MDRD Formula Research Articles

Novel biomarkers of kidney injury and fibrosis in patients with different severity of hypertension: relation to vascular reactivity and stiffness

Aim. To compare the relationships between conventional and new potentially more early investigational biomarkers (urine and ultrasound) of kidney injury and central aortic blood pressure, vascular stiffness and reactivity, endothelial dysfunction in patients with different severity of hypertension.Material and methods. Urine levels NGAL, KIM-1, L-FABP, albuminuria and serum levels of сystatin C and creatinine were measured in 92 hypertensive patients with mild and severe hypertension, 46 male (mean age 50,7±12,2 years). Glomerular filtration rate was estimated by the level of serum creatinine and cystatin C by MDRD and CKD-EPI formulas. Instrumental examination included measuring office blood pressure, 24-hour ambulatory blood pressure monitoring (SpaceLabs 90207), applanation tonometry (SphygmoCor, Artcor Medical) with the calculation of central aortic blood pressure, pulse wave velocity and augmentation index and Doppler ultrasonography with assessment of intraparenchymal renal arterial resistance indices — resistive index and pulsatility index (Vivid 7 dimension). Endothelial function was assessed by reactive hyperemia index with EndoPAT device (Itamar Medicals).Results. There were no differences in conventional levels of biomarkers between patients, however, cystatin C level increased and serum cystatin C estimated GFR and serum creatinine and cystatin C estimated GFR (CKD EPI formula) (sCr,Cys-estimated GFR) levels decreased with the severity of hypertension. These novel biomarkers were associated with increased central aortic blood pressure, arterial stiffness and intraparenchymal renal arterial resistance indices. Decreased sCr,Cys-estimated GFR levels were associated with lower reactive hyperemia index. There were no differences in NGAL, KIM-1 and L-FABP levels in patients with hypertension. However, NGAL levels were associated with increased augmentation index, resistive index in intralobular and pulsatility index in arcuate arteries, KIM-1 and L-FABP levels were associated with increased systolic and diastolic central aortic blood pressure, pulse wave velocity only in patients with severe and resistant hypertension.Conclusion. Serum cystatin C, NGAL, KIM-1 and L-FABP levels seem to be biomarkers of increased systemic and intrarenal vascular stiffness in patients with different severity of hypertension.

Erectile dysfunction in patients with arterial hypertension. Cardiovascular risk and impact on their quality of life

ObjectivesEstimate the frequency of erectile dysfunction in patients with essential hypertension and associated variables, degree of control, cardiovascular risk and the impact on quality of life. Material and methodsType of study: Observational study of prevalence in men with essential hypertension. Measurements: Sociodemographic and comorbidity variables were collected from each patient (age, Charlson index, dyslipidaemia and prostatic hyperplasia), degree of control of essential hypertension and treatment, cardiovascular risk and metabolic syndrome. The erectile dysfunction was diagnosed by the International Index of Erectile Function (IIEF-15). Quality of life questionnaires were carried out in essential hypertension (MINICHAL), and the international scale of prostatic symptoms (IPSS). ResultsThe study included 262 hypertensive men with an average age of 65.84 years. Erectile dysfunction was presented in 46.1%, being severe in 54.9%. The bivariate analysis shows an independent association between erectile dysfunction and the variables: age, Charlon index, dyslipidaemia, benign prostatic hypertrophy, diastolic blood pressure, years of diagnosis of hypertension, number of treatments, Regicor and Framingham-Wilson, glycaemia, creatinine and GPT, glomerular filtration through the MDRD formula, irritative symptomatology (IPSS) and somatic manifestations (MINICHAL). The final multivariate model found association with age, presentation of dyslipidaemia, prostatic hyperplasia and metabolic syndrome. ConclusionsErectile dysfunction is significantly associated with age, dyslipidaemia, benign prostatic hypertrophy and metabolic syndrome.

Antibiotic Dosing in Chronic Kidney Disease and End-Stage Renal Disease: A Focus on Contemporary Challenges.

Infections are an important cause of morbidity and mortality among patients with chronic kidney disease. Therefore, appropriate antibiotic dosing is imperative to achieve positive patient outcomes while minimizing antibiotic dose-related toxicity. Accurately assessing renal function and determining the influence of renal replacement therapy on antibiotic clearance makes drug dosing in this patient population challenging. Furthermore, as technological advances in hemodialysis and peritoneal dialysis occur, research incorporating newer dialysis parameters to guide drug dosing may not be readily available. Currently, there are limited data to guide drug dosing in the setting of automated peritoneal dialysis, short daily hemodialysis, and nocturnal hemodialysis. Antibiotic-dosing recommendations should be carefully evaluated considering the accuracy of the renal function assessment, the similarity of the operating characteristics of the renal replacement therapy studied compared with those being used, and whether the dosing strategy takes advantage of the pharmacodynamic profile of the antibiotic under consideration. After implementing the antibiotic-dosing regimen, therapeutic drug monitoring should occur when possible along with careful monitoring for antibiotic efficacy and safety.

Screening for chronic kidney disease in Belgrade primary health care centers

<p>Introduction. Academy of Medical Science of Serbian Medical Society introduced collaboration between Belgrade nephrologists and general practitioners with the aim of examining the prevalence of chronic kidney disease (CKD) in populations at risk as well as of checking whether collaboration with general practitioners contributed to implementation of regular CKD screening. Methods. The research encompassed two studies carried out in four Belgrade Primary Health Care Centers. The screening study involved 619 patients at risk for CKD (348 with hypertension, 206 with diabetes, 65 persons aged > 60 years without hypertension/dia-betes) in whom glomerular filtration rate (eGFR) was estimated by MDRD formula, while urine dipstick test was used for detection of proteinuria and albuminuria (Micral-test® strips).The second study was retrospective analysis of medical records of 450 patients who were examined in the screening study and whose blood pressure and eGFR recording were analyzed during three-year period. Results. In screening study, eGFR below 60 ml/min/1.73m 2 was detected in 121 (19.55%) and albuminuria in 242 (39.10%) patients. During three-year retrospective study, percentage of patients whose blood pressure and eGFR were recorded decreased from 42% to 22% and from 42% to 18%, respectively. Multivariate regression analysis selected health center, systolic blood pressure and hypertension as the variables significantly associated with the number of years in which blood pressure was recorded, while male gender, health center, hypertension and basal eGFR as variables associated with the number of years in which eGFR was recorded. Conclusion. Despite collaboration between nephrologists and general practitioners in screening study, the retrospective three-year study revealed insufficient recording of blood pressure and eGFR in patients' medical records.</p>

Functional Cure, Defined As PFS of More Than 7 Years, Is Achieved in 9% of Myeloma Patients in the Era of Conventional Chemotherapy and of First-Generation Novel Anti-Myeloma Agents; A Single-Center Experience over 20-Year Period

Advances in the management of multiple myeloma (MM) led to a significant prolongation of overall survival (OS), mainly of the younger patients; almost 10% of them experience more than 10-year OS. Although long progression-free survival (PFS) correlates with extended OS, there is very limited information for the characteristics of patients who manage to be progression-free for a long period after first-line therapy. The aim of this analysis was to evaluate the characteristics of patients who achieved at least 7-year of PFS after frontline therapy and compare them with those of all other patients who were treated in a single center during the same time period. Between January 1994 and December 2010, 406 consecutive newly diagnosed MM patients received first line therapy in the Department of Clinical Therapeutics (Athens, Greece). All patients had symptomatic disease, based on the IMWG criteria of that period (at least one CRAB symptom to start anti-myeloma therapy). Thirty-six (8.8%; 23M/13F) patients achieved a PFS of at least 7 years (long PFS group) after frontline treatment. The median PFS of these 36 patients is 10 years, while the other patients had a median PFS of 22 months. Long PFS patients were younger (median age 56 vs 68 years; p All patients received either conventional chemotherapy (CC) or first-generation novel anti-myeloma agent (bortezomib (B), thalidomide (T) or lenalidomide (R)-based regimens as frontline therapy. There was no difference between the two groups regarding CC versus novel agent-based induction treatment. Out of 36 long-term PFS patients, 11 (30%) received CC, 8 (22%) B-based, 8 (22%) RD, 6 (17%) T-based, and 3 (8%) VTD; 10 (28%) patients received first-line therapy participating in a clinical trial. Long PFS patients had received more often autologous stem cell transplantation (ASCT, 61% vs 23%; p=0.001) as part of first line therapy; therefore, more long PFS patients had also received consolidation and/or maintenance (50% vs 15%; p=0.001). Higher proportion of patients achieved at least VGPR (74% vs 41%) or at least CR (32% vs 18%) in the long PFS group. We performed next generation flow cytometry in 23 patients of the long PFS group to evaluate minimal residual disease (MRD) and 14 (61%) of them were MRD (-) at the level of the 10-6. The probability of achieving long PFS (≥7 years) for patients who managed to be progression-free at 2, 3 and 4 years was 11.6%, 13.2% and 15.3%, respectively. In the multivariate analysis, only younger age was associated with probability for long PFS (p In conclusion, our study in an unselected group of patients, the majority of whom did not participate in clinical trials, showed that 9% of patients with newly diagnosed myeloma experience prolonged PFS of more than 7 years (median: 10 years) even in the era of CC or first-generation novel agents. These patients have low risk disease, mainly of ISS-1 or -2, no high-risk cytogenetics, no or mild renal impairment, and achieve deep responses after ASCT. These patients may be considered as "functionally" cured. The incorporation of novel treatment approaches may lead to a significant improvement in the probability of achievement of this "functionally" cured status. Disclosures Terpos:Novartis: Consultancy; BMS: Consultancy; Takeda: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: travel grant, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: member of steering committee, Research Funding; Genesis: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: travel grant, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: member of DMC, Research Funding; Amgen Inc.: Consultancy, Honoraria, Membership on an entity9s Board of Directors or advisory committees, Other: travel grant, steering committee member, Research Funding. Kastritis:Prothena: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity9s Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity9s Board of Directors or advisory committees. Dimopoulos:Celgene: Honoraria; Amgen: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria.

Early Serum Free Light Chain (SFLC) Kinetics Is Highly Predictive of Renal Response in Carfilzomib/ Dexamethasone (Cfz/Dex) in Myeloma (MM) Patients with Renal Impairment (RI) — Interim Analysis of the Australian ALLG MM16 Trial

Early Serum Free Light Chain (SFLC) Kinetics Is Highly Predictive of Renal Response in Carfilzomib/ Dexamethasone (Cfz/Dex) in Myeloma (MM) Patients with Renal Impairment (RI) — Interim Analysis of the Australian ALLG MM16 Trial

Impact of renal impairment on outcomes after autologous stem cell transplantation in multiple myeloma: a multi-center, retrospective cohort study

BackgroundRenal impairment (RI) is a negative prognostic factor in Multiple Myeloma (MM) and affected patients are often excluded from autologous stem cell transplantation (ASCT). However, it remains unclear whether historically inferior outcome data still hold true.MethodsFrom a total of 475 eligible MM patients who had undergone ASCT between 1998 and 2016, 374 were included in this multi-centric retrospective cohort study. Renal function was determined both at the time of MM diagnosis and ASCT by estimated glomerular filtration rate (eGFR according to the MDRD formula, RI defined as eGFR < 60 ml/min/1.73m2). Patients were categorized into 3 groups: A) no RI diagnosis and ASCT, B) RI at diagnosis with normalization before ASCT and C) RI both at the time of diagnosis and ASCT. Log-rank testing was used for overall and progression-free survival (OS, PFS) analysis.ConclusionWhile severe RI at MM diagnosis confers a risk of shorter OS, MM progression after ASCT is not affected by any stage of renal failure. It can be concluded that ASCT can be safely carried out in MM patients with mild to moderate RI and should be pro-actively considered in those with severe RI.ResultsWhen comparing all groups, no difference in OS and PFS was found (p = 0.319 and p = 0.904). After further stratification according to the degree of RI at the time of diagnosis, an OS disadvantage was detected for patients with an eGFR < 45 ml/min/m2. PFS was not affected by any RI stage.

A5926 hypertension and renal function in patients with breast cancer

Objectives: Over time, particularly in the last 10 to 15 years, nephrology consult and/or critical care nephrology services, oncology patients make up a significant number of the patients we see for kidney related-problems while hypertension is the most commonly reported comorbidity in cancer patients. Breast cancer is the leading cause of morbidity and mortality in women of all ages. In general, women with early-stage breast cancer undergo primary surgery to the breast and regional nodes with or without radiation therapy (RT). The aim of the pilot study was to assess kidney function and prevalence of hypertension in patients with breast undergoing surgery. Methods: The pilot study included 100 consecutive patients with breast cancer undergoing primary surgery with curative intent. Using the MDRD and CKD-EPI formula, the glomerular filtration rate (eGRF) and creatinine clearance using the Cockcroft-Gault formula were estimated and a group of patients with chronic kidney disease were identified. Blood pressure was measured with standard protocols. Hypertension was defined as either a blood pressure of at least 140/90 mm Hg or hypotensive medication use. Results: Patients with breast cancer were 53 ± 14 years of age, with serum creatinine of 0.68 ± 0.14 mg/dl eGFR by CKD-EPI of 99 ± 18 ml/min/1.72m2. Prevalence of chronic kidney disease (eGFR below 60 ml/min by CKD-EPI) was 5% in breast cancer Hypertension was present in 37%, but in the elderly (over 65 years) prevalence was 74%. Conclusion: Hypertensive females with breast cancer had worse kidney function as reflected by higher serum creatinine and lower estimated glomerular filtration rate, higher BMI and fibrinogen, which reflects general inflammatory state. After dividing patients according to age ( ≤ vs > 65 years) and presence of hypertension, elderly hypertensive females

Risk factors for kidney disease among HIV-1 positive persons in the methadone program

Kidney injury is a serious comorbidity among HIV-infected patients. Intravenous drug use is listed as one of the risk factors for impaired renal function; however, this group is rarely assessed for specific renal-related risks. Patients attending methadone program from 1994 to 2015 were included in the study. Data collected included demographic data, laboratory tests, antiretroviral treatment history, methadone dosing and drug abstinence. Patients' drug abstinence was checked monthly on personnel demand. We have evaluated two study outcomes: (1) having at least one or (2) three eGFR < 60ml/min (MDRD formula). In total, 267 persons, with 2593 person-years of follow-up were included into analyses. At the time of analyses, 251 (94%) were on antiretroviral therapy (ARV). Fifty-two (19.5%) patients had 1eGFR and 20 (7.5%) 3eGFR < 60. In univariate analysis, factors significantly increasing the odds of impaired renal function were: female gender, detectable HIV RNA on ART, age at registration per 5years older, atazanavir use and time on antiretroviral treatment per 1year longer. In the multivariate model, only female gender (OR 4.7; p = 0.002), time on cART (OR 1.11; p = 0.01) and baseline eGFR (OR 0.71; p = 0.001) were statistically significant. We have demonstrated a high rate of kidney function impairment among HIV-1 positive patients in the methadone program. All risk factors for decreased eGFR in this subpopulation of patients were similar to those described for general HIV population with very high prevalence in women. These findings imply the need for more frequent kidney function monitoring in this subgroup of patients.

Relationship Among Serum Homocysteine, Serum Folate And Left Ventricular Ejection Fraction In Chronic Kidney Disease

Background: Homocysteine (Hcy) a sulfurcontaining, non-protein a-amino is now considered an independent non-traditional risk factor for vascular disease. In Chronic Kidney Disease (CKD) highly prevalent hyperhomocysteinemia which is often associated with decreased folate concentrations is thought to contribute to increased cardiovascular morbidity. So, the aim of this cross-sectional study was to investigate the relations among serum homocysteine, serum folate and Left Ventricular Ejection Fraction (LVEF) in the context of native CKD patients. Materials and methods: A total of one-thirty (130) participants were recruited between June and July 2016. Among them ninety (90) were CKD patients of stage III, IV &amp; V and forty (40) were healthy controls.eGFR was calculated by MDRD formula. Different groups were created based on serum homocysteine level and eGFR. Results: In this study, hyperhomocysteinemia was seen in 97% CKD patients compared to 52.50% in controls. The CKD patients with elevated homocysteine levels had higher serum creatinine, LDL and systolic BP but they had lower eGFR, serum folateand LVEF than those with normal homocysteine concentrations. As the severity of homocysteinemia increased, eGFR and serum folate decreased. LVEFalso reduced significantly with increasing severity of hyperhomocysteinemia i.e. from 68% in those withouthyperhomocysteinemia to 41.33% in those with severe hyperhomocysteinemia. Chi-squared tests and odds ratios proved significant associations of hyperhomocysteinemia and folate deficiency with CKD. Higher homocysteine concentrations were also associated with low folate and low LVEF. Here, serum homocysteine correlated negatively with eGFR, serum folate and LVEF and positively with LDL and systolic BP. Conclusion: Inconclusion, this study revealed significant associationsamong hyperhomocysteinemia, low serum folate and low LVEF in the native CKD patients. The consistency of homocysteine- eGFR and homocysteine-LVEF correlations suggests that serum homocysteine may provide useful additional information about CKD and associated high cardiovascular morbidity.&#x0D; JCMCTA 2018 ; 29 (1) : 35-41

Disfunción eréctil en pacientes con hipertensión arterial. Riesgo cardiovascular e impacto en su calidad de vida

ObjectivesEstimate the frequency of erectile dysfunction in patients with essential hypertension and associated variables, degree of control, cardiovascular risk and the impact on quality of life. Material and methodsType of study: Observational study of prevalence in men with essential hypertension. Measurements: Sociodemographic and comorbidity variables were collected from each patient (age, Charlson index, dyslipidaemia and prostatic hyperplasia), degree of control of essential hypertension and treatment, cardiovascular risk and metabolic syndrome. The erectile dysfunction was diagnosed by the International Index of Erectile Function (IIEF-15). Quality of life questionnaires were carried out in essential hypertension (MINICHAL), and the international scale of prostatic symptoms (IPSS). ResultsThe study included 262 hypertensive men with an average age of 65.84years. Erectile dysfunction was presented in 46.1%, being severe in 54.9%. The bivariate analysis shows an independent association between erectile dysfunction and the variables: age, Charlon index, dyslipidaemia, benign prostatic hypertrophy, diastolic blood pressure, years of diagnosis of hypertension, number of treatments, Regicor and Framingham-Wilson, glycaemia, creatinine and GPT, glomerular filtration through the MDRD formula, irritative symptomatology (IPSS) and somatic manifestations (MINICHAL). The final multivariate model found association with age, presentation of dyslipidaemia, prostatic hyperplasia and metabolic syndrome. ConclusionsErectile dysfunction is significantly associated with age, dyslipidaemia, benign prostatic hypertrophy and metabolic syndrome.

Factors Associated with the Development of Chronic Kidney Disease after Liver Transplantation

Background Renal dysfunction is a common complication after liver transplantation. The increased use of DCD livers has been associated with postoperative acute kidney injury (AKI). However, the relation between DCD grafts and development of chronic kidney disease (CKD) is less well defined. Our aim was therefore to assess risk factors, including graft type and AKI, with impact on development of CKD after liver transplantation. Methods We included all patients, who underwent primary liver-only transplantation between 2007-2015 for end-stage liver disease. Patients with a survival of less than 3 months after transplantation were excluded. eGFR was calculated using the MDRD-4 formula and renal function was divided into 3 groups: no CKD (eGFR ≥60), mild CKD (eGFR 30-59) and severe CKD (eGFR <30). Postoperative AKI was defined according to the KDIGO criteria. Results A total of 961 patients were included (72% DBD and 28% DCD grafts). During the study period, 43% of the patients developed CKD. Importantly, severe CKD and end-stage renal disease occurred in only 3% and 1%, respectively. DCD recipients had a more pronounced drop in kidney function in the first postoperative week, but they recovered quickly and long-term kidney function was comparable with those receiving a DBD graft (Figure 1). Only recipients requiring renal replacement therapy (RRT) in the immediate post-transplant period had significant impaired long-term kidney function (Figure 2). This was confirmed in a multivariable COX-regression analysis for development of CKD (AKI requiring RRT: HR 1.6, 95% CI 1.2-2.1, P=0.002). Conclusion Recipients with severe postoperative AKI requiring RRT are less likely to experience a full recovery in long-term kidney function. Interestingly, CKD did not occur more frequently after implantation of DCD grafts. Overall, it is essential to identify risk factors and treat recipients at risk for severe postoperative AKI to preserve long-term kidney function.

Clinical factors increasing discrepancies of renal function assessment with MDRD and Cockcroft\u2013Gault equations in old individuals

PurposeIn a daily clinical practice, glomerular filtration rate (GFR) is still estimated on the basis of short MDRD formula, whereas medications’ Summaries of Product Characteristics suggest that GFR used for the dosage adjustment should be estimated based on the Cockcroft–Gault (C–G) equation. The aim of the study was to compare eGFR values calculated on the basis of short and full MDRD and C–G equations in PolSenior study participants with decreased eGFR.MethodsWe have assessed differences in the estimation of GFR between short and full MDRD, as well as C–G formula, all equations utilizing non-isotope-dilution mass spectrometry-calibrated measurements of serum creatinine, in the community-based population of 760 persons aged 65 years or above (mean age 82 ± 8 years) with estimated GFR < 60 ml/min/1.73 m2 (according to short MDRD). In addition, in our analysis, we have included the detailed characteristics of comorbidities and different aspects of mobility and functional performance.ResultsThe better concordance, precision, and accuracy with MDRD short formula were found for MDRDfull than C–G equation. In logistic regression analysis, female gender, activities in daily living (ADL) ≤ 4, and age > 80 years diminished, while visceral obesity improved accuracy (P30) of eGFR calculated according to C–G equation as compared to MDRDshort. Similar analysis did not found factors influencing P30 for MDRDfull equation.ConclusionsIn very old subjects, especially females, dependent patients and those with visceral obesity, estimation of GFR based on short MDRD formula should not be used interchangeably with Cockcroft–Gault equation for the medicines dose tailoring.

FACTORS AFFECTING CAROTID-FEMORAL PULSE WAVE VELOCITY IN HIV-INFECTED INDIVIDUALS

Objective: Carotid-femoral PWV (cfPWV) is considered as the ‘gold-standard’ measurement of arterial stiffness. According to 2013 ESH/ESC Guidelines for the management of arterial hypertension, cfPWV > 10m/s is indicative of asymptomatic organ damage. The aim of this study is to determine possible correlation between cfPWV and HIV infection and by extension the effect of HIV infection in arterial stiffness. Design and method: We studied 69 male HIV-infected individuals over 50 years old (mean: 54.44 ± 3.5 years) without hypertension, diabetes mellitus and no known history of cardiovascular disease. HIV history, including time of first positive HIV test and years of antiretroviral therapy, smoking (pack years), alcohol abuse, body mass index (BMI) and physical activity described as metabolic equivalents (METS) were recorded. Furthermore, blood pressure and heart rate were measured and blood tests were performed for the calculation of eGFR using MDRD formula and lipid analysis (total, HDL, LDL cholesterol and triglycerides). cfPWV and central aortic blood pressure were determined by applanation tonometry using the Sphygmocor (Atcor, Australia) device in each patient. Simple and multiple linear regression analysis were performed to predict independent variables of cfPWV. Results: In simple linear regression analysis, cfPWV was associated with the years of HIV infection and antiretroviral therapy, age, heart rate, peripheral diastolic blood pressure and central diastolic aortic blood pressure (p < 0.05). In multiple linear regression analysis, years of HIV infection (b = 0.298, p = 0.009), pack-years (b = −0.242, p = 0.029) and age (b = 0.234, p = 0.034) were determined as the three independent variables of cfPWV predicting 32.3% of the variance of cfPWV (R2 = 0.323). Conclusions: Our study showed that duration of HIV infection, as well as smoking and age, are strongly associated with cfPWV in male HIV infected individuals over 50 years old without hypertension or diabetes mellitus. Therefore, HIV infection increases total cardiovascular risk through increasing arterial stiffness.

RESISTANT HYPERTENSION ASSOCIATED WITH TYPE 2 DIABETES MELLITUS, CLINICAL CHARACTERISTICS

Objective: Diabetes mellitus (DM) increases risk of resistant hypertension (RHT) but phenotype of RHT associated with DM has been poorly characterized. The aim of this study was to investigate the clinical characteristics of diabetic patients with true RHT. Design and method: We examined 65 diabetic patients with true RHT (with office systolic blood pressure (BP) >140 mmHg despite the use of 3 and more antihypertensive agents in optimal dosages, one of them being a diuretic) and 67 diabetic patients with controlled HT (with target BP on less than three drugs). Office and ambulatory 24 hour-BP measurements, evaluating of body mass index (BMI), serum HbA1c, aldosterone and creatinine levels with calculation of estimated glomerular filtration rate (eGRF) according to MDRD formula were performed. Results: The number of male gender (36% in RHT patients vs. 34% in control group) and body mass index (35.9 ± 5.5 in RHT+DM group vs. 34.5 ± 6.4 kg/m2 in control group) were similar. Compared with patient of control group, diabetic patients with RHT were not only older (by 7.9 years, p < 0.001), had longer duration of HT (by 13.8 years, p < 0.001) and DM (by 2.4 years, p=0.01), but also had earlier onset of HT (by 5.6 years, p < 0.000) and later onset of DM (by 5.7 years, p < 0.000). Average serum aldosterone level in diabetic patients with RHT was higher (by 168.2 pg/mL, p < 0.000) and eGRF was lower (by 10.7 ml/min/1.73m2, p = 0.03) than in patients with controlled HT. Frequency of insulin therapy in RHT patients were higher (25% vs. 10%, p = 0.02) and level of HbA1c was lower (7.1 ± 1.6% vs. 8.2 ± 1.4, p = 0.004) than those in control group. Conclusions: Clinical characteristics of diabetic patients with RHT include older age, long duration and early onset of HT, association with increase of aldosterone level and progression of chronic kidney disease. Diabetic patients with RHT characterized by long duration of but late onset of DM that may reflect difference in mechanisms of development DM in patients with RHT and controlled HT. Higher frequency of insulin-requiring patients in RHT can particularly explain better glycemic control in pts with RHT than in patients with controlled HT.

Comparison of MDRD and CKD-EPI Formulas for Estimating Glomerular Filtration Rate in Elderly Preoperative Patients

Comparison of MDRD and CKD-EPI Formulas for Estimating Glomerular Filtration Rate in Elderly Preoperative Patients

Carboplatin Dosing Accuracy by Estimation of Glomerular Filtration versus Creatinuria in Cancer Patients

Background: The glomerular filtration rate (GFR) is essential for calculating the dose and the monitoring of carboplatin. Although GFR measurement (mGFR) by external markers is ideal, in most cases these are not employed; the most used method is GFR estimation (eGFR) by formulae, hence the need to identify the formula with the best performance. Methods: Patients admitted between 2011 and 2017 and diagnosed with ovarian, endometrial, lung, esophageal, or testicular cancer were assessed retrospectively. The accuracy of the carboplatin dose calculated by creatinine concordance and by the Cockroft-Gault (CG), CKD-EPI, MDRD, Wright, and Jelliffe formulae was assessed using the intraclass correlation coefficient. Results: Fifty-six medical histories were analyzed. The best accuracy was observed between the Wright formula (i.e., 0.71) and the dose calculated based on the 24-h creatinine clearance. Stratification by CKD was made in depurations < 60 mL/min, where the Jelliffe value was excellent (i.e., 0.75). In depurations ≥60 mL/min, CKD-EPI was the best formula, with an accuracy of 0.65. CG was the formula with the worst performance in calculating the dose and glomerular filtration, losing its usefulness with very low filtrations. Conclusions: GFR formulae and calculation of the carboplatin dose have good accuracy with the GFR obtained based on the 24-h creatinine clearance, with the Wright formula being the one with best performance and CG the one with worst performance.

Biomarkers of kidney injury in hypertension: conventional versus novel

Objective. The aim of the present study was to compare conventional and novel, potentially earlier biomarkers of kidney injury in patients with different severity and duration of arterial hypertension (HTN) and healthy controls. Design and methods. Urine levels of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule‑1 (KIM‑1), liver fatty-acid binding protein (L‑FABP), albuminuria and serum levels of cystatin C and creatinine were measured in 92 hypertensive patients (46 male, mean age 50,7 ± 12,2 years) and 34 healthy control subjects (16 male, mean age 49,9 ± 11,4 years). Hypertensive patients were divided into four age- and sex-matched groups according to HTN severity: 1st grade (n = 24), 2nd grade (n = 26), 3rd grade (n = 17) and resistant hypertension (n = 25). Glomerular filtration rate (GFR) was estimated by the level of serum creatinine and cystatin C by MDRD and CKD-EPI formulas. Instrumental examination included measuring office blood pressure (BP), 24‑hour ambulatory BP monitoring (ABPM, SpaceLabs 90207), applanation tonometry (SphygmoCor, Artcor Medical) with the calculation of central aortic pressure. Results. As compared to healthy control subjects, hypertensive patients were characterized by higher creatinine and albuminuria levels, and lower GFR, however, creatinine levels remained within the normal range despite the increase in the severity of HTN. Levels of albuminuria increased only in patients with severe HTN. Also as compared to healthy controls, HTN patients had significantly higher levels of cystatin C, which already was found in patients with 1st and 2nd stages of HTN, which occurs more often than an increase of creatinine and albuminuria levels. Patients with HTN had significantly lower sCys-estimated GFR and creatinine-sCys-estimated GFR. In HTN patients these biomarkers were associated with office systolic BP (SBP), central aortic systolic and diastolic (CAP) and mean 24‑hour BP level. There were no differencesin NGAL, KIM‑1 levels between the groups, however, KIM‑1 levels were associated with office SBP, mean daily 24‑hour of diastolic BP (DBP) and systolic and diastolic CAP in patients with severe HTN. At the same time, as compared with healthy controls, patients with initial HTN were characterized by higher levels of urine L‑FABP and its concentration increased in patients with severe HTN. In addition, L‑FABP levels were associated with office SBP and DBP, mean 24‑hour BP and systolic and diastolic CAP. Conclusions. The simultaneous assessment of creatinine and cystatin C levels, and the calculation of GFR using the formula CKD-EPI seems to be more accurate method for CKD stage classification in general and, in particular, in hypertensive patients; in hypertensive patients L‑FABP appears to be earlier biomarker of kidney injury, reflecting the progression of tubulointerstitial injury.

OP-37 - Declining renal function and thresholds of estimated glomerular filtration rate: impact on biomarkers of oxidative stress in the BIOCLAIMS cohort

Impaired glomerular filtration rate (eGFR) is frequently observed in apparently healthy individuals, and even slightly and mildly impaired renal function may have an impact on metabolic health. The aim of this study was to investigate the effects of declining eGFR (MDRD formula) and identify possible thresholds of eGFR on biomarkers of oxidative stress and antioxidant status. In a cross-sectional study, 1310 study subjects, 606 F, 704 M, 18-85 years (BIOCLAIMS cohort), were enrolled for biomarker analysis, including plasma human mercaptalbumin (HMA) (HPLC), activation of NF-kB in PBMC (TransAM Active Motif assay), and plasma total peroxides (TOC assay, LDN), as well as plasma ascorbate, α- and g-tocopherol, and different carotenoids (HPLC), and grouped for eGFR (>90, 75-90, 60-75, 45-60, 30-45 ml/min/1.73 m2). Results showed eGFR-related significant differences already at 75 ml/min/1.73 m2 for plasma total peroxides; at 60 ml/min/1.73 m2 for plasma HMA, PBMC NF-kB p50 subunit as well as for plasma ascorbate, f3-cryptoxanthin, lutein/zeaxanthin, f3-carotene; and for all of the above further at 45 ml/min/1.73m2 (all P

P-267 - Effects of declining renal function and possible thresholds of renal function with an impact on the oxidative stress status

Impaired glomerular filtration rate (eGFR) is frequently observed in apparently healthy individuals, and even slightly and mildly impaired renal function may have an impact on metabolic health. The aim of this study was to investigate the effects of declining eGFR (MDRD formula) and identify possible thresholds of eGFR on biomarkers of oxidative stress and antioxidant status. In a cross-sectional study, 1310 study subjects, 606 F, 704 M, 18–85 years (BIOCLAIMS cohort), were enrolled for biomarker analysis, including plasma human mercaptalbumin (HMA) (HPLC); activation of NF-kB in PBMC (TransAM Active Motif assay) and plasma total peroxides (TOC assay, LDN), as well as plasma ascorbate, α- and g-tocopherol, and different carotenoids (HPLC), and grouped for eGFR (>90, 75–90, 60–75, 45–60, 30–45 ml/min/1.73 m2). Results showed eGFR-related significant differences already at 75 ml/min/1.73 m2 for plasma total peroxides; at 60 ml/min/1.73 m2 for plasma HMA, PBMC NF-kB p50 subunit as well as for plasma ascorbate, f3-cryptoxanthin, lutein/zeaxanthin, f3-carotene; and for all of the above further at 45 ml/min/1.73 m2 (all P