Renal Disease Mortality Research Articles

Association between Atherosclerotic Aortic Calcification-Associated Genetic Variation in <i>HDAC9</i> with Mortality, Cardiovascular Disease and Kidney Disease

Importance: Histone deacetylase 9 (HDAC9) has recently been demonstrated as a key regulator of vascular smooth muscle cell (VSMC) phenotype and is associated with abdominal aortic calcification, myocardial infarction and ischemic stroke. It is uncertain whether HDAC9 is also implicated in other VSMC-driven diseases. Objective: To investigate associations between abdominal aortic calcification-associated genetic variation in HDAC9 and VSMC-associated phenotypes. Design: Prospective population study.Setting: UK Biobank.Participants: 335,146 European, non-related person aged 40-69 years (mean 57±8 years, 54% women). Main outcomes: Blood pressure, heart rate, hypertension, myocardial infarction, stroke, arterial aneurysm, heart failure, glomerular filtration rate, albuminuria, end-stage renal disease, all-cause and cardiovascular mortality, HbA1c, diabetes, serum lipids, body mass index, and smoking. Results: We used the aortic calcification-raising A-allele of rs57301765 in HDAC9 as a genetic instrumental variable to query the long-term effects of HDAC9 variation. At the Bonferroni significance level, rs57301765 was associated with systolic blood pressure (effect per added risk allele in standard deviation units, 0.022; 95% CI, 0.016-0.029, P=1.71×10-11), pulse pressure (0.035; 95% CI, 0.028-0.041, P=5.76×10-27), hypertension (odds ratio, OR, 1.04; 95% CI, 1.02-1.05, P=1.26×10-6), myocardial infarction (OR, 1.08; 95% CI, 1.04-1.12, P=1.72×10-5, driven by non-ST segment elevation myocardial infarction, OR, 1.11; 95% CI, 1.04-1.17, P=0.001), and ischemic stroke (OR, 1.14; 95% CI, 1.07-1.22, P=6.29×10-5). There was a suggestive protective association with kidney disease outcomes that, however, did not reach experiment-wise significance. Look-ups in public genome-wide association study results concur with our findings for cardiovascular outcomes. Conclusions and Relevance: The genetic results in our study lend further support for HDAC9 as a key determinant of VSMC-associated cardiovascular pathology and its potential as a therapeutic target for arterial stenotic and calcific disease.

PUK11 COST EFFECTIVENESS OF PHARMACEUTICAL TREATMENT OF HYPERPHOSPHATEMIA WITH PHOSPHATE BINDERS: A SYSTEMATIC REVIEW

Hyperphosphatemia is associated with morbidity and mortality in end-stage renal disease (ESRD) patients. Phosphate binders (PBs) are the primary therapeutic treatment for hyperphosphatemia in ESRD patients receiving dialysis. Calcium-based binders are associated with an increased morbidity and mortality risk. Medicare spending on PBs has been estimated to be over $1.5 billion. The purpose of this study was to review economic evaluations of PBs to better understand their value. We conducted a systematic literature review of the Cochrane Database of Systematic Reviews, PubMed, and Google Scholar using the search terms “phosphate binder”, “hyperphosphatemia”, “ESRD”, “cost”, and “economic”. Results: were limited to recent economic evaluations published in English in peer reviewed journals between January 2015 and December 2019. Studies included in the review reported cost-effectiveness outcomes. Our search initially identified 84 publications. After removing irrelevant articles and duplicates, 5 publications met our inclusion criteria and were included in our review. Four of the five studies compared either sevelamer carbonate (SEV) or lanthanum carbonate (LC) to calcium-based binders. These analyses found SEV or LC to be cost-effective compared to calcium-based binders. A fifth study evaluated the cost effectiveness of two non-calcium-based phosphate binders, sucroferric oxyhydroxide (SO) and SEV, and found SO to be cost effective relative to SEV. This review demonstrates the need for more high-quality economic evaluations of phosphate binders. The use of calcium-based binders as a comparator group is sub-optimal given the risk they may pose to patients. Only one study, which found sucroferric oxyhydroxide to be cost-effective, was found that compared non-calcium-based binders.

Selenium and All-cause Mortality in End-Stage Renal Disease. Retrospective Observational Cohort Study

The objectives of the study were to determine whether low plasma selenium levels (<63μg/L according to population-based reference interval) were associated with poorer survival among adult patients with end-stage renal disease (ESRD) on dialysis treatment and to study whether plasma selenium behaved as a biomarker of mortality risk independent of other monitored biochemical markers. This is a retrospective observational cohort study that included 85 patients with ESRD on 3 modalities of dialysis, with a plasma selenium test performed 5-6years before the study. Patients with low selenium showed an increased risk of all-cause mortality (hazard ratio=2.952, 95% CI 1.402-6.217) compared with patients with normal or high selenium (>118μg/L), according to a Cox multivariate model that included age and history of cardiovascular disease as covariates. Patients with low selenium had an increased risk of all-cause mortality (hazard ratio=2.894, 95% CI 1.457-5.751) according to a model that included age, anemia, and low albumin as covariates. Low albumin patients had an increased risk of having low plasma selenium (odds ratio=5.778, 95% CI 2.212-15.098). Low plasma selenium group's survival was significantly lower than that of the group with normoselenemia or hyperselenemia. Plasma selenium behaved as a biomarker of mortality risk independent of other biochemical markers usually monitored in patients with ESRD.

Agreement Between Two Nutritional Assessment Scores as Markers of Malnutrition in Patients with End-stage Renal Disease.

BackgroundMalnutrition is directly related to morbidity and mortality in end-stage renal disease. This should be picked up using simple techniques.MethodsAdult patients on maintenance haemodialysis were included using a consecutive sampling technique. Compliance was assessed from attendance register (minimum 75% attendance for good compliance). Hypoalbuminemia signified malnutrition. Blood samples for measurement of haemoglobin, serum albumin, calcium and phosphate levels were drawn from the dialyser tubing at the start of the first of the two haemodialysis sessions for each patient. Height and weight were recorded at the end of the first haemodialysis session for each patient. Mini Nutritional Assessment Questionnaire and Council on Nutrition Appetite Questionnaire were administered in direct face-to-face interviews during two consecutive dialysis sessions.ResultsThere were 116 patients aged 53.46± 14.39 years. Majority were males (83.6%) and on twice a week haemodialysis (69.0%). Malnutrition was present in 30 (25.9%) patients. Serum albumin had a significant relationship with both haemoglobin (R = 0.399; p < 0.001) and serum phosphate levels (R = 0.253; p = 0.006) but not body mass index (R = 0.028; p = 0.769). Mean Mini Nutritional Assessment and Council on Nutrition Appetite scores were 19.45± 5.10 and 26.76± 6.28, respectively. Based on Mini Nutritional Assessment scores, 31 (26.7%) patients were malnourished, 59 (50.9%) were at risk of malnutrition, and 26 (22.4%) had normal nutritional status. Council on Nutrition Appetite scores were low in 65 (56.0%) patients, indicating risk of weight loss in next six months. Serum albumin had significant correlation with Mini Nutritional Assessment scores (R = 0.381; p < 0.001) and Council on Nutrition Appetite scores (R = 0.290; p = 0.002). Slopes of linear regression for Mini Nutritional Assessment and Council on Nutrition Appetite scores were not statistically different (p = 0.202).ConclusionsMini Nutritional Assessment and Council on Nutrition Appetite scores had a similar correlation with serum albumin levels. Either of the two could be used for evaluation of malnutrition in end-stage renal disease.

Abdominal aortic calcification in predialysis patients: Contribution of traditional and uremia-related risk factors.

Cardiovascular disease is the main cause of morbidity and mortality in end-stage renal disease (ESRD) patients. Recent population based epidemiological studies demonstrated a correlation between reduced renal function and risk for all causes and cardiovascular mortality, 50% of patients dying before the commencement of renal replacement therapy. Vascular calcifications (VC) and arterial stiffness are major contributors to cardiovascular disease and are independent predictors of cardiovascular mortality in ESRD patients. Scarce information is available on the risk factors and prognosis of predialysis patients with VC. The aim of this study was to evaluate the contribution of traditional and uremia related risk factors to abdominal aortic calcification in predialysis patients. A single center, retrospective study was performed on 305 adult patients monitored at the Bucharest University Emergency Hospital for at least 6 months. Our study reports an increased incidence of VC in predialysis chronic kidney disease (CKD) patients, higher in those with advanced age, history of cardiovascular disease, osteoporosis, and declining renal function.

Abstract P187: Pre-kidney Transplant Medical Arterial Calcification as a Risk for Post-transplant Mortality by a Propensity Score Weighting Analysis

Introduction: Medial arterial calcification (MAC) detected in the breast by mammography (MG) is exclusively medial and associated with cardiovascular mortality in end-stage renal disease (ESRD). This association is unclear in renal transplant recipients (RTR). Hypothesis: By comparing groups of study population balanced by propensity score weighting method, MAC is associated with an increased risk of post-transplant mortality. Methods: Female RTR was divided into 2 groups per presence or absence of pre-transplant MAC examined from MG (MAC and non-MAC), and both groups was balanced with by PS weighting leading to a new study population. Association between MAC and post-transplant mortality of the new study population was examined by multi-variable logistic regression analysis. Results: Of 51 patients, mean age±SD was 57.08±10.47 years old. The majority were white (54.9%) followed by African American (35.3%) and others (9.8%). Incidence rate of mortality was 0.0307 person-years. Median time to follow-up was 3.95 years (range 0.22 to 6.37). Among 20 patients in MAC group, 5 patients died; whereas, only 1 out of 31 patients in non-MAC died (25% vs. 3.23%, p 0.029). Baseline characteristics of both groups were not equal. After using PS weights with generalized boosted modeling, new study population’s characteristics were balanced (Figure 1). MAC is associated with 5.97 times higer the odd of morality compared to non-MAC, but the association was not significant (OR 5.97; 95%CI 0.61, 58.77). After adjusted for age, race, causes of ESRD, dialysis modality, dialysis vintage, donor type, donor age, and type of immunosuppressive medications, the magnitude of the association was increased and becomes significant (OR 38.40; 95%CI 2.44, 604.54). Conclusions: Similar to ESRD, MAC remains associated with higher mortality in RTR and this association is confirmed by well-matched study population. Prevention of pre-transplant MAC should be pursued to mitigate poor post-transplant outcomes.

SAT-207 Leucine-Rich a-2-Glycoprotein 1 predict mortality in end-stage renal disease

Plasma Leucine-Rich a-2-Glycoprotein 1(LRG1) as a novel serum biomarker for inflammation and angiogenetic diseases. Patients with end-stage renal disease (ESRD) are associated with several health-related adverse outcomes including inflammation, atherosclerosis and premature mortality in individuals. Whether level of Plasma Leucine-Rich a-2-Glycoprotein 1may associate with the clinical status of hemodialysis patients is unknown. The immunity in ESRD study (iESRD) recruited 406 hemodialysis patients from Taiwan. By history taking and detailed chart reviews, baseline co-morbidities were recorded. Peripheral blood was sampled before hemodialysis session and processed immediately. Co-morbid conditions like diabetes mellitus, cardiovascular diseases, liver diseases, neoplasms, vascular diseases, smoking and hypertension were considered. Laboratory investigations done at the initial and follow-up. Plasma levels of LRG1 and high-sensitivity C reactive protein were determined by ELISA. Medical records of all iESRD patients on dialysis were reviewed after 5 years. The cause of the mortality cases would be carefully discussed and recorded. Among these patients, 100% were LRG-1-seropositive. In a multivariate-adjusted logistic regression model, higher LRG1 tertile was significantly associated with Peripheral arterial occlusive disease (PAOD) after adjusting for gender, hemoglobin, DM, hypertension and hs-CRP. Level of LRG-1 positively correlated with both IL-6, CRP and WBC, indicating the accumulation of these cytokines participate in the progression of atherosclerosis. LRG-1 positively correlated with age and predict higher mortality in this population. Level of LRG-1 predicted mortality in end-stage renal disease . Role of LRG-1 and the associated aging, inflammation and possible atherosclerosis should be further investigated in the pathogenesis in this patient population.

Changes of MicroRNA-377 in Diabetic Nephropathy

Abstract Background as one of the most important long term complications of diabetes, Diabetic nephropathy is the major cause of end stage renal disease and high mortality. Purpose to identify the pattern of microRNA-377 changes specific for diabetic nephropathy in diabetic patients and in patients with chronic kidney disease of different etiology. Patients and Methods the study was conducted from 2016 to 2018, included 50 patients for analysis of MicroRNA-377 and its control gene U18 at El Demrdash Hospital Ain shams university and Quessena Hospital El Monfia. The miRNA-U18 was analyzed for normalization of correction ratio. Results the results of our research found that the highest median IQR of miR-377 was significantly present in DN stage 1&amp;2 and the lowest median IQR was significantly present in CKD stage 1&amp;2, and there was significant difference between group 1 (DN stage 1&amp;2) versus group 2 (DN stage 3&amp;4), group 3 (Diabetics without nephropathy) and all stages of CKD. Conclusion in diabetic nephropathy stage 1&amp;2, serum miR-377 was highly significant increased more than diabetics without nephropathy, diabetic nephropathy stage 3&amp;4 and all satges of CKD.

Increased long-term risk for hypertension in kidney donors - a retrospective cohort study.

Kidney donors may be at increased risk of end-stage renal disease and premature mortality. Elevated blood pressure after donation may contribute to the increased risks. In this cohort study, we have assessed long-term risk for the development of hypertension in kidney donors compared to a control group potentially eligible as donors. Follow-up data were obtained from previous living kidney donors. A healthy control group with baseline assessment from similar time periods as the donor nephrectomies was selected. Hypertension was defined as blood pressure >140/90, use of blood pressure medication, or established diagnosis of hypertension. Stratified logistic regression was used to estimate risk of hypertension at follow-up, adjusted for systolic blood pressure at baseline, age at follow-up, time since donation/baseline, gender, smoking at baseline, and BMI at baseline. A total of 368 donors (36%) had hypertension at follow-up, and 241 of these (23%) were using blood pressure medication. In adjusted stratified logistic regression analyses, odds ratio for hypertension was significantly increased (1.25, 95% confidence interval 1.12-1.39, P<0.001) in donors compared with controls. Kidney donors appear to be at increased long-term risk for hypertension compared with healthy controls. This finding supports regular follow-up of blood pressure in kidney donors.

The Charlson Comorbidity Index – its impact on hospitalization and mortality in chronic renal disease

The Charlson Comorbidity Index – its impact on hospitalization and mortality in chronic renal disease

Cardiovascular disease-related mortality risk in end stage renal disease and type 2 diabetes: A systematic review.

Background:Patients with uncontrolled type 2 diabetes can have microvascular and macrovascular complications, including renal impairment and cardiovascular diseases. However, it is unknown how diabetes and renal disease could influence cardiovascular mortality.Objective:This study aims at examining the medical literature to evaluate the risk of cardiovascular death in concomitant end stage renal disease with type 2 diabetes.Method:Medical literature was reviewed through Medline, PubMed, Embase, and Ovid database in the duration between 2009 and 2019. Searching terms included were a combination of “type 2 diabetes mellitus” AND “end-stage renal disease” AND “cardiovascular mortality”. Following this, results were filtered to include only original research articles investigating cardiovascular mortality in concomitant diabetes and end-stage renal disease. Selected trials mentioned diabetes control as well as the follow-up duration of the included patients.Result:A total of 1508 articles were retrieved. Following the exclusion of articles on animals and including only trials on humans, 32 articles appeared. A total of eight articles were identified as eligible, covering a total of 2,06,492 diabetic patients with end-stage renal disease. All the studies were prospective studies, except for three studies that were retrospective.Conclusion:There is an elevated cardiovascular mortality risk in concomitant type 2 diabetes mellitus and end-stage renal disease, especially with uncontrolled blood glucose levels.

Pharmacologic Therapies for Aortic Stiffness in End-Stage Renal Disease: A Systematic Review and Meta-Analysis.

Background:Increased carotid-femoral pulse wave velocity (cf-PWV), a surrogate of increased aortic stiffness, is a risk factor for cardiovascular events and all-cause mortality in end-stage renal disease (ESRD). To minimize the deleterious effects of an increased aortic stiffness in ESRD patients, several interventions have been developed and cf-PWV has been used to monitor responses.Objective:The aim of this study was to determine the effects of pharmacologic interventions that target aortic stiffness on cf-PWV and systolic blood pressure (SBP) in adults with ESRD.Study design:This study implements a systematic review and meta-analysis.Data sources:MEDLINE, EMBASE, Cochrane Central, Health Technology Assessment, and EBM databases were searched.Study eligibility, participants, and interventions:Randomized and non-randomized studies involving adults (>18 years) with ESRD of any duration, receiving or not renal replacement therapy (hemodialysis, peritoneal dialysis) and exposed to a pharmacologic intervention whose effects were assessed by cf-PWV.Methods:Study screening, selection, data extraction, and quality assessments were performed by 2 independent reviewers. Narrative synthesis and quantitative data analysis summarized the review.Results:We included 1027 ESRD participants from 13 randomized and 5 non-randomized studies. Most pharmacologic interventions targeted bone mineral metabolism disorder or hypertension. Treatment with vitamin D analogues or cinacalcet did not decrease cf-PWV or SBP over placebo or matched controls (P > .05). Calcium-channel blockers (CCB) decreased cf-PWV and SBP compared with placebo or standard care (P < .05). Renin-angiotensin system inhibitors did not show any advantage over placebo in decreasing cf-PWV (P > .05).Limitations:Quality of evidence ranged from very low to moderate. Overall evidence was limited by the low number of studies, small sample sizes, and methodological inconsistencies.Conclusions:Pharmacologic interventions targeting aortic stiffness in ESRD have mixed effects on reducing cf-PWV, with some strategies suggesting potential benefit. The quality of evidence, however, is insufficient to draw definitive conclusions on their use to slow progression of aortic stiffness in ESRD. Further well-designed studies are needed to confirm these associations and their impact on cardiovascular outcomes in ESRD.Registered in PROSPERO (CRD42016033463)

High-sensitivity C-reactive Protein as a Marker of Future Cardiovascular Events in Chronic Kidney Disease Stage-5 Patients

Introduction: Chronic Kidney Disease (CKD) has been recognised as a worldwide health threat and understanding its complex patho-physiological mechanisms could go a long way in taking care of patients with CKD. One of the most important causes for mortality in End Stage Renal Disease (ESRD) patients is Cardiovascular Disease (CVD). ESRD is a low grade chronic inflammatory state, suspected to promote atherosclerosis. Aim: To determine, if there is any association between elevated High-sensitivity C-Reactive Protein (hs-CRP) and development of future cardiovascular events in stage-5 CKD patients. Materials and Methods: Forty-five CKD stage-5 patients were included in the study, after ruling out patients with established CVD. According to categorisation proposed by the American Heart Association for the cut-off value of hs-CRP-value (3 mg/L), patients were divided into two groups. Those who had hs-CRP more than 3 mg/L were considered to have ‘elevated hs-CRP’ and those who had a value 3 mg/L and below were considered to have ‘normal hs-CRP’ levels. These patients were followed-up monthly, for a period of one year to record any occurrence of cardiovascular events (coronary events/cerebrovascular accidents/peripheral occlusive vascular disease). Statistical Package for the Social Sciences (SPSS) 16.0 was used for analysis. Chi-square test and Mann-Whitney U-test were used for statistical comparison between the groups and a p-value of 0.05 or less was considered to be statistically significant. Receiver Operating Characteristic (ROC) curve was also plotted to determine the cut-off value for hs-CRP based on the occurrence of any cardiovascular event. Results: Baseline hs-CRP level was more than 3 mg/L in 42% of patients. Among those who had elevated hs-CRP, 78.9% of patients developed cardiovascular events during the follow-up period. This signifies a strong association between elevated hs-CRP and CVD in ESRD patients. The hs-CRP cut-off point of 3 mg/L was obtained from ROC curve. Conclusion: There was a significant association between elevated hs-CRP and development of cardiovascular events in ESRD patients. Hence, hs-CRP can be used as a marker of future cardiovascular events in CKD stage-5 patients.

Association of serum phosphate with valvular and vascular calcification in patients with end-stage renal disease

Aim This study aims to evaluate the calcifying effect of phosphorus on vascular smooth muscle by detecting the association between serum phosphorus and valvular and vascular calcification. Patients and methods The study included 40 patients who were diagnosed to have end-stage renal disease within the last 5 years with their age ranging from 18 to 40 years. The patients were divided into two groups according to the duration of dialysis: group I included patients on regular hemodialysis for less than 1 year and group II included patients on regular hemodialysis for 1–5 years duration. All patients were subjected to full history taking and clinical examination: laboratory investigations (urea, creatinine, parathyroid hormone (PTH), calcium, phosphorus, liver function test, sodium, potassium level), measurement of coronary artery calcification by multi-slice computed tomography (MSCT) coronary calcium scoring, vavular calcification by echocardiography, and carotid intima media thickness by gray scale ultrasound. Results Coronary calcium score, valvular calcification, and carotid intima media thickness had insignificant correlation with age, duration of dialysis, serum calcium, and parathormone hormone; however, all of them had positive moderate significant correlation with serum phosphorous level. Conclusion Hyperphosphatemia has an effective role in the progression of valvular and vascular calcification; so, good control of hyperphosphatemia may participate in preventing and delaying the progress of cardiovascular calcification and subsequently decrease cardiovascular morbidity and mortality in end-stage renal disease.

Interleukin 18 as a new inflammatory mediator in left ventricular hypertrophy in children with end-stage renal disease.

Left ventricular hypertrophy (LVH) represents an important determinant of increased cardiovascular morbidity and mortality (CV) in end-stage renal disease (ESRD) patients. The role of inflammatory markers in pathogenesis of LVH in children with ESRD is not fully described. The aim of this study is to evaluate relation of some inflammatory markers [as hs C-reactive protein (hsCRP) and interleukin (IL) 18] with LVH in children with ESRD on regular hemodialysis (HD). This is a cross-sectional study performed on 50 children on regular HD. Demographic data were recorded. Echocardiography was performed at baseline to determine those with LVH. Biochemical parameters: hemoglobin (HB), hsCRP, IL 18, phosphorus, calcium, serum albumin, and lipid profile were evaluated and correlated with LVH. Data were analyzed using Student's t-test, and logistic regression to determine the relationship between LVH and other variables. LVH was present in 33 (66%) participants. Mean left ventricular mass index was 56.88 ± 22.23 g/m.2.7 Concentric remodeling, concentric hypertrophy, and eccentric hypertrophy were present in 4%, 22%, and 44% of the participants. In univariate analysis, children with LVH had significantly lower levels of HB and serum albumin but higher levels of hsCRP, and IL 18 compared to those without LVH. On multivariate analysis: only hsCRP, and IL 18 were significantly associated with LVH. This study shows that elevated hsCRP and IL-18 are independent determinants of LVH in HD children. Understanding the role of inflammatory molecules in the pathogenesis of LVH in ESRD is important for prediction of high-risk group and implementation of targeted anti-inflammatory therapies.

Association between Serum Uric Acid Level and ESRD or Death in a Korean Population

BackgroundSerum uric acid (SUA) is recognized as a risk factor for chronic kidney disease (CKD) and mortality. However, there is controversy as to whether a high or low level of SUA is related to the risk of CKD progression or death, and whether it differs between males and females.MethodsWe included 143,762 adults who underwent voluntary health screening between 1995 and 2009 in Korea. For each sex, we divided participants into sex-specific quintiles according to SUA levels and compared end-stage renal disease (ESRD) incidence and mortality between the groups with low and high SUA levels and those with middle SUA levels. Sex-specific Cox proportional hazard analyses were performed for ESRD and all-cause mortality.ResultsAmong the 143,762 participants, 0.2% (n = 272) developed ESRD. The hazard ratio (HR) of ESRD was higher in the highest (adjusted HR, 2.13; 95% confidence interval [CI], 1.18–3.84) and lowest (adjusted HR, 1.90; 95% CI, 1.02–3.51) SUA quintiles than in the middle SUA quintile in males and the highest SUA quintile in females (adjusted HR, 2.31; 95% CI, 1.10–4.84). Four-point three percent (n = 6,215) of participants died during a mean follow-up period of 157 months. The hazard ratio (HR) of all-cause mortality was higher in the highest SUA quintile than in the middle SUA quintile in males (adjusted HR, 1.15; 95% CI, 1.03–1.28) and females (adjusted HR, 1.17; 95% CI, 1.01–1.35).ConclusionElevated levels of SUA are associated with increased risk for ESRD and all-cause mortality in both sexes. Low levels of SUA might be related to ESRD and death only in males, showing U-shaped associations. Our findings suggest sex-specific associations between SUA levels and ESRD development and mortality.

Mechanism of diabetic nephropathy and traditional drugs for management

Diabetic nephropathy (DN) is a microvascular complication of diabetes mellitus which affects the kidneys. Recent reports of increasing prevalence of diabetes around the globe suggested that that the prevalence of DN will be doubled by 2025. There is an extremely high risk of progression of DN to end-stage renal disease and cardiovascular morbidity and mortality. Control of sugar levels, blood pressure control via renin–angiotensin–aldosterone system inhibition, and regular monitoring of renal functions have remained the principle of the management for DN for a long time. As conventional drugs cannot fulfill all the clinical needs due to accessibility, clinical efficacy, and safety issues, the need for novel inexpensive traditional drugs from Unani medicine to improve DN treatment and reduce the risk of complications has become urgent. Several herbal and mineral drugs have been mentioned in the old Unani books for the treatment of similar conditions stipulating DN. Through this article, an uttermost effort has been put to rememorize the mechanism of development of DN and available Unani drugs so that effect and mechanism of these drugs could be evidenced in the treatment of DN in future.

Predicting 6-Month Mortality in Incident Elderly Dialysis Patients: A Simple Prognostic Score

Aim: Mortality in end-stage renal disease (ESRD) remains high, particularly among elderly, who represents the most rapidly growing segment of the ESRD population in wealthier countries. We developed and validated a risk score in elderly patients to predict 6-month mortality after dialysis initiation. Methods: We used data from a cohort of 421 patients, aged 65 years and over who started dialysis between 2009 and 2016, in our Nephrology department. The predictive score was developed using a multivariable logistic regression analysis. A bootstrapping technique was used for internal validation. Results: The overall mortality within 6 months was 14.0%. Five independent predictors were identified, and a points system was constructed: age 75 years or older (2 points), coronary artery disease (2), cerebrovascular disease with hemiplegia (2), time of nephrology care before dialysis (<3.0 months [2]; ≥3 to <12 months [1]), and serum albumin levels (3.0–3.49 g/dL [1]; <3.0 g/dL [2]). A score of 6 identified patients with a 70% risk of 6-month mortality. Model performance was good in both discrimination (area under the curve of 0.793; [95% CI 0.73–0.86]) and validation (concordance statistics of 0.791 [95% CI 0.73–0.85]). Conclusions: We developed a simple prediction score based on readily available clinical and laboratory data that can be a practical and useful tool to assess short-term prognosis in elderly patients starting dialysis. It may help to inform patients and their families about ESRD treatment options and provide a more patient-centered overall approach to care.

Circulating TNF receptors and risk of renal disease progression, cardiovascular disease events and mortality in patients with diabetes: a systematic review and meta-analysis.

Inflammation plays an important role in the pathogenesis of diabetes complications. This study aims to assess the association between circulating inflammatory biomarkers TNF receptors (TNFRs) and the risk of renal disease progression, cardiovascular disease (CVD) events, and mortality in patients with diabetes. PubMed and Embase databases were comprehensively searched up to March 2019. Data were extracted independently by two reviewers. A random effects model was performed for the pooled analyses. Five studies in 3316 subjects assessed TNFRs with renal disease in patients with type 1 diabetes and showed both TNFR-1 and TNFR-2 were consistently associated with the renal outcomes. Fourteen studies in 7696 subjects evaluated TNFRs in patients with type 2 diabetes. The pooled risk ratio per doubling increase in TNFR-1 and TNFR-2 for renal disease progression was more than two (2.64 [1.98, 3.52] and 2.23 [1.69, 2.94]). The subgroup analyses and sensitivity analyses further illustrated these results of renal outcome and its robustness. Moreover, higher TNFR-1 and TNFR-2 was also significantly associated with CVD events and mortality in patients with type 2 diabetes. Circulating TNFR-1 and TNFR-2 are independently associated with higher risk of renal disease progression, CVD events, and mortality in patients with diabetes and might contribute to the clinical risk assessment in the future.

A Web-Based Self-Titration Program to Control Blood Pressure in Patients With Primary Hypertension: Randomized Controlled Trial

BackgroundHypertension is a major cause of mortality in cardiac, vascular, and renal disease. Effective control of elevated blood pressure has been shown to reduce target organ damage. A Web-based self-titration program may empower patients to control their own disease, share decisions about antihypertensive dose titration, and improve self-management, ultimately improving health-related quality of life.ObjectiveOur primary aim was to evaluate the effects of a Web-based self-titration program for improving blood pressure control in patients with primary hypertension. Our secondary aim was to evaluate the effects of that program on improving health-related quality of life.MethodsThis was a parallel-group, double-blind, randomized controlled trial with assessments at baseline, 3 months, and 6 months. We included patients with primary hypertension (blood pressure>130/80 mm Hg) from a cardiology outpatient department in northern Taiwan and divided them randomly into intervention and control groups. The intervention group received the Web-based self-titration program, while the control group received usual care. The random allocation was concealed from participants and outcome evaluators. Health-related quality of life was measured by the EuroQol five-dimension self-report questionnaire. We used generalized estimating equations to evaluate the effects of the intervention.ResultsWe included 222 patients and divided them equally into intervention (n=111) and control (n=111) groups. Patients receiving the Web-based self-titration program showed significantly greater improvement in the systolic and diastolic blood pressure control than those who did not receive this program, at 3 months (–21.4 mm Hg and –5.4 mm Hg, respectively; P<.001) and 6 months (–27.8 mm Hg and –9.7 mm Hg, respectively; P<.001). Compared with the control group, the intervention group showed a significant decrease in the overall defined daily dose at both 3 (–0.202, P=.003) and 6 (–0.236, P=.001) months. Finally, health-related quality of life improved significantly in the intervention group compared with the control group at both 3 and 6 months (both, P<.001).ConclusionsA Web-based self-titration program can provide immediate feedback to patients about how to control their blood pressure and manage their disease at home. This program not only decreases mean blood pressure but also increases health-related quality of life in patients with primary hypertension.Trial RegistrationClinicalTrials.gov NCT03470974; https://clinicaltrials.gov/ct2/show/NCT03470974