Individual Glomerular Filtration Rate Research Articles

Comparison of chronic kidney disease progression and associated complications between geriatric and non-geriatric groups.

There is no consensus on the physiologic decline in estimated glomerular filtration rate (GFR) due to geriatric conditions related with the aging or chronic kidney disease (CKD) itself. In this study, we aimed to compare the CKD progression and associated complications in a large sample of geriatric and non-geriatric patients. The data of in 506 patients at age between 30 to 90 years and diagnosed with CKD at stage 2 and above (15 mL/min/1.73 m2 ≤ eGFR < 90 mL/min/1.73 m2) were collected retrospectively and compared among geriatric (>65 years old) and non-geriatric individuals. The rate of hypertension was higher in geriatrics compared to non-geriatrics (96.6% vs 91.9%, P = .04). Among laboratory findings, only PTH level was significantly lower and HCO3 concentration was higher in geriatrics compared to non-geriatrics (P = .02, P < .001, respectively). There was no significant difference in last measured eGFR (P = .99) while that measured 4 years ago was lower in geriatrics compared to that of non-geriatrics (P < .001). eGFR change was smaller in geriatrics compared to non-geriatrics (P < .001), and rate of progressive renal disease among non-geriatric group (39%) was found to be significantly higher than in the geriatrics (17.2%) (P < .001). The prevalence of hyperkalemia was lower in geriatrics at stage 3a (P = .02); prevalence of hyperparathyroidism was lower in those at stage 3b (P = .02) and lastly the acidosis was observed significantly lower in geriatric patients at stage 3a, 3b, and 4 compared to the non-geriatrics at corresponding stages (P < .001, P = .03, and P = .04, respectively). The eGFR change was significantly smaller in geriatrics at stage 3b and 4 (P < .001 and P = .04, respectively) while the rate of progressed renal disease was lower in geriatrics at stage 3a and 3b (21.1% vs 9.9%, P = .03 and 41.2% vs 11.1%, P < .001, respectively). eGFR change in 4-year period and the rates of progressive renal disease are higher in the non-geriatrics and also the prevalence of secondary complications of CKD, such as hyperparathyroidism, acidosis, and hyperkalemia, are higher in non-geriatrics. This may reflect that decline of GFR in geriatric individuals is at least partially related to physiological aging rather than kidney disease. Therefore, devising age related CKD definitions might be appropriate.

Polygenic Prediction of Estimated Glomerular Filtration Rate in Individuals of African Descent and from the Americas

Polygenic Prediction of Estimated Glomerular Filtration Rate in Individuals of African Descent and from the Americas

Estimating Analytical Errors of Glomerular Filtration Rate Measurement.

Few studies are available on how to optimize time points for sampling and how to estimate effects of analytical uncertainty when glomerular filtration rate (GFR) is calculated. We explored the underlying regression mathematics of how analytical variation of a kidney filtration marker affects 1-compartment, slope-and-intercept GFR calculations, using 2 or 3 time points following a bolus injection, and used this to examine the results from 731 routine 3-point iohexol plasma clearance measurements. GFR calculations inflated analytical uncertainty if the time points were taken too late after the bolus injection and too close after each other. The uncertainty in GFR calculation was, however, the same as the analytical uncertainty if optimal time points were used. The middle of the 3 samples was of little value. The first sample should be taken as early as possible after the distribution phase. Sampling before the patient specific half-life of the kidney filtration marker resulted in an exponential error inflation whereas no error inflation was seen when sampling occurred later than 2 half-lives. Theoretical GFR uncertainty could be lowered 2.6-fold if individually optimized time points for sampling had been used in our 731 clearance measurements. Using Taylor expansions to approximate the moments of transformed random variables, the uncertainty of an individual GFR measurement could be calculated in a simple enough way to be applicable by laboratory software. We provide a theoretical foundation to select patient-optimal time points that may both limit errors and allow calculation of GFR uncertainty.

Preserved glomerular filtration rate in older people. A population-based study in the Southern Cone of Latin America

Introduction: Kidneys are affected by the aging process, usually suffering a progressive glomerular filtration rate (GFR) reduction of around 1 ml/year as of 30 years of age. Nevertheless, few older subjects show a stable GFR over time. This phenomenon has not been exhaustively studied, and even less in the Southern Cone. Aim: The aim was to estimate the prevalence of preserved GFR in a representative sample of older adults and explore the association between cardiovascular risk factors and preserved GFR in older individuals.&#x0D; Methods: We used data from a cross-sectional survey of a random sample of 1571 participants aged 65–74 years from 4 cities of the Southern Cone. We describe the prevalence of eGFR ?80 ml/min/1.73 m2 and sociodemographic, biological, behavioral risk factors and medication use. Backward stepwise logistic regression analysis was used to study the effect of cardiovascular risk factors on eGFR ?80 ml/min.&#x0D; Results: In this a study 962 had an eGFR &gt;80 ml/min/1.73 m2 and 154 were healthy adults (Prevalence= 17.01 % [95%CI 14.5%; 19.9%]). The median eGFR in the full sample was 85.53 ml/min/1.73 m² (IQR: 73.12-91.26). The prevalence of eGFR &gt;80 ml/min/1.73 m2 was higher among men. Overall, older adults with no cardiovascular risk factors and eGFR &gt;80 ml/min/1.73 m2 were predominantly men and showed a lower prevalence of dyslipidemia. &#x0D; Conclusion: In the present study was documented that there was 17% of healthy older individuals who have preserved glomerular filtration rate (eGFR &gt; 80 ml/min/1.73 m 2) despite their advanced age.

Effects of different sources of dietary protein on markers of kidney function in individuals with diabetes: a systematic review and meta-analysis of randomized controlled trials.

The type of dietary protein may modulate markers of diabetic kidney disease; however, no attempt to summarize the evidence from randomized controlled trials (RCTs) has been performed to date. To assess the effects of different types of dietary protein on urinary albumin excretion and glomerular filtration rate in individuals with diabetes. MEDLINE, EMBASE, and Scopus were searched for all published RCTs, with no language restriction, up to July 2020. Study selection and data extraction were performed independently by 3 authors. Risk of bias was assessed independently by 2 authors, and the GRADE approach was used to assess the quality of the evidence. Twelve RCTs were included, of which 11 (involving 228 participants) were compiled in meta-analyses of random-effects models. Interventions consisted of diets emphasizing plant or white meat protein, with reduced intake of animal or red meat protein. Pooled data from crossover trials (n = 8) favored intervention diets for urinary albumin excretion (ratio of means, 0.86; 95% confidence interval 0.80 to 0.94; I2 = 4%) and glomerular filtration rate (ratio of means, 0.90; 95% confidence interval 0.87 to 0.94; I2 = 45%), compared with control diets. Results from parallel-design studies (n = 3), however, were not statistically significant for any outcome. The quality of the evidence ranged from very low to moderate, and most studies were judged with at least some concerns in terms of risk of bias. This meta-analysis found weak evidence for small to moderate improvements in markers of kidney function in favor of interventions with lower animal protein (or red meat protein) compared with usual diets in short-term crossover trials. These findings require confirmation in well-designed randomized controlled trials.

Dietary Acid Load and Relationship with Albuminuria and Glomerular Filtration Rate in Individuals with Chronic Kidney Disease at Predialysis State.

The Western diet, characterized by excessive consumption of animal protein and reduced intake of vegetables and fruits, is also rich in sulfur, chlorine, and organic acids, which are the main sources of dietary acid load. A relationship between dietary acid load, renal function, and progression of chronic kidney disease has been demonstrated. Dietary modifications seem to contribute to a reduction in dietary acid load, and are associated with improved outcomes in individuals with chronic kidney disease (CKD). The aim of this paper was to review the existing evidence concerning the association between dietary acid load and renal function in nondialyzed individuals with CKD. A systematic review was conducted by gathering articles in electronic databases (MEDLINE/PubMed, Scopus, and Web of Science) from January 2018 to May 2021. Dietary acid load and GFR and/or albuminuria were analyzed. A total of 1078 articles were extracted, of which 5 met the inclusion criteria. Only one study found no statistically significant associations between the study variables. The remaining showed a negative association between dietary acid load and renal function. This systematic review confirmed the existence of an association between dietary acid load and renal function, with a high dietary acid load contributing to a decreased renal function.

Biomarkers of Inflammation and Glomerular Filtration Rate in Individuals with Recent-Onset Type 1 and Type 2 Diabetes.

While inflammation has been associated with kidney function in long-standing diabetes, its possible association in newly diagnosed diabetes is unknown. To investigate cross-sectional and prospective associations between biomarkers of inflammation and kidney function in recent-onset diabetes. The study included individuals with type 1 and type 2 diabetes with known diabetes duration of <1 year from the German Diabetes Study. Baseline serum concentrations of 74 biomarkers were measured using proximity extension assay technology and their associations with estimated glomerular filtration rate (eGFR) and kidney function decline over 5 years were tested using multiple linear and logistic regression analysis. The cross-sectional analysis included 165 individuals with type 1 diabetes and 291 with type 2 diabetes. Baseline eGFR was higher in type 1 compared with type 2 diabetes (102 ± 15 vs 90 ± 16 mL/min/1.73 m2; P < 0.0001). After full adjustment for covariates and multiple testing, 7 biomarkers were associated with lower baseline eGFR in type 1 diabetes and 24 were associated with lower baseline eGFR in type 2 diabetes. Among these biomarkers, 6 biomarkers (CD5, CCL23, CST5, IL-10RB, PD-L1, TNFRSF9) were inversely associated with eGFR in both diabetes types. The prospective analysis did not detect associations between inflammatory biomarkers and kidney function decline. No evidence of an interaction between diabetes type and inflammatory biomarkers was found. Several biomarkers of inflammation associate with lower baseline eGFR in recent-onset type 1 and type 2 diabetes, but do not associate with kidney function loss during the first 5 years after the diagnosis of diabetes.

Risk of chronic kidney disease defined by decreased estimated glomerular filtration rate in individuals with different prediabetic phenotypes: results from a prospective cohort study in China

ObjectiveWe aimed to investigate the effects of prediabetes and its phenotypes of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and elevated glycated hemoglobin A1c (EHbA1c) on chronic kidney disease...

Punctures versus shocks: a comparison of renal functional and structural changes after percutaneous nephrolithotomy and shockwave lithotripsy for solitary renal stone

Objective: To evaluate renal functional and structural changes following percutaneous nephrolithotomy and shockwave lithotripsy for solitary non-obstructing non-staghorn renal stone. Materials and methods: Patients with solitary unilateral non-staghorn renal stones who were planned for percutaneous nephrolithotomy (20 patients) and shockwave lithotripsy (20 patients) were prospectively evaluated for renal functional and structural changes 60 days after the procedure and complete clearance of stones. Tc99-dimercaptosuccinic acid was used to assess cortical scarring and Tc99-diethylenetriamine pentaacetic acid and Tc99-levo levo ethylecysteine were used for glomerular filtration rate calculations, respectively. Results: The mean stone size was 24.4 mm and 13.7 mm in the percutaneous nephrolithotomy group and the shockwave lithotripsy group, respectively. No new cortical scars developed in either of the groups on Tc99-dimercaptosuccinic acid scan. Both the treated and untreated kidneys showed an overall insignificant fall in glomerular filtration rate in both the groups. The number of patients showing significant deterioration in the individual glomerular filtration rate in both the treated and untreated renal unit was more in the shockwave lithotripsy group. Conclusion: Both percutaneous nephrolithotomy and shockwave lithotripsy are comparable in terms of adverse effects on renal parenchyma and renal function. Level of evidence: Not applicable for this multicentre audit.

Measured GFR by Utilizing Population Pharmacokinetic Methods to Determine Iohexol Clearance

IntroductionThere is an increasing demand for accurately measured glomerular filtration rate (GFR). Iohexol serum clearance has become a new gold standard, but it is challenging when GFR is low and 24-hour sampling is required for accurate results. The primary aim of this study was to develop an iohexol pharmacokinetic population model for accurate determination of individual GFR using limited sampling for up to 5 hours also when renal function is <40 ml/min.MethodsA nonparametric iohexol population pharmacokinetic model was developed with rich data from 176 patients. In a validation cohort of 43 patients, a model-determined GFR (iohexol clearance) using different limited sampling strategies for up to 5 hours was compared with the strategy currently used in routine care, a log-linear 2-point method. In all, 1526 iohexol concentrations were used, from patients ranging in age from 1 to 82 years and GFR from 14 to 149 ml/min.ResultsThe clinical 2-point method showed insufficient agreement compared with reference values; 15% of GFR values had an error of greater than ±10% even when sampling for 24 hours when estimating GFR <40 ml/min per 1.73 m2 (standard procedure). Restricted sampling the first 5 hours with the population model required 4 samples to determine GFR accurately. This strategy showed excellent agreement with the reference; <3% of GFR values had an error greater than ±10 %.ConclusionUsing an iohexol population pharmacokinetic model allows for accurate determination of GFR within 5 hours when applying 4 optimally timed samples, even in patients with GFR <40 ml/min.

Association Between Serum C-Peptide Level and Cardiovascular Autonomic Neuropathy According to Estimated Glomerular Filtration Rate in Individuals with Type 2 Diabetes.

To investigate the association between serum C-peptide level and cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes mellitus (DM) according to estimated glomerular filtration rate (eGFR) METHODS: In a cross-sectional study, we examined 939 individuals with type 2 DM. We measured fasting C-peptide, 2-hour postprandial C-peptide, and ΔC-peptide (postprandial C-peptide minus fasting C-peptide) levels. The individuals were classified into 2 groups based on eGFR: individuals without impaired renal function (eGFR ≥60 ml∙min-1 1.73m-2) and those with impaired renal function (eGFR <60 ml∙min-1 1.73m-2). Individuals with CAN had lower fasting C-peptide, postprandial C-peptide, and ΔC-peptide levels in patients both with and without impaired renal function. Multivariate logistic regression analyses adjusted for gender, age, and other confounders, including eGFR, showed that serum C-peptide level was significantly associated with CAN (odds ratio [OR] per standard deviation increase in the log-transformed value, 0.67; 95% confidence interval [CI], 0.52-0.87 for fasting C-peptide, P < 0.01; OR, 0.62; 95% CI, 0.47-0.83 for postprandial C-peptide, P < 0.01; OR, 0.71; 95% CI, 0.54-0.93 for ΔC-peptide, P < 0.05). Serum C-peptide level was negatively associated with CAN in individuals with type 2 DM independent of eGFR.

Economic Modelling of Chronic Kidney Disease: A Systematic Literature Review to Inform Conceptual Model Design.

BackgroundChronic kidney disease (CKD) is a progressive condition that leads to irreversible damage to the kidneys and is associated with an increased incidence of cardiovascular events and mortality. As novel interventions become available, estimates of economic and clinical outcomes are needed to guide payer reimbursement decisions.ObjectiveThe aim of the present study was to systematically review published economic models that simulated long-term outcomes of kidney disease to inform cost-effectiveness evaluations of CKD treatments.MethodsThe review was conducted across four databases (MEDLINE, Embase, the Cochrane library and EconLit) and health technology assessment agency websites. Relevant information on each model was extracted. Transition and mortality rates were also extracted to assess the choice of model parameterisation on disease progression by simulating patient’s time with end-stage renal disease (ESRD) and time to ESRD/death. The incorporation of cardiovascular disease in a population with CKD was qualitatively assessed across identified models.ResultsThe search identified 101 models that met the criteria for inclusion. Models were classified into CKD models (n = 13), diabetes models with nephropathy (n = 48), ESRD-only models (n = 33) and cardiovascular models with CKD components (n = 7). Typically, published models utilised frameworks based on either (estimated or measured) glomerular filtration rate (GFR) or albuminuria, in line with clinical guideline recommendations for the diagnosis and monitoring of CKD. Generally, two core structures were identified, either a microsimulation model involving albuminuria or a Markov model utilising CKD stages and a linear GFR decline (although further variations on these model structures were also identified). Analysis of parameter variability in CKD disease progression suggested that mean time to ESRD/death was relatively consistent across model types (CKD models 28.2 years; diabetes models with nephropathy 24.6 years). When evaluating time with ESRD, CKD models predicted extended ESRD survival over diabetes models with nephropathy (mean time with ESRD 8.0 vs. 3.8 years).DiscussionThis review provides an overview of how CKD is typically modelled. While common frameworks were identified, model structure varied, and no single model type was used for the modelling of patients with CKD. In addition, many of the current methods did not explicitly consider patient heterogeneity or underlying disease aetiology, except for diabetes. However, the variability of individual patients’ GFR and albuminuria trajectories perhaps provides rationale for a model structure designed around the prediction of individual patients’ GFR trajectories. Frameworks of future CKD models should be informed and justified based on clinical rationale and availability of data to ensure validity of model results. In addition, further clinical and observational research is warranted to provide a better understanding of prognostic factors and data sources to improve economic modelling accuracy in CKD.Electronic supplementary materialThe online version of this article (10.1007/s40273-019-00835-z) contains supplementary material, which is available to authorized users.

Measurement of Glomerular Filtration Rate using Quantitative SPECT/CT and Deep-learning-based Kidney Segmentation

Quantitative SPECT/CT is potentially useful for more accurate and reliable measurement of glomerular filtration rate (GFR) than conventional planar scintigraphy. However, manual drawing of a volume of interest (VOI) on renal parenchyma in CT images is a labor-intensive and time-consuming task. The aim of this study is to develop a fully automated GFR quantification method based on a deep learning approach to the 3D segmentation of kidney parenchyma in CT. We automatically segmented the kidneys in CT images using the proposed method with remarkably high Dice similarity coefficient relative to the manual segmentation (mean = 0.89). The GFR values derived using manual and automatic segmentation methods were strongly correlated (R2 = 0.96). The absolute difference between the individual GFR values using manual and automatic methods was only 2.90%. Moreover, the two segmentation methods had comparable performance in the urolithiasis patients and kidney donors. Furthermore, both segmentation modalities showed significantly decreased individual GFR in symptomatic kidneys compared with the normal or asymptomatic kidney groups. The proposed approach enables fast and accurate GFR measurement.

Assessment of renal function before contrast media injection: right decisions based on inaccurate estimates.

Information on renal function required before specified radiological examinations with contrast agents is usually obtained through prediction equations using serum creatinine and anthropometric data. The aim of our study was to demonstrate discrepancy between poor prediction and good diagnostic accuracy of glomerular filtration rate (GFR) estimated by prediction equations. In 50 patients, reference GFR was measured as plasma clearance of 51-chromium labeled ethylene-diamine-tetraacetic-acid (51Cr-EDTA) and compared with GFR assayed by creatinine clearance (CC) and estimated by Cockcroft-Gault prediction equation (CG). For comparisons, CC and CG were considered as continuous, categorical, and binary variables. Accuracy of the reference GFR prediction was expressed in terms of prediction errors and diagnostic accuracy indices. As continuous variable, CG estimated individual values of GFR with large prediction error exceeding that of CC. As categorical variable, it classified the patient stage of chronic kidney disease (CKD) with medium diagnostic accuracy of 74% (CKD 3) and 62% (CKD 4). As binary variable, CG classified individual patient's GFR below 30 and 60ml/min/1.73m2 with good diagnostic accuracy of 80 and 94%, respectively. Performance of other prediction equations did not significantly differ from CG. Despite large variance and poor prediction accuracy of individual GFR estimates, most of them correctly classified individual patient's GFR below specified level. Results of prediction equations thus should be used and reported exclusively as binary variables, while numerical values of GFR, if required, should be measured by more accurate radionuclide or laboratory methods. • Radiological guidelines on contrast media require estimation of glomerular filtration rate to assess kidney function before specified contrast examinations. • Estimated glomerular filtration rate is obtained through prediction equations using serum creatinine and anthropometric data as predictors. • While numerical estimates of glomerular filtration rate are inaccurate (their prediction accuracy is poor), diagnostic accuracy of binary estimates (ability to classify patient's glomerular filtration rate below or above a specified level) is very good.

Usefulness of left ventricular mass change to predict progression of renal dysfunction in Hispanics

ABSTRACTThere is a strong relation between metabolic syndrome (MetS) and left ventricular (LV) mass in Hispanic patients. This population also tends to have a higher incidence of kidney disease, with progression to dialysis. We analyzed the change in LV mass in 982 Hispanic patients with MetS and used these data to anticipate the progression of renal dysfunction. Glomerular filtration rate (GFR) was calculated using the formula described by the Chronic Kidney Disease Epidemiology Collaboration. Echocardiographic data were collected using 2-dimensionally guided M-mode echocardiography measures. The data collected were then analyzed using linear regression analyses. Results showed a lower average GFR in individuals classified as having a severe change in LV mass in comparison to those with milder change in LV mass (P < 0.0001). This relation was also demonstrated when those with severe change in LV mass were compared with the control group (P < 0.0001). In those ≥54 years old, the presence of MetS and LV mass were negatively correlated with GFR (regression coefficient [RC] = 14.76, P < 0.063; RC = 0.11, P < 0.0001 respectively). In patients <54 years old, no statistically significant association between the presence of MetS and GFR was seen. However, LV mass was once again negatively correlated with GFR (RC = 0.15, P < 0.0001). In conclusion, results demonstrated the association between the MetS, change in LV mass, and chronic kidney disease progression.

OP.2B.01] CIGARETTE USE ALTERS ASSESSMENT OF GLOMERULAR FILTRATION RATE

Objective: Accurate assessment of glomerular filtration rate (GFR) is important in ascertaining health status, especially in older individuals and in populations at risk of chronic kidney disease. Recently we observed that smokers with renal artery stenosis and renovascular hypertension had lower GFR when estimated by cystatin-C, than with creatinine-based estimates. We sought to resolve this issue. Design and method: Data from the Diabetes Control and Complications Trial (DCCT) were used to estimate GFR in individuals with diabetes. Iohexol clearance was used as the standard, and was compared to GFR estimates using creatinine and cystatin-C. Creatinine and cystatin-C estimates were calculated with the 24-hour urine creatinine clearance and the CKD-EPI cystatin-C. formula, and compared to iohexol based estimates using the Bland-Altman method. Results: There were 441 patients with iohexol, creatinine and cystatin-C values. The average age was 27.6 ± 6.6 years. The mean iohexol GFR for the population was 127.5 ± 19.2 ml/min. The cystatin-C and creatinine-based estimates were close to the iohexol estimates in non-smokers (differing by −7.7 ± 24.7 and −2.7 ± 31.1 ml/min respectively, p = ns). However in smokers, the cystatin-C estimates were considerably lower than iohexol-based GFR estimates (difference = −21.4 ± 25.1 ml/min p < 0.001), while creatinine based estimates were not (difference = −4.6 ± 21.6 ml/min, p = 0.58). Conclusions: Cystatin-C based estimates of GFR are accurate in non-smoking diabetics and yet substantially and significantly underestimate GFR in diabetics that smoke cigarettes.

PP.21.02] INDIVIDUALS WITH HYPERTENSIVE EMERGENCY PRESENT ASSOCIATION BETWEEN RENAL DYSFUNCTION AND INFLAMMATORY CYTOKINES

Objective: Chronic hypertension and renal dysfunction are associated. However, scarce studies have evaluated the participation of the inflammatory process in the pathogenesis of acute elevation of blood pressure (BP) (characterized by hypertensive crisis - HC) and kidney dysfunction. Thus, this study had objectives: 1- to identify clinical profile and renal function of the individuals with HC, subdivided in urgency (HU) and hypertensive emergency (HE) and 2- to evaluate relationship between kidney function and inflammatory cytokines: interleukins (IL-1β,IL-6, IL-8, IL-18), tumoral necrosis factor (TNF-α) and anti-inflammatory cytokine 10 (IL-10) in subjects with HC (HU and HE). Design and method: We studied 274 individuals: 74 normotensive (NT), 74 controlled hypertensive (CHT), 50 with HU and 78 individuals with HE. The glomerular filtration rate (GFR) was calculated by the Modification of Diet in Renal Disease equation (MDRD). The serum levels of cytokines were made by MULTIPLEX and ELISA technique. The Kruskall Wallis and Mann Whitney tests, and Spearman correlation were used for comparison between groups, with a significance level for p-value <0.05. Results: The diastolic BP and heart rate were significantly higher in the HC group (120mmHg and 85bpm, respectively) compared to the CHT group (75mmHg and 68 bpm, respectively). Individuals with HE were older. Potassium was significantly lower in HE group (4,2mEq/l) compared to NT, CH and HU groups (4.5, 4.4 and 4.4mEq/L, respectively; p < 0.05). The GFR was significantly lower in HE group (65 ml/min/m2) in comparison to HU (73), CHT (82) and NT (88 mL/min/m2) (p < 0,001). All measured cytokines were significantly higher in patients with HE compared to NT and CHT groups. It was observed negative correlation among GFR, diastolic BP, and creatinine for all the groups (p < 0,0001). There was also negative correlation between GFR and cytokines in HE individuals (p < 0,05). Conclusions: Individuals with HE present GFR reduction in comparison to others studied groups. It is also observed higher cytokines levels in HE group and negative correlation between GFR and inflammatory cytokines. This suggests the involvement of inflammatory cytokines in the pathogenesis of acute hypertensive event and kidney dysfunction.

The rs12917707 polymorphism at the UMOD locus and glomerular filtration rate in individuals with type 2 diabetes: evidence of heterogeneity across two different European populations.

UMOD variability has been associated at a genome-wide level of statistical significance with glomerular filtration rate (GFR) in Swedish individuals with type 2 diabetes (T2D; n = 4888). Whether this finding is extensible also to diabetic patients from other populations deserves further study. Our aim was to investigate the relationship between UMOD variability and GFR in patients with T2D from Italy. Genotyping of the single nucleotide polymorphism (SNP) rs12917707 at the UMOD locus has been carried out in 3087 individuals from four independent Italian cohorts of patients with T2D by TaqMan allele discrimination. In none of the four study cohorts was rs12917707 significantly associated with GFR (P > 0.05 for all). Similar results were obtained when the four samples were pooled and analyzed together (β = 0.83, P = 0.19). Such effect was strikingly smaller than that previously reported in Swedish patients (P for heterogeneity = 1.21 × 10-7). The previously reported strong association between rs12917707 and GFR in diabetic patients from Sweden is not observed in Italian diabetic patients, thus clearly pointing to a heterogeneous effect across the two different samples. This suggests that UMOD is a strong genetic determinant of kidney function in patients with T2D in some, but not all, populations.

Abstract 15998: Inflammatory Cytokines and Kidney Dysfunction are Associated in Individuals With Hypertensive Emergency

Introduction: Chronic hypertension and kidney dysfunction are associated. However, scarce studies have evaluated the participation of the inflammatory process in the pathogenesis of acute elevation of blood pressure (BP) (characterized by hypertensive crisis - HC) and kidney dysfunction. Thus, this study had objectives: 1- to identify clinical profile and renal function of the individuals with HC, subdivided in urgency (HU) and hypertensive emergency (HE) and 2- to evaluate relationship between kidney function and inflammatory cytokines: interleukins (IL-1β, IL-6, IL-8, IL-18), tumoral necrosis factor (TNF-α) and anti-inflammatory cytokine 10 (IL-10) in subjects with HC (HU and HE). Methods: We studied 274 individuals: 74 normotensive (NT), 74 controlled hypertensive (CH), 50 with HU and 78 individuals with HE. The glomerular filtration rate (GFR) was calculated by the Modification of Diet in Renal Disease equation (MDRD). The serum levels of cytokines were made by MULTIPLEX and ELISA technique. The Kruskall Wallis and Mann Whitney tests, and Spearman correlation were used for comparison between groups, with a significance level for p-value &lt;0.05. Results: The diastolic BP and heart rate were significantly higher in the HC group (120mmHg and 85bpm, respectively) compared to the CH group (75mmHg and 68 bpm, respectively). Individuals with HE were older. Potassium was significantly lower in HE group (4,2mEq/l) compared to NT, CH and HU groups (4.5, 4.4 and 4.4mEq/L, respectively; p&lt;0.05). The GFR was significantly lower in HE group (65ml/min/m2) in comparison to HU (73), CH (82) and NT (88mL/min/m2) (p&lt;0,001). All measured cytokines were significantly higher in patients with HE compared to NT and CH groups. It was observed negative correlation among GFR, diastolic BP, and creatinine for all the groups (p&lt;0,0001). There was also negative correlation between GFR and cytokines in HE individuals (p&lt;0,05). Conclusions: Individuals with HE present GFR reduction in comparison to others studied groups. It is also observed higher cytokines levels in HE group and negative correlation between GFR and inflammatory cytokines. This suggests the involvement of inflammatory cytokines in the pathogenesis of acute hypertensive event and kidney dysfunction.

Hypertension and Prehypertension and Prediction of Development of Decreased Estimated GFR in the General Population: A Meta-analysis of Cohort Studies

Whether blood pressure (BP) plays an independent predictive role in the onset of decreased glomerular filtration rate (GFR) remains ill-defined because existing meta-analyses have incorporated data from studies that included individuals with low GFRs at baseline. This question is critical to optimize chronic kidney disease prevention in the general population. Systematic review and meta-analysis of longitudinal cohort studies. Adults from general population. We identified in PubMed, EMBASE, and the Cochrane Library database all cohort studies evaluating the role of BP in the incidence of decreased estimated GFR (eGFR; defined as eGFR<60 mL/min/1.73 m2) in individuals without decreased kidney function at baseline. Hypertension (BP>140/90 mmHg), prehypertension (systolic BP of 120-139 and/or diastolic BP of 80-89 mmHg), and BP as a continuous variable. Risk for decreased eGFR reported as relative risk (RR) and 95% CI. Heterogeneity (I2) was also evaluated. Data from 16 cohorts (315,321 participants) were analyzed. All studies had a Newcastle-Ottawa score in the range of 6 to 8, denoting high quality. During a mean follow-up of 6.5 years, decreased eGFR occurred in 6.6% of participants. The presence of prehypertension and hypertension increased renal risk (RRs of 1.19 [95% CI, 1.07-1.33; I2=23.8%] and 1.76 [95% CI, 1.58-1.97; I2=37.7%], respectively). Similarly, we found that every 10-mm Hg increase in systolic and diastolic BPs associated with higher risk for decreased eGFR (RRs of 1.08 [95% CI, 1.04-1.11; I2=60.0%] and 1.12 [95% CI, 1.04-1.20; I2=51.4%], respectively). Metaregression analysis showed greater risk with older age (P=0.03), whereas other covariates were not significant. No individual patient-level data. Prehypertension and hypertension, as BP levels, are independent predictors of decreased GFR in the general population, with the effect being more pronounced in the elderly. These findings are important for improving risk stratification in the general population.