Predictors of renal replacement therapy in patients with continuous flow left ventricular assist devices.

Renal replacement therapy (RRT) after continuous flow left ventricular assist device (CF-LVAD) implantation significantly affects patients' quality of life and survival. To identify preoperative prognostic markers in patients requiring RRT after CF-LVAD implantation, we retrospectively reviewed data from patients who underwent implantation of a CF-LVAD at our institution during 2012-2017. Patients who required preoperative RRT were excluded. Preoperative and operative characteristics, as well as survival and adverse events, were compared between 74 (22.2%) patients requiring any duration of postoperative RRT and 259 (77.8%) not requiring RRT. Patients requiring RRT experienced more postoperative complications than patients who did not, including respiratory failure necessitating tracheostomy (35.7% vs 2.5%, p < 0.001), reoperation for bleeding (34.3% vs 11.7%, p < 0.001), and right heart failure necessitating perioperative mechanical circulatory support (32.4% vs 6.9%, p < 0.001). Patients requiring postoperative RRT also had poorer survival at 30 days (74.7% vs 98.8%), 6 months (48.2% vs 95.1%), and 12 months (45.3% vs 90.2%) (p < 0.001). Significant predictors of RRT after CF-LVAD implantation included urine proteinuria (odds ratio [OR] 3.6, 95% confidence interval [CI] [1.7-7.6], p = 0.001), estimated glomerular filtration rate < 45 mL/min/1.73 m2 (OR 3.4, 95% CI [1.5-17.8], p = 0.004), and mean right atrial pressure to pulmonary capillary wedge pressure ratio ≥ 0.54 (OR 2.6, 95% CI [1.3-5.], p = 0.01). Of the 74 RRT patients, 11 (14.9%) recovered renal function before discharge, 36 (48.6%) still required RRT after discharge, and 27 (36.5%) died before discharge. We conclude that preoperative renal and right ventricular dysfunction significantly predict postoperative renal failure and mortality after CF-LVAD implantation.

Nonesterified Fatty Acids and Kidney Function Decline in Older Adults: Findings From the Cardiovascular Health Study.

RATIONALE & OBJECTIVE: Circulating nonesterified fatty acids (NEFAs) make up a small portion of circulating lipids but are a metabolically important energy source. Excessive circulating NEFAs may contribute to lipotoxicity in many tissues, including the kidneys. We investigated the relationship between total circulating NEFA concentration and kidney outcomes in older, community-dwelling adults. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 4,698 participants≥65 years of age in the Cardiovascular Health Study who underwent total fasting serum NEFA concentration measurements in 1992-1993. EXPOSURE: Fasting serum NEFA concentration at one time point. OUTCOME: Three primary outcomes: estimated glomerular filtration rate (eGFR) decline of≥30%, the composite of eGFR decline≥30% or kidney failure with replacement therapy, and change in eGFR. These outcomes were assessed over 4- and 13-year periods. ANALYTICAL APPROACH: Logistic regression for the dichotomous outcomes and mixed effects models for the continuous outcome, with sequential adjustment for baseline covariates. Inverse probability of attrition weighting was implemented to account for informative attrition during the follow-up periods. RESULTS: Serum NEFA concentrations were not independently associated with kidney outcomes. In unadjusted and partially adjusted analyses, the highest quartile of serum NEFA concentration (compared with lowest) was associated with a higher risk of≥30% eGFR decline at 4 years and faster rate of decline of eGFR. No associations were evident after adjustment for comorbidities, lipid levels, insulin sensitivity, medications, and vital signs: the odds ratio for the eGFR decline outcome was 1.33 (95% CI, 0.83-2.13), and the difference in eGFR slope in the highest versus lowest quartile of serum NEFA concentration was-0.15 (95% CI, -0.36 to 0.06) mL/min/1.73m2 per year. LIMITATIONS: Single NEFA measurements, no measurements of post-glucose load NEFA concentrations or individual NEFA species, no measurement of baseline urine albumin. CONCLUSIONS: A single fasting serum NEFA concentration was not independently associated with long-term adverse kidney outcomes in a cohort of older community-living adults.

Prevalence, correlates and outcomes of absolute and functional iron deficiency anemia in nondialysis-dependent chronic kidney disease.

BACKGROUND: Anemia is associated with adverse outcomes in those with chronic kidney disease (CKD). We examined the association of absolute and functional iron deficiency anemia (IDA) with adverse outcomes (cardiovascular hospitalization, dialysis and mortality) in those with nondialysis-dependent CKD. METHODS: Nondialysis-dependent CKD patients followed in the US Veterans Administration with hemoglobin level measured within 90 days of the date of the second estimated glomerular filtration rate <60 mL/min/1.73 m2 were included. Logistic regression, multivariate Cox proportional hazards and Poisson regression models adjusted for demographics and comorbidities were used to assess the prevalence and correlates of absolute [transferrin saturation (TSAT) ≤20%, ferritin <100 ng/mL] and functional (TSA T≤20%, ferritin >100-500 ng/mL) IDA and the associations of absolute and functional IDA with mortality, dialysis and cardiovascular hospitalization. RESULTS: Of 933 463 patients with CKD, 20.6% had anemia. Among those with anemia, 23.6% of patients had both TSAT and ferritin level measured, of whom 30% had absolute IDA and 19% had functional IDA. Absolute IDA in CKD was not associated with an increased risk of mortality or dialysis but was associated with a higher risk of 1-year {risk ratio [RR] 1.20 [95% confidence interval (CI) 1.12-1.28]} and 2-year cardiovascular hospitalization [RR 1.11 (95% CI 1.05-1.17)]. CKD patients with functional IDA had a higher risk of mortality [hazard ratio (HR) 1.11 (95% CI 1.07-1.14)] along with a higher risk of 1-year [RR 1.21 (95% CI 1.1-1.30)] and 2-year cardiovascular hospitalization [RR 1.13 (95% CI 1.07-1.21)]. Ferritin >500 ng/mL (treated as a separate category) was only associated with an increased risk of mortality [HR 1.38 (95% CI 1.26-1.51)]. CONCLUSIONS: In a large population of CKD patients with anemia, absolute and functional IDA were associated with various clinical covariates. Functional IDA was associated with an increased risk of mortality and cardiovascular hospitalization, but absolute IDA was associated only with a higher risk of hospitalization.

Iron deficiency and iron therapy in heart failure and chronic kidney disease.

PURPOSE OF REVIEW: Iron deficiency is common and associated with adverse outcomes in heart failure, regardless of anemia. Iron deficiency, absolute and functional, with and without anemia, is associated with adverse outcomes in chronic kidney disease (CKD). Heart failure and CKD frequently occur together. Intravenous iron therapy has been shown to reduce heart failure symptoms and improve physical function in heart failure with reduced ejection fraction with iron deficiency. In CKD, intravenous or oral iron therapy are often used for management of anemia, along with erythropoiesis stimulating agents, yet the risks and benefits of intravenous iron use is controversial. In this review, we survey available evidence and ongoing studies of iron deficiency and iron supplementation in heart failure, and integrate with recent evidence on effectiveness and safety of intravenous iron therapy in CKD. RECENT FINDINGS: Intravenous iron therapy improves heart failure symptoms and physical function in heart failure with reduced ejection fraction and iron deficiency, regardless of anemia, and may reduce heart failure hospitalizations and cardiovascular mortality. Sustained intravenous iron therapy regardless of hemoglobin level in selected patients with end-stage kidney disease receiving hemodialysis improves outcomes, and does not appear to cause infectious complications. SUMMARY: Iron therapy has important effects in heart failure and CKD, and appears safe in the short term. Ongoing trials will provide additional important information.

[Hospitalization and Critical Illness in Chronic Kidney Disease].

BACKGROUND: Patients with chronic kidney disease (CKD) who are hospitalized with a critical illness are at increased risk for adverse outcomes. We studied the predictors of hospitalization with critical illness among patients with non-dialysis-dependent CKD stages 3 and 4 in a safety-net healthcare setting. METHODS: A retrospective cohort study was conducted among patients ≥18 years of age with CKD stages 3 and 4 using a CKD registry from a safety-net healthcare system. Hospitalizations with critical illness were identified among patients requiring nonelective admission or transfer to the intermediate or intensive care unit during a 3-year period after the diagnosis of CKD. Poisson regression was used to determine associations between baseline characteristics and hospitalization requiring intermediate or intensive care among all CKD patients and in those with different stages of CKD. Outcomes of these hospitalizations were also tabulated. RESULTS: Among 8,302 patients with CKD stages 3 and 4, 1,298 were hospitalized and 495 required intermediate or intensive care during a 3-year follow-up period. In the adjusted analysis, advanced CKD, Hispanics (incident rate ratio [IRR]: 1.88), non-Hispanic Blacks (IRR: 1.48), presence of congestive heart failure (IRR: 2.09), cardiovascular disease (IRR: 1.57), chronic pulmonary disease (IRR: 1.60), liver disease, malignancy, and anemia were associated with higher risk of hospitalization requiring intermediate or intensive care. The association of age, gender, race/ethnicity, congestive heart failure, anemia, and body mass index with hospitalization requiring intermediate or intensive care differed significantly by CKD stage (p value for interaction term <0.05). Congestive heart failure and severity of anemia were associated with a higher risk of hospitalization requiring intermediate or intensive care among patients with mild CKD, and the magnitude of association attenuated among patients with advanced CKD. CONCLUSIONS: The burden of hospitalization with critical illness among patients with non-dialysis-dependent CKD stages 3 and 4 remains high and was associated with demographic factors and comorbid medical conditions, especially among those with congestive heart failure and cardiovascular disease. Targeted, effective interventions to reduce the burden of hospitalization and critical illness in CKD patients within safety-net healthcare systems are needed.

High-density lipoprotein cholesterol and causes of death in chronic kidney disease.

BACKGROUND: Recent data suggest a U-shaped association between high-density lipoprotein cholesterol (HDL-c) and death in chronic kidney disease (CKD). However, whether the increased mortality in patients with extreme levels is explained by specific causes of death remains unclear. OBJECTIVES: We studied the associations between HDL-c and cause-specific deaths in CKD. METHODS: We included 38,377 patients with estimated glomerular filtration rate 15-59 mL/min/1.73 m2. We classified deaths into 3 major categories: (1) cardiovascular; (2) malignant; and (3) noncardiovascular/nonmalignant causes. We fitted Cox regression models for overall mortality and separate competing risk models for each major cause of death category to evaluate their respective associations with categories of HDL-c (≤30, 31-40, 41-50 [referent], 51-60, >60 mg/dL). Separate analyses were conducted for men and women. RESULTS: During a median follow-up of 4.5 years, 9665 patients died. After adjusting for relevant covariates, in both sexes, HDL-c 31 to 40 mg/dL and ≤30 mg/dL were associated with higher risk of all-cause mortality, cardiovascular mortality, malignancy-related deaths, and noncardiovascular/nonmalignancy-related deaths. HDL-c >60 mg/dL was associated with lower all-cause (hazard ratio: 0.75, 95% confidence interval: 0.69, 0.81), cardiovascular, malignancy-related, and noncardiovascular/nonmalignancy-related deaths among women but not in men. Similar results were noted when HDL-c was examined as a continuous measure. CONCLUSIONS: In a non-dialysis-dependent CKD population, HDL-c ≤40 mg/dL was associated with risk of higher all-cause, cardiovascular, malignant, and noncardiovascular/nonmalignant mortality in men and women. HDL >60 mg/dL was associated with lower risk of all-cause, cardiovascular, malignant, and noncardiovascular/nonmalignant mortality in women but not in men.

Serum albumin concentration and risk of end-stage renal disease: the REGARDS study.

Background: Serum albumin concentration is a commonly available biomarker with prognostic value in many disease states. It is uncertain whether serum albumin concentrations are associated with incident end-stage renal disease (ESRD) independently of urine albumin-to-creatinine ratio (ACR). Methods: A longitudinal evaluation was performed of a population-based community-living cohort from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study. Participants were ≥45 years of age at study entry and had serum albumin, creatinine, cystatin C and spot urine ACR measured at the baseline visit (n = 19 633). Estimated glomerular filtration rate (eGFR) was from the Chronic Kidney Disease Epidemiology Collaboration combined creatinine-cystatin C equation. Baseline serum albumin concentration was the predictor variable, and hazard ratios (HRs) for incident ESRD (from US Renal Data System linkage) were calculated in sequentially adjusted models. Results: Age at study entry was 63.9 ± 9.7 years, 62% of the participants were female and 40% were black. Mean eGFR at baseline was 83.3 ± 20.8 mL/min/1.73 m2. Over a median 8-year follow-up, 1.2% (n = 236) developed ESRD. In models adjusted for baseline eGFR, ACR and other ESRD risk factors, the HR for incident ESRD was 1.16 [95% confidence interval (CI) 1.01-1.33] for each standard deviation (0.33 g/dL) lower serum albumin concentration. The HR comparing the lowest (<4 g/dL) and highest quartiles (≥4.4 g/dL) of serum albumin was 1.61 (95% CI 0.98-2.63). Results were qualitatively similar among participants with eGFR <60 and ≥60 mL/min/1.73 m2, and those with and without diabetes. Conclusions: In community-dwelling US adults, lower serum albumin concentration is associated with higher risk of incident ESRD independently of baseline urine ACR, eGFR and other ESRD risk factors.

Treatment of acute kidney injury with cast nephropathy.

Nearly 50% of patients with multiple myeloma develop renal disease; acute kidney injury (AKI) from cast nephropathy, or "myeloma kidney" is the most common type. Development of AKI is associated with worse 1-year survival and reduces the therapeutic options available to patients. Therefore, there is a great need to develop more effective therapies. Cast nephropathy is due to the interaction and aggregation of filtered free light chains (FLCs) and Tamm- Horsfall protein (THP) causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of FLCs as this correlates with renal recovery. Newer chemotherapy agents lower FLCs and have been referred to as "renoprotective". However there remains great interest in using various extracorporeal therapies to remove serum FLCs. Initially, therapeutic plasma exchange (TPE) was thought to improve renal outcomes in cast nephropathy based on small trials. The largest randomized trial of TPE, however, failed to show any benefit. A newer technique is extended high cut-off hemodialysis (HCO-HD). This modality uses a high molecular weight cut-off filter to remove FLCs. To date, trials with HCO-HD in patients with cast nephropathy have been encouraging. However, there are no randomized trials demonstrating the benefit of HCOHD when used in addition to newer chemotherapeutic regimens. Until these studies are available, HCO-HD cannot be recommended as standard of care.