULTS: We extracted a total of 3,937,928 and 696,754 hospitalizations with AIS and ICH, respectively. AKI-D occurred in 1.5 and 3.5 per 1000 in AIS and ICH admissions, respectively. Incidence of admissions complicated by AKI-D doubled from 0.9/1000 to 1.7/1000 in AIS and from 2.1/1000 to 4.3/1000 in ICH admissions. In AIS admissions, AKI-D was associated with 30% higher odds of mortality (aOR, 1.30; 95% confidence interval, 1.12-1.48; P<0.001) and 18% higher odds of adverse discharge (aOR, 1.18; 95% confidence interval, 1.02-1.37; P<0.001). Similarly, in ICH admissions, AKI-D was associated with twice the odds of mortality (aOR, 1.95; 95% confidence interval, 1.61-2.36; P<0.01) and 74% higher odds of adverse discharge (aOR, 1.74; 95% confidence interval, 1.34-2.24; P<0.01). Attributable risk percent of mortality was high with AKI-D (98%-99%) and did not change significantly over the study period. CONCLUSIONS: Incidence of AKI-D complicating hospitalizations with cerebrovascular accident continues to grow and is associated with increased mortality and adverse discharge. This highlights the need for early diagnosis, better risk stratification, and preparedness for need for complex long-term care in this vulnerable population.

A clinical score to predict recovery in end-stage kidney disease due to acute kidney injury.

Background: Acute kidney injury (AKI) is a major contributor to end-stage kidney disease (ESKD). About one-third of patients with ESKD due to AKI recover kidney function. However, the inability to accurately predict recovery leads to improper triage of clinical monitoring and impacts the quality of care in ESKD. Methods: Using data from the United States Renal Data System from 2005 to 2014 (n = 22 922), we developed a clinical score to predict kidney recovery within 90 days and within 12 months after dialysis initiation in patients with ESKD due to AKI. Multivariable logistic regressions were used to examine the effect of various covariates on the primary outcome of kidney recovery to develop the scoring system. The resulting logistic parameter estimates were transformed into integer point totals by doubling and rounding the estimates. Internal validation was performed. Results: Twenty-four percent and 34% of patients with ESKD due to AKI recovered kidney function within 90 days and 12 months, respectively. Factors contributing to points in the two scoring systems were similar but not identical, and included age, race/ethnicity, body mass index, congestive heart failure, cancer, amputation, functional status, hemoglobin and prior nephrology care. Three score categories of increasing recovery were formed: low score (0-6), medium score (7-9) and high score (10-12), which exhibited 90-day recovery rates of 12%, 26% and 57%. For the 12-month scores, the low, medium and high groups consisted of scores 0-5, 6-8 and 9-11, with 12-month recovery rates of 16%, 33% and 62%, respectively. The internal validation assessment showed no overfitting of the models. Conclusion: A clinical score derived from information available at incident dialysis predicts renal recovery at 90 days and 12 months in patients with presumed ESKD due to AKI. The score can help triage appropriate monitoring to facilitate recovery and begin planning long-term dialysis care for others.

Sex Differences in Cardiovascular Outcomes in Patients With Kidney Failure.

BACKGROUND: Cardiovascular disease is the leading cause of mortality in patients with kidney failure, and their risk of cardiovascular events is 10 to 20 times higher as compared with the general population. METHODS AND RESULTS: We evaluated 508 822 patients who initiated dialysis between January 1, 2005 and December 31, 2014 using the United States Renal Data System with linked Medicare claims. We determined hospitalization rates for cardiovascular events, defined by acute coronary syndrome, heart failure, and stroke. We examined the association of sex with outcome of cardiovascular events, cardiovascular death, and all-cause death using adjusted time-to-event models. The mean age was 70±12 years and 44.7% were women. The cardiovascular event rate was 232 per thousand person-years (95% CI, 231-233), with a higher rate in women than in men (248 per thousand person-years [95% CI, 247-250] versus 219 per thousand person-years [95% CI, 217-220]). Women had a 14% higher risk of cardiovascular events than men (hazard ratio [HR], 1.14 [95% CI, 1.13-1.16]). Women had a 16% higher risk of heart failure (HR, 1.16 [95% CI, 1.15-1.18]), a 31% higher risk of stroke (HR, 1.31 [95% CI, 1.28-1.34]), and no difference in risk of acute coronary syndrome (HR, 1.01 [95% CI, 0.99-1.03]). Women had a lower risk of cardiovascular death (HR, 0.89 [95% CI, 0.88-0.90]) and a lower risk of all-cause death than men (HR, 0.96 [95% CI, 0.95-0.97]). CONCLUSIONS: Among patients undergoing dialysis, women have a higher risk of cardiovascular events of heart failure and stroke than men. Women have a lower adjusted risk of cardiovascular mortality and all-cause mortality.

KDOQI US commentary on the 2012 KDIGO clinical practice guideline for acute kidney injury.

In response to the recently released 2012 KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for acute kidney injury (AKI), the National Kidney Foundation organized a group of US experts in adult and pediatric AKI and critical care nephrology to review the recommendations and comment on their relevancy in the context of current US clinical practice and concerns. The first portion of the KDIGO guideline attempts to harmonize earlier consensus definitions and staging criteria for AKI. While the expert panel thought that the KDIGO definition and staging criteria are appropriate for defining the epidemiology of AKI and in the design of clinical trials, the panel concluded that there is insufficient evidence to support their widespread application to clinical care in the United States. The panel generally concurred with the remainder of the KDIGO guidelines that are focused on the prevention and pharmacologic and dialytic management of AKI, although noting the dearth of clinical trial evidence to provide strong evidence-based recommendations and the continued absence of effective therapies beyond hemodynamic optimization and avoidance of nephrotoxins for the prevention and treatment of AKI.

Definition, Staging, and Role of Biomarkers in Acute Kidney Injury in the Context of Cardiovascular Interventions.

Acute kidney injury (AKI) is a frequently occurring complication of cardiovascular interventions, and associated with adverse outcomes. Therefore, a clear definition of AKI is of paramount importance to enable timely recognition and treatment. Historically, changes in the serum creatinine and urine output have been used to define AKI, and the criteria have evolved over time with better understanding of the impact of AKI on the outcomes. However, the reliance on serum creatinine for these AKI definitions carries numerous limitations including delayed rise, inability to differentiate between hemodynamics versus structural injury and assay variability to name a few.

Social determinants of patiromer adherence and abandonment: An observational, retrospective, real-world claims analysis.

BACKGROUND: Hyperkalemia is a frequent and serious complication in chronic kidney disease (CKD) that can impede continuation of beneficial evidence-based therapies. Recently, novel therapies such as patiromer have been developed to treat chronic hyperkalemia, but their optimal utility hinges on adherence. Social determinants of health (SDOH) are critically important and can impact both medical conditions and treatment prescription adherence. This analysis examines SDOH and their influence on adherence to patiromer or abandonment of prescriptions for hyperkalemia treatment. METHODS: This was an observational, retrospective, real-world claims analysis of adults with patiromer prescriptions and 6- and 12-months pre- and post-index prescription data in Symphony Health's Dataverse during 2015-2020, and SDOH from census data. Subgroups included patients with heart failure (HF), hyperkalemia-confounding prescriptions, and any CKD stages. Adherence was defined as >80% of proportion of days covered (PDC) for ≥60 days and ≥6 months, and abandonment as a portion of reversed claims. Quasi-Poisson regression modeled the impact of independent variables on PDC. Abandonment models used logistic regression, controlling for similar factors and initial days' supply. Statistical significance was p<0.05. RESULTS: 48% of patients at 60 days and 25% at 6 months had a patiromer PDC >80%. Higher PDC was associated with older age, males, Medicare/Medicaid coverage, nephrologist prescribed, and those receiving renin-angiotensin-aldosterone system inhibitors. Lower PDC correlated with higher out-of-pocket cost, unemployment, poverty, disability, and any CKD stage with comorbid HF. PDC was better in regions with higher education and income. CONCLUSIONS: SDOH (unemployment, poverty, education, income) and health indicators (disability, comorbid CKD, HF) were associated with low PDC. Prescription abandonment was higher in patients with prescribed higher dose, higher out-of-pocket costs, those with disability, or designated White. Key demographic, social, and other factors play a role in drug adherence when treating life-threatening abnormalities such as hyperkalemia and may influence patient outcomes.