AKI in Hospitalized Patients with and without COVID-19: A Comparison Study.

BACKGROUND: Reports from centers treating patients with coronavirus disease 2019 (COVID-19) have noted that such patients frequently develop AKI. However, there have been no direct comparisons of AKI in hospitalized patients with and without COVID-19 that would reveal whether there are aspects of AKI risk, course, and outcomes unique to this infection. METHODS: In a retrospective observational study, we evaluated AKI incidence, risk factors, and outcomes for 3345 adults with COVID-19 and 1265 without COVID-19 who were hospitalized in a large New York City health system and compared them with a historical cohort of 9859 individuals hospitalized a year earlier in the same health system. We also developed a model to identify predictors of stage 2 or 3 AKI in our COVID-19. RESULTS: We found higher AKI incidence among patients with COVID-19 compared with the historical cohort (56.9% versus 25.1%, respectively). Patients with AKI and COVID-19 were more likely than those without COVID-19 to require RRT and were less likely to recover kidney function. Development of AKI was significantly associated with male sex, Black race, and older age (>50 years). Male sex and age >50 years associated with the composite outcome of RRT or mortality, regardless of COVID-19 status. Factors that were predictive of stage 2 or 3 AKI included initial respiratory rate, white blood cell count, neutrophil/lymphocyte ratio, and lactate dehydrogenase level. CONCLUSIONS: Patients hospitalized with COVID-19 had a higher incidence of severe AKI compared with controls. Vital signs at admission and laboratory data may be useful for risk stratification to predict severe AKI. Although male sex, Black race, and older age associated with development of AKI, these associations were not unique to COVID-19.

Progressive kidney disease may not alter the association of hyponatremia with mortality.

BACKGROUND: Hyponatremia is a common electrolyte disorder and a prognostic marker for mortality. We hypothesize that in advanced chronic or acute kidney disease, hyponatremia is not independently associated with mortality because of the contribution of kidney failure to its pathophysiology. METHODS: Clinical Looking Glass, Montefiore's clinical database, was used to build a cohort of all patients hospitalized between January of 2009 and December of 2011. A chronic kidney disease (CKD) group and an acute kidney injury (AKI) group were defined based on GFR measurements during and before index hospitalization. Cox regression models assessed the hazard for death for those with community acquired hyponatremia as compared to those without hyponatremia, stratified by stage of kidney disease within each cohort. RESULTS: Forty-four thousand four hundred and seventy-six patients were studied. Forty six percent (46.2%) of subjects were in the CKD cohort and 53.8% were in the AKI cohort. Hyponatremic patients were older, and had a higher prevalence of CKD and AKI. A total of 7,934 subjects died (17.8%) during 22 months of follow-up. In CKD and AKI cohorts, hyponatremia, age, race, illness severity and Charlson score were associated with mortality. Hyponatremia had similar hazard ratios (HR) across kidney disease stages despite loss of statistical significance in later stages due to smaller sample size. CONCLUSIONS: The association between community acquired hyponatremia and mortality showed consistent HRs across progressive stages of CKD and AKI suggesting that the contribution of tubular dysfunction to hyponatremia in advanced kidney disease does not alter this association.

Female sex reduces the risk of hospital-associated acute kidney injury: a meta-analysis.

BACKGROUND: Female sex has been included as a risk factor in models developed to predict the development of AKI. In addition, the commentary to the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for AKI concludes that female sex is a risk factor for hospital-acquired AKI. In contrast, a protective effect of female sex has been demonstrated in animal models of ischemic AKI. METHODS: To further explore this issue, we performed a meta-analysis of AKI studies published between January, 1978 and April, 2018 and identified 83 studies reporting sex-stratified data on the incidence of hospital-associated AKI among nearly 240,000,000 patients. RESULTS: Twenty-eight studies (6,758,124 patients) utilized multivariate analysis to assess risk factors for hospital-associated AKI and provided sex-stratified ORs. Meta-analysis of this cohort showed that the risk of developing hospital-associated AKI was significantly greater in men than in women (OR 1.23 (1.11,1.36). Since AKI is not a single disease but instead represents a heterogeneous group of disorders characterized by an acute reduction in renal function, we performed subgroup meta-analyses. The association of male sex with AKI was strongest among studies of patients who underwent non-cardiac surgery. Male sex was also associated with AKI in studies which included unselected hospitalized patients and in studies of critically ill patients who received care in an intensive care unit. In contrast, cardiac surgery-associated AKI and radiocontrast-induced AKI showed no sexual dimorphism. CONCLUSIONS: Our meta-analysis contradicts the established belief that female sex confers a greater risk of AKI and instead suggests a protective role.

Sex differences in acute kidney injury requiring dialysis.

BACKGROUND: Female sex has been included as a risk factor in models developed to predict the risk of acute kidney injury (AKI) associated with cardiac surgery, aminoglycoside nephrotoxicity and contrast-induced nephropathy. The commentary acompanying the Kidney Disease Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury concludes that female sex is a shared susceptibility factor for acute kidney injury based on observations that female sex is associated with the development of hospital-acquired acute kidney injury. In contrast, female sex is reno-protective in animal models. In this context, we sought to examine the role of sex in hospital-associated acute kidney injury in greater detail. METHODS: We utilized the Hospital Episode Statistics database to calculate the sex-stratified incidence of AKI requiring renal replacement therapy (AKI-D) among 194,157,726 hospital discharges reported for the years 1998-2013. In addition, we conducted a systematic review of the English literature to evaluate dialysis practices among men versus women with AKI. RESULTS: Hospitalized men were more likely to develop AKI-D than hospitalized women (OR 2.19 (2.15, 2.22) p < 0.0001). We found no evidence in the published literature that dialysis practices differ between men and women with AKI. CONCLUSIONS: Based on a population of hospitalized patients which is more than 3 times larger than all previously published cohorts reporting sex-stratified AKI data combined, we conclude that male sex is associated with an increased incidence of hospital-associated AKI-D. Our study is among the first reports to highlight the protective role of female gender in AKI.

Association between antiphospholipid antibodies and all-cause mortality among end-stage renal disease patients with and without SLE: a retrospective cohort study.

OBJECTIVE: To investigate the association between the presence of aPL and/or LA and all-cause mortality among end-stage renal disease (ESRD) patients with and without SLE. METHODS: We included ESRD patients >18 years old followed at an urban tertiary care centre between 1 January 2006 and 31 January 2014 who had aPL measured at least once after initiating haemodialysis. All SLE patients met ACR/SLICC criteria. APL/LA+ was defined as aCL IgG or IgM >40 IU, anti-ß2glycoprotein1 IgG or IgM >40 IU or LA+. Deaths as at 31 January 2014 were captured in the linked National Death Index data. Time to death was defined from the first aPL measurement. RESULTS: We included 34 SLE ESRD and 64 non-SLE ESRD patients; 30 patients died during the study period. SLE ESRD patients were younger [40.4 (12.5) vs 51.9 (18.1) years, P = 0.001] and more were women (88.2% vs 54.7%, P < 0.001) vs non-SLE ESRD patients. The frequency of aPL/LA+ was 24% in SLE and 13% in non-SLE ESRD (P = 0.16). Median (inter-quartile range) follow-up time was 1.6 (0.3-3.5) years in SLE and 1.4 (0.4-3.2) years in non-SLE, P = 0.74. The adjusted hazard ratio (HR) for all-cause mortality for SLE patients who were aPL/LA+ vs aPL/LA- was 9.93 (95% CI 1.33, 74.19); the adjusted HR for non-SLE aPL/LA+ vs aPL/LA- was 0.77 (95% CI 0.14, 4.29). CONCLUSION: SLE ESRD patients with aPL/LA+ had higher all-cause mortality risk than SLE ESRD patients without these antibodies, while the effects of aPL/LA on mortality were comparable among non-SLE ESRD patients.

The effect of gender on aminoglycoside-associated nephrotoxicity
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AIMS: The kidney disease improving global outcomes (KDIGO) clinical practice guidelines for acute kidney injury (AKI) has endorsed the widely held belief that female gender is a risk factor for aminoglycoside-associated nephrotoxicity (AAN). In contrast, female gender is protective in animal models. In light of this dichotomy, we sought to explore this relationship in greater detail. METHODS: We performed a meta-analysis of studies published between 1978 and 2015 which examined aminoglycoside nephrotoxicity and provided gender-specific data. RESULTS: 24 studies were identified that provided univariate gender-specific data. The incidence of AAN did not differ between the sexes (odds ratio (OR) for females vs. males 1.00 (0.81, 1.22), p = 0.97, n = 5,980). Twelve studies utilized logistic regression analysis with gender as a covariate. Meta-analysis of the 5 studies that utilized multivariate analysis and reported gender-specific OR found no effect of gender on the risk of AAN (OR 0.99 (0.58, 1.69), p = 0.96, n = 2,994). Similarly, gender was not an independent risk factor for AAN in the remaining 7 studies that utilized multivariate analysis with gender as a covariate but failed to report gender-specific OR (n = 1,636). DISCUSSION: Our meta-analysis contradicts the generally held consensus that female gender is an independent risk factor for the development of AAN. Our findings may have much wider implications insofar as AAN cannot be used as an example to support the conclusion of the KDIGO Clinical Practice Guidelines that female gender is an independent risk factor for AKI.
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Glomerular size reduction associated with severe cardiorenal syndrome.

BACKGROUND: Pathologic changes that are associated with the cardiorenal syndrome (CRS) are seldom described. The two theories that address renal physiology in CRS include chronic indolent ischemia from renal vasoconstriction and chronic glomerular venous congestion from increased venous pressures. We report on the glomerular histologic changes that occur with long standing heart failure. OBJECTIVE: To examine whether CRS causes renal ischemia that manifests as glomerular size reduction. METHODS: We performed a case-control study where we measured total glomerular areas in 16 adult cases with end-stage heart disease and compared them with matched controls. Control biopsy samples were obtained from renal tissue included in nephrectomies. Glomerular size was measured using the BioQuant Image Analysis program. Cases and controls were matched on the following variables: age (within 10 years), race, body mass index (BMI), diabetes mellitus (DM), glomerular filtration rate (GFR) (within 10 mL/min/1.73 m2), and history of tobacco use. RESULTS: The age range of all patients at the time of biopsy was 40 - 73 years. Nine of the case patients had DM. Estimated GFR ranged from 29 to 55 mL/min/1.73 m2. Mean BMI was 30.8 (SD 4.7) kg/m2. The average median glomerular area in the case patients was 23,944 pixels (1 pixel = 1 µm2), (IQR 22,549 - 27,990) vs. in controls 38,566 pixels (IQR 31, 227 - 45,938) (p = 0.004). CONCLUSIONS: This case-controlled cohort study demonstrates that patients with long standing heart failure have smaller glomerular size as compared with controls matched for relevant clinical variables but not for heart failure.

Improving outcomes in patients with lupus and end-stage renal disease.

The development of lupus-related end-stage renal disease (ESRD) confers the highest mortality rates among individuals with lupus. Lupus-related ESRD is also associated with higher morbidity and mortality rates compared with non-lupus ESRD. We review the evidence that persistent lupus activity, hypercoagulability, and continuing immunosuppression may contribute to unfavorable outcomes in dialysis and renal transplantation among lupus patients. Robust epidemiologic studies are needed to develop individualized evidence-based approaches to treating lupus-related ESRD. In the meantime, managing lupus-related ESRD presents a significant challenge for clinicians and requires a team approach involving nephrologists and rheumatologists. Goals of therapy after developing ESRD should include continuing monitoring of lupus activity, minimizing corticosteroid exposure, and choosing the most appropriate renal replacement therapy based on patient's risk profile and quality-of-life considerations.

Renal BOLD-MRI and assessment for renal hypoxia.

Renal tissue hypoxia may play a major role in the progression of chronic renal disease. Michaely et al. used blood oxygen level-dependent magnetic resonance imaging to test this hypothesis. They found no relationship between renal oxygenation and stage of chronic kidney disease (CKD). However, renal tissue oxygenation may be related not only to the severity of renal disease but also to its underlying etiology. This added complexity confounds interpretation of data obtained from subjects with CKD due to multiple etiologies.

Sex Differences in Acute Kidney Injury.

Female sex confers renoprotection in chronic progressive kidney disease. It is less well recognized that sexual dimorphism also is evident in the development of ischemic and nephrotoxic acute kidney injury (AKI). Animal studies consistently have shown that female sex protects against the development of renal injury in experimental models of ischemic AKI. However, the consensus opinion is that in human beings, female sex is an independent risk factor for AKI. Based on a systematic review of experimental and clinical literature, we present data to support the conclusion that, contrary to consensus opinion, it is male sex, not female sex, that is associated with the development of AKI.

Does comorbidity burden explain the higher COVID-19 mortality risk among men? A retrospective cross-sectional analysis of a well-defined cohort of patients in Bronx, New York.

OBJECTIVES: Men have a higher mortality rate and more severe COVID-19 infection than women. The mechanism for this is unclear. We hypothesise that innate sex differences, rather than comorbidity burden, drive higher male mortality. DESIGN: Retrospective cohort. SETTING: Montefiore Health System (MHS) in Bronx, New York, USA. PARTICIPANTS: A cohort population of 364 992 patients at MHS between 1 January 2018 and 1 January 2020 was defined, from which individuals hospitalised during the pre-COVID period (1 January 2020-15 February 2020) (n=5856) and individuals hospitalised during the COVID-19 surge (1 March 2020-15 April 2020) (n=4793) were examined for outcomes. A subcohort with confirmed COVID-19+ hospitalisation was also examined (n=1742). PRIMARY AND SECONDARY OUTCOME MEASURES: Hospitalisation and in-hospital mortality. RESULTS: Men were older, had more comorbidities, lower body mass index and were more likely to smoke. Unadjusted logistic regression showed a higher odds of death in hospitalised men than women during both the pre-COVID-19 and COVID-19 periods (pre-COVID-19, OR: 1.66 vs COVID-19 OR: 1.98). After adjustment for relevant clinical and demographic factors, the higher risk of male death attenuated towards the null in the pre-COVID-19 period (OR 1.36, 95% CI 1.05 to 1.76) but remained significantly higher in the COVID-19 period (OR 2.02; 95% CI 1.73 to 2.34).In the subcohort of COVID-19+ hospitalised patients, men had 1.37 higher odds of in-hospital death (95% CI 1.09 to 1.72), which was not altered by adjustment for comorbidity (OR remained at 1.38 (95% CI 1.08 to 1.76)) but was attenuated with addition of initial pulse oximetry on presentation (OR 1.26, 95% CI 0.99 to 1.62). CONCLUSIONS: Higher male mortality risk during the COVID-19 period despite adjustment for comorbidity supports the role of innate physiological susceptibility to COVID-19 death. Attenuation of higher male risk towards the null after adjustment for severity of lung disease in hospitalised COVID-19+ patients further supports the role of higher severity of COVID-19 pneumonia in men.

Raloxifene, a selective estrogen receptor modulator, is renoprotective: a post-hoc analysis.

Estrogens have a protective effect on kidney fibrosis in several animal models. Here, we tested the effect of raloxifene, an estrogen receptor modulator, on the change in serum creatinine or estimated glomerular filtration rate (eGFR) and incident kidney-related adverse events. We performed a post-hoc analysis of the multiple outcomes of raloxifene evaluation trial, a double-masked, placebo-controlled randomized clinical trial encompassing 7705 post-menopausal women (aged 31-80 years) with osteoporosis. Participants were randomized to either of two doses of raloxifene, 60 or 120 mg/day, or placebo. Serum creatinine was measured at a central laboratory at baseline and annually. Adverse events were assessed every 6 months and uniformly categorized. Compared with those in the placebo group, participants on raloxifene had a slower yearly rate of increase in creatinine (significant at the low dose) and a significantly slower yearly rate of decrease in eGFR for both doses over 3 years of follow-up. Raloxifene was associated with significantly fewer kidney-related adverse events compared with placebo. Thus, treatment with raloxifene was safe and renoprotective. Clinical trials of raloxifene in post-menopausal women with kidney disease designed to look at kidney outcomes are needed to confirm these findings.

The association of race and COVID-19 mortality.

BACKGROUND: COVID-19 mortality disproportionately affects the Black population in the United States (US). To explore this association a cohort study was undertaken. METHODS: We assembled a cohort of 505,992 patients receiving ambulatory care at Bronx Montefiore Health System (BMHS) between 1/1/18 and 1/1/20 to evaluate the relative risk of hospitalization and death in two time-periods, the pre-COVID time-period (1/1/20-2/15/20) and COVID time-period (3/1/20-4/15/20). COVID testing, hospitalization and mortality were determined with the Black and Hispanic patient population compared separately to the White population using logistic modeling. Evaluation of the interaction of pre-COVID and COVID time periods and race, with respect to mortality was completed. FINDINGS: A total of 9,286/505,992 (1.8%) patients were hospitalized during either or both pre-COVID or COVID periods. Compared to Whites the relative risk of hospitalization of Black patients did not increase in the COVID period (p for interaction=0.12). In the pre- COVID period, compared to Whites, the odds of death for Blacks and Hispanics adjusted for comorbidity was statistically equivalent. In the COVID period compared to Whites the adjusted odds of death for Blacks was 1.6 (95% CI 1.2-2.0, p = 0.001). There was a significant increase in Black mortality risk from pre-COVID to COVID periods (p for interaction=0.02). Adjustment for relevant clinical and social indices attenuated but did not fully explain the observed difference in Black mortality. INTERPRETATION: The BMHS COVID experience demonstrates that Blacks do have a higher mortality with COVID incompletely explained by age, multiple reported comorbidities and available metrics of sociodemographic disparity. FUNDING: N/A.

Influence of Sex on the Progression of Chronic Kidney Disease.

The role that sex plays in the development and progression of chronic kidney disease remains a subject of controversy. The lack of clarity in this important area reflects complex interactions between biological factors and cultural and socioeconomic influences that impact the relationship between sex and renal disease. Certainly, additional observational studies are indicated; however, innovative approaches are required to isolate biological processes from cultural influences. Despite these limitations, available data suggest that the progression of renal disease is slower in women than in men and that this sexual dimorphism is primarily due to direct actions of sex hormones on cellular metabolism. The extent to which differences in lifestyle factors between the sexes influence sexual dimorphism in the progression of chronic kidney disease remains to be elucidated.

Sex and the kidneys: current understanding and research opportunities.

Concerns regarding sex differences are increasingly pertinent in scientific and societal arenas. Although biological sex and socio-cultural gender are increasingly recognized as important modulators of renal function under physiological and pathophysiological conditions, gaps remain in our understanding of the mechanisms underlying sex differences in renal pathophysiology, disease development, progression and management. In this Perspectives article, we discuss specific opportunities for future research aimed at addressing these knowledge gaps. Such opportunities include the development of standardized core data elements and outcomes related to sex for use in clinical studies to establish a connection between sex hormones and renal disease development or progression, development of a knowledge portal to promote fundamental understanding of physiological differences between male and female kidneys in animal models and in humans, and the creation of new or the development of existing resources and datasets to make them more readily available for interrogation of sex differences. These ideas are intended to stimulate thought and interest among the renal research community as they consider sex as a biological variable in future research projects.

Gender and human chronic renal disease.

BACKGROUND: Gender affects the incidence, prevalence, and progression of renal disease. In animal models of the disease, female sex appears to modify the course of progression. Hormonal manipulation by male or female castration also changes the course of renal disease progression, suggesting direct effects of sex hormones in influencing the course of these maladies. OBJECTIVE: This review examines the pertinent animal and human studies assessing the role of gender, and strives to shed light on the possible physiologic mechanisms underlying the effect of gender, on renal disease progression. METHODS: A summary and evaluation of past and recent studies describing the rate of renal disease progression in animal models and humans as it pertains to gender is provided. In addition, studies elucidating the factors involved in the more modest renal progression rate in females are reviewed and conclusions drawn. Relevant English-language publications were identified by searching the PubMed database from January 1990 until November 2007 using the search terms gender, sex, renal disease, and kidney. RESULTS: In polycystic kidney disease, membranous nephropathy, immunoglobulin A nephropathy, and "chronic renal disease of unknown etiology," men progress at a faster rate to end-stage renal failure than do women. In type 1 diabetes mellitus, there is evidence that males are more likely to manifest signs of renal disease, such as proteinuria. The factors involved in this gender disparity may include diet, kidney and glomerular size, differences in glomerular hemodynamics, and the direct effects of sex hormones. In many, but not all, animal models of renal disease, estrogens slow progression rate. Several studies have recently evaluated the effect of selective estrogen receptor modulators on renal function in humans. CONCLUSION: Further studies assessing the factors involved in the gender disparity in renal disease progression and the effects of hormonal treatments are warranted.

Avoidable visits to the emergency department(ED) and their association with sex, age and race in a cohort of low socio-economic status patients on hemodialysis in the Bronx.

BACKGROUND: In national samples drawn from the USRDS, female patients utilize the hospital ED and inpatient services at a higher rate than their male counterparts and have a higher rate of re-hospitalization. We wanted to explore the association of sex with avoidable ED visits made by a cohort of patients on hemodialysis in a mostly minority, lower socioeconomic status (SES), population in the Bronx to test the applicability of the USRDS findings. METHODS: We used Montefiore's clinical database to build a cohort of patients on hemodialysis with a first ED visit between 2013 and 2017. All ED visits after the index ED visit and those within one year prior to the index visit were recorded. None of the ED visits resulted in a hospitalization and were thus labeled "avoidable". Bivariate analysis tested the association of demographic and clinical variables with sex. We used negative binomial regression to test the association of each variable with avoidable ED visit count. The multivariate model used negative binomial regression with avoidable ED visit count as outcome and sex as the exposure variable and included ancestral variables age and race. Potential mediators were added to the model to measure their effects on the association of sex with avoidable ED visits. RESULTS: Four thousand six hundred and seventy three subjects on hemodialysis were identified as having at least one avoidable ED visit, in the period of 2013-2017 at one of four ED sites affiliated with Montefiore Medical Center in the Bronx. Over 5 years (2012-2017), the median number of ED visits made by the study sample was 4 (25-75% IQR: 2-8). Female patients on hemodialysis in our cohort were older, more commonly black, had lower SES scores, less commonly had commercial insurance and were less commonly married than their male counterparts. Female sex was not significantly associated with a higher rate of avoidable ED visits in the total cohort.(1.053(0.99-1.12) Female sex was significantly associated with outcome in non-Hispanic whites only and in those subjects younger than 44 years old.(IRR 1.30(1.06-1.69), 1.17(1.00-1.38) in non-Hispanic White and younger age group, respectively.) Marital status, SES and hemoglobin levels possibly mediated the association of sex and outcome in our population. (>25% change in the coefficient for sex with respect to outcome when variable added to the model). CONCLUSION: In this single center study of a lower-socioeconomic status, mostly minority dialysis population, the association of female sex with avoidable ED visits was not significant. These results suggest the association of sex with hospitalization outcomes, described by national datasets that determine quality indicators, are not consistent across different types of populations with some mediation possible by SES and marital status in poorer neighborhoods.

Dual Organ Duel: The Hepatorenal Axis.

Recent developments in our understanding of the pathogenesis of kidney disease in the setting of liver failure have highlighted that kidney injury, rather than occurring in isolation, is a marker of systemic disease and poor prognosis. The differential diagnosis of kidney disease associated with liver failure is broader than formerly described and new biopsy data, along with better acute kidney injury classification tools, have increased appreciation for distinct pathophysiological mechanisms. Evidence suggests that acute kidney injury contributes to worsening hepatic failure by directly injuring hepatic cells and by imposing restrictions on therapeutic strategies for portal hypertension. Furthermore, kidney injury limits the use of various therapeutic agents and increases their toxicity due to altered pharmacodynamics. A greater appreciation of CKD in this population is also overdue because management decisions are affected and increased vigilance may avoid further kidney injury. A multidisciplinary approach to kidney injury in the setting of liver failure will enable targeted therapeutic strategies that are safe and effective and serve to guide further research, while limiting clinical potential for harm. Finally, new hepatitis C antiviral therapies promise to change the landscape of liver failure, and a discussion of kidney risk factors and antiviral therapy of patients with kidney disease and hepatitis C is worthwhile.

Hepatic vein pressure predicts GFR in cirrhotic patients with hemodynamic kidney dysfunction.

The role of "nephrocongestion" in hemodynamic renal disease is understudied. Intra-abdominal hypertension accompanies liver disease and renal disease. Our hypothesis states that in those patients with liver disease, hepatic vein pressure measured during a transjugular intrahepatic portosystemic shunt (TIPS) procedure reflects intra-abdominal pressure and predicts estimated glomerular filtration rate (eGFR). We gathered data from our clinical database and chart review on a cohort of cirrhotic patients who received TIPS at Montefiore as part of their clinical care between 2004 and 2014. We evaluated association of demographic and measured variables with eGFR in those subjects without end-stage renal disease (ESRD). Using multivariate regression, we examined the relationship between eGFR and hepatic vein pressure while adjusting for age, proteinuria, and ultrasound evidence for parenchymal kidney disease. The mean age of the subjects was 57 years old. Two thirds of the patients were male, 23% were White, and 20% were Black. A higher percentage of patients with chronic kidney disease (CKD), as determined by lower than 60 mL/min/1.73 m2, had proteinuria and ultrasound evidence for parenchymal kidney disease. A multivariate linear regression showed a significant and negative association between hepatic vein pressure and eGFR when adjusting for age, race, and proteinuria. Hepatic vein pressure is negatively and significantly associated with eGFR in those patients with liver failure. This finding has major implications for the way we evaluate hemodynamic renal disease.