Variation In Glomerular Filtration Rate Research Articles

#1179 Early change of eGFR predicts long-term renal event in patients with hypertensive chronic kidney disease using a RAS blocker

Abstract Background and Aims The renin-angiotensin-aldosterone inhibitor (RASI) is one of the important medications for chronic kidney disease (CKD) with potential decrease of glomerular filtration rate (GFR) after initiation. There are few studies about the effect of GFR change by the RASI on variations of GFR and albuminuria. Method This observational cohort study was the extension of an open-label, case-controlled randomized clinical trial (NCT01552954) including adult hypertensive CKD patients with estimated GFR ≥30 ml/min/1.73 m2 and random urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g creatinine. In the trial phase, the angiotensin receptor blocker (ARB: Olmesartan 40 mg/day) was prescribed to participants after cessation of RASIs for 8 weeks of screening phase. (0-week). Participants had the second visit at 8 weeks after initiation of ARB (8-week) with randomization into the intensive education for low salt diet and the conventional education. Third visit was conducted at 16 weeks after 0-week (16-week). After 27 (19∼38) months later, we recruited participants for the cohort observation and finished at 38 (29∼48) months after 0-week visit. We grouped patients by tertiles of percent change of initial GFR during the first 8 weeks (from 0-week to 8-week) (pcGFRi) and compared the change of UACR from 24-hour urine and estimated GFR during trial and observational period. Results We analyzed data from 174 people finished 38-month observation among 235 participants enrolled for the trial phase. Initial GFR and 24-h urine UACR were 67 ± 24 ml/min/1.73 m2 and 829 ± 829 mg/g cr, respectively. There were −16.0 (−41.5∼−8.1) %, −2.8 (−7.3∼1.6) %, and 8.3 (1.8∼28.4) % pcGFRi in the first tertile group (group 1), the second tertile group (group 2), and the third tertile group (group 3), respectively. There were no differences in age, gender, GFR, 24-hour UACR, and 24-hour sodium excretion among the tertile groups at 0-week visit. The pcGFRi and the tertile group showed positive correlation with GFR change during 16 weeks of the trial, however, were not related to the percent change of 24-hour UACR during the trial phase. They were also positively correlated to the percent change of GFR during whole study period of 38 months (factor B = 8.180 and p-value< 0.001 for the group and factor B = 0.801 and p-value< 0.001 for pcGFRi), although, they did not show relationships with the percent change of 24-hour UACR during whole study period and UACR at last visit. The GFR slopes per year during 38 (29∼48) months were −2.9 (−4.0∼ −1.8), −1.3 (−2.4∼-0.3), and 0.1 (−1.0∼1.2) ml/min/1.73 m2/year in group 1, group 2, and group 3, respectively (p = 0.001 by the ANCOVA test). The relative risks to estimate GFR decrease ≥ 30% during whole study period were 0.237 (0.07∼0.798) (p = 0.020) and 0.035 (0.004∼0.302) (p = 0.035) in group 2 and group 3 compared to group 1, respectively. The AUC to estimate GFR decline ≥ 30% by the pcGFRi was 0.787 (0.685∼0.889, p< 0.001). The cut-off value 7.25% of pcGFRi estimates GFR decline ≥ 30% with 71.4% sensitivity and 70.9% specificity. Conclusion The decline of GFR by initiation of RASI predicts long-term renal event of GFR decline ≥ 30% in users of RASI, strongly. We need to compare the renal outcomes between RASI users with initial decrease of GFR and non-users to make guideline adjusting RASI usage according to initial change of GFR with RASI prescription.

#6649 SIGNIFICANT CLINICAL IMPROVEMENT OF PAEDIATRIC AND ADULT PATIENTS WITH DISTAL RENAL TUBULAR ACIDOSIS AFTER 6 YEARS OF TREATMENT WITH SIBNAYAL®

Abstract Background and Aims Distal renal tubular acidosis (dRTA) is a rare disease, inherited or acquired, characterized by hyperchloremic metabolic acidosis leading to negative effects on growth, bone and kidney, with growth retardation, rickets in children and osteomalacia in adults, nephrolithiasis and chronic kidney disease. No alkalizing treatment, necessary to control the metabolic acidosis and its consequences in growth, bone and kidney, has been shown, to date, to control the disease in the long term. The aim of this clinical study is to describe a cohort of adult and pediatric dRTA patients treated during 6 years by Sibnayal®, a new prolonged-release alkalizing formulation, in term of metabolic control, growth and long-term complications on bone mineralization and kidney function. Method Thirty patients with genetic dRTA taking Sibnayal®, previously treated with alkalizing standard of care and enrolled in the short-term B21CS study, were followed up for six years on average in a multicenter open-label extension trial (B22CS) to evaluate long-term impact of treatment on standard deviation score (SDS) of height, SDS weight, body mass index (BMI), Z-score spine bone mineral density (BMD), phosphocalcic metabolism (up to 4 years). glomerular filtration rate (GFR), nephrolithiasis, metabolic acidosis control, safety and compliance were also evaluated. Paired t-tests were done from baseline to end of study (EoS) when appropriate. The covariance ANCOVA test was performed to analyze spine BMD Z-score. Data are presented as mean ± standard error of mean. Results Clinical observations in this cohort, after an average of six years of treatment with Sibnayal®, confirmed the adequate control of metabolic acidosis (plasma bicarbonate from 22.0±0;6 mmol/L at baseline to 22.8±0.56 mmol/L at study end). The phosphocalcic metabolism analysis, from baseline to Month 48, demonstrated no significant change on Z-score for age of blood bone alkaline phosphatases, and a significant decrease of Z-score for age of blood phosphorus level (from to -0.5±0.7 to -1.3±1.0, p = 0.03). From baseline to EoS, SDS of height and weight increased significantly (-0.6±1.0 to -0.3±0.9 p = 0.04 and 0.2±1.5 to 0.7±1.4 p = 0.03, respectively), without significant difference in BMI. The spine BMD Z-score, relevant skeletal area for both pediatric and adult patients, underwent a continuous and significant increase of the change from baseline values over 6 years of treatment (difference [95% CI] = 0.404 [0.170; 0.639]). At EoS, spine BMD Z-score was improved in pre- and post-pubertal patients (mean 0.76±0.54 and 0.56±0.22 respectively), while it was stabilized in pubertal patients (mean -0.01±0.39). There was no significant variation of GFR between baseline and EoS. Nephrolithiasis increased slightly according to the increased age of the patient, without surgical intervention for stones removal. Safety and adherence to treatment remained good throughout the study. Conclusion Our data show the positive effect of the long-term treatment with Sibnayal® on growth and spine BMD, nicely improved, in the dRTA patients who participated to this long-term follow-up clinical study. The kidney function is also stabilized in these patients during the follow-up. This is the first report describing the prevention effect on the long-term complications of the distal Renal Tubular Acidosis patients under 6 years of Sibnayal® treatment.

How kidney clock works: circadian pattern of eGFR based on a population data group.

A circadian regulation of renal function it has been described in the last few years. An intradaily variation in glomerular filtration rate (eGFR) has also been discovered at the individual level. The aim of this study was to check if there exists a circadian pattern of eGFR at population data group level and to compare the population results with those described at individual level. We have studied a total of 446,441 samples analysed in the emergency laboratories of two Spanish hospitals between January 2015 and December 2019. We selected all the records of eGFR values between 60 and 140 mL/min/1.73 m2 using CKD-EPI formula from patients between 18 and 85 years. The intradaily intrinsic eGFR pattern was computed using the extraction time of day in four nested mixed linear and sinusoidal regression models. All models showed an intradaily eGFR pattern, but the estimated model coefficients differed depending on whether age was included. The inclusion of age improved the performance of the model. In this model, the acrophase occurred at 7:46 h. We describe the distribution of eGFR values depending on the time in two different populations. This distribution is adjusted to a circadian rhythm that behaves similarly to the individual rhythm. This pattern is similar in each of the years studied from each hospital as well as between both hospitals. The results found suggest the incorporation of the concept of "population circadian rhythm" into the scientific world.

Continuous Infusion of Iohexol to Monitor Perioperative Glomerular Filtration Rate.

Continuous monitoring of the glomerular filtration rate (GFR) in the perioperative setting could provide valuable information about acute kidney injury risk for both clinical and research purposes. This pilot study aimed to demonstrate that GFR measurement by a continuous 72 hrs iohexol infusion in patients undergoing colorectal cancer surgery is feasible. Four patients undergoing robot-assisted colorectal cancer surgery were recruited from elective surgery listings. GFR was determined preoperatively by the single-sample iohexol clearance method, and postoperatively at timed intervals by a continuous iohexol infusion for 72 hrs. Plasma concentrations of creatinine and cystatin C were measured concurrently. GFR was calculated as (iohexol infusion rate (mg/min))/(plasma iohexol concentration (mg/mL)). The association of the three different filtration markers and GFR with time were analysed in generalized additive mixed models. The continuous infusion of iohexol was established in all four patients and maintained throughout the study period without interfering with ordinary postoperative care. Postoperative GFR at 2 hours were elevated compared to the preoperative measurements for patients 1, 2, and 3, but not for patient 4. Whereas patients 1, 2, and 3 had u-shaped postoperative mGFR curves, patient 4 demonstrated a linear increase in mGFR with time. We conclude that obtaining continuous measurements of GFR in the postoperative setting is feasible and can detect variations in GFR. The method can be used as a tool to track perioperative changes in renal function.

Should Estimated Glomerular Filtration Rate Be Adjusted for Race?

Should Estimated Glomerular Filtration Rate Be Adjusted for Race?

The Impact of the 2017 Kidney Allocation Policy Change on Simultaneous Liver-Kidney Utilization and Outcomes.

Historically in the United States, kidneys for simultaneous liver-kidney transplantation (SLKT) candidates were allocated with livers, prioritizing SLKT recipients over much of the kidney waiting list. A 2017 change in policy delineated renal function criteria for SLKT and implemented a safety net for kidney-after-liver transplantation. We compared the use and outcomes of SLKT and kidney-after-liver transplant with the 2017 policy. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify adults who received liver transplantations (LT) from August 10, 2007 to August 10, 2012; from August 11, 2012 to August 10, 2017; and from August 11, 2017 to June 12, 2019. LT recipients with end-stage renal disease (ESRD) were defined by dialysis requirement or estimated glomerular filtration rate <25. We evaluated outcomes and center-level, regional, and national practice before and after the policy change. Nonparametric cumulative incidence of kidney-after-liver listing and transplant were modeled by era. A total of 6332 patients received SLKTs during the study period; fewer patients with glomerular filtration rate (GFR)≥50 mL/min underwent SLKT over time (5.8%, 4.8%, 3.0%; P= 0.01). There was also less variability in GFR at transplant after policy implementation on center and regional levels. We then evaluated LT-alone (LTA) recipients with ESRD (n=5408 from 2012-2017; n = 2321 after the policy). Listing for a kidney within a year of LT increased from 2.9% before the policy change to 8.8% after the policy change, and the rate of kidney transplantation within 1 year increased from 0.7% to 4% (P<0.001). After the policy change, there was no difference in patient survival rates between SLKT and LTA among patients with ESRD. Implementation of the 2017 SLKT policy change resulted in reduced variability in SLKT recipient kidney function and increased access to deceased donor kidney transplantation for LTA recipients with kidney disease without negatively affecting outcomes.

MO449VALIDATION OF MAYO CLINIC CLASSIFICATION AS A PREDICTOR OF FUTURE RENAL FUNCTION IMPAIRMENT IN PATIENTS WITH AUTOSOMAL POLYCYSTIC KIDNEY DISEASE (ADPKD) IN A POPULATION IN THE SOUTH OF SPAIN

Abstract Background and Aims The Mayo Clinic classification (MCC) is used in patients with ADPKD to identify those who may experience a more rapid deterioration of glomerular filtration rate (GFR). It has been developed in the American population but has not been validated in other populations. Our objective was to analyze whether the CCM predictive model is valid in an ADPKD population from southern Spain and whether it can identify populations with different renal survival. Method We selected patients with ADPKD with measurements of height-adjusted total renal volume (HtTKV) performed with CT or MR and with GFR CKD-EPI&amp;gt; 15 mL / min / 1.73 m2. We estimated the GFR at the end of the follow-up using the Irazábal equation and the rate of GFR deterioration, bias and precision were calculated. We analyzed the predictive power of BC using survival analysis using the Kaplan-Meier technique and using Cox regression models. Results We included 128 patients, aged 44 ± 13 years and a follow-up time of 79 ± 45 months (median 88), at the end of which 22 (17.2%) patients had a GFR &amp;lt;10 mL / min / 1.73 m2 or were included in renal replacement therapy. The distribution of patients according to the CM classification was: 1A 4.7%, 1B 28.1%, 1C 33.6%, 1D 22.7%, 1E 10.9%. Age decreased progressively: 1A 58 ± 11, 1B 48 ± 14, 1C 46 ± 13, 1D 40 ± 8, 1E 30 ± 7 (p &amp;lt;0.001). In contrast, HtTKV increased significantly: 1A 275 ± 52, 1B 486 ± 191, 1C 887 ± 410, 1D 1222 ± 510, 1E 1324 ± 800 mL / m (p &amp;lt;0.001). While the initial GFR was not different between classes, the GFR at the end of the follow-up decreased significantly: 1A 59 ± 36, 1B 63 ± 29, 1C54 ± 35, 1D 48 ± 26, 1E 44 ± 33 mL / min / 1.73 m2 (p &amp;lt;0.001). The GFR variation rate was significantly different according to the MCC classes: 1A 1.31 ± 6.80, 1B -2.48 ± 3.12, 1C -4.13 ± 4.33, 1D -4.70 ± 2.66, 1E -6.18 ± 3.03 mL / min / 1.73 m2 / year (p = 0.008). The final GFR predicted with the Irazábal equation was not significantly different from the real one. The absolute bias of the final GFR estimated with the MC equation was 2.6 ± 16.0 mL / min / 1.73 m2 and the relative bias was 38.7 ± 110, and it was not significantly different in the MCC classes. The P10 precision was low, with values of 65.1%, 51.7% and 50% for classes 1C, 1C and 1E respectively. The rate of deterioration of the GFR was underestimated in classes 1C, 1D and 1E. In the renal survival analysis with the Cox regression analysis, we found that the MCC classification is a predictor of survival, with classes 1D and 1E having the worst prognosis. Conclusion The MCC classification is capable of identifying populations that will suffer a more rapid deterioration of the GFR and constitutes a marker of renal survival in a Spanish population of patients with ADPKD. The prediction of future GFR with the Irazábal equation is acceptable as a group, although it shows a loss of precision at the individual level, especially in patients with higher GFR at baseline.

Renal Precision Medicine in Neonates and Acute Kidney Injury: How to Convert a Cloud of Creatinine Observations to Support Clinical Decisions.

Renal precision medicine in neonates is useful to support decision making on pharmacotherapy, signal detection of adverse (drug) events, and individual prediction of short- and long-term prognosis. To estimate kidney function or glomerular filtration rate (GFR), the most commonly measured and readily accessible biomarker is serum creatinine (Scr). However, there is extensive variability in Scr observations and GFR estimates within the neonatal population, because of developmental physiology and superimposed pathology. Furthermore, assay related differences still matter for Scr, but also exist for Cystatin C. Observations in extreme low birth weight (ELBW) and term asphyxiated neonates will illustrate how renal precision medicine contributes to neonatal precision medicine. When the Kidney Disease Improving Global Outcome (KDIGO) definition of acute kidney injury (AKI) is used, this results in an incidence up to 50% in ELBW neonates, associated with increased mortality and morbidity. However, urine output criteria needed adaptations to broader time intervals or weight trends, while Scr and its trends do not provide sufficient detail on kidney function between ELBW neonates. Instead, we suggest to use assay-specific centile Scr values to better describe postnatal trends and have illustrated its relevance by quantifying an adverse drug event (ibuprofen) and by explaining individual amikacin clearance. Term asphyxiated neonates also commonly display AKI. While oliguria is a specific AKI indicator, the majority of term asphyxiated cases are non-oliguric. Asphyxia results in a clinical significant—commonly transient—mean GFR decrease (−50%) with a lower renal drug elimination. But there is still major (unexplained) inter-individual variability in GFR and subsequent renal drug elimination between these asphyxiated neonates. Recently, the Baby-NINJA (nephrotoxic injury negated by just-in-time action) study provided evidence on the concept that a focus on nephrotoxic injury negation has a significant impact on AKI incidence and severity. It is hereby important to realize that follow-up should not be discontinued at discharge, as there are concerns about long-term renal outcome. These illustrations suggest that integration of renal (patho)physiology into neonatal precision medicine are an important tool to improve contemporary neonatal care, not only for the short-term but also with a positive health impact throughout life.

Time changes of renal dimensions and variations of glomerular filtration rate in chronic kidney disease patients.

The aim of this longitudinal prospective study was to search if even in the absence of total or partial nephrectomy the kidney size can increase as the kidney function improves. We randomly enrolled 80 adult patients with various degrees of chronic renal failure but non-dialysis dependent neither totally or partially nephrectomized nor affected by any of the pathological conditions that can increase kidney size. The patients underwent a first examination comprehensive of a blood sample and renal ultrasonography and then were submitted to a therapeutic intervention aimed at removing all nephrotoxic agents to finally be subjected to a last similar medical examination. The statistical analysis displayed a strong positive correlation between the percentage variation of the renal diameters' average and the time changes of the GFR (r 0.731; p < 0.01) as well as the percentage variation of the GFR and the time changes variations of the right (r 0.487; p < 0.01) and left cortical kidney thickness (r 0.519; p < 0.01) and finally a strong negative correlation between the removal of nephrotoxic agents and the percentage variation of the renal diameters' average (r - 0.293; p < 0.01) and the time changes of the GFR (r - 0.429; p < 0.01). In patients with chronic kidney disease, even in the absence of total or partial nephrectomy, under the stimulus of the removal of any nephrotoxic agents, there may be a limited increase in renal size according to a model that sees them vary according to the changes in GFR.

Renal Function 1Year After Bariatric Surgery: Influence of Roux-en-Y Gastric Bypass and Identification of Pre-Operative Predictors of Improvement.

While evidence of improved renal function following gastric bypass exists, pre-operative predictors of this improvement are not completely known. To assess the glomerular filtration rate (GFR) 1year after Roux-en-Y gastric bypass (RYGB) and to identify pre-operative predictors associated with the improvement of renal function. A historical cohort study, which included 109 obese patients before and 12months after RYGB, was classified into subgroups according to GFR (normofiltration, hypofiltration (GFR < 5th percentile), and hyperfiltration (GFR > 95th percentile)). The 5th and 95th percentiles were 90 and 120mL/min/1.73m2, respectively. The primary outcome was the variation of GFR (%GFR) estimated by the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) formula, calculated using serum creatinine, ethnicity, and gender. The mean age was 38.3 ± 10.3years and 77% were female; 52.3% presented hypertension and 27.5% type 2 diabetes. One year after surgery, the mean BMI decreased from 36.7 ± 3.6 to 28.8 ± 3.3kg/m2 (p < 0.001). Pre-surgically, 37.6% presented hypofiltration, 47.7% normofiltration, and 14.7% hyperfiltration. The overall GFR increased from 95.5 ± 19 to 104 ± 16.4mL/min (10.9%) (p < 0.001). The overall post-surgical %GFR was negatively correlated with the pre-surgical GFR (R = - 0.687; p < 0.001). In the hypofiltration and normofiltration subgroups, the post-surgical %GFR was negatively correlated with age (R = - 0.328, p = 0.036; and R = - 0.355, p = 0.004, respectively) and pre-surgical GFR (R = - 0.436, p = 0.04; and R = - 0.528, p < 0.001, respectively). RYGB led to a significant improvement in renal function, mainly among patients with a worse pre-operative renal function. In the hypofiltration and normofiltration subgroups, a younger age was associated with better outcomes.

P5464Visit-to-visit glomerular filtration rate variability as a predictor for cardiovascular and renal outcomes in essential hypertension: Data from a Greek 8-year-follow-up study

Abstract Background/Introduction Renal dysfunction is related with adverse prognosis in hypertension, however there are scarce data on the predictive cardiovascular and renal impact of kidney function variability in this setting. Purpose The aim of the present study was to assess the predictive role of visit-to-visit renal function changes on the incidence of coronary artery disease (CAD), stroke and end-stage renal disease in a cohort of essential hypertensive patients. Methods We followed up 2380 essential hypertensives (mean age 58.9 years, 1240 males, office blood pressure (BP)=144/91 mmHg) free of cardiovascular disease for a mean period of 8 years. All subjects had at least one annual visit and blood sampling was performed in all visits for estimation of glomerular filtration rate (GFR). We calculated standard deviation (SD) of mean GFR from visits from 6 months onward in patients with ≥5 visits during follow-up. CAD was defined as the history of myocardial infarction or significant coronary artery stenosis revealed by angiography or coronary revascularization procedure, while stroke was defined as rapid onset of a new neurological deficit persisting at least 24 hours unless death supervened confirmed by imaging findings. End-stage renal disease was defined as GFR&lt;15 mL/min/1.73 m2 or the need for long-term dialysis or transplantation. Results The incidence of CAD, stroke and end-stage renal disease over the follow-up period were 2.8% (n=68), 1.09% (n=26) and 0.6% (n=14). Hypertensives who developed CAD compared to those without CAD at follow-up (n=2312) had at baseline higher left ventricular mass index (115.7±24.6 vs 103.7±27.3 g/m2, p&lt;0.0001), whereas there was no difference with respect to baseline GFR (78±19.6 vs 79.3±18.6 mL/min/1.73 m2 (p=0.573). In multivariate Cox regression models visit-to-visit glomerular filtration rate predicted end-stage renal disease (hazard ratio=1.758, p=0.01) but not CAD and stroke (p=NS for both). Baseline left ventricular mass index independently predicted CAD (hazard ratio=1.042, p=0.015) and stroke (hazard ratio=1.035, p=0.002). Conclusions In essential hypertensive patients GFR variability predicts future development of end-stage renal disease but exhibits no independent prognostic value for CAD and stroke. These results suggest that fluctuations of renal function are related with damage at the kidneys and not at the cardiac and cerebrovascular level.

Fundamental problems with pediatric adaptive dosing of carboplatin using nuclear-medicine-based estimates of renal function.

Carboplatin is often adaptively dosed based on glomerular filtration rate (GFR), usually estimated by nuclear medicine tests. At least five pediatric adaptive dosing formulas have been developed. In an effort to standardize dosing in Children's Oncology Group protocols, we explored methodologic variation in GFR estimation and adaptive-dosing formula performance. Nuclear medicine GFR data from published series of ≥100 children with cancer were compared. Data from patients for whom body surface area, weight, GFR, and tracer half-life were available were used to compare formulas. Differences in methods used to estimate GFR in children with cancer resulted in highly variable population results, with median GFRs ranging from 96 to 150mL/min/1.73m2 . The choice of adaptive formula had a major impact on calculated dose. When targeting an area under the curve of 7.9mg/mL • min, the median difference between the formula yielding the lowest and highest carboplatin dose for individual subjects was 289 (range 96-1737) mg/m2 . Wide variation in GFR obtained with nuclear-medicine-based tests in children with cancer primarily results from systematic methodologic errors. Formulas for calculating carboplatin dose produce additional and substantial variation that may place children with cancer at unnecessary risk for excessive toxicity or underdosing. These findings indicate a need for the development of a uniform, validated method for GFR determination in children that should be utilized in all centers. Currently, adaptive dosing of carboplatin based on GFR has serious limitations and in most clinical settings should arguably not be used in place of body-surface-area-based dosing.

Factors associated with glomerular filtration rate variation in primary hyperparathyroidism after parathyroidectomy

Background/aimProlonged hypercalcemia impairs renal function, and a reduced glomerular filtration rate (GFR) is typical in advanced primary hyperparathyroidism (PHPT). There are scarce data related to predictors of renal impairment in patients with PHPT. Hence, we aimed to evaluate changes in kidney function in PHPT patients after parathyroidectomy (PTX) and identify factors associated with GFR variation in these patients.Materials and methodsOne hundred and twenty-five patients with PHPT who underwent surgery between 2012 and 2014 were enrolled in the study. Patients were divided into two groups according to GFR values: patients whose GFR was lower than 60 mL/min/1.73 m2 and higher than 60 mL/min/1.73 m2. Demographic and laboratory parameters were compared before and 6 months after parathyroidectomy.Results Prevalence of antihypertensive drug users and patients with renal cysts and parathormone (PTH) and alkaline phosphatase levels were higher in patients with GFR of ≥60 than in GFR of <60 mL/min/1.73 m2 (P < 0.05). Systolic BP, uric acid, and magnesium were decreased in patients with GFR of ≥60, but GFR did not change in the two groups after parathyroidectomy. After parathyroidectomy, calcium and PTH decreased but 25(OH)D3 and phosphorus increased in the two groups. In multiple regression analysis, age, calcium, and baseline GFR were independent predictors of GFR variation. Parathyroid adenoma volume and urinary calcium were not independent predictors of GFR change.ConclusionOlder age, higher preoperative calcium, and GFR were factors associated with GFR increase in PHPT patients after parathyroidectomy. Further renal impairment was prevented by parathyroidectomy in PHPT patients.

Designing and Implementing an ANFIS Based Medical Decision Support System to Predict Chronic Kidney Disease Progression.

Background and objective: Chronic kidney disease (CKD) has a covert nature in its early stages that could postpone its diagnosis. Early diagnosis can reduce or prevent the progression of renal damage. The present study introduces an expert medical decision support system (MDSS) based on adaptive neuro-fuzzy inference system (ANFIS) to predict the timeframe of renal failure.Methods: The core system of the MDSS is a Takagi-Sugeno type ANFIS model that predicts the glomerular filtration rate (GFR) values as the biological marker of the renal failure. The model uses 10-year clinical records of newly diagnosed CKD patients and considers the threshold value of 15 cc/kg/min/1.73 m2 of GFR as the marker of renal failure. Following the evaluation of 10 variables, the ANFIS model uses the weight, diastolic blood pressure, and diabetes mellitus as underlying disease, and current GFR(t) as the inputs of the predicting model to predict the GFR values at future intervals. Then, a user-friendly graphical user interface of the model was built in MATLAB, in which the user can enter the physiological parameters obtained from patient recordings to determine the renal failure time as the output.Results: Assessing the performance of the MDSS against the real data of male and female CKD patients showed that this decision support model could accurately estimate GFR variations in all sequential periods of 6, 12, and 18 months, with a normalized mean absolute error lower than 5%. Despite the high uncertainties of the human body and the dynamic nature of CKD progression, our model can accurately predict the GFR variations at long future periods.Conclusions: The MDSS GUI could be useful in medical centers and used by experts to predict renal failure progression and, through taking effective actions, CKD can be prevented or effectively delayed.

Repeated measurements of renal function in evaluating its decline in cats.

The aim of this study was to describe the variability in renal function markers in non-azotaemic and azotaemic cats, and also the rate of change in the markers. Plasma creatinine concentration and its reciprocal, glomerular filtration rate (GFR) and urine specific gravity (USG) were studied as markers of renal function in client-owned cats. GFR was determined using a corrected slope-intercept iohexol clearance method. Renal function testing was performed at baseline and a second time point. The within-population variability (coefficient of variation; CV%) was determined at the baseline time point. Within-individual variability (CV%) and rate of change over time were determined from the repeated measurements. Twenty-nine cats were included in the study, of which five had azotaemic chronic kidney disease. The within-individual variability (CV%) in creatinine concentration was lower in azotaemic cats than in non-azotaemic cats (6.81% vs 8.82%), whereas the within-individual variability in GFR was higher in azotaemic cats (28.94% vs 19.98%). The within-population variability was greatest for USG (67.86% in azotaemic cats and 38.00% in non-azotaemic cats). There was a negative rate of change in creatinine concentration in azotaemic and non-azotaemic cats (-0.0265 and -0.0344 µmol/l/day, respectively) and a positive rate of change of GFR in azotaemic and non-azotaemic cats (0.0062 and 0.0028 ml/min/day, respectively). The within-individual variability data suggest creatinine concentration to be the more useful marker for serial monitoring of renal function in azotaemic cats. In contrast, in non-azotaemic cats, GFR is a more useful marker for serial monitoring of renal function. The majority of cats with azotaemic CKD did not have an appreciable decline in renal function during the study.

High temperatures and nephrology: The climate change problem

It is well known that climate change greatly affects human health, even though there are few studies on renal outcomes. Heat waves have been found to increase cardiovascular and respiratory morbidity and mortality, as well as the risk of acute renal failure and hospitalisation due to renal diseases, with related mortality. Recurrent dehydration in people regularly exposed to high temperatures seems to be resulting in an unrecognised cause of proteinuric chronic kidney disease, the underlying pathophysiological mechanism of which is becoming better understood. However, beyond heat waves and extreme temperatures, there is a seasonal variation in glomerular filtration rate that may contribute to the onset of renal failure and electrolyte disorders during extremely hot periods. Although there are few references in the literature, serum sodium disorders seem to increase. The most vulnerable population to heat-related disease are the elderly, children, chronic patients, bedridden people, disabled people, people living alone or with little social contact, and socioeconomically disadvantaged people.

Altas temperaturas y nefrología: a propósito del cambio climático

It is well known that climate change greatly affects human health, even though there are few studies on renal outcomes. Heat waves have been found to increase cardiovascular and respiratory morbidity and mortality, as well as the risk of acute renal failure and hospitalisation due to renal diseases, with related mortality. Recurrent dehydration in people regularly exposed to high temperatures seems to be resulting in an unrecognised cause of proteinuric chronic kidney disease, the underlying pathophysiological mechanism of which is becoming better understood. However, beyond heat waves and extreme temperatures, there is a seasonal variation in glomerular filtration rate that may contribute to the onset of renal failure and electrolyte disorders during extremely hot periods. Although there are few references in the literature, serum sodium disorders seem to increase. The most vulnerable population to heat-related disease are the elderly, children, chronic patients, bedridden people, disabled people, people living alone or with little social contact, and socioeconomically disadvantaged people.

Comparison of the effectiveness and renal safety of tenofovir versus entecavir in patients with chronic hepatitis B

ObjectiveTo compare the effectiveness and renal safety of treatment with tenofovir versus entecavir in patients with chronic hepatitis-B. MethodsRetrospective study in hepatitis-B patients who initiated treatment with tenofovir or entecavir since January 1998 until 2013. The primary effectiveness variable was defined as viral DNA < 20 UI/ml (HBV-DNA) and the variable for renal safety was variations in glomerular filtration rate (eGFR) after 48 weeks of treatment. ResultsThe analysis was conducted in 64 patients (1:1), with similar characteristics except for the prevalence of naive patients (p=0.036), comorbidities (p=0.077) and nephrotoxic drugs (p=0.088) in the entecavi arm, while the tenofovir arm presented a prevalence of patients with HBV-DNA < 20 UI/ml (p=0.032) and HBeAg-positive (p=0.050). Statistical univariate analysis and adjustment for confounding variables was conducted through the Propensity Score (PS). The outcomes for the primary effectiveness variable showed tenofovir superiority after PS adjustment, with an ORadj=6.7 (95% CI:1.2-35.3; p=0.028). Three patients on tenofovir experienced seroconversion (p=0.148). The outcomes for the primary safety variable (eGFR < 60 ml/min/1.73m2) showed no difference between both arms after adjustment, achieving an ORadj=0.6 (95% CI:0.1-2.8; p=0.521). The tenofovir arm registered two cases of treatment interruption due to renal toxicity, with subsequent recovery, including one Fanconi Syndrome. ConclusionsIn our study, there are significant differences between both treatments regarding effectiveness, with tenofovir demonstrating superiority. In terms of renal safety, we have not found any significant differences, but two cases of treatment interruption due to renal toxicity with tenofovir lead us to the conclusion that treatment decision in patients with renal function alteration should include an individualized assessment of each case.

Predicting Renal Failure Progression in Chronic Kidney Disease Using Integrated Intelligent Fuzzy Expert System.

Background. Chronic kidney disease (CKD) is a covert disease. Accurate prediction of CKD progression over time is necessary for reducing its costs and mortality rates. The present study proposes an adaptive neurofuzzy inference system (ANFIS) for predicting the renal failure timeframe of CKD based on real clinical data. Methods. This study used 10-year clinical records of newly diagnosed CKD patients. The threshold value of 15 cc/kg/min/1.73 m2 of glomerular filtration rate (GFR) was used as the marker of renal failure. A Takagi-Sugeno type ANFIS model was used to predict GFR values. Variables of age, sex, weight, underlying diseases, diastolic blood pressure, creatinine, calcium, phosphorus, uric acid, and GFR were initially selected for the predicting model. Results. Weight, diastolic blood pressure, diabetes mellitus as underlying disease, and current GFR(t) showed significant correlation with GFRs and were selected as the inputs of model. The comparisons of the predicted values with the real data showed that the ANFIS model could accurately estimate GFR variations in all sequential periods (Normalized Mean Absolute Error lower than 5%). Conclusions. Despite the high uncertainties of human body and dynamic nature of CKD progression, our model can accurately predict the GFR variations at long future periods.

Measuring glomerular filtration rate by iohexol clearance on filter paper is feasible in adolescents with type 1 diabetes in the ambulatory setting.

The American Diabetes Association recently recommended routine screening of glomerular filtration rate (GFR) in adolescents with type 1 diabetes, although this is not routinely performed clinically [1]. Current estimates of GFR lack precision and accuracy before stage 3 of chronic kidney disease (GFR \60 mL/min/1.73 m). Also, measurement of urinary albumin excretion, currently recommended as part of routine screening, does not directly measure kidney function. This is of particular concern in adolescents and young adults with type 1 diabetes, in whom renal hyperfiltration may promote renal injury, or rapid change in GFR may be missed due to the lack of acceptable screening methods for GFR. Perrin and Berg [2] recently reported that estimated GFR cannot accurately replace measured GFR to defect hyperfiltration in young patients with type 1 diabetes. We recently reported that iohexol clearance measured with dried blood spots (DBS) on filter paper performed better than the estimates of GFR using the CKD-EPI equations and was comparable to gold-standard iohexol plasma clearance in adults with type 1 diabetes [3]. GFR measured by iohexol clearance on DBS has also been evaluated in adults with a wide range of GFRs showing strong agreement to gold-standard measurements [4]. Standard iohexol GFR (iGFR) measurement requires more than 4 h in a research center, making it impractical for routine clinical monitoring of GFR. Here, we present data from a pilot study in youth with type 1 diabetes (n = 8, 70 % female, 17 ± 4 years, type 1 diabetes duration of 6.3 ± 5.0 years, HbA1c 8.9 ± 2.5 %) with the goal of demonstrating feasibility of translating this method to an ambulatory setting. Kidney function was measured by iGFR with DBS and estimated by Bouvet (cystatin C and creatinine-based GFR equation) and Schwartz (creatinine-based GFR equation). The participants had blood drawn, then iohexol injected intravenously prior to their regular diabetes visit and were sent home with filter paper to collect DBS at 120, 150, 180, 210 and 240 min after iohexol injection followed by mailing the filter paper back to our laboratory. There appeared to be less variability of GFR with the iGFR than the estimated GFR methods (Bouvet and Schwartz) (Fig. 1). As this study was performed on an outpatient basis to determine feasibility, we did not perform an in-patient gold-standard iGFR study to serve as a comparator for these three GFR measurements. However, our previous publication in adults with type 1 diabetes demonstrated that iGFR measured in DBS on filter paper was significantly less biased and more comparable to a gold-standard iGFR measurement than estimated GFR [3]. Moreover, using two spots at 120 and 240 min was comparable to using five spots [3], which if validated would further decrease burden to the patient and cost of this method. The adolescents also rated eight statements on a 7-point non-validated Likert scale (Fig. 2). All participants agreed or strongly agreed that the procedure was preferable Managed by Massimo Federici.