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Biomedical subjects

Chirag R Parikh

Publications and source records attributed to Chirag R Parikh.

At least 19 recordsLinked to original sources

Metabolomic Signatures of Inflammation in Chronic Kidney Disease.

RATIONALE & OBJECTIVE: Inflammation is associated with adverse kidney, cardiovascular, and mortality outcomes. Investigation of the metabolic milieu as it relates to inflammation may provide important insights into these disease processes. STUDY DESIGN: Prospective cohort. SETTING & PARTICIPANTS: African American Study of Kidney Disease and Hypertension (AASK), Atherosclerosis Risk in Communities (ARIC) study, and Boston Kidney Biopsy Cohort (BKBC) participants with available metabolomics and inflammatory protein data. PREDICTORS: Baseline blood levels of 718 metabolites. OUTCOMES: Baseline and longitudinal changes in blood levels of tumor necrosis factor receptors 1 and 2 (TNFR1, TNFR2), tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), interleukins 6, 8, and 10 (IL-6, IL-8, IL-10), uromodulin (UMOD), and epidermal growth factor (EGF). ANALYTICAL APPROACH: Multivariable linear regression and linear mixed-effects models. RESULTS: Among 491 AASK participants (mean age 54 years; 37% women; mean glomerular filtration rate, 45 mL/min/1.73 m2), 367 cross-sectional associations between metabolites and inflammatory proteins were significant after correction for multiple comparisons. The direction of association was mostly positive for TNFR1 (97%), TNFR2 (97%), IL-8 (77%), and IL-10 (100%); negative for UMOD (80%) and EGF (97%); and variable for TNF-⍺, IFN-γ, and IL-6. Pathways were distinct for several inflammatory proteins (eg, tryptophan metabolism for TNFR2). Forty-five associations between metabolites and longitudinal change in inflammatory proteins were identified. Notable metabolites included tigylcarnitine and N 2,N 5-diacetylornithine, which were associated with 2-year increases in TNFR1 and/or TNFR2, and 1,5-anhydroglucitol, where lower levels were associated with decreases in UMOD. In ARIC (n = 3,773) and BKBC (n = 413), replication of cross-sectional associations was excellent for TNFR1 (ARIC 83%; BKBC 85%) and TNFR2 (ARIC 64%; BKBC 79%) but poor for IL-8 (ARIC 3%; BKBC 3%). LIMITATIONS: Metabolite data limited to baseline visit; potential for residual confounding. CONCLUSIONS: Using an untargeted approach, multiple metabolites were cross-sectionally and longitudinally associated with inflammatory proteins in persons with chronic kidney disease.

Chronic kidney disease↗

Impact of chronic kidney disease on health-related quality-of-life improvement after coronary artery bypass surgery.

BACKGROUND: Little is known about the impact of chronic kidney disease (CKD) on health-related quality-of-life outcomes after coronary artery bypass grafting (CABG). METHODS: Our objective was to examine the changes in physical function (PF) and mental health (MH) 6 months after CABG in 1055 patients with and without CKD. The primary end points were mean change in score and status of "improved" or "worsened" in both PF and MH subscales of the Medical Outcomes Trust Short Form 36-Item Health Survey from baseline to 6 months after CABG, stratified by CKD stage (0-5). RESULTS: Absolute PF and MH scores at baseline and at 6 months varied by renal impairment level. Patients with severe CKD (stages 4-5) had a mean (SD) decrease in PF score at 6 months of 3 (3) compared with increases in the rest of the cohort (P<.001). After adjustment for baseline score, 21% of patients with advanced CKD experienced worsened PF scores, compared with 0% of patients with stages 0 to 2 and stage 3 CKD (P<.001). In contrast to PF scores, patients with and without CKD had similar improvements in mean MH scores at 6 months, and patients with stages 4 to 5 CKD had the highest frequency of those with improved MH scores (77%). After adjustment, no patients experienced worsened MH scores. CONCLUSIONS: After 6 months, patients with severe CKD who underwent CABG had improvement in MH but not improvement in PF and may have had worsened PF compared with those without severe CKD. Comparable evidence regarding quality-of-life outcomes in the absence of CABG is needed to more fully inform decision making regarding patients with severe CKD and coronary artery disease.

Activities of Daily Living↗

Underrepresentation of renal disease in randomized controlled trials of cardiovascular disease.

CONTEXT: Patients with renal disease are at high risk for cardiovascular mortality. Determining which interventions best offset this risk remains a health priority. OBJECTIVE: To quantify the representation of patients with renal disease in randomized controlled trials for interventions proven efficacious for cardiovascular disease. DATA SOURCES: We searched MEDLINE for trials published from 1985 through 2005 in 11 major medical and subspecialty journals. STUDY SELECTION: Randomized controlled trials for chronic congestive heart failure and acute myocardial infarction of treatments that are currently listed as class I or II recommendations in the current American College of Cardiology/American Heart Association guidelines were included. DATA EXTRACTION: Two reviewers independently abstracted data on study and patient characteristics, renal measurements, outcomes, and prognostic features. DATA SYNTHESIS: A total of 153 trials were reviewed. Patients with renal disease were reported as excluded in 86 (56%) trials. Patients with renal disease were more likely to be excluded from trials that were multicenter; of moderate enrollment size; North American; that tested renin-angiotensin-aldosterone system antagonists and anticoagulants; and that tested chronic congestive heart failure. Only 8 (5%) original articles reported the proportion of enrolled patients with renal disease, and only 15 (10%) reported mean baseline renal function. While 81 (53%) trials performed subgroup analyses of some baseline characteristic in the original article, only 4 (3%) subgroup analyses of treatment stratified by renal disease were performed. CONCLUSION: Major cardiovascular disease trials frequently exclude patients with renal disease and do not provide adequate information on the renal function of enrollees or the effect of interventions on patients with renal disease.

Cardiovascular Diseases↗

Effect of angiotensin-converting enzyme inhibitors on arterial stiffness in hypertension: systematic review and meta-analysis.

Arterial stiffness is an independent cardiovascular prognostic factor and is modulated by angiotensin-converting enzyme inhibitors (ACEIs). The authors performed a meta-analysis of clinical trials investigating the effects of ACEIs on pulse wave velocity (PWV) or augmentation index. The search included randomized clinical trials as well as uncontrolled studies that measured in-treatment changes in arterial stiffness. The authors performed separate analyses for carotid-femoral PWV, brachioradial PWV, and augmentation index. Average absolute and relative reduction in mean arterial pressure and PWV were -15.4 mm Hg and -13.04% and -1.15 m/s and -9.74% for carotid-femoral PWV studies; and -11.2 mm Hg and -9.3% and -1.9 m/s and -16.7% for brachioradial PWV studies. There was a greater reduction in augmentation index by ACEIs when compared with controls (-1.0% to -5.3%). The authors conclude that ACEIs have modest beneficial effects on arterial stiffness measured as PWV and augmentation index, and this effect is at least partly independent of changes in blood pressure.

Angiotensin-Converting Enzyme Inhibitors↗

Urine IL-18 is an early diagnostic marker for acute kidney injury and predicts mortality in the intensive care unit.

Serum creatinine is not an ideal marker of renal function in patients with acute kidney injury (AKI). Previous studies demonstrated that urinary IL-18 is increased in human AKI. Thus, whether urine IL-18 is an early diagnostic marker of AKI was investigated. A nested case-control study was performed within the Acute Respiratory Distress Syndrome (ARDS) Network trial. AKI was defined as an increase in serum creatinine by at least 50% within the first 6 d of ARDS study enrollment. A total of 400 urine specimens that were collected on study days 0, 1, and 3 of the ARDS trial were available from 52 case patients and 86 control patients. The data were analyzed in a cross-sectional manner and according to the time before development of AKI. The median urine IL-18 levels were significantly different at 24 and 48 h before AKI in case patients as compared with control patients. On multivariable analysis, urine IL-18 values predicted development of AKI 24 and 48 h later after adjustment for demographics, sepsis, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) III score, serum creatinine, and urine output. Urine IL-18 levels of >100 pg/ml are associated with increased odds of AKI of 6.5 (95% confidence interval 2.1 to 20.4) in the next 24 h. On diagnostic performance testing, urine IL-18 demonstrates an area under the receiver operating characteristic curve of 73% to predict AKI in the next 24 h. The urine IL-18 values were also significantly different between survivors and nonsurvivors (P < 0.05), and on multivariable analysis, the urine IL-18 value on day 0 is an independent predictor of mortality. Urinary IL-18 levels can be used for the early diagnosis of AKI. Urine IL-18 levels also predict the mortality of patients who have ARDS and are in the intensive care unit.

Acute Kidney Injury↗

Characterization of acute liver failure and development of a continuous risk of death staging system in children.

BACKGROUND/AIMS: Acute liver failure (ALF) in children has been associated with an overall mortality of approximately 70% in the pretransplant era and 50-80% survival in those undergoing orthotopic liver transplantation. There is currently no system for staging severity of ALF in children. The aim of this study was to characterize pediatric ALF in a tertiary hospital and to derive a scoring system to stratify severity of ALF based on predicted mortality. METHODS: Prospective data collection of 81 children from December 1993-2003 who presented with ALF. Data recorded included peak laboratory values, clinical characteristics, and survival. RESULTS: Transplant-free survival was 56% with overall survival including those undergoing OLT of 72%. Transplantation rate was 22% with transplant survival of 72%. Of the peak laboratory values analyzed, total bilirubin, prothrombin time/INR, and ammonia were the most predictive of death or a need for liver transplant. A simple risk staging system was developed based on the ability of these three laboratory measurements to predict mortality. CONCLUSIONS: The survival in pediatric ALF has improved in recent years. Risk staging for ALF could potentially be used in clinical research for risk-adjusted outcomes analysis and to help stratify patients for clinical studies according to mortality risk.

Ammonia↗

Vasopressin, not octreotide, may be beneficial in the treatment of hepatorenal syndrome: a retrospective study.

BACKGROUND: Hepatorenal syndrome (HRS) is a severe complication of cirrhosis and is associated with high mortality. Ornipressin and terlipressin are effective in treatment of HRS, but are not available in the USA. The efficacy of vasopressin (AVP) and octreotide (OCT) infusions, commonly utilized in the USA, in the treatment of HRS is unknown. This study aims to evaluate the effects of AVP and OCT on renal function, systemic haemodynamics and clinical outcomes in HRS. METHODS: This observational study evaluated patients receiving AVP or OCT therapy for HRS from January 2000 to December 2003. Recovery from HRS was defined as a decrease in the serum creatinine (SCr) to a value < or =1.5 mg/dl. RESULTS: Forty-three patients were identified: eight received AVP, 16 received OCT and 19 received both AVP and OCT. Patients who received AVP alone or in combination with OCT had significantly greater recovery rates than those receiving OCT monotherapy (42 vs 38 vs 0%, respectively, P = 0.01). The average time to response in serum creatinine (SCr) was 7+/- 2 days. The mean AVP doses were 0.23+/-0.19 U/min in patients demonstrating clinical response. Therapy with AVP was an independent predictor of recovery (odds ratio 6.4, 95% confidence interval 1.3-31.8). Patients who responded to therapy had significantly lower mortality (23 vs 67%, P = 0.008) and higher rates of liver transplantation (23 vs 0%, P = 0.005). No adverse effects related to AVP therapy were observed. CONCLUSION: When compared with OCT, HRS patients treated with AVP had significantly higher recovery rates, improved survival and were more likely to receive a liver transplant.

Antidiuretic Agents↗

Comparison of ARF after myeloablative and nonmyeloablative hematopoietic cell transplantation.

BACKGROUND: Acute renal failure (ARF) occurs with significant frequency after myeloablative and nonmyeloablative allogeneic hematopoietic cell transplantation (HCT). Myeloablative (conventional) HCT is the standard of care for cure of various malignant disorders. The newer modality of nonmyeloablative ("mini-allo") HCT is reserved for patients with advanced age and comorbidities who are ineligible for myeloablative HCT. The present study compares the incidence of ARF between patients undergoing concurrent myeloablative and nonmyeloablative HCT in the same period at the same institution. METHODS: This retrospective cohort study from 1997 to 2003 compares 140 myeloablative and 129 nonmyeloablative patients from the Fred Hutchinson Cancer Research Center. Severity of ARF was classified into 4 grades based on the increase in serum creatinine levels in the first 100 days after HCT. Mortality was studied at 100 days and 1 year. RESULTS: Nonmyeloablative patients were significantly older and had greater pretransplantation comorbidity at baseline. Despite this, patients undergoing myeloablative HCT had a greater incidence of severe ARF (grades 2 and 3, 73% versus 47%; P < 0.001). The incidence of dialysis also was 4-fold greater (12% versus 3%; P < 0.001) in the myeloablative than nonmyeloablative group. On multivariate analysis after controlling for baseline characteristics, myeloablative HCT was associated with a 4.8-fold greater incidence of ARF compared with nonmyeloablative HCT. Nonrelapse mortality also was greater in the myeloablative group at 100 days and 1 year. CONCLUSION: The incidence and severity of ARF, as well as nonrelapse mortality, occurring after nonmyeloablative HCT is significantly lower compared with myeloablative HCT.

Acute Kidney Injury↗

Uncomplicated acute renal failure and hospital resource utilization: a retrospective multicenter analysis.

BACKGROUND: Although acute renal failure (ARF) complicating nonrenal organ dysfunction in the intensive care unit is associated with significant mortality and hospital costs, hospital resource utilization attributed to uncomplicated ARF is not well known. The goal of this study is to characterize the costs and lengths of stay (LOSs) incurred by hospitalized patients with uncomplicated ARF and their important determining factors. METHODS: We obtained hospital case-mix data sets from 23 Massachusetts hospitals for a 2-year period (1999 to 2000) from the Massachusetts Division of Health Care Finance and Policy. A total of 2,252 records of patients hospitalized with uncomplicated ARF were identified. Patient records of other common medical diagnoses were studied for comparison. RESULTS: Patients hospitalized with uncomplicated ARF incurred median direct hospital costs of 2,600 dollars, median hospital LOS of 5 days, and mortality of 8%. Dialysis was independently associated with significantly greater hospital costs and LOSs for patients with uncomplicated ARF (P < 0.05). Male sex and nonwhite race were associated with significantly lower hospital costs and LOSs, whereas type of hospital had opposing effects on these 2 resource utilization outcomes (P < 0.05). Unadjusted aggregate resource utilization associated with uncomplicated ARF exceeded that of many other common illnesses. CONCLUSION: Demographic and hospital factors, as well as dialysis therapy, are significant determinants of hospital resource utilization for patients with uncomplicated ARF. Uncomplicated ARF appears to incur greater hospital costs and longer LOSs compared with other common medical conditions. Greater focus should be directed toward further understanding of the factors influencing resource utilization for ARF.

Acute Kidney Injury↗

Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers.

Urinary tract infections (UTIs) are the most common infectious complication following renal transplantation. Previous studies uniformly report that renal transplant recipients develop UTIs more often than the general population, but widely differ on how frequently UTIs occur after transplantation. These studies also disagree on the risk factors associated with developing post-transplant UTIs, as well as the effect that UTIs may have on graft outcomes and patient mortality. We performed a retrospective cohort study including all the adult patients who received a renal transplant at two US transplant centers from January 1996 to December 2002 (500 patients). Two hundred and thirteen (43%) patients developed one or more post-transplant UTIs over a mean follow-up period of 42 months. Significant risk factors for post-transplant UTIs were advanced age, female gender, reflux kidney disease, use of azathioprine and cadaveric donor. UTIs did not increase risk for renal graft loss, but were associated with increased mortality (3.5 odds ratio, 95% confidence interval 1.68-7.23). We conclude UTIs may be associated with an increased mortality risk in renal transplant recipients. Prevention of UTIs in high-risk renal transplant patients or those with recurrent UTIs may possibly decrease post-transplant mortality.

Adolescent↗

Acute renal failure independently predicts mortality after myeloablative allogeneic hematopoietic cell transplant.

BACKGROUND: Patients undergoing myeloablative allogeneic hematopoietic cell transplantation (HCT) have a high incidence of acute renal failure (ARF). However, it is unclear if ARF is independently associated with mortality after this procedure. METHODS: We performed meta-analysis of published reports on ARF after myeloablative allogeneic HCT. Four databases (MEDLINE, Cochrane Library, PubMed, Web of Science) and hand searching of conference proceedings were used to identify the studies. ARF was defined as the doubling of serum creatinine occurring within the first 100 days after HCT. The absolute and the relative risks for death after ARF were calculated for every study. The combined relative risk was calculated using the random effects model. Also, multivariate analysis of patient level data was performed on patients from The University of Colorado to establish independent association between ARF and mortality. RESULTS: One thousand two hundred and eleven patients were included in the meta-analysis from the 6 published reports in the literature. The overall incidence of ARF varied from 42% to 84% in these studies. On combining the studies by random-effects model, the relative risk of death after ARF was 2.22 (95%CI 1.38-3.5, P < 0.001). The analysis of patient level data from the University of Colorado demonstrated increasing mortality with worsening grades of ARF. After controlling for various demographic and clinical variables with logistic regression, patients who required dialysis had a 6.8-fold higher association with mortality. CONCLUSION: ARF appears to independently influence mortality after myeloablative allogeneic HCT. Future studies should be aimed at interventions that can reduce the incidence and severity of ARF with this procedure.

Acute Kidney Injury↗

Rapid microalbuminuria screening in type 2 diabetes mellitus: simplified approach with Micral test strips and specific gravity.

BACKGROUND: Microalbuminuria is known to be a harbinger of serious complications in type 2 diabetes mellitus. Since medical intervention at the onset of microalbuminuria can be critical in reducing these adverse outcomes, it is widely agreed that type 2 diabetic patients should be screened for microalbuminuria. The purpose of the present study is to evaluate Micral test strips in conjunction with a urine specific gravity determination as a rapid and accurate method for detecting microalbuminuria in type 2 diabetic patients. METHODS: In this prospective study, a total of 444 urine samples of type 2 diabetic patients were obtained from the ABCD study cohort for analysis. Urinary albumin concentrations were determined using Micral test strips and compared to results measuring albumin by the immunoturbidimetry method of timed collections. Urine specific gravity was measured by a standard urine dipstick. RESULTS: The performance characteristics of the Micral test strips for detecting microalbuminuria (30-300 mg albumin/24 h) were adequate but not optimal: sensitivity 88%, specificity 80%, positive predictive value 69%, negative predictive value 92%. A concomitant specific gravity determination was useful in indexing the magnitude of false negative and false positive readings by the Micral test strips. CONCLUSIONS: While the use of Micral test strips provides a rapid approach to detecting microalbuminuria in type 2 diabetic patients, this method has limitations. The simultaneous measurement of specific gravity is helpful in addressing some of the shortcomings of this screening test.

Albuminuria↗

Reversal of end-stage renal disease after aortic dissection using renal artery stent: a case report.

BACKGROUND: Medical management is the conventional treatment for Stanford Type B aortic dissections as surgery is associated with significant morbidity and mortality. The advent of endovascular interventional techniques has revived interest in treating end-organ complications of Type B aortic dissection. We describe a patient who benefited from endovascular repair of renal artery stenosis caused by a dissection flap, which resulted in reversal of his end-stage renal disease (ESRD). CASE PRESENTATION: A 69 y/o male with a Type B aortic dissection diagnosed two months earlier was found to have a serum creatinine of 15.2 mg/dL (1343.7 micromol/L) on routine visit to his primary care physician. An MRA demonstrated a rightward spiraling aortic dissection flap involving the origins of the celiac artery, superior mesenteric artery, and both renal arteries. The right renal artery arose from the false lumen with lack of blood flow to the right kidney. The left renal artery arose from the true lumen, but an intimal dissection flap appeared to be causing an intermittent stenosis of the left renal artery with compromised blood flow to the left kidney. Endovascular reconstruction with of the left renal artery with stent placement was performed. Hemodialysis was successfully discontinued six weeks after stent placement. CONCLUSION: Percutaneous intervention provides a promising alternative for patients with Type B aortic dissections when medical treatment will not improve the likelihood of meaningful recovery and surgery entails too great a risk. Nephrologists should therefore be aggressive in the workup of ischemic renal failure associated with aortic dissection as percutaneous intervention may reverse the effects of renal failure in this population.

Aged↗

Urinary interleukin-18 is a marker of human acute tubular necrosis.

BACKGROUND: Interleukin-18 (IL-18) is a mediator of ischemic acute tubular necrosis (ATN) in mice. METHODS: IL-18 was measured in human urine to determine whether it might serve as a marker of ATN. Seventy-two patients, including healthy controls, patients with different forms of acute renal failure, and patients with other renal diseases, were studied. RESULTS: Patients with ATN had significantly greater median urinary IL-18 concentrations than those with all other conditions: patients with ATN, 644 pg/mg creatinine (mean, 814 +/- 151 [SE] pg/mg creatinine; P <0.0001) versus healthy controls, 16 pg/mg creatinine (mean, 23 +/- 9 pg/mg creatinine); patients with prerenal azotemia, 63 pg/mg creatinine (mean, 155 +/- 68 pg/mg creatinine); patients with urinary tract infection, 63 pg/mg creatinine (mean, 149 +/- 110 pg/mg creatinine); those with chronic renal insufficiency, 12 pg/mg creatinine (mean, 84 +/- 45 pg/mg creatinine); and patients with nephrotic syndrome, 34 pg/mg creatinine (mean, 67 +/- 47 pg/mg creatinine). Median urinary IL-18 concentrations measured in the first 24 hours after kidney transplantation were 924 pg/mg creatinine (mean, 1,199 +/- 187 pg/mg creatinine) in patients who received a cadaveric kidney that developed delayed graft function compared with 171 pg/mg creatinine (mean, 367 +/- 102 pg/mg creatinine) in patients who received a cadaveric kidney with prompt graft function and 73 pg/mg creatinine (mean, 176 +/- 107 pg/mg creatinine) in patients who received a kidney with prompt graft function from a living donor (P <0.002). In kidney transplant recipients, lower urinary IL-18 levels were associated with a steeper decline in serum creatinine concentrations postoperative days 0 to 4 (P = 0.009). CONCLUSION: IL-18 levels are elevated in urine in patients with ATN and delayed graft function compared with other renal diseases. Urinary IL-18 may serve as a marker for proximal tubular injury in ATN. The clinical application of this test may be substantial because it is reliable, inexpensive, and easy to perform.

Adult↗