Epidemiology and Management of Patients With Kidney Disease and Heart Failure With Preserved Ejection Fraction.

Heart failure with preserved ejection fraction (HFpEF) comprises approximately one-half of all diagnoses of heart failure. There is significant overlap of this clinical syndrome with chronic kidney disease (CKD), with many shared comorbid conditions. The presence of CKD in patients with HFpEF is one of the most powerful risk factors for adverse clinical outcomes, including death and heart failure hospitalization. The pathophysiology linking HFpEF and CKD remains unclear, but it is postulated to consist of numerous bidirectional pathways, including endothelial dysfunction, inflammation, obesity, insulin resistance, and impaired sodium handling. The diagnosis of HFpEF requires certain criteria to be satisfied, including signs and symptoms consistent with volume overload caused by structural or functional cardiac abnormalities and evidence of increased cardiac filling pressures. There are numerous overlapping metabolic clinical syndromes in patients with HFpEF and CKD that can serve as targets for intervention. With an increasing number of therapies available for HFpEF and CKD as well as for obesity and diabetes, improved recognition and diagnosis are paramount for appropriate management and improved clinical outcomes in patients with both HFpEF and CKD.

Mitochondrial genetic variation and risk of chronic kidney disease and acute kidney injury in UK Biobank participants.

Experimental models suggest an important role for mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD) and acute kidney injury (AKI), but little is known regarding the impact of common mitochondrial genetic variation on kidney health. We sought to evaluate associations of inherited mitochondrial DNA (mtDNA) variation with risk of CKD and AKI in a large population-based cohort. We categorized UK Biobank participants who self-identified as white into eight distinct mtDNA haplotypes, which were previously identified based on their associations with phenotypes associated with mitochondrial DNA copy number, a measure of mitochondrial function. We used linear and logistic regression models to evaluate associations of these mtDNA haplotypes with estimated glomerular filtration rate by serum creatinine and cystatin C (eGFRCr-CysC, N = 362,802), prevalent (N = 416 cases) and incident (N = 405 cases) end-stage kidney disease (ESKD), AKI defined by diagnostic codes (N = 14,170 cases), and urine albumin/creatinine ratio (ACR, N = 114,662). The mean age was 57 ± 8 years and the mean eGFR was 90 ± 14 ml/min/1.73 m2. MtDNA haplotype was significantly associated with eGFR (p = 2.8E-12), but not with prevalent ESKD (p = 5.9E-2), incident ESKD (p = 0.93), AKI (p = 0.26), or urine ACR (p = 0.54). The association of mtDNA haplotype with eGFR remained significant after adjustment for diabetes mellitus and hypertension (p = 1.2E-10). When compared to the reference haplotype, mtDNA haplotypes I (ß = 0.402, standard error (SE) = 0.111; p = 2.7E-4), IV (ß = 0.430, SE = 0.073; p = 4.2E-9), and V (ß = 0.233, SE = 0.050; p = 2.7E-6) were each associated with higher eGFR. Among self-identified white UK Biobank participants, mtDNA haplotype was associated with eGFR, but not with ESKD, AKI or albuminuria.

Changes in Cognitive Function After Kidney Transplantation: A Longitudinal Cohort Study.

RATIONALE & OBJECTIVE: Kidney disease negatively affects cognition. We assessed the effect of kidney transplantation (KT) on different cognitive domains. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: We examined pre- versus post-KT cognition in patients waitlisted for KT at an academic center. PREDICTORS: Transplant status. We measured cognitive function before KT (n=101), 3 months after KT (n=78), and 1 year after KT (n = 83). OUTCOMES: Our primary outcome was change in cognitive function before versus after KT. We used standard neuropsychological tests to assess global cognition (Mini-Mental State Exam [MMSE]), episodic/declarative memory (Logical Memory), psychomotor speed/visuospatial function (Digit Symbol Substitution Test [DSST], Trail Making Test [TMT] A), working memory/attention (Digit Span), executive function (TMT B), and semantic memory/verbal fluency/language (Category Fluency). ANALYTICAL APPROACH: Using linear mixed model analysis, we evaluated the changes in neuropsychological test scores adjusted for age, sex, race, education, and number of assessments. RESULTS: Before KT, Logical Memory I and II, DSST, MMSE, Category Fluency (animal naming), and Digit Span backward scores were low compared with normative values from the National Alzheimer's Coordinating Center data. Logical Memory I and II scores improved after KT (pre- vs post-KT, estimated group difference [d]=3.3, P<0.001 for Logical Memory I; d=4.27, P<0.001 for Logical Memory II), such that post-KT scores were similar to normative values (post-KT vs normative values, d = -0.37, P=0.06 for Logical Memory I; d = -0.89, P=0.08 for Logical Memory II). Category Fluency (animal naming; d=2.4, P<0.001) and DSST (d=3.12, P=0.01) scores also improved with KT, but post-KT DSST scores remained lower than normative values (post-KT vs normative values, d = -5.17, P<0.001). MMSE, Digit Span, and TMT A and B scores did not change after KT. LIMITATIONS: Single-center study. CONCLUSIONS: Episodic and verbal declarative memory normalize after KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function show partial improvement. Cognitive impairment in kidney disease is therefore at least partly reversible with KT. PLAIN-LANGUAGE SUMMARY: Cognitive impairment in kidney disease affects self-esteem, vocational abilities, quality of life, health care costs, and mortality. It is not clear whether kidney transplantation (KT) improves cognition and whether the improvement is uniform across cognitive domains. The distinction between reversible and irreversible cognitive impairment has important implications in the clinical care of patients before and after KT. We assessed cognition before KT and 3 months and 12 months after KT and discovered that episodic and verbal declarative memory normalized with KT. Semantic memory, verbal fluency, language, psychomotor speed, and visuospatial function also improved with KT but did not reach normal levels. Cognitive impairment in kidney disease is therefore at least partly reversible.

Home Dialysis in Patients with Cardiovascular Diseases.

Kidney failure with replacement therapy and cardiovascular disease are frequently comorbid. In patients with kidney failure with replacement therapy, cardiovascular disease is a major contributor to morbidity and mortality. Conventional thrice-weekly in-center dialysis confers risk factors for cardiovascular disease, including acute hemodynamic fluctuations and rapid shifts in volume and solute concentration. Home hemodialysis and peritoneal dialysis (PD) may offer benefits in attenuation of cardiovascular disease risk factors primarily through improved volume and BP control, reduction (or slowing progression) of left ventricular mass, decreased myocardial stunning, and improved bone and mineral metabolism. Importantly, although trial data are available for several of these risk factors for home hemodialysis, evidence for PD is limited. Among patients with prevalent cardiovascular disease, home hemodialysis and PD may also have potential benefits. PD may offer particular advantages in heart failure given it removes volume directly from the splanchnic circulation, thus offering an efficient method of relieving intravascular congestion. PD also avoids the risk of blood stream infections in patients with cardiac devices or venous wires. We recognize that both home hemodialysis and PD are also associated with potential risks, and these are described in more detail. We conclude with a discussion of barriers to home dialysis and the critical importance of interdisciplinary care models as one component of advancing health equity with respect to home dialysis.

Plasma Biomarkers and Incident CKD Among Individuals Without Diabetes.

Rationale & Objective: Biomarkers of kidney disease progression have been identified in individuals with diabetes and underlying chronic kidney disease (CKD). Whether or not these markers are associated with the development of CKD in a general population without diabetes or CKD is not well established. Study Design: Prospective observational cohort. Setting & Participants: In the Atherosclerosis Risk in Communities) study, 948 participants were studied. Exposures: The baseline plasma biomarkers of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), soluble urokinase plasminogen activator receptor (suPAR), tumor necrosis factor receptor 1 (TNFR-1), tumor necrosis factor receptor 2 (TNFR-2), and human cartilage glycoprotein-39 (YKL-40) measured in 1996-1998. Outcome: Incident CKD after 15 years of follow-up defined as ≥40% estimated glomerular filtration rate decline to <60 mL/min/1.73 m2 or dialysis dependence through United States Renal Data System linkage. Analytical Approach: Logistic regression and C statistics. Results: There were 523 cases of incident CKD. Compared with a random sample of 425 controls, there were greater odds of incident CKD per 2-fold higher concentration of KIM-1 (OR, 1.49; 95% CI, 1.25-1.78), suPAR (OR, 2.57; 95% CI, 1.74-3.84), TNFR-1 (OR, 2.20; 95% CI, 1.58-3.09), TNFR-2 (OR, 2.03; 95% CI, 1.37-3.04). After adjustment for all biomarkers, KIM-1 (OR, 1.42; 95% CI, 1.19-1.71), and suPAR (OR, 1.86; 95% CI, 1.18-2.92) remained associated with incident CKD. Compared with traditional risk factors, the addition of all 6 biomarkers improved the C statistic from 0.695-0.731 (P < 0.01) and using the observed risk of 12% for incident CKD, the predicted risk gradient changed from 5%-40% (for the 1st-5th quintile) to 4%-44%. Limitations: Biomarkers and creatinine were measured at one time point. Conclusions: Higher levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with higher odds of incident CKD among individuals without diabetes. Plain-Language Summary: For people with diabetes or kidney disease, several biomarkers have been shown to be associated with worsening kidney disease. Whether these biomarkers have prognostic significance in people without diabetes or kidney disease is less studied. Using the Atherosclerosis Risk in Communities study, we followed individuals without diabetes or kidney disease for an average of 15 years after biomarker measurement to see if these biomarkers were associated with the development of kidney disease. We found that elevated levels of KIM-1, suPAR, TNFR-1, and TNFR-2 were associated with the development of kidney disease. These biomarkers may help identify individuals who would benefit from interventions to prevent the development of kidney disease.

Development and Validation of Novel Free Vitamin D Equations: The Health Aging and Body Composition Study.

Vitamin D deficiency is prevalent in 25% of Americans. However, 25(OH)D may not be an accurate measure of vitamin D because the majority (85%-90%) of 25(OH)D is bound to vitamin D binding protein (VDBP), which varies by over 30% across individuals. Free 25(OH)D may be a better measure, but it is difficult to measure accurately and precisely. The existing free 25(OH)D estimating equation does not include VDBP phenotypes; therefore, new equations that include this variable may be more accurate. A total of 370 participants in the Health, Aging, and Body Composition Study, a cohort of healthy community-dwelling individuals aged 70-79 years old, underwent VDBP and vitamin D metabolite [25(OH)D, 24,25(OH)2D, 1,25(OH)2D, free 25(OH)D] measurements and were randomly allocated into equation development (two out of three) and internal validation (one out of three) groups. New equations were developed with multiple linear regression and were internally validated with Bland-Altman plots. The mean age was 75 ± 3 years, 53% were female, and the mean measured free 25(OH)D was 5.37 ± 1.81 pg/mL. Three equations were developed. The first equation included albumin, 25(OH)D3, 25(OH)D2, VDBP, 1,25(OH)2D3, and 24,25(OH)2D3. The second equation included all variables in Eq. (1) plus VDBP phenotypes. The third equation included albumin, 25(OH)D3, intact parathyroid hormone, and 1,25(OH)2D3. In internal validation, all three new equations predicted free 25(OH)D values within 30% and 15% of the measured free 25(OH)D concentrations in 76%-80% and 48%-52% of study participants, respectively. Equation (2) was the most precise, with a mean bias of 0.06 (95% limits of agreement -2.41 to 2.30) pg/mL. The existing equation estimated free 25(OH)D within 30% and 15% of measured free 25(OH)D in 43% and 22% of participants, respectively. Free 25(OH)D can be estimated with clinically available biomarkers as well as with more laboratory-intensive biomarkers with moderate precision. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Acute Declines in Estimated GFR in Blood Pressure Target Trials and Risk of Adverse Outcomes.

RATIONALE & OBJECTIVE: Acute decreases in glomerular filtration rate (GFR) occur commonly during intensive blood pressure (BP) lowering. Our objective was to determine the relationship between acute decreases in estimated GFR and patient outcomes. STUDY DESIGN: Retrospective observational study. SETTING & PARTICIPANTS: Participants from 4 randomized controlled trials of intensive BP lowering in chronic kidney disease (Modification of Diet in Renal Disease study, African American Study of Kidney Disease and Hypertension, Systolic Blood Pressure Intervention Trial, and Action to Control Cardiovascular Risk in Diabetes trial). EXPOSURE: A 4-category exposure defined by the level of acute decrease in estimated GFR (defined as>15% vs≤15% between baseline and month 4) and the randomization to intensive versus usual BP control. OUTCOMES: Risk of kidney replacement therapy (primary outcome), defined as the need for dialysis or transplant except in the Action to Control Cardiovascular Risk in Diabetes trial, which defined its kidney outcome as a composite occurrence of serum creatinine concentration>3.3mg/dL, kidney failure, or kidney replacement therapy. ANALYTICAL APPROACH: Multivariable Cox models. RESULTS: We included 4,473 individuals randomly assigned to intensive versus usual BP control who had a total of 351 kidney outcomes and 304 deaths during median follow-up durations of 22 and 24 months, respectively. Approximately 14% of participants exhibited an acute decrease in eGFR, 11.0% in the usual BP treatment arm and 17.8% in the intensive BP treatment arm. In adjusted models, compared with a≤15% eGFR decrease in the usual BP arm, a≤15% eGFR decrease in the intensive BP control arm was associated with lower risk of the kidney outcome (HR, 0.75; 95% CI, 0.57-0.98). In contrast, a>15% decrease in eGFR was associated with a higher risk of the kidney outcome in the usual (HR, 2.47; 95% CI, 1.80-3.38) and intensive BP treatment arms (HR, 1.99; 95% CI, 1.45-2.73) compared with a≤15% decrease in the usual BP arm. LIMITATIONS: Observational study, residual confounding. CONCLUSIONS: Decreases in eGFR of>15% in the usual and intensive BP treatment arms were associated with a higher risk of kidney outcomes compared with a≤15% decrease in the usual BP arm and may be a harbinger of adverse outcomes.

Association of Longitudinal B-Type Natriuretic Peptide Monitoring With Kidney Failure in Patients With CKD: A Cohort Study.

RATIONALE & OBJECTIVE: Both hypervolemia and hypovolemia are associated with chronic kidney disease (CKD) progression. Although longitudinal monitoring of B-type natriuretic peptide (BNP) may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. This study assessed the association between BNP monitoring and the risk of incident kidney replacement therapy (KRT). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A total of 2,998 outpatients with stages 3-5 of nondialyzed CKD referred to the department of nephrology at an academic hospital. EXPOSURE: BNP monitoring. OUTCOME: KRT, acute kidney injury (AKI), and heart failure hospitalization. ANALYTICAL APPROACH: Marginal structural models, which create a balanced pseudo population at each time point, were applied to account for potential time-dependent confounders. Inverse probability weighted pooled logistic regression models were employed to estimate hazard ratios. RESULTS: At baseline, the median age and estimated glomerular filtration rate were 66 years and 38.1mL/min/1.73m2, respectively. During the follow-up period (median, 5.9 [IQR, 2.8-9.9] years), 449 patients required KRT, 765 had AKI, and 236 were hospitalized for heart failure. After adjustment for time-updated clinical characteristics and physician-specific practice styles, BNP monitoring was associated with lower risks of KRT (HR, 0.44 [95% CI, 0.21-0.92]), AKI (HR, 0.36 [95% CI, 0.18-0.72]), and heart failure hospitalization (HR, 0.37 [95% CI, 0.14-0.95]). The association between BNP monitoring and KRT was attenuated after additional adjustment for AKI or heart failure hospitalization as a time-varying covariate. LIMITATIONS: Residual confounding by measured and unmeasured variables or indications for BNP measurements. CONCLUSIONS: BNP monitoring was associated with a lower risk of KRT among patients with CKD that did not require dialysis. This association is potentially mediated through a reduced risk of AKI or heart failure hospitalization. PLAIN-LANGUAGE SUMMARY: Both volume overload and volume depletion are deleterious to kidney function. B-type natriuretic peptide (BNP) is a biomarker that reflects volume status not only in heart failure but also in nondialysis chronic kidney disease (CKD). Although longitudinal BNP monitoring may aid physicians' decision making about the optimization of volume status, its clinical benefit remains uncertain in CKD. In this cohort study analyzing 2,998 patients with nondialyzed CKD, BNP monitoring was associated with a lower risk of kidney replacement therapy, acute kidney injury, and heart failure hospitalization over the follow-up period. The association with kidney replacement therapy may be mediated through a reduced risk of acute kidney injury or heart failure hospitalization. BNP monitoring may aid physicians in optimal fluid management, potentially conferring better kidney outcomes.

Vadadustat for treatment of anemia in patients with dialysis-dependent chronic kidney disease receiving peritoneal dialysis.

BACKGROUND: Hypoxia-inducible factor prolyl hydroxylase inhibitors such as vadadustat may provide an oral alternative to injectable erythropoiesis-stimulating agents for treating anemia in patients receiving peritoneal dialysis. In two randomized (1:1), global, phase 3, open-label, sponsor-blind, parallel-group, active-controlled noninferiority trials in patients with dialysis-dependent chronic kidney disease (INNO2VATE), vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and hematological efficacy. Vadadustat's effects in patients receiving only peritoneal dialysis is unclear. METHODS: We conducted a post hoc analysis of patients in the INNO2VATE trials receiving peritoneal dialysis at baseline. The prespecified primary safety endpoint was time to first major cardiovascular event (MACE; defined as all-cause mortality or nonfatal myocardial infarction or stroke). The primary efficacy endpoint was mean change in hemoglobin from baseline to the primary evaluation period (Weeks 24-36). RESULTS: Of the 3923 patients randomized in the two INNO2VATE trials, 309 were receiving peritoneal dialysis (vadadustat, n = 152; darbepoetin alfa, n = 157) at baseline. Time to first MACE was similar in the vadadustat and darbepoetin alfa groups [hazard ratio 1.10; 95% confidence interval (CI) 0.62, 1.93]. In patients receiving peritoneal dialysis, the difference in mean change in hemoglobin concentrations was -0.10 g/dL (95% CI -0.33, 0.12) in the primary evaluation period. The incidence of treatment-emergent adverse events (TEAEs) was 88.2% versus 95.5%, and serious TEAEs was 52.6% versus 73.2% in the vadadustat and darbepoetin alfa groups, respectively. CONCLUSIONS: In the subgroup of patients receiving peritoneal dialysis in the phase 3 INNO2VATE trials, safety and efficacy of vadadustat were similar to darbepoetin alfa.

Association of Kidney Tubule Biomarkers With Cardiac Structure and Function in the Multiethnic Study of Atherosclerosis.

Markers of glomerular disease, estimated glomerular filtration rate (eGFR) and albuminuria, are associated with cardiac structural abnormalities and incident cardiovascular disease (CVD). We aimed to determine whether biomarkers of kidney tubule injury, function, and systemic inflammation are associated with cardiac structural abnormalities. Among 393 Multi-Ethnic Study of Atherosclerosis participants without diabetes, CVD, or chronic kidney disease, we assessed the association of 12 biomarkers of kidney tubule injury, function, and systemic inflammation with the left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging using linear regression. The average age was 60 ± 10 years; 48% were men; mean eGFR was 96±16 ml/min/1.73 m2; mean LVmvr was 0.93±0.18 g/ml, and mean LVEF was 62±6%. Each twofold greater concentration of plasma soluble urokinase plasminogen activator receptor was associated with a 0.04 g/ml (95% confidence interval [CI] 0.01 to 0.08 g/ml) higher LVmvr and 2.1% (95% CI 0.6 to 3.5%) lower LVEF, independent of risk factors for CVD, eGFR, and albuminuria. Each twofold greater plasma monocyte chemoattractant protein 1 was associated with higher LVmvr with a similar coefficient to that of plasma soluble urokinase plasminogen activator receptor. Each twofold greater concentration of plasma chitinase-3-like protein 1 and urine alpha-1-microglobulin was associated with a 1.1% (95% CI 0.4 to 1.7%) and 1.2% (95% CI 0.2 to 2.2%) lower LVEF, respectively. In conclusion, abnormal kidney tubule health may lead to cardiac dysfunction above and beyond eGFR and albuminuria.

Cardiorenal Syndrome in the Hospital.

The cardiorenal syndrome refers to a group of complex, bidirectional pathophysiological pathways involving dysfunction in both the heart and kidney. Upward of 60% of patients admitted for acute decompensated heart failure have CKD, as defined by an eGFR of <60 ml/min per 1.73 m2. CKD, in turn, is one of the strongest risk factors for mortality and cardiovascular events in acute decompensated heart failure. Although not well understood, the mechanisms in the cardiorenal syndrome include venous congestion, arterial underfilling, neurohormonal activation, inflammation, and endothelial dysfunction. Arterial underfilling may lead to activation of the renin-angiotensin-aldosterone system and sympathetic nervous system, leading to sodium reabsorption and vasoconstriction. Venous congestion likely also mediates and perpetuates these maladaptive pathways. To rule out intrinsic kidney disease that is distinct from the cardiorenal syndrome, one should obtain a careful history, review longitudinal eGFR trends, assess albuminuria and proteinuria, and review the urine sediment and kidney imaging. The hallmark of the cardiorenal syndrome is intense sodium avidity and diuretic resistance, often requiring a combination of diuretics with varying pharmacological targets, and monitoring of urinary response to guide escalations in therapy. Invasive means of decongestion may be required including ultrafiltration or kidney RRT such as peritoneal dialysis, which is often better tolerated from a hemodynamic perspective than intermittent hemodialysis. Strategies for increasing forward perfusion in states of low cardiac output and cardiogenic shock may include afterload reduction and inotropes and, in the most severe cases, mechanical circulatory support devices, many of which have kidney-specific considerations.

Intensive BP Control in Patients with CKD and Risk for Adverse Outcomes.

SIGNIFICANCE STATEMENT: Although most guidelines recommend tightly controlling BP in patients with CKD, individuals with advanced kidney disease or severe albuminuria were not well-represented in trials examining the effect of this intervention on kidney outcomes. To examine the effect of intensive BP control on the risk of kidney outcomes in patients with CKD, the authors pooled individual-level data from seven trials. They found that overall, intensive BP control was associated with a 13% lower, but not significant, risk of a kidney outcome. However, the intervention's effect on the kidney outcome differed depending on baseline eGFR. Data from this pooled analysis suggested a benefit of intensive BP control in delaying KRT onset in patients with stages 4-5 CKD, but not necessarily in those with stage 3 CKD. BACKGROUND: The effect of intensive BP lowering (to systolic BP of <120 mm Hg) on the risk of kidney failure requiring KRT remains unclear in patients with advanced CKD. Such patients were not well represented in trials evaluating intensive BP control. METHODS: To examine the effect of intensive BP lowering on KRT risk-or when not possible, trial-defined kidney outcomes-we pooled individual-level data from seven trials that included patients with eGFR<60 ml/min per 1.73 m 2 . We performed prespecified subgroup analyses to evaluate the effect of intensive BP control by baseline albuminuria and eGFR (CKD stages 4-5 versus stage 3). RESULTS: Of 5823 trial participants, 526 developed the kidney outcome and 382 died. Overall, intensive (versus usual) BP control was associated with a lower risk of kidney outcome and death in unadjusted analyses but these findings did not achieve statistical significance. However, the intervention's effect on the kidney outcome differed depending on baseline eGFR ( P interaction=0.05). By intention-to-treat analysis, intensive (versus usual) BP control was associated with a 20% lower risk of the primary kidney outcome in those with CKD GFR stages 4-5, but not in CKD GFR stage 3. There was no interaction between intensive BP control and the severity of albuminuria for kidney outcomes. CONCLUSIONS: Data from this pooled analysis of seven trials suggest a benefit of intensive BP control in delaying KRT onset in patients with stages 4-5 CKD but not necessarily with stage 3 CKD. These findings suggest no evidence of harm from intensive BP control, but also point to the need for future trials of BP targets focused on populations with advanced kidney disease. PODCAST: This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_02_27_JASN0000000000000060.mp3.

Lipid accumulation product, visceral adiposity index and risk of chronic kidney disease.

BACKGROUND: Lipid accumulation product (LAP) and visceral adiposity index (VAI) are novel, non-imaging markers of visceral adiposity that are calculated by using body mass index (BMI), waist circumference (WC) and serum lipid concentrations. We hypothesized that LAP and VAI are more strongly associated with adverse kidney outcomes than BMI and WC. METHODS: Using data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, we used multivariable logistic regression to evaluate associations of LAP, VAI, BMI and WC with incident chronic kidney disease (CKD), (incident eGFR < 60 ml/min/1.73m2 and > 25% decline). RESULTS: Among the overall cohort of 27,550 participants, the mean baseline age was 65 years; 54% were women; and 41% were African American. After a median of 9.4 years (IQR 8.6, 9.9) of follow-up, a total of 1127 cases of incident CKD were observed. Each two-fold higher value of VAI (OR 1.12, 95% CI 1.04, 1.20), LAP (OR 1.21, 95% CI 1.13, 1.29), WC (OR 2.10, 95% CI 1.60, 2.76) and BMI (OR: 2.66, 95% CI 1.88, 3.77), was associated with greater odds of incident CKD. CONCLUSIONS: LAP and VAI as measures of visceral adiposity are associated with higher odds of incident CKD but may not provide information beyond WC and BMI.