Renoprotective Effects of Metabolic Surgery Versus GLP1 Receptor Agonists on Progression of Kidney Impairment in Patients with Established Kidney Disease.

OBJECTIVE: To examine the renoprotective effects of metabolic surgery in patients with established chronic kidney disease (CKD). BACKGROUND: The impact of metabolic surgery compared with glucagon-like peptide-1 receptor agonists (GLP-1RA) in patients with established CKD has not been fully characterized. METHODS: Patients with obesity (body mass index ≥30 kg/m 2 ), type 2 diabetes, and baseline estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m² who underwent metabolic bariatric surgery at a large US health system (2010-2017) were compared with nonsurgical patients who continuously received GLP-1RA. The primary end point was CKD progression, defined as a decline of eGFR by ≥50% or to <15 mL/min/1.73 m 2 , initiation of dialysis, or kidney transplant. The secondary end point was the incident kidney failure (eGFR <15 mL/min/1.73 m 2 , dialysis, or kidney transplant) or all-cause mortality. RESULTS: 425 patients, including 183 patients in the metabolic surgery group and 242 patients in the GLP-1RA group, with a median follow-up of 5.8 years (IQR, 4.4-7.6), were analyzed. The cumulative incidence of the primary end point at 8 years was 21.7% (95% CI: 12.2-30.6) in the surgical group and 45.1% (95% CI: 27.7 to 58.4) in the nonsurgical group, with an adjusted hazard ratio of 0.40 (95% CI: 0.21 to 0.76), P =0.006. The cumulative incidence of the secondary composite end point at 8 years was 24.0% (95% CI: 14.1 to 33.2) in the surgical group and 43.8% (95% CI: 28.1 to 56.1) in the nonsurgical group, with an adjusted HR of 0.56 (95% CI: 0.31 to 0.99), P =0.048. CONCLUSIONS: Among patients with type 2 diabetes, obesity, and established CKD, metabolic surgery, compared with GLP-1RA, was significantly associated with a 60% lower risk of progression of kidney impairment and a 44% lower risk of kidney failure or death. Metabolic surgery should be considered as a therapeutic option for patients with CKD and obesity.

Factors Associated With Non-vaccination for Influenza Among Patients With CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.

RATIONALE & OBJECTIVE: Vaccination for influenza is strongly recommended for people with chronic kidney disease (CKD) due to their immunocompromised state. Identifying risk factors for not receiving an influenza vaccine (non-vaccination) could inform strategies for improving vaccine uptake in this high-risk population. STUDY DESIGN: Longitudinal observational study. SETTING & PARTICIPANTS: 3,692 Chronic Renal Insufficiency Cohort Study (CRIC) participants. EXPOSURE: Demographic factors, social determinants of health, clinical conditions, and health behaviors. OUTCOME: Influenza non-vaccination, which was assessed based on a receipt of influenza vaccine ascertained during annual clinic visits in a subset of participants who were under nephrology care. ANALYTICAL APPROACH: Mixed-effects Poisson models to estimate adjusted prevalence ratios (APRs). RESULTS: Between 2009 and 2020, the pooled mean vaccine uptake was 72% (mean age, 66 years; 44% female; 44% Black race). In multivariable models, factors significantly associated with influenza non-vaccination were younger age (APR, 2.16 [95% CI, 1.85-2.52] for<50 vs≥75 years), Black race (APR, 1.58 [95% CI, 1.43-1.75] vs White race), lower education (APR, 1.20 [95% CI, 1.04-1.39 for less than high school vs college graduate]), lower annual household income (APR, 1.26 [95% CI, 1.06-1.49] for <$20,000 vs >$100,000), formerly married status (APR, 1.22 [95% CI, 1.09-1.35] vs currently married), and nonemployed status (APR, 1.13 [95% CI, 1.02-1.24] vs employed). In contrast, participants with diabetes (APR, 0.80 [95% CI, 0.73-0.87] vs no diabetes), chronic obstructive pulmonary disease (COPD) (APR, 0.80 [95% CI, 0.70-0.92] vs no COPD), end-stage kidney disease (APR, 0.64 [0.56 to 0.76] vs estimated glomerular filtration rate≥60mL/min/1.73m2), frailty (APR, 0.86 [95% CI, 0.74-0.99] vs no frailty), and ideal physical activity (APR, 0.90 [95% CI, 0.82-0.99] vs. physically inactive) were less likely to have non-vaccination status. LIMITATIONS: Possible residual confounding. CONCLUSIONS: Among adults with CKD receiving nephrology care, younger adults, Black individuals, and those with adverse social determinants of health were more likely to have the influenza non-vaccination status. Strategies are needed to address these disparities and reduce barriers to vaccination. PLAIN-LANGUAGE SUMMARY: Identifying risk factors for not receiving an influenza vaccine ("non-vaccination") in people living with kidney disease, who are at risk of influenza and its complications, could inform strategies for improving vaccine uptake. In this study, we examined whether demographic factors, social determinants of health, and clinical conditions were linked to the status of not receiving an influenza vaccine among people living with kidney disease and receiving nephrology care. We found that younger adults, Black individuals, and those with adverse social determinants of health were more likely to not receive the influenza vaccine. These findings suggest the need for strategies to address these disparities and reduce barriers to vaccination in people living with kidney disease.

Estimated Glomerular Filtration Rate Using Cystatin C is a More Sensitive Marker for Kidney Dysfunction in Nonweight-bearing Individuals.

PURPOSE: Individuals with neuromuscular disorders and neurogenic lower urinary tract dysfunction are commonly nonweight-bearing with lower lean muscle mass than the general population. We sought to compare estimated glomerular filtration rate equations that include creatinine, cystatin C, or both, in nonweight-bearing individuals and matched ambulatory controls. MATERIALS AND METHODS: Records were reviewed for individuals with serum creatinine (Cr) and cystatin C (Cys) and diagnosis consistent with nonweight-bearing status, and matched ambulatory controls. The 2021 CKD-EPI (Chronic Kidney Disease-Epidemiology Collaboration) race agnostic equations were used to calculate estimated glomerular filtration rate. Renal function was compared by equation in the overall cohorts and in a patient subset with imaging and/or urinalysis evidence of renal dysfunction. RESULTS: Nonweight-bearing (n = 102) and control populations (n = 204) had similar demographics. In the nonweight-bearing population, estimated glomerular filtration rate differed when calculated using CKD-EPICr, CKD-EPICr+Cys, and CKD-EPICys (107, 93, 80 mL/min/1.73 m2, respectively, P < .001). The differences in estimated glomerular filtration rate were greater in the nonweight-bearing relative to the control group regardless of CKD-EPI equation pairs compared (P < .001). In the patient subset with imaging and/or proteinuria evidence of renal dysfunction, the nonweight-bearing population again had different estimated glomerular filtration rate when calculated using CKD-EPICr, CKD-EPICr+Cys, and CKD-EPICys (P < .001). Fifty-eight percent of nonweight-bearing individuals with evidence of renal dysfunction on imaging or urinalysis were reclassified into a lower estimated glomerular filtration rate category when using estimated glomerular filtration rateCys relative to estimated glomerular filtration rateCr. CONCLUSIONS: Estimated glomerular filtration rate equations containing serum creatinine, cystatin C, or both, validated in mostly ambulatory populations, are not equivalently accurate in estimating kidney function in nonweight-bearing individuals. Comparison of these equations against gold standard glomerular filtration rate measurement is needed to determine which most closely approximates true glomerular filtration rate.

Upper Reference Limits for High-Sensitivity Cardiac Troponin T and N-Terminal Fragment of the Prohormone Brain Natriuretic Peptide in Patients With CKD.

RATIONALE & OBJECTIVE: The utility of conventional upper reference limits (URL) for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hsTnT) in chronic kidney disease (CKD) remains debated. We analyzed the distribution of hsTnT and NT-proBNP in people with CKD in ambulatory settings to examine the diagnostic value of conventional URL in this population. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: We studied participants of the Chronic Renal Insufficiency Cohort (CRIC) with CKD and no self-reported history of cardiovascular disease. EXPOSURE: Estimated glomerular filtration rate (eGFR). OUTCOME: NT-proBNP and hsTnT at baseline. ANALYTICAL APPROACH: We described the proportion of participants above the conventional URL for NT-proBNP (125pg/mL) and hsTnT (14ng/L) overall and by eGFR. We then estimated 99th percentile URL for NT-proBNP and hsTnT. Using quantile regression of the 99th percentile, we modeled the association of eGFR with NT-proBNP and hsTnT. RESULTS: Among 2,312 CKD participants, 40% and 43% had levels of NT-proBNP and hsTnT above the conventional URL, respectively. In those with eGFR <30mL/min/1.73m2, 71% and 68% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, respectively. Among all CKD participants, the 99th percentile for NT-proBNP was 3,592 (95% CI, 2,470-4,849) pg/mL and for hsTnT it was 126 (95% CI, 100-144) ng/L. Each 15mL/min/1.73m2 decrement in eGFR was associated with a ~40% higher threshold for the 99th percentile of NT-proBNP (1.43 [95% CI, 1.21-1.69]) and hsTnT (1.45 [95% CI, 1.31-1.60]). LIMITATIONS: Study included ambulatory patients, and we could not test the accuracy of the URL of NT-proBNP and hsTnT in the acute care setting. CONCLUSIONS: In this ambulatory CKD population with no self-reported history of cardiovascular disease, a range of 40%-88% of participants had concentrations of NT-proBNP and hsTnT above the conventional URL, depending on eGFR strata. Developing eGFR-specific thresholds for these commonly used cardiac biomarkers in the setting of CKD may improve their utility for evaluation of suspected heart failure and myocardial infarction.

High-Throughput Metabolomics and Diabetic Kidney Disease Progression: Evidence from the Chronic Renal Insufficiency (CRIC) Study.

INTRODUCTION: Metabolomics could offer novel prognostic biomarkers and elucidate mechanisms of diabetic kidney disease (DKD) progression. Via metabolomic analysis of urine samples from 995 CRIC participants with diabetes and state-of-the-art statistical modeling, we aimed to identify metabolites prognostic to DKD progression. METHODS: Urine samples (N = 995) were assayed for relative metabolite abundance by untargeted flow-injection mass spectrometry, and stringent statistical criteria were used to eliminate noisy compounds, resulting in 698 annotated metabolite ions. Utilizing the 698 metabolites' ion abundance along with clinical data (demographics, blood pressure, HbA1c, eGFR, and albuminuria), we developed univariate and multivariate models for the eGFR slope using penalized (lasso) and random forest models. Final models were tested on time-to-ESKD (end-stage kidney disease) via cross-validated C-statistics. We also conducted pathway enrichment analysis and a targeted analysis of a subset of metabolites. RESULTS: Six eGFR slope models selected 9-30 variables. In the adjusted ESKD model with highest C-statistic, valine (or betaine) and 3-(4-methyl-3-pentenyl)thiophene were associated (p < 0.05) with 44% and 65% higher hazard of ESKD per doubling of metabolite abundance, respectively. Also, 13 (of 15) prognostic amino acids, including valine and betaine, were confirmed in the targeted analysis. Enrichment analysis revealed pathways implicated in kidney and cardiometabolic disease. CONCLUSIONS: Using the diverse CRIC sample, a high-throughput untargeted assay, followed by targeted analysis, and rigorous statistical analysis to reduce false discovery, we identified several novel metabolites implicated in DKD progression. If replicated in independent cohorts, our findings could inform risk stratification and treatment strategies for patients with DKD.

New Devices and Technologies for Hemodialysis Vascular Access: A Review.

In the United States, hemodialysis remains the most common treatment modality for kidney failure, chosen by almost 90% of incident patients. A functioning vascular access is key to providing adequate hemodialysis therapy. Recently, major innovations in devices and technology for hemodialysis vascular access care have rapidly changed the landscape. Novel endovascular devices for creation of arteriovenous fistulas may offer a solution to the barriers encountered in initiating maintenance hemodialysis with a permanent vascular access rather than a central venous catheter (CVC). Furthermore, in the prevalent hemodialysis population, the minimally invasive endovascular arteriovenous fistula procedure should help improve long wait times for vascular access creation, which remains a major barrier to reducing CVC dependence. Bioengineered grafts are being developed and may offer another option to polytetrafluoroethylene grafts. Early studies with these biocompatible grafts are promising, as additional studies continue to evaluate their clinical outcomes in comparison to cryopreserved or synthetic options. Prolonging the vascular access patency with appropriate use of devices such as drug-coated balloons and stent grafts may complement the novel techniques of creating arteriovenous access. Finally, innovative solutions to treat stenosed and occluded thoracic central veins can provide an approach to creating a vascular access and allow patients with exhausted vasculature to remain on hemodialysis. The robust developments in hemodialysis vascular access are likely to change practice patterns in the near future.

Adiposity, Physical Function, and Their Associations With Insulin Resistance, Inflammation, and Adipokines in CKD.

RATIONALE & OBJECTIVES: Adiposity and physical fitness levels are major drivers of cardiometabolic risk, but these relationships have not been well-characterized in chronic kidney disease (CKD). We examined the associations of visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), intrahepatic fat, and physical function with inflammation, insulin resistance, and adipokine levels in patients with CKD. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Participants with stages 3-5 CKD not receiving maintenance dialysis, followed up at one of 8 clinical sites in the Chronic Renal Insufficiency Cohort (CRIC) Study, and who underwent magnetic resonance imaging of the abdomen at an annual CRIC Study visit (n = 419). PREDICTORS: VAT volume, SAT volume, intrahepatic fat, body mass index, waist circumference, and time taken to complete the 400-m walk test (physical function). OUTCOMES: Markers of inflammation (interleukin 1ß [IL-1ß], IL-6, tumor necrosis factor receptor 1 [TNFR1], and TNFR2), insulin resistance (homeostasis model assessment of insulin resistance), and adipokine levels (adiponectin, total and high molecular weight, resistin, and leptin). ANALYTICAL APPROACH: Multivariable linear regression of VAT and SAT volume, intrahepatic fat, and physical function with individual markers (log-transformed values), adjusting for relevant covariates. RESULTS: Mean age of the study population was 64.3 years; 41% were women, and mean estimated glomerular filtration rate was 53.2±14.6 (SD) mL/min/1.73m2. More than 85% were overweight or obese, and 40% had diabetes. Higher VAT volume, SAT volume, and liver proton density fat fraction were associated with lower levels of total and high-molecular-weight adiponectin, higher levels of leptin and insulin resistance, and lower high-density lipoprotein cholesterol and higher serum triglyceride levels. A slower 400-m walk time was associated only with higher levels of leptin, total adiponectin, plasma IL-6, and TNFR1 and did not modify the associations between fat measures and cardiometabolic risk factors. LIMITATIONS: Lack of longitudinal data and dietary details. CONCLUSIONS: Various measures of adiposity are associated with cardiometabolic risk factors. Physical function was also associated with the cardiometabolic risk factors studied and does not modify associations between fat measures and cardiometabolic risk factors. Longitudinal studies of the relationship between body fat and aerobic fitness with cardiovascular and kidney disease progression are warranted.

Proton-pump inhibitor vs. H2-receptor blocker use and overall risk of CKD progression.

BACKGROUND: The relationship between proton-pump inhibitor (PPI) use and chronic kidney disease (CKD) progression remains controversial. Specifically, there is a lack of data evaluating renal outcomes in established CKD patients. The aim of our study is to determine the risk of progression to end-stage kidney disease (ESKD) or death amongst CKD patients on PPI, histamine-2 receptor blocker (H2B), or no anti-acid therapy. METHODS: Using our CKD registry, we evaluated the relationship between PPI and H2B use and outcomes amongst patients with CKD (eGFR < 60), with at least 2 PCP visits in the year prior. A Cox proportional hazards model was used to evaluate the relationship between medication groups and overall mortality, while competing risks regression models were used to determine the risk of ESKD with death as a competing risk. RESULTS: 25,455 patients met inclusion criteria and were stratified according to medication group: no antacid therapy (15,961), PPI use (8646), or H2B use (848). At 4 years, the cumulative incidence of ESKD with death as a competing risk was 2.0% (95% CI: 1.7, 2.4), 1.5% (0.8, 2.8), and 1.6%(1.4, 1.9) among PPI, H2B, and no medication respectively (P = 0.22). The cumulative incidence of death with ESKD as a competing risk was 17.6% (95% CI: 16.6, 18.6), 16.7% (13.7, 19.8), and 17.3% (16.6, 18.0) (P = 0.71). CONCLUSIONS: Use of PPI in a CKD population was not associated with increased mortality or progression to ESKD when compared to H2 blocker and to no acid suppressing therapy.

"What do you think about nephrology?" A national survey of internal medicine residents.

BACKGROUND: Interest in nephrology has been declining among internal medicine residents but the reasons behind this observation are not well characterized. Our objective was to evaluate factors influencing residents' choice of subspecialty. METHODS: This is a mixed-method QUAL-QUAN design study that used the results of our previously published qualitative analysis on residents' perception of nephrology to create and pilot a questionnaire of 60 questions. The final questionnaire was distributed to 26 programs across the United States and a total of 1992 residents. We calculated response rates and tabulated participant characteristics and percentage of participant responses. We categorized choice of fellowship into 2 medical categories (Highly Sought After vs. Less Sought After) and fitted a logistic regression model of choosing a highly vs. less sought after fellowship. RESULTS: Four hundred fifteen out of 1992 (21%) US residents responded to the survey. Of the 268 residents planning to pursue fellowship training, 67 (25%) selected a less sought after fellowship. Female sex was associated with significantly higher odds of selecting a less sought after fellowship (OR = 2.64, 95% CI: 1.47, 4.74). Major factors deterring residents from pursuing nephrology were perception of inadequate financial compensation, broad scope of clinical practice and complexity of patient population. We observed a decline in exposure to nephrology during the clinical years of medical school with only 35.4% of respondents rotating in nephrology versus 76.8% in residency. The quality of nephrology education was rated less positively during clinical medical school years (median of 50 on a 0-100 point scale) compared to the pre-clinical years (median 60) and residency (median 75). CONCLUSION: Our study attempts to explain the declining interest in nephrology. Results suggest potential targets for improvement: diversified trainee exposure, sub-specialization of nephrology, and increased involvement of nephrologists in the education of trainees.

Correction to: Serum magnesium, mortality and disease progression in chronic kidney disease.

Following publication of the original article [1], we have been notified that the name of one author was spelled incorrectly as Georges N. Na khoul, when the correct spelling is Georges N. Nakhoul.

Serum magnesium, mortality and disease progression in chronic kidney disease.

INTRODUCTION: Magnesium disorders are commonly encountered in chronic kidney disease (CKD) and are typically a consequence of decreased kidney function or frequently prescribed medications such as diuretics and proton pump inhibitors. While hypomagnesemia has been linked with increased mortality, the association between elevated magnesium levels and mortality is not clearly defined. Additionally, associations between magnesium disorders, type of death, and CKD progression have not been reported. Therefore, we studied the associations between magnesium levels, CKD progression, mortality, and cause specific deaths in patients with CKD. METHODS: Using the Cleveland Clinic CKD registry, we identified 10,568 patients with estimated Glomerular Filtration Rate (eGFR) between 15 and 59 ml/min/1.73 m2 in this range for a minimum of 3 months with a measured magnesium level. We categorized subjects into 3 groups based on these magnesium levels (≤ 1.7, 1.7-2.6 and > 2.6 mg/dl) and applied cox regression modeling and competing risk models to identify associations with overall and cause-specific mortality. We also evaluated the association between magnesium level and slope of eGFR using mixed models. RESULTS: During a median follow-up of 3.7 years, 4656 (44%) patients died. After adjusting for relevant covariates, a magnesium level < 1.7 mg/dl (vs. 1.7-2.6 mg/dl) was associated with higher overall mortality (HR = 1.14, 95% CI: 1.04, 1.24), and with higher sub-distribution hazards for non-cardiovascular non-malignancy mortality (HR = 1.29, 95% CI: 1.12, 1.49). Magnesium levels > 2.6 mg/dl (vs. 1.7-2.6 mg/dl) was associated with a higher risk of all-cause death only (HR = 1.23, 95% CI: 1.03, 1.48). We found similar results when evaluating magnesium as a continuous measure. There were no significant differences in the slope of eGFR across all three magnesium groups (p = 0.10). CONCLUSIONS: In patients with CKD stage 3 and 4, hypomagnesemia was associated with higher all-cause and non-cardiovascular non-malignancy mortality. Hypermagnesemia was associated with higher all-cause mortality. Neither hypo nor hypermagnesemia were associated with an increased risk of CKD progression.

Impact of AKI on Urinary Protein Excretion: Analysis of Two Prospective Cohorts.

BACKGROUND: Prior studies of adverse renal consequences of AKI have almost exclusively focused on eGFR changes. Less is known about potential effects of AKI on proteinuria, although proteinuria is perhaps the strongest risk factor for future loss of renal function. METHODS: We studied enrollees from the Assessment, Serial Evaluation, and Subsequent Sequelae of AKI (ASSESS-AKI) study and the subset of the Chronic Renal Insufficiency Cohort (CRIC) study enrollees recruited from Kaiser Permanente Northern California. Both prospective cohort studies included annual ascertainment of urine protein-to-creatinine ratio, eGFR, BP, and medication use. For hospitalized participants, we used inpatient serum creatinine measurements obtained as part of clinical care to define an episode of AKI (i.e., peak/nadir inpatient serum creatinine ≥1.5). We performed mixed effects regression to examine change in log-transformed urine protein-to-creatinine ratio after AKI, controlling for time-updated covariates. RESULTS: At cohort entry, median eGFR was 62.9 ml/min per 1.73 m2 (interquartile range [IQR], 46.9-84.6) among 2048 eligible participants, and median urine protein-to-creatinine ratio was 0.12 g/g (IQR, 0.07-0.25). After enrollment, 324 participants experienced at least one episode of hospitalized AKI during 9271 person-years of follow-up; 50.3% of first AKI episodes were Kidney Disease Improving Global Outcomes stage 1 in severity, 23.8% were stage 2, and 25.9% were stage 3. In multivariable analysis, an episode of hospitalized AKI was independently associated with a 9% increase in the urine protein-to-creatinine ratio. CONCLUSIONS: Our analysis of data from two prospective cohort studies found that hospitalization for an AKI episode was independently associated with subsequent worsening of proteinuria.

The Associations between Peripheral Artery Disease and Physical Outcome Measures in Men and Women with Chronic Kidney Disease.

BACKGROUND: Peripheral artery disease (PAD) is highly prevalent and associated with significant morbidity and mortality, but sex-based differences are incompletely understood. We sought to define the associations between PAD and physical outcome measures and to determine if these associations differed by sex in the Chronic Renal Insufficiency Cohort. METHODS: Among 3,543 participants, we assessed the cross-sectional relationship between PAD severity defined by ankle-brachial index; and (1) physical activity (metabolic equivalent [MET]-hr/wk), (2) walking pace (slow versus medium and/or fast), and (3) physical function (12-item Short Form Health Survey [SF-12]) at baseline. RESULTS: In a multivariable linear regression model, PAD severity was not associated with physical activity defined by total MET-hr per wk in men or women (P = 0.432). However, PAD severity was significantly associated with walking activity (P = 0.037), although this relationship did not differ by sex (P = 0.130). Similarly, PAD severity was significantly associated with walking pace (P < 0.001), although this relationship did not differ by sex (P = 0.086). In contrast, there was an independent association between PAD severity and SF-12 (P = 0.018), with a significant interaction by sex (P < 0.001). CONCLUSIONS: These data suggest that tools used to evaluate the functional consequences of PAD should focus on walking activity and walking pace, as well as physical function, where sex-specific associations should be accounted for.

Renal failure requiring dialysis complicating slow continuous ultrafiltration in acute heart failure: importance of systolic perfusion pressure.

BACKGROUND: Recent reports have raised concerns regarding renal outcomes in patients with decompensated acute heart failure (HF) treated with slow continuous ultrafiltration (SCUF). The purpose of this study was to identify risk factors for renal failure (RF) requiring dialysis in patients with acute HF initiated on SCUF. METHODS AND RESULTS: We studied 63 consecutive patients with acute HF who required SCUF because of congestion refractory to hemodynamically guided intensive medical therapy. Median serum creatinine at SCUF initiation was higher in patients who developed RF requiring dialysis [2.5 (interquartile range 1.8-3.3) vs 1.6 (1.2-2.3) mg/dL; P < .001]. Weight loss within 48 hours of SCUF initiation was larger in patients who did not progress to RF [-6 (-10 to -2) vs -4 (-6 to -2) kg; P = .03]. Systolic perfusion pressure had a nonlinear association with RF requiring dialysis, with a threshold effect noted at 90 mm Hg. Twelve-month mortality in patients who were moved to dialysis versus those who were not was 95% versus 35%, respectively (P < .001). CONCLUSIONS: In patients with acute HF initiated on SCUF, onset of RF requiring dialysis is associated with high mortality. Systolic perfusion pressure which incorporates both perfusion and venous congestion parameters may present a modifiable risk factor for worsening RF during SCUF in acute HF patients.

Virtual Nephron: Evaluation of a Novel Virtual Reality Educational Tool.

Introduction: Recent technological advancements allowed the development of engaging technological tools. Using ASN funding from the ASN, we developed a 3D Virtual Reality (VR) physiology course entitled DiAL-Neph (Diuretic Action and eLectrolyte transport in the Nephron). We hereby present its evaluation. Methods: The study consisted of 2 parts: evaluation of knowledge gain, and qualitative evaluation of platform reception. Internal medicine PGY1 residents were randomly assigned into 2 groups: a VR group and a conventional group. Knowledge acquisition was assessed with a post-test administered at the end of the course and repeated within 6 to 12 weeks. Independent t-tests were used to compare the number of correct answers between the groups. A survey and focus groups composed of medicine residents evaluated the platform. Sessions were recorded and transcribed verbatim. Data was analyzed through the content analysis approach by two independent reviewers. Results: Of 117 PGY1 resident participants, 64 were randomized to the VR group and 53 were randomized to the traditional group. Initial test results showed higher scores among VR compared to the traditional group (76.5% correct vs. 68.8%). Seventy-eight PGY1s participated in the follow up testing (46 VR group vs. 32 traditional group) and results showed no significant difference in test results. Greater than 90% of the residents rated the platform positively and 77% preferred it as a teaching method. Conclusion: The DiAL-Neph VR platform appeared to improve short-term learning but not long-term retention. Further studies are needed to investigate the impact of such teaching platforms on overall interest in nephrology.

Prognostic importance of serum alkaline phosphatase in CKD stages 3-4 in a clinical population.

BACKGROUND: Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2)) were identified using the Cleveland Clinic CKD Registry. CKD was defined as 2 estimated glomerular filtration rate values <60 mL/min/1.73 m(2) drawn more than 90 days apart using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. PREDICTOR: ALP levels measured using the calorimetric assay were examined as quartiles (quartile [Q]1, <66 U/L; Q2, 66-81 U/L; Q3, 82-101 U/L; and Q4, ≥102 U/L) and as a continuous measure. OUTCOMES & MEASUREMENTS: All-cause mortality and end-stage renal disease (ESRD) were ascertained using the Social Security Death Index and US Renal Data System. RESULTS: After a median follow-up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in risk of mortality with higher ALP quartiles (Q2, Q3, and Q4) compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications, and liver function test results. The highest ALP quartile was associated with an HR for ESRD of 1.38 (95% CI, 1.09-1.76). Each 1-SD (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09-1.22) and 16% (95% CI, 1.14-1.18) increased risk of ESRD and mortality, respectively. LIMITATIONS: Single-center observational study; lack of complete data, including parathyroid hormone level, for all study participants, and attrition bias. CONCLUSIONS: Higher serum ALP levels in patients with CKD stages 3-4 were associated independently with all-cause mortality and ESRD.

C3 glomerulopathy.

C3 glomerulopathy (C3G) is a rare kidney disease that causes kidney dysfunction as a result of dysregulation of the complement system alternate pathway (AP). C3G encompasses 2 separate disorders, C3 glomerulonephritis and dense deposit disease. The presentation and natural history is variable and kidney biopsy is needed to confirm the diagnosis. The overall prognosis is poor with high recurrence rates after transplant. A better understanding of C3G is needed as is high-quality evidence to guide therapy, which currently includes mycophenolate mofetil and steroids for moderate to severe disease, and terminal complement blockade with anti-C5 therapy in unresponsive cases.

IgA nephropathy.

Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis in the world. The etiology is unknown but a dysregulated T-cell immune response to viral, bacterial, and food antigens activating mucosal plasma cells to produce polymeric IgA has been proposed. No serological test exists to diagnosis IgAN. A definitive diagnosis requires kidney biopsy which is not always necessary. Kidney failure occurs in 20% to 40% of patients within 10 to 20 years.

Resistant hypertension: A stepwise approach.

Resistant hypertension can be challenging to manage, but a stepwise approach to diagnosis, evaluation, and treatment can lead to better blood pressure control. In this article, we review the definition and prevalence of resistant hypertension and its diagnostic workup and management, including lifestyle modifications, drugs, and experimental interventional therapies.