Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Chen CH
PROVIDER: S-EPMC4873744 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Publications
Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study.
Chen Chang-Hsu CH Wu Hon-Yen HY Wang Chieh-Li CL Yang Feng-Jung FJ Wu Pei-Chen PC Hung Szu-Chun SC Kan Wei-Chih WC Yang Chung-Wei CW Chiang Chih-Kang CK Huang Jenq-Wen JW Hung Kuan-Yu KY
Scientific reports 20160520
Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m(2) and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as c ...[more]
Similar Datasets
Project description:Cellular metabolic changes during chronic kidney disease (CKD) may induce higher production of oxygen radicals that play a significant role in the progression of renal damage and in the onset of important comorbidities. This condition seems to be in part related to dysfunctional mitochondria that cause an increased electron "leakage" from the respiratory chain during oxidative phosphorylation with a consequent generation of reactive oxygen species (ROS). ROS are highly active molecules that may oxidize proteins, lipids and nucleic acids with a consequent damage of cells and tissues. To mitigate this mitochondria-related functional impairment, a variety of agents (including endogenous and food derived antioxidants, natural plants extracts, mitochondria-targeted molecules) combined with conventional therapies could be employed. However, although the anti-oxidant properties of these substances are well known, their use in clinical practice has been only partially investigated. Additionally, for their correct utilization is extremely important to understand their effects, to identify the correct target of intervention and to minimize adverse effects. Therefore, in this manuscript, we reviewed the characteristics of the available mitochondria-targeted anti-oxidant compounds that could be employed routinely in our nephrology, internal medicine and renal transplant centers. Nevertheless, large clinical trials are needed to provide more definitive information about their use and to assess their overall efficacy or toxicity.
| S-EPMC4660721 | biostudies-literature
Project description:Background and purposeChronic kidney disease is associated with an increased risk of cardiovascular events. However, the impact of chronic kidney disease on cerebrovascular disease is less well understood. We hypothesized that renal function severity would be predictive of stroke risk, independent of other vascular risk factors.MethodsThe study population included 3939 subjects enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study, a prospective observational cohort. Stroke events were reported by participants and adjudicated by 2 vascular neurologists. Cox proportional hazard models were used to compare measures of baseline renal function with stroke events. Multivariable analysis was performed to adjust for key covariates.ResultsIn 3939 subjects, 143 new stroke events (0.62 events per 100 person-years) occurred over a mean follow-up of 6.4 years. Stroke risk was increased in subjects who had worse baseline measurements of renal function (estimated glomerular filtration rate and total proteinuria or albuminuria). When adjusted for variables known to influence stroke risk, total proteinuria or albuminuria, but not estimated glomerular filtration rate, were associated with an increased risk of stroke. Treatment with blockers of the renin-angiotensin system did not decrease stroke risk in individuals with albuminuria.ConclusionsProteinuria and albuminuria are better predictors of stroke risk in patients with chronic kidney disease than estimated glomerular filtration rate. The impact of therapies targeting proteinuria/albuminuria in individuals with chronic kidney disease on stroke prevention warrants further investigation.
| S-EPMC4519405 | biostudies-literature
Project description:The prevalence of chronic kidney disease (CKD) is increasing annually in Taiwan. In addition to traditional risk factors, heavy metals contribute to the development of CKD. The aim of this study was to investigate associations among heavy metals and proteinuria and CKD in the general population in Southern Taiwan. We also explored the interaction and synergetic effects among heavy metals on proteinuria. We conducted a health survey in the general population living in Southern Taiwan between June 2016 and September 2018. Seven heavy metals were measured: blood lead (Pb) and urine nickel (Ni), chromium (Cr), manganese (Mn), arsenic (As), copper (Cu), and cadmium (Cd). Proteinuria was measured using reagent strips. CKD was defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2. The mean age of the 2447 participants was 55.1 ± 13.2 years and included 977 males and 1470 females. Participants with high blood Pb and high urine Ni, Mn, Cu, and Cd were significantly associated with proteinuria. Interactions between blood Pb and urine Cr, and between urine Cd and Cu, had significant effects on proteinuria. The participants with high blood Pb and high urine Cu were significantly associated with an eGFR of <60 mL/min/1.73 m2. High blood Pb and high urine Cu may be associated with proteinuria and an eGFR of <60 mL/min/1.73 m2. High urine Ni, Mn, and Cd were significantly associated with proteinuria. Co-exposure to Cd and Cu, and Pb and Cr, may have synergistic effects on proteinuria.
| S-EPMC7918558 | biostudies-literature
Project description:The accumulation of advanced glycation end products (AGEs) has been reported to be a major contributor to chronic systemic inflammation. AGEs are not efficiently removed by hemodialysis or the kidney of a chronic kidney disease (CKD) patient. The goal of this study was to develop a receptor for AGEs (RAGE)-based bioadsorbent device that was capable of removing endogenous AGEs from human blood. The extracellular domain of RAGE was immobilized onto agarose beads to generate the bioadsorbent. The efficacy of AGE removal from saline, serum, and whole blood; biological effects of AGE reduction; and hemocompatibility and stability of the bioadsorbent were investigated. The bioadsorbent bound AGE-modified bovine serum albumin (AGE-BSA) with a binding capacity of 0.73?±?0.07?mg AGE-BSA/mL bioadsorbent. The bioadsorbent significantly reduced the concentration of total AGEs in serum isolated from end-stage kidney disease patients by 57%. AGE removal resulted in a significant reduction of vascular cell adhesion molecule-1 expression in human endothelial cells and abolishment of osteoclast formation in osteoclast progenitor cells. A hollow fiber device loaded with bioadsorbent-reduced endogenous AGEs from recirculated blood to 36% of baseline levels with no significant changes in total protein or albumin concentration. The bioadsorbent maintained AGE-specific binding capacity after freeze-drying and storage for 1 year. This approach provides the foundation for further development of soluble RAGE-based extracorporeal therapies to selectively deplete serum AGEs from human blood and decrease inflammation in patients with diabetes and/or CKD.
| S-EPMC4016998 | biostudies-literature
Project description:BACKGROUND:Acute kidney injury (AKI) has been extensively studied in hospital settings. Limited data exist regarding outcomes for patients with outpatient AKI who are not subsequently admitted. We investigated whether outpatient AKI, defined by a 50% increase in creatinine (Cr), is associated with increased mortality and renal events. METHODS:In this retrospective study, outpatient serum Cr values from adults receiving primary care at a health system during an 18-month exposure period were used to categorize patients into one of five groups (no outpatient AKI, outpatient AKI with recovery, outpatient AKI without recovery, outpatient AKI without repeat Cr and no Cr). Principal outcomes of all-cause mortality and renal events (50% decline in estimated glomerular filtration rate to <30?mL/min/1.73?m2) were examined using Cox proportional hazards models. RESULTS:Among 384 869 eligible patients, 51% had at least one Cr measured during the exposure period. Outpatient AKI occurred in 1.4% of patients while hospital AKI occurred in only 0.3% of patients. The average follow-up was 5.3?years. Outpatient AKI was associated with an increased risk of all-cause mortality {adjusted hazard ratio [aHR] 1.90 [95% confidence interval (CI) 1.76-2.06]} and results were consistent across all AKI groups. Outpatient AKI was also associated with an increased risk of renal events [aHR 1.33 (95% CI 1.11-1.59)], even among those who recovered. CONCLUSIONS:Outpatient AKI is more prevalent than inpatient AKI and is a risk factor for all-cause mortality and renal events, even among those who recover kidney function. Further research is necessary to determine risk factors and identify strategies for preventing outpatient AKI.
| S-EPMC6399485 | biostudies-literature
Project description:Resistant hypertension is still a challenge and reserve antihypertensive agents are often necessary to achieve blood pressure control. One reserve antihypertensive is minoxidil, a direct vasodilator that is known for its strong blood pressure-lowering effect, but contemporary studies are sparse. The authors retrospectively analyzed 54 inpatients with uncontrolled hypertension despite the combined use of current antihypertensive agents. To investigate the effect of minoxidil when added to other antihypertensive agents, blood pressure was evaluated at the time minoxidil treatment was initiated and at discharge. Minoxidil treatment was associated with a significant reduction in blood pressure from 162.4±15.1/83.2±12.7 mm Hg to 135.8±12.2/72.8±6.9 mm Hg (P<.0001). This effect was sustained across all analyzed subgroups. Although the well-known adverse events of minoxidil limit its widespread use, these data show that minoxidil as a reserve antihypertensive agent still has a niche indication in the particular subgroup of patients with treatment-resistant or uncontrolled hypertension.
| S-EPMC8031757 | biostudies-literature
Project description:The benefit of therapeutic hypothermia (TH) in acute liver failure (ALF) has not been previously demonstrated in a controlled fashion. This study sought to determine the impact of TH on 21-day survival and complications in ALF patients at high risk for cerebral edema. This was a retrospective cohort study of ALF patients in the US Acute Liver Failure Study Group with grade III or IV hepatic encephalopathy. TH (32°C-35°C) was used in 97 patients (8%); 1135 (92%) who were not cooled were controls. Intracranial pressure was monitored in 38 TH ALF patients (39.2% versus 22% of controls, P?<?0.001). Rates of bleeding (12% for both) and bloodstream (17% versus 18%) and tracheal infections (21% versus 23%, P?>?0.5 for all) were similar. Unadjusted 21-day overall (62% versus 60%) and transplant-free survival rates (45% versus 39%, P?>?0.4 for both) were similar. Multivariate models were created for acetaminophen (APAP) patients (n?=?582) and non-APAP patients (n?=?613). For APAP patients, the Model for End-Stage Liver Disease [MELD; odds ratio (OR)?=?0.91 per increment, 95% confidence interval (CI)?=?0.89-0.94, P?<?0.001] and vasopressors (OR?=?0.16, 95% CI?=?0.11-0.24, P?<?0.001) were associated with decreased 21-day spontaneous survival. Survival was improved with TH in APAP patients who were <25 years old (age of 25 years: OR?=?2.735, 95% CI?=?1.001-7.467) but worsened for APAP patients who were 64 years old or older (age of 64 years: OR?=?0.167, 95% CI?=?0.028-0.999). For non-APAP patients, MELD (OR?=?0.93 per increment, 95% CI?=?0.91-0.95, P?<?0.001) and vasopressors (OR?=?0.60, 95% CI?=?0.40-0.90, P?=?0.01) were associated with worse outcomes, whereas TH had no impact (P?=?0.93). In conclusion, TH in ALF was not associated with increased bleeding or infections. Although young APAP ALF patients may benefit, TH did not consistently affect 21-day survival. A prospective trial is required to clarify the utility of TH in ALF patients.
| S-EPMC4939841 | biostudies-literature
Project description:Although lower estimated glomerular filtration rate (eGFR) and higher proteinuria are high risks for mortality and kidney outcomes, the prognosis of chronic kidney disease (CKD) in patients with normal-range proteinuria remains unclear.In this prospective cohort study, 1138 newly visiting stage G2-G5 CKD patients were stratified into normal-range and abnormal-range proteinuria groups. Study endpoints were CKD progression (>50% eGFR loss or initiation of dialysis), cardiovascular events, and all-cause death.In total, 927 patients who were followed for >6 months were included in the analysis. The mean age was 67 years, and 70.2% were male. During a median follow-up of 35 months, CKD progression, cardiovascular events, and mortality were observed in 223, 110, and 55 patients, respectively. Patients with normal-range proteinuria had a significantly lower risk for CKD progression (hazard ratio, 0.20; 95% confidence interval, 0.10-0.38) than those with abnormal-proteinuria by multivariate Cox proportional hazard analysis. We also analyzed patients with normal-range proteinuria (n = 351). Nephrosclerosis was the most frequent cause of CKD among all patients with normal-range proteinuria (59.7%). During a median follow-up of 36 months, CKD progression, cardiovascular events, and mortality were observed in 10, 28, and 18 patients, respectively. The Kaplan-Meyer analysis demonstrated that the risks of CKD progression and cardiovascular events were not significantly different among CKD stages, whereas the risk of death was significantly higher in patients with advanced-stage CKD. Multivariate Cox proportional hazard analysis showed that the risk of three endpoints did not significantly differ among CKD stages.Newly visiting CKD patients with normal-range proteinuria, who tend to be overlooked during health checkups did not exhibit a decrease in kidney function even in advanced CKD stages under specialized nephrology care.
| S-EPMC5771558 | biostudies-literature
Project description:The nuclear factor erythroid 2-related factor 2 (Nrf2) pathway upregulates key cellular defenses. Clinical trials are utilizing pharmacologic Nrf2 inducers such as bardoxolone methyl to treat chronic kidney disease, but Nrf2 activation has been linked to a paradoxical increase in proteinuria. To understand this effect, we examined genetically engineered mice with elevated Nrf2 signaling due to reduced expression of the Nrf2 inhibitor, Kelch-like ECH-associated protein 1 (Keap1). These Keap1FA/FA mice lacked baseline proteinuria but exhibited increased proteinuria in experimental models evoked by adriamycin, angiotensin II, or protein overload. After injury, Keap1FA/FA mice had increased glomerulosclerosis, nephrin disruption and shedding, podocyte injury, foot process effacement, and interstitial fibrosis. Keap1FA/FA mice also had higher daytime blood pressures and lower heart rates measured by radiotelemetry. Conversely, Nrf2 knockout mice were protected from proteinuria. We also examined the pharmacologic Nrf2 inducer CDDO-Im. Compared to angiotensin II alone, the combination of angiotensin II and CDDO-Im significantly increased proteinuria, a phenomenon not observed in Nrf2 knockout mice. This effect was not accompanied by additional increases in blood pressure. Finally, Nrf2 was found to be upregulated in the glomeruli of patients with focal segmental glomerulosclerosis, diabetic nephropathy, fibrillary glomerulonephritis, and membranous nephropathy. Thus, our studies demonstrate that Nrf2 induction in mice may exacerbate proteinuria in chronic kidney disease.
| S-EPMC7785672 | biostudies-literature
Project description:Childhood chronic kidney disease commonly progresses toward end-stage renal failure, largely independent of the underlying disorder, once a critical impairment of renal function has occurred. Hypertension and proteinuria are the most important independent risk factors for renal disease progression. Therefore, current therapeutic strategies to prevent progression aim at controlling blood pressure and reducing urinary protein excretion. Renin-angiotensin-system (RAS) antagonists preserve kidney function not only by lowering blood pressure but also by their antiproteinuric, antifibrotic, and anti-inflammatory properties. Intensified blood pressure control, probably aiming for a target blood pressure below the 75th percentile, may exert additional renoprotective effects. Other factors contributing in a multifactorial manner to renal disease progression include dyslipidemia, anemia, and disorders of mineral metabolism. Measures to preserve renal function should therefore also comprise the maintenance of hemoglobin, serum lipid, and calcium-phosphorus ion product levels in the normal range.
| S-EPMC2275772 | biostudies-other