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CKD Associates with Cognitive Decline in Middle-Aged and Older Adults with Long-Standing Type 1 Diabetes

Khatri, Minesh; Ryan, Christopher M; Gao, Xiaoyu; de Boer, Ian H; Braffett, Barbara H; Molitch, Mark; Karger, Amy B; Lorenzi, Gayle M; Lee, Pearl; Trapani, Victoria R; Lachin, John M; Jacobson, Alan M
KEY POINTS:We found that development of both albuminuria and reduced eGFR was associated with clinically significant cognitive decline, particularly in the psychomotor and mental efficiency domain. There was also a significant interaction between worsened albuminuria and eGFR, the combination of which augmented cognitive deficits. A more comprehensive longitudinal phenotype of albuminuria showed that regressed albuminuria did not associate with worsened cognitive decline, as opposed to persistent albuminuria. BACKGROUND:Individuals with CKD or type 1 diabetes (T1D) are at risk for cognitive decline, but it is unclear whether these associations are with albuminuria, eGFR, or both. METHODS:) in models using eGFR and albuminuria measurements over the first 15–20 years with subsequent change in cognitive function over the ensuing 14 years (when decline in cognition was greatest). RESULTS:−0.915; 95% CI, −1.613 to −0.217). CONCLUSIONS:In T1D, development of CKD was associated with a subsequent reduction on cognitive tasks requiring psychomotor and mental efficiency. These data highlight the need for increased recognition of risk factors for neurologic sequelae in patients with T1D, as well as preventive and treatment strategies to ameliorate cognitive decline.
PMCID:10476689
PMID: 37291722
ISSN: 2641-7650
CID: 5589972

Outcomes among Hospitalized Chronic Kidney Disease Patients with COVID-19

Khatri, Minesh; Charytan, David M; Parnia, Sam; Petrilli, Christopher M; Michael, Jeffrey; Liu, David; Tatapudi, Vasishta; Jones, Simon; Benstein, Judith; Horwitz, Leora I
Background/UNASSIGNED:Patients with CKD ha ve impaired immunity, increased risk of infection-related mortality, and worsened COVID-19 outcomes. However, data comparing nondialysis CKD and ESKD are sparse. Methods/UNASSIGNED:Patients with COVID-19 admitted to three hospitals in the New York area, between March 2 and August 27, 2020, were retrospectively studied using electronic health records. Patients were classified as those without CKD, those with nondialysis CKD, and those with ESKD, with outcomes including hospital mortality, ICU admission, and mortality rates. Results/UNASSIGNED:Of 3905 patients, 588 (15%) had nondialysis CKD and 128 (3%) had ESKD. The nondialysis CKD and ESKD groups had a greater prevalence of comorbidities and higher admission D-dimer levels, whereas patients with ESKD had lower C-reactive protein levels at admission. ICU admission rates were similar across all three groups (23%-25%). The overall, unadjusted hospital mortality was 25%, and the mortality was 24% for those without CKD, 34% for those with nondialysis CKD, and 27% for those with ESKD. Among patients in the ICU, mortality was 56%, 64%, and 56%, respectively. Although patients with nondialysis CKD had higher odds of overall mortality versus those without CKD in univariate analysis (OR, 1.58; 95% CI, 1.31 to 1.91), this was no longer significant in fully adjusted models (OR, 1.11; 95% CI, 0.88 to 1.40). Also, ESKD status did not associate with a higher risk of mortality compared with non-CKD in adjusted analyses, but did have reduced mortality when compared with nondialysis CKD (OR, 0.57; 95% CI, 0.33 to 0.95). Mortality rates declined precipitously after the first 2 months of the pandemic, from 26% to 14%, which was reflected in all three subgroups. Conclusions/UNASSIGNED:In a diverse cohort of patients with COVID-19, we observed higher crude mortality rates for patients with nondialysis CKD and, to a lesser extent, ESKD, which were not significant after risk adjustment. Moreover, patients with ESKD appear to have better outcom es than those with nondialysis CKD.
PMCID:8786103
PMID: 35368350
ISSN: 2641-7650
CID: 5219372

Decreasing Incidence of AKI in Patients with COVID-19 critical illness in New York City

Charytan, David M; Parnia, Sam; Khatri, Minesh; Petrilli, Christopher M; Jones, Simon; Benstein, Judith; Horwitz, Leora I
Introduction/UNASSIGNED:Reports from the United States suggest that acute kidney injury (AKI) frequently complicates COVID-19, but understanding of AKI risks and outcomes is incomplete. Additionally, whether kidney outcomes have evolved during the course of the pandemic is unknown. Methods/UNASSIGNED:We used electronic records to identify COVID-19 patients with and without AKI admitted to 3 New York Hospitals between March 2 and August 25, 2020. Outcomes included AKI overall and according to admission week, AKI stage, the requirement for new renal replacement therapy (RRT), mortality and recovery of kidney function. Logistic regression was utilized to assess associations of patient characteristics and outcomes. Results/UNASSIGNED:Out of 4732 admissions 1386 (29.3%) patients had AKI. Among those with AKI, 717 (51.7%) had Stage 1, 132 (9.5%) Stage 2, 537 (38.7%) stage 3, and 237 (17.1%) required RRT initiation. In March 536/1648 (32.5%) of patients developed AKI compared with 15/87 (17.2%) in August (P<0.001 for monthly trend) whereas RRT initiation was required in 6.9% and 0% of admission, in March and August respectively. Mortality was higher with than without AKI (51.6% vs 8.6%) and was 71.9% in individuals requiring RRT. However, most patients with AKI who survived hospitalization (77%) recovered to within 0.3 mg/dL of baseline creatinine. Among those surviving to discharge, 62% discontinued RRT. Conclusions/UNASSIGNED:AKI impacts a high proportion of admitted COVID-19 patients and is associated with high mortality, particularly when RRT is required. AKI incidence appears to be decreasing over time and kidney function frequently recovers in those who survive.
PMCID:7857986
PMID: 33558853
ISSN: 2468-0249
CID: 4779502

COVID-19 Antibodies and Outcomes among Outpatient Maintenance Hemodialysis Patients

Khatri, Minesh; Islam, Shahidul; Dutka, Paula; Carson, John; Drakakis, James; Imbriano, Louis; Jawaid, Imran; Mehta, Tapan; Miyawaki, Nobuyuki; Wu, Elain; Yang, Stephen; Ali, Nicole; Divers, Jasmin; Grant, Candace; Masani, Naveed
Background/UNASSIGNED:Patients on maintenance hemodialysis are particularly vulnerable to infection and hospitalization from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Due to immunocompromised patients and the clustering that occurs in outpatient dialysis units, the seroprevalence of COVID-19 antibodies in this population is unknown and has significant implications for public health. Also, little is known about their risk factors for hospitalization. Methods/UNASSIGNED:nasopharyngeal, real-time, reverse-transcriptase PCR (RT-PCR); SARS-CoV-2 IgG seropositivity; hospitalization; and mortality. Results/UNASSIGNED:<0.001) compared with those who tested negative. Higher positivity rates were also observed among those who took taxis and ambulettes to and from dialysis, compared with those who used personal transportation. Antibodies were detected in all of the patients with a positive PCR result who underwent serologic testing. Of those that were seropositive, 32% were asymptomatic. The hospitalization rate on the basis of either antibody or PCR positivity was 35%, with a hospital mortality rate of 33%. Aside from COPD, no other variables were more prevalent in patients who were hospitalized. Conclusions/UNASSIGNED:We observed significant differences in rates of COVID-19 infection within three outpatient dialysis units, with universal seroconversion. Among patients with ESKD, rates of asymptomatic infection appear to be high, as do hospitalization and mortality rates.
PMCID:8740990
PMID: 35373027
ISSN: 2641-7650
CID: 5219442

The association between serum chloride levels and chronic kidney disease progression: a cohort study

Khatri, Minesh; Zitovsky, Joshua; Lee, Dale; Nayyar, Kamal; Fazzari, Melissa; Grant, Candace
BACKGROUND:Limited data suggest serum chloride levels associate with mortality in heart failure, chronic kidney disease (CKD), and pulmonary arterial hypertension. Randomized trials have also shown that administration of crystalloid intravenous fluids with lower chloride concentration may have better renal outcomes. However, chloride has not been studied longitudinally for CKD progression. METHODS:We used a prospective cohort of subjects with stage 3 and 4 CKD recruited from a nephrology clinic at a single medical center. Linear regression, linear regression with generalized estimating equations, and Cox proportional hazards models were created for outcomes of overall change in estimated glomerular filtration rate (eGFR), longitudinal changes in eGFR, and time to > 30% decline in eGFR, respectively. Baseline chloride was modeled continuously and categorically, and models were adjusted for potential confounders. RESULTS:compared to the lowest quartile (p = 0.004). No association between serum chloride and time to 30% decline in eGFR was observed in multivariable analysis (hazard ratio 1.05 per 1 mEq/L increase in serum chloride, p = 0.103). CONCLUSIONS:In CKD patients, higher serum chloride associated with a modestly steeper rate of eGFR decline, and may be a useful biomarker to predict CKD progression. Further studies are needed to determine causality.
PMCID:7203999
PMID: 32375681
ISSN: 1471-2369
CID: 4439312

Capillary leak syndrome: etiologies, pathophysiology, and management

Siddall, Eric; Khatri, Minesh; Radhakrishnan, Jai
In various human diseases, an increase in capillary permeability to proteins leads to the loss of protein-rich fluid from the intravascular to the interstitial space. Although sepsis is the disease most commonly associated with this phenomenon, many other diseases can lead to a "sepsis-like" syndrome with manifestations of diffuse pitting edema, exudative serous cavity effusions, noncardiogenic pulmonary edema, hypotension, and, in some cases, hypovolemic shock with multiple-organ failure. The term capillary leak syndrome has been used to describe this constellation of disease manifestations associated with an increased capillary permeability to proteins. Diseases other than sepsis that can result in capillary leak syndrome include the idiopathic systemic capillary leak syndrome or Clarkson's disease, engraftment syndrome, differentiation syndrome, the ovarian hyperstimulation syndrome, hemophagocytic lymphohistiocytosis, viral hemorrhagic fevers, autoimmune diseases, snakebite envenomation, and ricin poisoning. Drugs including some interleukins, some monoclonal antibodies, and gemcitabine can also cause capillary leak syndrome. Acute kidney injury is commonly seen in all of these diseases. In addition to hypotension, cytokines are likely to be important in the pathophysiology of acute kidney injury in capillary leak syndrome. Fluid management is a critical part of the treatment of capillary leak syndrome; hypovolemia and hypotension can cause organ injury, whereas capillary leakage of administered fluid can worsen organ edema leading to progressive organ injury. The purpose of this article is to discuss the diseases other than sepsis that produce capillary leak and review their collective pathophysiology and treatment.
PMID: 28318633
ISSN: 1523-1755
CID: 3534222

The association between a Mediterranean-style diet and kidney function in the Northern Manhattan Study cohort

Khatri, Minesh; Moon, Yeseon P; Scarmeas, Nikolaos; Gu, Yian; Gardener, Hannah; Cheung, Ken; Wright, Clinton B; Sacco, Ralph L; Nickolas, Thomas L; Elkind, Mitchell S V
BACKGROUND AND OBJECTIVES/OBJECTIVE:Various dietary strategies have been investigated to slow kidney function decline. However, it is unknown whether a Mediterranean diet, which has been associated with improved cardiovascular risk, is associated with change in kidney function. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS/METHODS:This study used the Northern Manhattan Study, a prospective, multiethnic, observational cohort of participants who were stroke free at baseline. Data were collected between 1993 and 2008. Serum creatinine measurements were taken a mean 6.9 years apart. A baseline dietary questionnaire was extrapolated into a previously used 9-point scoring system (MeDi). The primary outcome was incident eGFR<60 ml/min per 1.73 m(2)using the Modification of Diet in Renal Disease formula. A secondary outcome was the upper quartile of annualized eGFR decline (≥ 2.5 ml/min per 1.73 m(2) per year). Conditional logistic regression models adjusted for demographics and baseline vascular risk factors. RESULTS:Mean baseline age was 64 years, with 59% women and 65% Hispanics (N=900); mean baseline eGFR was 83.1 ml/min per 1.73 m(2). Incident eGFR<60 ml/min per 1.73 m(2) developed in 14% . In adjusted models, every 1-point increase in the MeDi score, indicating increasing adherence to a Mediterranean diet, was associated with decreased odds of incident eGFR<60 ml/min per 1.73 m(2) (odds ratio, 0.83; 95% confidence interval, 0.71 to 0.96) and decreased odds of being in the upper quartile of eGFR decline (odds ratio, 0.88; 95% confidence interval, 0.79 to 0.98). CONCLUSIONS:A Mediterranean diet was associated with a reduced incidence of eGFR<60 ml/min per 1.73 m(2) and upper quartile of eGFR decline in a multiethnic cohort.
PMID: 25359387
ISSN: 1555-905x
CID: 3534212

Acute kidney injury is associated with increased hospital mortality after stroke

Khatri, Minesh; Himmelfarb, Jonathan; Adams, Derk; Becker, Kyra; Longstreth, W T; Tirschwell, David L
BACKGROUND:Acute kidney injury (AKI) is common and is associated with poor clinical outcomes. Information about the incidence of AKI and its effect on stroke outcomes is limited. METHODS:Data were analyzed from a registry of subjects with ischemic stroke and intracerebral hemorrhage (ICH) hospitalized at a single academic medical center. Admission creatinine was considered to be the baseline. AKI was defined as a creatinine increase during hospitalization of 0.3 mg/dL or a percentage increase of at least 50% from baseline. Multivariate logistic regression models were created for both stroke types, with hospital mortality as the outcome. Covariates included gender, race, age, admission creatinine, National Institutes of Health Stroke Scale score at admission, the performance of a contrast-enhanced computed tomographic scan of the head and neck, and medical comorbidities. RESULTS:There were 528 cases of ischemic stroke with 70 deaths (13%), and 829 cases of ICH with 268 deaths (32%). The mean age was 64 years; 56% of patients were men and 71% were white. AKI complicated 14% of ischemic stroke and 21% of ICH hospitalizations. In multivariate analysis stratified by stroke type, AKI was associated with increased hospital mortality from ischemic stroke (odds ratio [OR] 3.08; 95% confidence interval [CI] 1.49-6.35) but not ICH (OR 0.82; 95% CI 0.50-1.35), except for those surviving at least 2 days (OR 2.11; 95% CI 1.18-3.77). CONCLUSIONS:AKI occurs frequently after stroke and is associated with increased hospital mortality. Additional studies are needed to establish if the association is causal and if measures to prevent AKI would result in decreased mortality.
PMCID:3507321
PMID: 22818389
ISSN: 1532-8511
CID: 3534202

A prospective study of frailty in nephrology-referred patients with CKD

Roshanravan, Baback; Khatri, Minesh; Robinson-Cohen, Cassianne; Levin, Greg; Patel, Kushang V; de Boer, Ian H; Seliger, Stephen; Ruzinski, John; Himmelfarb, Jonathan; Kestenbaum, Bryan
BACKGROUND:Frailty is a construct developed to characterize a state of reduced functional capacity in older adults. However, there are limited data describing the prevalence or consequences of frailty in middle-aged patients with chronic kidney disease (CKD). STUDY DESIGN/METHODS:Observational study. SETTING & PARTICIPANTS/METHODS:336 non-dialysis-dependent patients with stages 1-4 CKD with estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m(2) (by the CKD-EPI [CKD Epidemiology Collaboration] serum creatinine-based equation) or evidence of microalbuminuria enrolled in the Seattle Kidney Study, a clinic-based cohort study. Findings were compared with community-dwelling older adults in the Cardiovascular Health Study. OUTCOME/RESULTS:Prevalence and determinants of frailty in addition to its association with the combined outcome of all-cause mortality or renal replacement therapy. MEASUREMENTS/METHODS:We defined frailty according to established criteria as 3 or more of the following characteristics: slow gait, weakness, unintentional weight loss, exhaustion, and low physical activity. We estimated kidney function using serum cystatin C concentrations (eGFR(cys)) to minimize confounding due to relationships of serum creatinine levels with muscle mass and frailty. RESULTS:The mean age of the study population was 59 years and mean eGFR(cys) was 51 mL/min/1.73 m(2). The prevalence of frailty (14.0%) was twice that of the much older non-CKD reference population (P < 0.01). The most common frailty components were physical inactivity and exhaustion. After adjustment including diabetes, eGFR(cys) categories of <30 and 30-44 mL/min/1.73 m(2) were associated with a 2.8- (95% CI, 1.3-6.3) and 2.1 (95% CI, 1.0-4.7)-fold greater prevalence of frailty compared with GFR(cys) ≥60 mL/min/1.73 m(2). There were 63 events during a median 987 days of follow-up. After adjustment, the frailty phenotype was associated with an estimated 2.5 (95% CI, 1.4-4.4)-fold greater risk of death or dialysis therapy. LIMITATIONS/CONCLUSIONS:Cross-sectional study design obscures inference regarding temporal relationships between CKD and frailty. CONCLUSIONS:Frailty is relatively common in middle-aged patients with CKD and is associated with lower eGFR(cys) and increased risk of death or dialysis therapy.
PMCID:3491110
PMID: 22770927
ISSN: 1523-6838
CID: 3534192

Association of serum soluble receptor for advanced glycation end-products with subclinical cerebrovascular disease: the Northern Manhattan Study (NOMAS)

Hudson, Barry I; Moon, Yeseon Park; Kalea, Anastasia Z; Khatri, Minesh; Marquez, Chensy; Schmidt, Ann Marie; Paik, Myunghee C; Yoshita, Mitsuhiro; Sacco, Ralph L; DeCarli, Charles; Wright, Clinton B; Elkind, Mitchell S V
OBJECTIVE: Serum levels of the soluble receptor for advanced glycation end-products (sRAGE) have been associated with risk of cardiovascular disease. We hypothesized that sRAGE levels are associated with subclinical cerebrovascular disease in an ethnically diverse population. METHODS: Clinically stroke-free participants in the multi-ethnic Northern Manhattan Study (NOMAS) underwent brain MRI to quantify subclinical brain infarcts (SBI) and white matter hyperintensity volume (WMHV) (n = 1102). Serum levels of sRAGE were measured by ELISA. Logistic and multiple linear regression were employed to estimate associations of sRAGE with SBI and WMHV, after adjusting for demographics and vascular risk factors. RESULTS: Median sRAGE levels were significantly lower in Hispanics (891.9 pg/ml; n = 708) and non-Hispanic blacks (757.4 pg/ml; n = 197) than in non-Hispanic whites (1120.5 pg/ml; n = 170), and these differences remained after adjusting for other risk factors. Interactions were observed by race-ethnicity between sRAGE levels and MRI measurements, including for SBI in Hispanics (p = 0.04) and WMHV among blacks (p = 0.03). In Hispanics, increasing sRAGE levels were associated with a lower odds of SBI, with those in the upper sRAGE quartile displaying a 50% lower odds of SBI after adjusting for sociodemographic and vascular risk factors (p = 0.05). Among blacks, those in the upper quartile of sRAGE had a similarly reduced increased risk of SBI (p = 0.06) and greater WMHV (p = 0.04). CONCLUSION: Compared to whites, Hispanics and blacks have significantly lower sRAGE levels, and these levels were associated with more subclinical brain disease. Taken together, these findings suggest sRAGE levels may be significantly influence by ethnicity. Further studies of sRAGE and stroke risk, particularly in minorities, are warranted.
PMCID:3089661
PMID: 21316677
ISSN: 0021-9150
CID: 778852