PubMed Health⌕ Search

Biomedical subjects

Ravindra L Mehta

Publications and source records attributed to Ravindra L Mehta.

At least 19 recordsLinked to original sources

Survival by dialysis modality in critically ill patients with acute kidney injury.

Among critically ill patients, acute kidney injury (AKI) requiring dialysis is associated with mortality rates generally in excess of 50%. Continuous renal replacement therapies (CRRT) often are recommended and widely used, although data to support its superiority over intermittent hemodialysis (IHD) are lacking. Data from the Program to Improve Care in Acute Renal Disease (PICARD), a multicenter observational study of AKI, were analyzed. Among 398 patients who required dialysis, the risk for death within 60 d was examined by assigned initial dialysis modality (CRRT [n = 206] versus IHD [n = 192]) using standard Kaplan-Meier product limit estimates, proportional hazards ("Cox") regression methods, and a propensity score approach to account for selection effects. Crude survival rates were lower for patients who were treated with CRRT than IHD (survival at 30 d 45 versus 58%; P = 0.006). Adjusted for age, hepatic failure, sepsis, thrombocytopenia, blood urea nitrogen, and serum creatinine and stratified by site, the relative risk for death associated with CRRT was 1.82 (95% confidence interval 1.26 to 2.62). Further adjustment for the propensity score did not materially alter the association (relative risk 1.92; 95% confidence interval 1.28 to 2.89). Among critically ill patients with AKI, CRRT was associated with increased mortality. Although the results could reflect residual confounding by severity of illness, these data provide no evidence for a survival benefit afforded by CRRT. Larger, prospective, randomized clinical trials to compare CRRT and IHD in severe AKI are needed.

Acute Disease↗

Acute kidney injury in critical care: time for a paradigm shift?

PURPOSE OF REVIEW: Acute alterations in renal function are commonly encountered in various settings with varied clinical manifestations ranging from a minimal elevation in serum creatinine to anuric renal failure. Our knowledge of human acute kidney injury has been fairly stagnant, until recently largely limited by a lack of concerted efforts in the field. This review summarizes the recent advances and provides an overview of emerging trends in this field. RECENT FINDINGS: One of the limitations in our knowledge of human acute kidney injury has been the lack of a standardized definition and staging criteria for this disorder. New information on the epidemiology and outcomes of acute kidney injury has emerged providing an opportunity to reappraise our approach to this disease. Also, there has been new work on the relationship of alterations of renal function to short and long-term outcomes, particularly mortality. SUMMARY: To translate advances from basic research to clinical application a multidisciplinary approach is required. New research in the field of biomarkers combined with clinical markers will lead to therapies that can be introduced earlier in the course of the disease and, hopefully, lead to a decrease in mortality from this potentially reversible condition.

Acute Kidney Injury↗

Insulin resistance in critically ill patients with acute renal failure.

Mortality in critically ill patients with acute renal failure (ARF) remains high. Hyperglycemia associated with insulin resistance has been associated with adverse outcomes in critically ill intensive care unit (ICU) patients but has not been examined specifically in patients with ARF. We used data from a subcohort (n = 90) of the Program to Improve Care in Acute Renal Disease (PICARD), an observational study of 618 adult ICU patients with ARF in whom nephrology service consultation was obtained. We obtained simultaneous measurements of serum glucose, insulin, insulin-like growth factor (IGF)-I, and IGF-1 binding proteins (IGFBP) in 90 patients. Daily glucose determinations were obtained from a larger fraction of the PICARD cohort (n = 509). Among the 90 patients with intensive metabolic monitoring, glucose concentrations in survivors were significantly lower than in nonsurvivors throughout the 5-wk period (P = 0.008, adjusted P = 0.013). In the larger PICARD cohort (n = 509), hyperglycemia was also significantly associated with in-hospital mortality. Mean insulin concentrations were significantly higher (431 +/- 508 vs. 234 +/- 189 pmol/l, P = 0.03), mean homeostasis model of insulin resistance levels were significantly higher (24.1 +/- 30.0 vs. 11.7 +/- 12.5, P = 0.04), and IGFBP-3 concentrations were significantly lower (1,190 +/- 498 vs. 1,470 +/- 581 microg/l, P = 0.02) among nonsurvivors compared with survivors. Insulin resistance as defined by hyperglycemia in the setting of higher insulin concentrations may be associated with mortality in critically ill patients with ARF. The IGF-IGFBP axis may play an important role in this process.

Acute Kidney Injury↗

Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.

INTRODUCTION: There is no consensus definition of acute renal failure (ARF) in critically ill patients. More than 30 different definitions have been used in the literature, creating much confusion and making comparisons difficult. Similarly, strong debate exists on the validity and clinical relevance of animal models of ARF; on choices of fluid management and of end-points for trials of new interventions in this field; and on how information technology can be used to assist this process. Accordingly, we sought to review the available evidence, make recommendations and delineate key questions for future studies. METHODS: We undertook a systematic review of the literature using Medline and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated recommendations and/or directions for future research. RESULTS: We found sufficient consensus on 47 questions to allow the development of recommendations. Importantly, we were able to develop a consensus definition for ARF. In some cases it was also possible to issue useful consensus recommendations for future investigations. We present a summary of the findings. (Full versions of the six workgroups' findings are available on the internet at http://www.ADQI.net) CONCLUSION: Despite limited data, broad areas of consensus exist for the physiological and clinical principles needed to guide the development of consensus recommendations for defining ARF, selection of animal models, methods of monitoring fluid therapy, choice of physiological and clinical end-points for trials, and the possible role of information technology.

Acute Kidney Injury↗

Effect of mechanical ventilation on the kidney.

Mechanical ventilation is a standard component of intensive care unit management of critically ill patients and is widely used for respiratory support. Recent animal and clinical studies have shown that positive pressure ventilation can worsen pre-existing lung injury and produce ventilator-induced lung injury, which has been linked with the development of systemic inflammation and multi-system organ dysfunction, including renal failure. Although the physiological consequences of mechanical ventilation on pulmonary and cardiovascular function have been extensively studied, its effects on renal function are not as well defined. Previous experimental studies and few clinical reports have shown a significant effect of mechanical ventilation on renal function. Interestingly, recent data are emerging which suggest that renal dysfunction also has a direct, adverse effect on pulmonary function. This chapter reviews the information in these areas and provides a framework for future investigation in this field.

Animals↗

Plasma cytokine levels predict mortality in patients with acute renal failure.

BACKGROUND: Critically ill patients with acute renal failure (ARF) experience a high mortality rate. Animal and human studies suggest that proinflammatory cytokines lead to the development of a systemic inflammatory response syndrome (SIRS), which is temporally followed by a counter anti-inflammatory response syndrome (CARS). This process has not been specifically described in critically ill patients with ARF. METHODS: The Program to Improve Care in Acute Renal Disease (PICARD) is a prospective, multicenter cohort study designed to examine the natural history, practice patterns, and outcomes of treatment in critically ill patients with ARF. In a subset of 98 patients with ARF, we measured plasma proinflammatory cytokines [interleukin (IL)-1beta, IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)], the acute-phase reactant C-reactive protein (CRP), and the anti-inflammatory cytokine IL-10 at study enrollment and over the course of illness. RESULTS: When compared with healthy subjects and end-stage renal disease patients on maintenance hemodialysis, patients with ARF had significantly higher plasma levels of all measured cytokines. Additionally, the proinflammatory cytokines IL-6 and IL-8 were significantly higher in nonsurvivors versus survivors [median 234.7 (interdecile range 64.8 to 1775.9) pg/mL vs. 113.5 (46.1 to 419.3) pg/mL, P= 0.02 for IL-6; 35.5 (14.1 to 237.9) pg/mL vs. 21.2 (8.5 to 87.1) pg/mL, P= 0.03 for IL-8]. The anti-inflammatory cytokine IL-10 was also significantly higher in nonsurvivors [3.1 (0.5 to 41.9) pg/mL vs. 2.4 (0.5 to 16.9) pg/mL, P= 0.04]. For each natural log unit increase in the levels of IL-6, IL-8, and IL-10, the odds of death increased by 65%, 54%, and 34%, respectively, corresponding to increases in relative risk of approximately 30%, 25%, and 15%. The presence or absence of SIRS or sepsis was not a major determinant of plasma cytokine concentration in this group of patients. CONCLUSION: There is evidence of ongoing SIRS with concomitant CARS in critically ill patients with ARF, with higher levels of plasma IL-6, IL-8, and IL-10 in patients with ARF who die during hospitalization. Strategies to modulate inflammation must take into account the complex cytokine biology in patients with established ARF.

Acute Kidney Injury↗

Spectrum of acute renal failure in the intensive care unit: the PICARD experience.

BACKGROUND: Acute renal failure (ARF) in the critically ill is associated with extremely high mortality rates. Understanding the changing spectrum of ARF will be necessary to facilitate quality improvement efforts and to design successful interventional trials. METHODS: We conducted an observational cohort study of 618 patients with ARF in intensive care units at five academic medical centers in the United States. Participants were required to sign (or have a proxy sign) informed consent for data collection. A comprehensive data collection instrument captured more than 800 variables, most on a daily basis, throughout the course of ARF. Patient characteristics, dialysis status, and major outcomes were determined and stratified by clinical site. RESULTS: The mean age was 59.5 years, 41% were women, and 20% were of minority race or ethnicity. There was extensive comorbidity; 30% had chronic kidney disease, 37% had coronary artery disease, 29% had diabetes mellitus, and 21% had chronic liver disease. Acute renal failure was accompanied by extrarenal organ system failure in most patients, even those who did not require dialysis. Three hundred and ninety-eight (64%) patients required dialysis. The in-hospital mortality rate was 37%, and the rate of mortality or nonrecovery of renal function was 50%. The median hospital length of stay was 25 days (26 days, excluding patients who died). CONCLUSION: There is a changing spectrum of ARF in the critically ill, characterized by a large burden of comorbid disease and extensive extrarenal complications, obligating the need for dialysis in the majority of patients. There is wide variation across institutions in patient characteristics and practice patterns. These differences highlight the need for additional multicenter observational and interventional studies in ARF.

Acute Kidney Injury↗

Outcomes research in acute renal failure.

Acute renal failure (ARF) is associated with morbidity and mortality in excess of 50% in the intensive care unit (ICU) setting. A variety of outcome measures have been described in published reports of ARF, however, the studies often do not distinguish between clinical outcomes and surrogate endpoints. Multiple factors can influence these outcomes, including variations in practice. It is important to be aware of the potential effects of these factors when clinical trials are planned and executed for ARF patients. For any intervention trial, knowledge of the natural history of the disease and process of care informs the design and conduct of the trial. Standardization of a definition for ARF and of the criteria for initiation, frequency, duration, and withdrawal of dialysis support would be of great benefit. This article provides a critical appraisal of outcomes research in ARF and describes an approach for selecting appropriate endpoints for future clinical research in ARF.

Acute Kidney Injury↗

Reasons for non-enrollment in a cohort study of ARF: the Program to Improve Care in Acute Renal Disease (PICARD) experience and implications for a clinical trials network.

BACKGROUND: Acute renal failure (ARF) is associated strongly with in-hospital mortality and morbidity. Previous clinical trials of ARF have been hampered by the heterogeneous population affected, difficulty defining ARF, delays in identification of ARF, and significant comorbid conditions, among other factors. METHODS: The Program to Improve Care in Acute Renal Disease (PICARD) phase I was a multicenter cohort study aimed to identify clinical characteristics and practice patterns associated with adverse and favorable outcomes in patients with ARF in intensive care units. Although PICARD used no interventions, signed informed consent was required of all study subjects or their proxies. RESULTS: Signed informed consent was obtained in 645 of 1,243 ARF episodes (52%). The fraction of patients not enrolled and reasons for non-enrollment varied widely across the 5 PICARD centers. Refusal by potential study subjects was infrequent, although the absence of family or proxy (15%) and refusal by family or proxy (18%) accounted for large fractions of non-enrolled subjects. Death (23%) and discharge (11%) before study personnel could evaluate patients were additional important reasons for non-enrollment. CONCLUSION: Understanding reasons for non-enrollment may help rationalize mortality and other outcome differences seen in clinical trials and cohort studies that require informed consent compared with historic reports of "all comers" with ARF.

Acute Kidney Injury↗

Diuretics, mortality, and nonrecovery of renal function in acute renal failure.

CONTEXT: Acute renal failure is associated with high mortality and morbidity. Diuretic agents continue to be used in this setting despite a lack of evidence supporting their benefit. OBJECTIVE: To determine whether the use of diuretics is associated with adverse or favorable outcomes in critically ill patients with acute renal failure. DESIGN: Cohort study conducted from October 1989 to September 1995. PATIENTS AND SETTING: A total of 552 patients with acute renal failure in intensive care units at 4 academic medical centers affiliated with the University of California. Patients were categorized by the use of diuretics on the day of nephrology consultation and, in companion analyses, by diuretic use at any time during the first week following consultation. MAIN OUTCOME MEASURES: All-cause hospital mortality, nonrecovery of renal function, and the combined outcome of death or nonrecovery. RESULTS: Diuretics were used in 326 patients (59%) at the time of nephrology consultation. Patients treated with diuretics on or before the day of consultation were older and more likely to have a history of congestive heart failure, nephrotoxic (rather than ischemic or multifactorial) origin of acute renal failure, acute respiratory failure, and lower serum urea nitrogen concentrations. With adjustment for relevant covariates and propensity scores, diuretic use was associated with a significant increase in the risk of death or nonrecovery of renal function (odds ratio, 1.77; 95% confidence interval, 1.14-2.76). The risk was magnified (odds ratio, 3.12; 95% confidence interval, 1.73-5.62) when patients who died within the first week following consultation were excluded. The increased risk was borne largely by patients who were relatively unresponsive to diuretics. CONCLUSIONS: The use of diuretics in critically ill patients with acute renal failure was associated with an increased risk of death and nonrecovery of renal function. Although observational data prohibit causal inference, it is unlikely that diuretics afford any material benefit in this clinical setting. In the absence of compelling contradictory data from a randomized, blinded clinical trial, the widespread use of diuretics in critically ill patients with acute renal failure should be discouraged.

Acute Kidney Injury↗

Nephrology consultation in acute renal failure: does timing matter?

PURPOSE: Patients who develop acute renal failure in the intensive care unit (ICU) have extremely high rates of mortality and morbidity. The goals of this study were to identify correlates of the timing of nephrology consultation in acute renal failure, and to explore the relation between timing of consultation and outcomes. METHODS: We explored associations among timing of nephrology consultation and in-hospital mortality, lengths of hospital and ICU stay, and recovery of renal function in 215 ICU patients with acute renal failure at four U.S. teaching hospitals. We used multivariable logistic regression and propensity scores to adjust for confounding and selection effects. RESULTS: Nephrology consultation was delayed (>or=48 hours) in 61 patients (28%) (median time to consultation, 4 days). Lower serum creatinine levels (P <0.0001) and higher urine output (P = 0.002) were associated with delayed consultation. Delayed consultation was associated with increased mortality among dialyzed (31/42 [74%] vs. 50/103 [49%], P = 0.006) and nondialyzed patients (10/19 [53%] vs. 11/51 [22%], P = 0.01), and increases in lengths of hospital (median, 19 days vs. 16 days, P = 0.01) and ICU stay (17 days vs. 6 days, P <0.0001). The association between delayed consultation and mortality was attenuated by covariate adjustment, and was no longer statistically significant after adjustment for propensity score (odds ratio = 2.0; 95% confidence interval: 0.8 to 5.1). CONCLUSION: In acute renal failure, delayed nephrology consultation was associated with increased mortality and morbidity, whether or not dialysis was ultimately required. Using observational data, we cannot determine whether these findings reflect residual confounding, selection bias, adverse effects of delayed recognition of acute renal failure, or the benefits of nephrology consultation.

Acute Kidney Injury↗

Economic and health consequences of selling a kidney in India.

CONTEXT: Many countries have a shortage of kidneys available for transplantation. Paying people to donate kidneys is often proposed or justified as a way to benefit recipients by increasing the supply of organs and to benefit donors by improving their economic status. However, whether individuals who sell their kidneys actually benefit from the sale is controversial. OBJECTIVE: To determine the economic and health effects of selling a kidney. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey conducted in February 2001 among 305 individuals who had sold a kidney in Chennai, India, an average of 6 years before the survey. MAIN OUTCOME MEASURES: Reasons for selling kidney, amount received from sale, how money was spent, change in economic status, change in health status, advice for others contemplating selling a kidney. RESULTS: Ninety-six percent of participants sold their kidneys to pay off debts. The average amount received was 1070 US dollars. Most of the money received was spent on debts, food, and clothing. Average family income declined by one third after nephrectomy (P<.001), and the number of participants living below the poverty line increased. Three fourths of participants were still in debt at the time of the survey. About 86% of participants reported a deterioration in their health status after nephrectomy. Seventy-nine percent would not recommend that others sell a kidney. CONCLUSIONS: Among paid donors in India, selling a kidney does not lead to a long-term economic benefit and may be associated with a decline in health. Physicians and policy makers should reexamine the value of using financial incentives to increase the supply of organs for transplantation.

Cross-Sectional Studies↗

Dialysis modalities in the intensive care unit.

Acute renal failure in the ICU is a clinically diverse entity. Consequently, the indications for initiation of dialysis therapy are varied. In general, the indications are solute control, volume control, or both. A variety of dialysis modalities are available; however, there is no consensus as to the optimal modality for any particular group of patients. A careful understanding of the particular benefits, limitations, and potential complications of each modality coupled with a thorough assessment of the individual patient's need formulate the basis for dialysis modality selection. In certain circumstances, the more conventional intermittent therapies are sufficient, whereas in other settings, CRRT techniques are advantageous. The impact of modality selection on outcome remains an area of significant controversy. Future studies in which more uniformity within specific subgroups of patients with ARF is sought may shed light on the optimal modality for a particular patient group. Newer therapies aimed at more optimal and more specific blood purification may prove promising in the management of complex critically ill patients with ARF and other comorbid conditions.

Decision Making↗