The Potential for Renal Injury Elicited by Physical Work in the Heat.

An epidemic of chronic kidney disease (CKD) is occurring in laborers who undertake physical work in hot conditions. Rodent data indicate that heat exposure causes kidney injury, and when this injury is regularly repeated it can elicit CKD. Studies in humans demonstrate that a single bout of exercise in the heat increases biomarkers of acute kidney injury (AKI). Elevations in AKI biomarkers in this context likely reflect an increased susceptibility of the kidneys to AKI. Data largely derived from animal models indicate that the mechanism(s) by which exercise in the heat may increase the risk of AKI is multifactorial. For instance, heat-related reductions in renal blood flow may provoke heterogenous intrarenal blood flow. This can promote localized ischemia, hypoxemia and ATP depletion in renal tubular cells, which could be exacerbated by increased sodium reabsorption. Heightened fructokinase pathway activity likely exacerbates ATP depletion occurring secondary to intrarenal fructose production and hyperuricemia. Collectively, these responses can promote inflammation and oxidative stress, thereby increasing the risk of AKI. Equivalent mechanistic evidence in humans is lacking. Such an understanding could inform the development of countermeasures to safeguard the renal health of laborers who regularly engage in physical work in hot environments.

Progression of kidney disease in elderly stage 3 and 4 chronic kidney disease patients.

PURPOSE: The prevalence of chronic kidney disease (CKD) has been rising steadily in the elderly population. We studied the rate of progression of CKD in this population and the factors associated with progression of CKD to better identify patients who are likely to progress to ESRD. METHODS: This was an observational study including 4562 patients older than 65 years with two outpatient estimated glomerular filtration rates (eGFRs) of <60 ml/min/1.73 m2, at least 90 days apart with no intervening eGFR >60 ml/min/1.73 m2 (March 1, 2001, and March 31, 2008) at VA healthcare facilities. Patients with eGFR <15 ml/min/1.73 m2 were excluded. Annual rate of decline of eGFR was studied and categorized as <1 ml/min/1.73 m2, 1-4 ml/min/1.73 m2, and >4 ml/min/1.73 m2. RESULTS: Mean age of the study participants was 77.2 years. 24.3% were diabetics. 4.3% had proteinuria. In univariate comparison of different rates of progression, 54.2% patients had an annual rate of progression of <1 ml/min/1.73 m2. Multivariable mixed model analyses revealed that increasing age, body mass index, presence of cardiovascular disease, diabetes mellitus, and proteinuria were associated with significantly increased rate of progression of CKD. Serum albumin and hemoglobin level were inversely associated with progression of CKD. CONCLUSIONS: CKD progresses at a slower rate in the elderly population. We have identified risk factors associated with an increased risk of progression of CKD in the elderly. This may help to improve health care planning and resource utilization.

Prevalence of chronic kidney disease in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND: The incidence and prevalence of chronic kidney disease (CKD) continue to rise worldwide. Increasing age, diabetes, hypertension, and cigarette smoking are well-recognized risk factors for CKD. Chronic obstructive pulmonary disease (COPD) is characterized by chronic airway inflammation leading to airway obstruction and parenchymal lung destruction. Due to some of the common pathogenic mechanisms, COPD has been associated with increased prevalence of CKD. METHODS: Systematic review of medical literature reporting the incidence and prevalence of CKD in patients with COPD using the Cochrane Collaboration Methodology, and conduct meta-analysis to study the cumulative effect of the eligible studies. We searched Medline via Ovid, PubMed, EMBASE and ISI Web of Science databases from 1950 through May, 2016. We included prospective and retrospective observational studies that reported the prevalence of CKD in patients with COPD. RESULTS: Our search resulted in 19 eligible studies of which 9 have been included in the meta-analysis. The definition of CKD was uniform across all the studies included in analysis. COPD was found to be associated with CKD in the included epidemiological studies conducted in many countries. Our meta-analysis showed that COPD was found to be associated with a significantly increased prevalence of CKD (Odds Ratio [OR] = 2.20; 95% Confidence Interval [CI] 1.83, 2.65). STUDY LIMITATIONS: Studies included are observational studies. However, given the nature of our research question there is no possibility to perform a randomized control trial. CONCLUSIONS: Patients with COPD have increased odds of developing CKD. Future research should investigate the pathophysiological mechanism behind this association, which may lead to better outcomes.

Proton pump inhibitors are associated with increased risk of development of chronic kidney disease.

BACKGROUND: Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. METHODS: Two separate retrospective case-control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. RESULTS: A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case-control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI 1.67-1.84) among patients taking PPIs versus those not on PPIs. CONCLUSIONS: Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.

Prevalence of various comorbidities among veterans with chronic kidney disease and its comparison with other datasets.

Chronic kidney disease (CKD) has a complicated interrelationship with various comorbidities. The purpose of this study was to describe the prevalence of various comorbidities among veterans with CKD and compare it with other datasets like Kidney Early Evaluation Program (KEEP), National Health and Nutrition Examination Survey (NHANES) and Medicare. Patients who had at least one outpatient visit in year 2007 (1 January 2007 to 31 December 2007) were included in the study (n = 75,787). Glomerular filtration rate (eGFR) was estimated by the Modification of Diet in Renal Disease (MDRD) study equation. CKD prevalence was calculated based on one or two serum creatinine values at least 3 months apart. Demographic data were obtained including age, gender, race, weight, height and body mass index (BMI). The prevalence of various comorbidities was also collected based on ICD 9 codes from the problem list. The prevalence of CKD among veterans was 47.3%, much higher than estimated in the US population. Patients with CKD were more likely to have any vascular disease (36.89% vs. 14.87%), diabetes (34.18% vs. 17.83%), hypertension (86.65% vs. 57.56%), and cancer (18.69% vs. 9.23%). Irrespective of age, the prevalence of vascular disease was much higher among veterans with CKD. The prevalence of coronary artery disease, peripheral vascular disease, and cancer was much higher among elderly veterans with CKD as compared to other datasets. CKD is a growing endemic associated with a high frequency of concomitant chronic illnesses. Public health resources should be applied for early recognition and risk modification of CKD.

Renin-Angiotensin-Aldosterone System Blockers in Elderly Adults with Chronic Kidney Disease without Diabetes Mellitus or Proteinuria.

OBJECTIVES: To compare the effect of renin-angiotensin-aldosterone system (RAAS) blockers with that of other antihypertensive agents on outcomes in a cohort of elderly veterans with incident chronic kidney disease (CKD) without diabetes mellitus or proteinuria. DESIGN: Retrospective cohort study. SETTING: Veterans Affairs (VA) Upstate New York Healthcare System. PARTICIPANTS: All participants were seen in primary care clinic in Veterans Integrated Service Network 2, which comprises five VA medical centers and 29 community-based outpatient clinics, from April 2001 to April 2008. Veterans with incident CKD who were taking antihypertensive medications and did not have proteinuria or diabetes mellitus on the date of onset of CKD were selected from this population. MEASUREMENTS: The outcome variables studied were progression of kidney disease (doubling of serum creatinine level or Stage 5 CKD (estimated glomerular filtration rate <15 mL/min per 1.73 m2 )), all-cause mortality, and combined outcome. RESULTS: Analysis included 2,474 participants, 47.9% of whom were taking RAAS blockers at baseline and the rest other antihypertensives. Time-varying Cox proportional hazards analyses did not reveal a statistically significant difference in primary combined outcome in participants taking RAAS blockers and those taking other antihypertensives (hazard ratio = 1.09, 95% confidence interval = 0.93-1.27). There was also no significant effect on individual outcomes (death or progression of kidney disease). CONCLUSION: Use of RAAS blockers was not associated with less hazard of combined and individual outcomes (doubling of serum creatinine, Stage 5 CKD, death) in elderly veterans with incident CKD without diabetes mellitus or proteinuria.

Elevated systolic blood pressure is associated with increased incidence of chronic kidney disease but not mortality in elderly veterans.

The optimal blood pressure to prevent development of chronic kidney disease (CKD) and mortality in the elderly is unclear. Our objective was to determine the effect of differing levels of blood pressure on incidence of CKD and mortality in elderly veterans. This retrospective cohort study included 15,221 individuals ≥70 years of age without CKD (outpatient estimated glomular filtration rate >60 mL/min/1.73 m(2)) seen in the primary care clinic in the Veterans Affairs Health Care Upstate New York with Veterans Integrated Service Network 2 between 2001 and 2008. To examine the association of explanatory variables on hazard ratios for outcomes of interest, incident CKD, and death, competing risk analysis (with death as competing risk) was used for the analysis of incident CKD outcome, and time-dependent Cox model with CKD as the time-dependent covariate was used for the analysis of death outcome. The incidence of CKD was 16% over a median follow-up of 19 quarters. Compared with reference of systolic blood pressure of 130-139 mm Hg, there was an increased hazard of development of CKD with systolic blood pressure of 140-149 mm Hg or higher. As compared with a reference range of 130-139 mm Hg systolic blood pressure, the relative risk of mortality was higher in the range of 120-129 mm Hg systolic or less. The optimal achieved systolic blood pressure in elderly patients to prevent the development of CKD was <140 mm Hg. However, lowering the systolic blood pressure below 130 mm Hg was associated with increased mortality.

Low levels of high-density lipoproteins are associated with acute kidney injury following revascularization for chronic limb ischemia.

OBJECTIVES: Perioperative acute kidney injury (AKI) is not uncommon, following revascularization. HDL has been shown to reduce organ injury in animal models. The aim of the study is to examine the association of HDL on AKI in patients undergoing revascularization for chronic limb ischemia. METHODS: All patients who underwent revascularization between June 2001 and December 2009 were analyzed. Patients on dialysis and with incomplete data were excluded. Patients were grouped for HDL < or ≥40 mg/dL. Univariate and multivariate analysis were used to identify factors associated with AKI. RESULTS: A total of 684 patients were included. Eighty-two (12.0%) patients developed postoperative AKI (15.7% in low HDL group vs. 6.3% in high HDL group, p < 0.001). The AKI group were more likely to be older (71.5 ± 10.1 vs. 68.0 ± 10.8, p = 0.01), ASA 4 class (26% vs. 14%, p < 0.001), to have albumin <3 g/dL (59% vs. 32%, p < 0.001), low HDL levels (79% vs. 58%, p < 0.001), DM (61% vs. 44%, p = 0.005), CAD (67% vs. 55%, p = 0.003), preoperative chronic kidney disease (CKD) stage III-IV (55% vs.39%, p < 0.001), to present with critical limb ischemia (82% vs. 63%, p = 0.001), and to be on ACEI (67% vs. 51%, p = 0.006). Multivariate logistic regression analysis showed low HDL (Odds Ratio (OR) 1.66 [1.23-2.24]) and serum albumin levels <3 g/dL (OR 1.66 [1.29-2.13], p < 0.001) were independently associated with increased odds for developing AKI. Propensity score analyses showed low HDL was independently associated with increased odds of AKI (OR 2.4 (1.4-4.2)). CONCLUSIONS: AKI following revascularization is not uncommon (12.0%), and lower concentrations of HDL and serum albumin are associated with increased odds of postoperative AKI. There was also a trend of higher prevalence of AKI among those with pre-existing CKD.

Acute kidney injury and death associated with renin angiotensin system blockade in cardiothoracic surgery: a meta-analysis of observational studies.

BACKGROUND: Acute kidney injury (AKI) is a common complication after cardiovascular surgery. The use of renin angiotensin system (RAS) blockers preoperatively is controversial due to conflicting results of their effect on the incidence of postoperative AKI and mortality. STUDY DESIGN: Meta-analysis of prospective or retrospective observational studies (1950 to January 2013) using MEDLINE, EMBASE, the Cochrane Library, conferences, and ClinicalTrials.gov, without language restriction. SETTING & POPULATION: Patients undergoing cardiovascular surgery. SELECTION CRITERIA FOR STUDIES: Retrospective or prospective studies evaluating the effect of preoperative use of RAS blockers in the development of postoperative AKI and/or mortality in adult patients. INTERVENTION: Preoperative use of RAS blockers. RAS-blocker use was defined as long-term use of either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers until the day of surgery. OUTCOMES: The primary outcome was the development of postoperative AKI; the secondary outcome was mortality. AKI was defined by different authors using different criteria. Death was ascertained in the hospital, at 30 days, or at 90 days in different studies. RESULTS: 29 studies were included (4 prospective and 25 retrospective); 23 of these involving 69,027 patients examined AKI, and 18 involving 54,418 patients studied mortality. Heterogeneity was found across studies regarding AKI (I2 = 82.5%), whereas studies were homogeneous regarding mortality (I2 = 20.5%). Preoperative RAS-blocker use was associated with increased odds for both postoperative AKI (OR, 1.17; 95% CI, 1.01-1.36; P = 0.04) and mortality (OR, 1.20; 95% CI, 1.06-1.35; P = 0.005). LIMITATIONS: Lack of randomized controlled trials, different definitions of AKI, different durations of follow-up used to analyze death outcome, and inability to exclude outcome reporting bias. CONCLUSIONS: In retrospective studies, preoperative use of RAS blockers was associated with increased odds of postoperative AKI and mortality in patients undergoing cardiovascular surgery. A large, multicenter, randomized, controlled trial should be performed to confirm these findings.

The MDRD equation underestimates the prevalence of CKD among blacks and overestimates the prevalence of CKD among whites compared to the CKD-EPI equation: a retrospective cohort study.

BACKGROUND: Black individuals are far more likely than white individuals to develop end stage renal disease (ESRD). However, earlier stages of chronic kidney disease (CKD) have been reported to be less prevalent among blacks. This disparity remains poorly understood. The objective of this study was to evaluate whether the lower prevalence of CKD among blacks in early stages of CKD might be due in part to an inability of the MDRD equation to accurately determine early stages of CKD in both the black and white population. METHODS: We conducted a retrospective cohort study of 97, 451 patients seen in primary care clinic in Veterans Integrated Service Network 2 (VISN 2) over a 7 year period to determine the prevalence of CKD using both the Modification of Diet in Renal Disease (MDRD) Study equation and the more recently developed CKD Epidemiology Collaboration (CKD-EPI) equation. Demographic data, comorbid conditions, prescription of medications, and laboratory data were recorded. Logistic regression and quantile regression models were used to compare the prevalence of estimated glomerular filtration rate (eGFR) categories between black and white individuals. RESULTS: The overall prevalence of CKD was lower when the CKD-EPI equation was used. Prevalence of CKD in whites was 53.2% by MDRD and 48.4% by CKD-EPI, versus 34.1% by MDRD and 34.5% by CKD-EPI in blacks. The cumulative logistic regression and quantile regression showed that when eGFR was calculated by the EPI method, blacks were as likely to present with an eGFR value less than 60 mL/min/1.73 m2 as whites. Using the CKD-EPI equation, blacks were more likely than white individuals to have stage 3b, 4 and 5 CKD. Using the MDRD method, the prevalence in blacks was only higher than in whites for stage 4 and 5 CKD. Similar results were obtained when the analysis was confined to patients over 65 years of age. CONCLUSIONS: The MDRD equation overestimates the prevalence of CKD among whites and underestimates the prevalence of CKD in blacks compared to the CKD-EPI equation.

Rituximab-based therapy for gemcitabine-induced hemolytic uremic syndrome in a patient with metastatic pancreatic adenocarcinoma: a case report.

PURPOSE: The purpose of this report is to describe the management and outcome of an unusual complication of a commonly used chemotherapeutic agent. Gemcitabine is a known risk factor for hemolytic uremic syndrome (HUS), which can often have a rapidly fatal clinical course despite intervention with steroids, plasmapheresis and hemodialysis. METHODS: A retrospective report of the first case of gemcitabine-related HUS, in a patient with metastatic pancreatic adenocarcinoma, treated with a variety of standard therapies in addition to rituximab is presented. The hematologic response parameters and clinical outcomes to each of the therapies given are described. RESULTS: Chemotherapy-induced HUS was aggressively treated with plasmapheresis, high-dose steroids, vincristine and rituximab. Platelet recovery and clinical improvement coincided with administration of rituximab. In addition, aggressive supportive measures to manage renal failure (hemodialysis) and labile hypertension, allowed this patient to have an extended survival as a result of successful therapy for this complication despite an underlying rapidly fatal malignancy. CONCLUSION: This case highlights the importance of timely application of aggressive measures even in patients with known diagnosis of a fatal malignancy as these interventions can prolong life and be of palliative benefit.