eGFR Measurements Research Articles

Point of Care eGFR and the Prediction of Outcomes in Pneumonia

Pneumonia is a leading cause of mortality. Severity-assessment scores in pneumonia guide treatment crucially, but the ones currently in existence are limited in their use. Community-based studies demonstrated the association between pre-existing low estimated glomerular filtration rate (eGFR) and outcomes in pneumonia. However, whether a single emergency department-eGFR measurement could predict outcomes in pneumonia remains unclear. This retrospective cohort study included 1554 patients hospitalized with pneumonia. The predictor was the first eGFR measurement. Outcomes included mortality, intensive care unit (ICU) admission, durations of hospital and ICU stay, and ventilator use. Receiver operating characteristic curves was used to determine optimal cutoff values to predict mortality. Of 1554 patients, 263 had chronic kidney disease, demonstrated higher C-reactive protein and SMART-COP scores, and had more multilobar pneumonia, acute kidney injury, ICU admission, and mortality. Patients with higher pneumonia severity scores tended to have lower eGFR. For predicting in-hospital mortality, the optimal eGFR cutoff value was 56 mL/min/1.73 m2. eGFR < 56 mL/min/1.73 m2 had an odds ratio of 2.5 (95% confidence interval, 1.6–4.0) for mortality by multivariate logistic regression. In Conclusion, eGFR < 56 mL/min/1.73 m2 is an independent predictor of mortality, indicating that even mild renal impairment affects the outcome of pneumonia adversely.

Soluble Urokinase Plasminogen Activator Receptor and Decline in Kidney Function in Autosomal Dominant Polycystic Kidney Disease.

Levels of soluble urokinase plasminogen activator receptor (suPAR), an inflammation marker, are strongly predictive of incident kidney disease. Patients with autosomal dominant polycystic kidney disease (ADPKD) experience progressive decline in renal function, but rates of decline and outcomes vary greatly. Whether suPAR levels are predictive of declining kidney function in patients with ADPKD is unknown. We assessed suPAR levels in 649 patients with ADPKD who underwent scheduled follow-up for at least 3 years, with repeated measurements of height-adjusted total kidney volume and creatinine-derived eGFR. We used linear mixed models for repeated measures and Cox proportional hazards to characterize associations between baseline suPAR levels and follow-up eGFR or incident ESRD. The median suPAR level was 2.47 ng/ml and median height-adjusted total kidney volume was 778, whereas mean eGFR was 84 ml/min per 1.73 m2. suPAR levels were associated with height-adjusted total kidney volume (β=0.02; 95% confidence interval, 0.01 to 0.03), independent of age, sex, race, hypertension, and eGFR. Patients in the lowest suPAR tertile (<2.18 ng/ml) had a 6.8% decline in eGFR at 3 years and 22% developed CKD stage 3, whereas those in the highest tertile (suPAR>2.83 ng/ml) had a 19.4% decline in eGFR at 3 years and 68% developed CKD stage 3. suPAR levels >2.82 ng/ml had a 3.38-fold increase in the risk of incident ESRD. suPAR levels were associated with progressive decline in renal function and incident ESRD in patients with ADPKD, and may aid early identification of patients at high risk of disease progression.

533-P: Association of Serum Branched-Chain Amino Acids with Kidney Function Decline in Type 2 Diabetes: The Hong Kong Diabetes Register

Background: There are recent claims that high dietary BCAA may improve insulin resistance although this conflicts with the recommendation that low protein/BCAA diet may confer renoprotection in patients with chronic kidney disease (CKD) stages 3-5. Type 2 diabetes (T2D) has dysregulated energy metabolism where excessive BCAA intake can be harmful. We examined the risk association of BCAA and rate of estimated glomerular filtration rate (eGFR) decline in a prospective T2D cohort. Method: We measured serum BCAA in 2340 adults with CKD stages 1-2 at baseline with available stored sera. By using linear regression analysis, we examined the association of serum BCAA with annual change in eGFR, which was estimated from a linear mixed model using at least three eGFR measurements from baseline until the onset of CKD or data censored on June 2017. Results: In this study cohort with mean±SD follow-up of 10.0±5.3 years (age 55.2±11.2 years, BMI 25.4±4.3 kg/m2, HbA1c 7.6±1.7%, annual change in eGFR -1.37±1.28 ml/min/1.73m2), patients with incident CKD had higher serum BCAA (median [IQR]: 622.7 [540.3-730] vs. 595.8 [518.3-680.3] µM; P&amp;lt;0.001) and usage of blood pressure (BP)-lowering drugs (56.2% vs. 33.7%; P&amp;lt;0.001) at baseline than those without CKD. Every doubling of serum BCAA was associated with faster eGFR decline (β -0.24 [95% CI -0.34, -0.14]; P&amp;lt;0.001) that remained significant after adjusting for age, sex and diabetes duration (β -0.27 [-0.37, -0.18]; P&amp;lt;0.001). The effect was attenuated by further adjustment of HbA1c, BMI, lipids, BP and related drug usage (β -0.16 [-0.27, -0.05]; P=0.003), as well as by retinopathy, albuminuria and eGFR at baseline (β -0.13 [-0.23, -0.02]; P=0.016). There was no significant BCAA-sex interaction. Conclusions: In Chinese T2D patients with CKD stages 1-2, high serum BCAA was independently associated with a modest decline in eGFR, suggesting the renoprotective effect of a low BCAA diet may be extended to early CKD with careful monitoring. Disclosure L. Lim: Research Support; Self; AstraZeneca. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc. E.S. Lau: None. H. Lee: None. C.H. Tam: None. C.K. Lim: None. A. Luk: None. E. Chow: Research Support; Self; Powder Pharmaceuticals Inc., Sanofi-Aventis. R.C. Ma: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; AstraZeneca, Bayer AG, Pfizer Inc. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca. J.C. Chan: Board Member; Self; Asia Diabetes Foundation. Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Merck Sharp &amp; Dohme Corp., Sanofi-Aventis. Research Support; Self; Amgen Inc., AstraZeneca, Lee Powder, Lilly Diabetes, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; Ascensia Diabetes Care. Stock/Shareholder; Self; GemVCare. A.P. Kong: Advisory Panel; Self; Lilly Diabetes. Research Support; Self; AstraZeneca, Lilly Diabetes. Speaker's Bureau; Self; Abbott. Other Relationship; Self; AstraZeneca, Novartis Pharmaceuticals Corporation, Sanofi. Funding Hong Kong Society of Endocrinology, Metabolism and Reproduction; Hong Kong Association for the Study of Obesity

2357-PUB: Dapagliflozin for 52 Weeks Improves Diastolic Dysfunction and Vascular Reactivity in T2D

Background: SGLT2i proved efficacy in reducing cardiovascular morbidity and mortality in T2D patients at high cardiovascular risk. Aims: In real-word setting, we prospectively evaluated long-term effects of Dapagliflozin (DAPA) on left diastolic ventricular function (LDVF) and vascular reactivity in T2D patients without known cardiovascular disease. Population, Study and Methods: 13 patients (9 male, 57± 8 years, BMI 29.6± 3.6, HbA1c 8.9±1.2%, years of T2D 9±5, fasting glucose 185±51 mg/dl) initiated DAPA 10 mg daily as add-on to metformin. Following data were collected at baseline (T0), after 12 weeks (T1) and 52 weeks (T2) of treatment: blood pressure, anthropometrics, fasting glucose, HbA1c, eGFR and lipids. Ratio of the early (E) to late (A) ventricular filling velocities (E/A) was used to evaluate LDVF. Arterial stiffness was evaluated by Pulse Wave Velocity (PWV) and Augmentation Index (AIxHR75) with radial approach (SphygmoCor System). Endothelial function was assessed by non-invasive flow mediated dilatation (FMD). Results: We observed significant percent variation in HbA1c (T1 vs. T0 -17.9%, p=0.001; T2 vs. T0 -17.4%, p=0.01), fasting glucose (T1 vs. T0 -25.9%, p=0.002, T2 vs. T0 -31.8%, p=0.005) systolic blood pressure (T1 vs. T0 -6.7%, p=0.03; T2 vs. T0 -10.2% p=0.02) and BMI (T1 vs. T0 -3.3%, p=0.001; T2 vs. T0 -3%, p=0.02). Significant improvements from baseline of E/A ratio (T1 vs. T0 +15%, p=0.03; T2 vs. T0 +27.5%, p=0.003) and brachial FMD (T1 vs. T0 +50.7%, p=0.02; T2 vs. T0 +39.4%, p=0.04) were also seen. No significant changes in eGFR, lipids and arterial stiffness measures were seen. Conclusions: Intensification of treatment with DAPA 10 mg was accompanied by significant improvements in LVDF and endothelial-dependent vasodilation measures, which persist after 52 weeks of treatment. These preliminary observational results shed light on potential mechanisms responsible for cardiovascular protection with SGLT2i in T2D patients, even in absence of overt cardiovascular disease. Disclosure I. D'ippolito: None. E. De Carli: None. A. Andreadi: None. M. Romano: None. A. Galli: None. A. Capria: None. M. Massaro: None. P. Sbraccia: None. D. Della-Morte: None. A. Bellia: None. D. Lauro: None. Funding University of Rome

Urinary Sodium Profiling in Chronic Heart Failure to Detect Development of Acute Decompensated Heart Failure

ObjectivesThis study sought to determine the relationship between urinary sodium (Una) concentration and the pathophysiologic interaction with the development of acute heart failure (AHF) hospitalization. BackgroundNo data are available on the longitudinal dynamics of Una concentration in patients with chronic heart failure (HF), including its temporal relationship with AHF hospitalization. MethodsStable, chronic HF patients with either reduced or preserved ejection fraction were prospectively included to undergo prospective collection of morning spot Una samples for 30 consecutive weeks. Linear mixed modeling was used to assess the longitudinal changes in Una concentration. Patients were followed for the development of the clinical endpoint of AHF. ResultsA total of 80 chronic HF patients (71 ± 11 years of age; an N-terminal pro–B-type natriuretic peptide [NT-proBNP] concentration of 771 [interquartile range: 221 to 1,906] ng/l; left ventricular ejection fraction [LVEF] 33 ± 7%) prospectively submitted weekly pre-diuretic first void morning Una samples for 30 weeks. A total of 1,970 Una samples were collected, with mean Una concentration of 81.6 ± 41 mmol/l. Sodium excretion remained stable over time on a population level (time effect p = 0.663). However, interindividual differences revealed the presence of high (88 mmol/l Una [n = 39]) and low (73 mmol/l Una [n = 41]) sodium excreters. Only younger age was an independent predictor of high sodium excretion (odds ratio [OR]: 0.91; 95% confidence interval [CI]: 0.83 to 1.00; p = 0.045 per year). During 587 ± 54 days of follow-up, 21 patients were admitted for AHF. Patients who developed AHF had significantly lower Una concentrations (F[1.80] = 24.063; p < 0.001). The discriminating capacity of Una concentration to detect AHF persisted after inclusion of NT-proBNP and estimated glomerular filtration rate (eGFR) measurements as random effects (p = 0.041). Furthermore, Una concentration dropped (Una = 46 ± 16 mmol/l vs. 70 ± 32 mmol/l, respectively; p = 0.003) in the week preceding the hospitalization and returned to the individual’s baseline (Una = 71 ± 22 mmol/l; p = 0.002) following recompensation, while such early longitudinal changes in weight and dyspnea scores were not apparent in the week preceding decompensation. ConclusionsOverall, Una concentration remained relatively stable over time, but large interindividual differences existed in stable, chronic HF patients. Patients who developed AHF exhibited a chronically lower Una concentration and exhibited a further drop in Una concentration during the week preceding hospitalization. Ambulatory Una sample collection is feasible and may offer additional prognostic and therapeutic information.

Asociación entre hiperkaliemia y evolución clínica en la enfermedad renal crónica avanzada

IntroductionPatients with advanced chronic kidney disease (CKD) are at greatest risk of hyperkalemia (HK). The relationship between HK and negative outcomes (mortality or progression of renal insufficiency) in non-dialysis dependent CKD patients is controversial. AimsTo determine the incidence, prevalence, and factors related with HK in a cohort of CKD patients, and its relationship with mortality, hospitalization rate, CKD progression, and dialysis initiation. Material and methodsA retrospective, observational study in an incident cohort of adult patients with stage 4 or 5 CKD not on dialysis. Inclusion criteria were: having at least three consecutive estimated glomerular filtration rate (eGFR) measurements in a follow-up period >3 months. Decline in renal function was estimated as the slope of the individual linear regression line of eGFR over follow-up time. HK was defined as serum K levels ≥5.5 meq/l. Associations of HK with outcomes were adjusted for major confounding variables in the multivariate analysis. ResultsThe study group consisted of 1079 patients (574 males, mean age: 65±14 years) with mean baseline eGFR 14.8±4.5 ml/min/1,73 m2. Mean follow-up time was 15 months with a median of 7 serum sample determinations per patient. HK was observed at baseline in 26% of patients; in at least one serum sample during the individual follow-up period in 68%; or chronically (>50% of samples) in 33% of patients. By multivariate logistic regression, the best determinants of chronic HK were: male sex (OR = 1.529; 95% CI [1.154-2.025], p = .003), serum bicarbonate (OR = 0.863 [0.829-0.900], p <.0001), diuretic treatment (OR = 0.743 [0.556-0.992], p = .044), and angiotensin converting enzyme inhibitor and/or angiotensin receptor blockers (OR = 4.412 [2.915-6.678], p <.0001). Patients whose serum K levels were in the upper quartile showed a significantly faster CKD progression (−4.05±5.22 vs. −2.69±5.61 ml/min/1.73 m2/year, p <.0001), and more frequent dialysis initiation (63% vs. 57%, p = .115), though lower mortality (9% vs. 17%, p = .003) and hospitalization rates (2.68±5.94 vs. 3.16±6.77 days per year, p = .301) than the other study patients. However, in the multivariate analysis, average serum K levels were not independently associated with the clinical outcomes investigated. ConclusionHK is a common biochemical finding in non-dialysis dependent CKD patients, mainly associated with prescribed medication. However, HK was not independently associated with major negative clinical outcomes.

Exposure to vitamin k antagonists and kidney function decline in patients with atrial fibrillation and chronic kidney disease

BackgroundExposure to vitamin K antagonists (VKA) has been suggested to accelerate progression of chronic kidney disease (CKD) but robust clinical data are currently lacking. MethodsWe retrospectively evaluated the impact of VKA exposure on kidney function in patients with atrial fibrillation (AF) and CKD stage 3/4. Patients were prospectively followed within a primary care electronic database (median follow‐up of 1.45 years). The kidney function trajectory over time, defined as the annualized change in estimated glomerular filtration rate (eGFR), was analyzed with linear mixed‐effects regression including propensity score adjustment. Results14 432 patients (median age 78 years, median CHA2DS2‐VASc score 4 points) contributed 97 792 eGFR measurements (mean 6.8 measurements/patient; range: 1‐197). Mean baseline eGFR was 50.3 mL/min/1.73 m2; and declined by 1.10 mL/min/1.73 m2/year (95% CI: 0.91‐1.28, P<0.0001). In 7409 patients with VKA exposure, CKD progression was significantly faster compared to patients without VKA exposure (5‐year absolute eGFR loss from baseline: 6.0 mL/min/1.73 m2 vs 4.5 mL/min/1.73 m2, for an absolute 5‐year excess eGFR decline with VKA exposure of 1.5 mL/min/1.73 m2 (95% CI: 0.4‐2.7, P = 0.002). These results prevailed upon adjusting for CHA2DS2‐VASc score and other potential imbalances in prognostic variables, and in several sensitivity analyses. In the group without documented VKA exposure, 1775 VKA patients (24%) and 1012 patients (14%) developed a 30% decline in eGFR during follow‐up (P<0.0001). ConclusionsIn patients with AF and CKD, VKA use is associated with accelerated eGFR decline. Within the limitations of a retrospective analysis, this finding supports the “VKA‐renal‐calcification hypothesis.” However, although statistically significant, the excess loss in eGFR over 5 years with VKA was modest.

Hyperthyroidism influences renal function.

While the effects of hypothyroidism on renal function have been studied extensively, there is less information concerning the effect of hyperthyroidism. We aimed to elucidate the effect of overt and subclinical hyperthyroidism, on estimated glomerular filtration rate (eGFR) with large number of patients treated for hyperthyroidism and after euthyroidism was achieved. A total of 433 consecutive overt and subclinical hyperthyroid patients were included in the study. We assessed serum fT3, fT4, TSH, BUN, creatinine, and eGFR measurements during both hyperthyroid and euthyroid states of the same patients. The eGFR was calculated using the simplified modification of diet in renal disease (MDRD) Formula. Among these patients, 367 had overt, and 66 had subclinical hyperthyroidism. fT3, fT4, and eGFR measurements decreased, meanwhile BUN, creatinine and TSH levels increased significantly after euthyroidism was achieved (p < 0.0001 for all). The correlation analyses revealed that eGFR in hyperthyroid state (eGFRh) and fT3 in hyperthyroid state (fT3h) (r = 0,210, p < 0,0001), and fT4 in hyperthyroid state (fT4h) (r = 0,176, p < 0,0001) were significantly correlated. ∆GFR did not differ between overt hyperthyroid group and subclinical hyperthyroid group. We observed a significant decline in eGFR measurements after the patients became euthyroid. Some of these patients had lower values than 60 mL/min/1.73 m2, which mean that hyperthyroidism may be masking mild renal failure.

Clinical evidence that treatment of metabolic acidosis slows the progression of chronic kidney disease.

Purpose of reviewWe review the growing clinical evidence that metabolic acidosis mediates chronic kidney disease (CKD) progression and that treatment to increase the associated low serum bicarbonate (HCO3) in CKD is disease-modifying.Recent findingsSeven prospective studies of patients with wide ranges of estimated glomerular filtration rates (eGFRs) and serum HCO3 examined the effect on CKD of increasing serum HCO3 using dietary acid reduction with either oral alkali (sodium bicarbonate or sodium citrate), a vegetarian diet very low in acid-producing protein (0.3 g/kg/day) supplemented with ketoanalogues or added base-producing fruits and vegetables. Clinical outcomes included slower kidney function decline (using eGFR measurements) and fewer patients progressing to end-stage kidney disease. Post hoc analyses demonstrated that: treatment of metabolic acidosis for 2 years decreased the number of patients with at least a 40% eGFR decline, a validated surrogate for progression to end-stage kidney disease and across four studies, treatment to increase serum HCO3 by 4–6.8 mEq/l in acidotic patients with CKD was associated with a ∼4 ml/min/1.73 m2 reduction in the rate of eGFR decline over 6–24 months compared with controls.SummaryMetabolic acidosis appears to enhance CKD progression and its treatment should be studied further as a potential disease-modifying intervention.

Functional capacity, renal function and vitamin D in community-dwelling oldest old.

The aim of this study was to evaluate the association between the decline in estimated glomerular filtration rate (eGFR) and serum 25(OH)D with the physical and mental functional capacity of elderly individuals aged 80years or older. We evaluated the functional capacity in its multidomain aspects: Geriatric Depression Scale (GDS), Instrumental Activities of Daily Living (IADL), Mental State Mini-Exam (MMSE), Verbal Fluency Test (VF), handgrip strength and time to sit and rise from a chair five times, combined creatinine and cystatin C-based eGFR and 25(OH)D levels in 205 independent asymptomatic and community-dwelling elderly subjects in a cross-sectional study. Every 1year of life, there was reduction of about 10% chance of adequate performance in functional capacity. Each 1ml/min/m2 in eGFR was associated with 2% better chance of adequate performance in the IADL. We found no association between eGFR and cognition. Serum 25(OH)D between 15.00 and 22.29ng/ml increased the chance of better performance in VF, IADL, handgrip strength and sit and rise from the chair compared to the lower level of serum vitamin D. Decreased renal function associated with age compromises the ability to perform activities for independent life in the community, but we did not observe influence in specific domains of cognition and physical performance. Low serum level of 25(OH)D appears to be a marker of greater risk of functional decline than eGFR measurement in independent oldest old dwelling in the community.

Longitudinal kidney function trajectories predict major bleeding, hospitalization and death in patients with atrial fibrillation and chronic kidney disease

BackgroundChronic kidney disease (CKD), commonly described by estimated glomerular filtration rate (eGFR), is a frequent comorbidity in patients with atrial fibrillation (AF) and associated with thromboembolic and bleeding complications. Instead of single eGFR measurements, kidney function decline over time may better predict clinical outcomes but this has not been studied so far. MethodsPatients with AF and stage 3/4 CKD were prospectively followed within a primary care electronic database from the United Kingdom (IMS-THIN). The associations between the longitudinal eGFR trajectory of these patients and stroke/systemic embolism, major bleeding, first hospitalization-for-any-cause, and death-from-any-cause were estimated with joint models of longitudinal and time-to-event data. Results18,240 patients were included (median age 80.4 years, median CHA2DS2-VASc score 4). In 133,676 eGFR measurements (mean: 6 per patient) median “baseline” eGFR was 49 ml/min/1.73m2 [41–55] and mean eGFR decline was 0.54 ml/min/1.73m2/year (95%CI: 0.47–0.62). During follow-up (median 3.2 years; 50,841 patient-years at risk), 5-year cumulative incidence estimates were 9%, 3%, 32% and 76% for stroke/systemic embolism, major bleeding, hospitalization and death, respectively. In joint modeling, an accelerated decline in kidney function strongly predicted for a higher risk of major bleeding (hazard ratio [HR] 1.09 per ml/min/1.73m2/year increase in eGFR decline), hospitalization (HR 1.06), and death-from-any-cause (HR 1.11; all p < 0.05), but not for stroke/systemic embolism (HR 0.97; p = 0.239). ConclusionsDeclining kidney function is a critical determinant of unfavourable outcomes in patients with AF and CKD. Longitudinal kidney function trajectories may enable a much more individualized prediction of adverse outcomes in this vulnerable patient population.

Efficacy and Safety of Delayed Prolonged-Release Tacrolimus Initiation in De Novo Hepatitis C Virus-Negative Orthotopic Liver Transplant Recipients: A Single-Center, Single-Arm, Prospective Study.

BackgroundDelaying initiation of tacrolimus after liver transplantation (LT) is a potential renal-sparing strategy. We assessed safety and efficacy of delayed initiation of prolonged-release tacrolimus (PR-T) in de novo LT.Material/MethodsThis was a single-center, single-arm, prospective, 12-month observational study of hepatitis C virus-negative orthotopic LT patients. Immunosuppression included PR-T (initially 0.1 or 0.2 mg/kg/day) initiated on Day 3 post LT, basiliximab (20 mg) on post-transplantation Day 0 and Day 4, and intraoperative corticosteroids (500 mg). Patients received maintenance corticosteroids and mycophenolate mofetil (MMF) according to center protocol. MMF dose was adjusted according to thrombocyte count. The primary endpoint was the estimated glomerular filtration rate (eGFR) measured using the Modification of Diet in Renal Disease 4-variable formula at 12 months. Secondary endpoints included biopsy-confirmed acute rejection (BCAR) and dialysis requirement. Adverse events were recorded.ResultsSixty-nine patients (mean age 55.0 years) were included. Most patients started MMF on Day 1 (60.9%) or Day 2 (10.1%), and PR-T on Day 3 (55.1%) or Day 4 (29.0%). Mean tacrolimus trough levels (ng/mL) were: Day 7, 9.5±6.3; Day 10, 9.4±5.4; Month 1, 8.0±3.1; Month 3, 7.8±3.7; Month 6, 8.0±4.1; and Month 12, 7.2±3.1. Mean 12-month eGFR was 77.2±24.5 mL/min/1.73 m2; 72.5% of patients had eGFR >60 mL/min/1.73 m2 at 12 months; 89.9% had no eGFR measurements <40 mL/min/1.73 m2 during the study. Renal insufficiency (any eGFR <60 mL/min/1.73 m2) was diagnosed in 27.5% of patients; one patient required dialysis. There were no BCAR episodes; the infection rate was 36.2%, and 3 patients died. Overall, 19 patients (27.5%) developed de novo diabetes mellitus, 18 patients (26.1%) had hypercholesterolemia, and 12 patients (17.4%) had hypertriglyceridemia.ConclusionsQuadruple therapy with delayed administration of PR-T was well tolerated and efficacious, and was associated with acceptable renal function over 12 months.

Identification of young adults at risk of an accelerated loss of kidney function in an area affected by Mesoamerican nephropathy

BackgroundAfter two-years of follow-up of 263 apparently healthy 18- to 30-year-old men in communities affected by Mesoamerican nephropathy (MeN), we identified three distinct case groups: a subgroup with (i) established renal dysfunction (case-group 1); individuals with (ii) a rapid decline in kidney function (case-group 2); and individuals with (iii) stable kidney function (non-cases). This paper investigates whether local tests are potentially useful for the timely identification of these case groups.MethodsCreatinine levels were measured in local laboratories every six months for two years. Aliquots were sent to a centralized laboratory for measurements of cystatin C and creatinine levels. We investigated agreement between the locally and centrally measured creatinine-based Chronic Kidney disease Epidemiology Collaboration (CKD-EPI) equation for estimating the Glomerular Filtration Rate (eGFR). A logistic regression analysis was used to assess predictive factors for case groups 1 and 2 compared to non-cases. Predictive variables were locally measured eGFR, and urinary neutrophil gelatinase-associated lipocalin (uNGAL) levels. The discrimination performance of the model was assessed using the area under the receiver operating characteristic curve (AUC).ResultsConsiderable variation in local eGFR measurements was observed. The prediction model for case-group 1 included baseline kidney function and with or without uNGAL (AUC = 0.98, 95% confidence interval (CI), 0.91–1.00). The prediction model for case-group 2 also required eGFRScr at six and twelve months after baseline, with or without uNGAL levels (AUC = 0.88; 95% CI 0.80–0.99).ConclusionsEstablished renal dysfunction was detected at a single time point using local measurements and uNGAL. For the detection of a rapid decline in kidney function over time, at least 2 more measurements at six and twelve months are needed.

Estimation of renal function in patients with liver cirrhosis: Impact of muscle mass and sex

Accurate evaluation of renal function in patients with liver cirrhosis is critical for clinical management. However, there are still discrepancies between the measured glomerular filtration rate (mGFR) and creatinine-based estimated GFR (eGFR). In this study, we compared the performance of 2 common eGFR measurements with mGFR and evaluated the impact of low muscle mass on overestimation of renal function in patients with cirrhosis. This study included 779 consecutive cirrhotic patients who underwent 51Cr-ethylenediamine tetra acetic acid (EDTA) (as a mGFR) and abdominal computed tomography (CT). The eGFR was calculated using creatinine or cystatin C. Muscle mass was assessed in terms of the total skeletal muscle at L3 level using CT. Modification of diet in renal disease (MDRD)-eGFR was overestimated in 47% of patients. A multivariate analysis showed that female sex (adjusted odds ratio [aOR] 4.91), Child B and C vs. A (aOR 1.69 and 1.84) and skeletal muscle mass (aOR 0.89) were independent risk factors associated with overestimation. Interestingly, the effect of skeletal muscle mass on overestimation varied based on sex. Decreased muscle mass significantly enhanced the risk of overestimation of MDRD-eGFR in male patients, but not in female patients. Cystatin C-based eGFR showed a better correlation with mGFR than MDRD-eGFR; it was also better at predicting overall survival and the incidence of acute kidney injury than MDRD-eGFR. The risk factors associated with overestimation included female sex, impaired liver function, and decreased muscle mass in males. In particular, eGFR in male patients with sarcopenia should be carefully interpreted. Creatinine-based eGFR was overestimated more often than cystatin C-based eGFR, with overestimation of eGFR closely related to poor prognostic performance. Overestimation of renal function frequently occurs in patients with liver cirrhosis when using serum creatinine. Decreased muscle mass has a great impact on overestimation of kidney function especially in male patients with cirrhosis. Compared with creatinine, cystatin C was more closely correlated with measured glomerular filtration rate and had a higher predictive ability for renal complications and survival than creatinine.

Significance of the difference in the estimates of glomerular filtration rate obtained using different models.

Chronic kidney disease (CKD) prevalence is rising in Nigeria. Most cases are diagnosed as end stage disease despite availability of formulae to estimate glomerular filtration rate (GFR). Existing formulae, none of which is modelled on Nigerian variables, give different estimates. This study tests the significance of the difference in the estimates obtained using Modified Diet in Renal Disease (MDRD) Study and Chronic Kidney Disease-Epidemiology (CKD-Epi) formulae. This is a cross-sectional study. Data on age, gender, and serum creatinine were used to estimate GFR. Paired sample t test was used to check for difference in means, Pearson correlation test for correlation and Bland and Altman plot for systematic bias. Simple linear regression was used to check for presence and significance of proportional bias. Of the 166 patients studied, 62 were males and 104 were females. Mean age was 49.06 years ± 15.26. Youngest was 18 years and the oldest 81 years. Mean eGFR of 69.4 and 72.77 ml/min/1.73m2 for MDRD and CKD-Epi models respectively differed significantly, P < 0.001. Bland and Altman plot showed lack of agreement of eGFR estimates from the two models with significant bias of -3.37ml/min/1.73m2 despite good correlation, r = 0.984. There was significant proportional bias, P < 0.001. MDRD significantly underestimated GFR compared to CKD-Epi in a Nigerian population. This bias was proportional and increased as mean eGFR increased. MDRD and CKD-Epi models do not agree in their measurements of eGFR and should not be used interchangeably. There is urgent need for further studies to develop GFR estimating model on Nigerian variables.

Presence of Carotid Plaque Is Associated with Rapid Renal Function Decline in Patients with Type 2 Diabetes Mellitus and Normal Renal Function.

BackgroundRecent evidences indicate that early rapid renal function decline is closely associated with the development and progression of diabetic kidney disease. We have investigated the association between carotid atherosclerosis and rapid renal function decline in patients with type 2 diabetes mellitus and preserved renal function.MethodsIn a prospective, multicenter cohort, a total of 967 patients with type 2 diabetes mellitus and preserved renal function were followed for 6 years with serial estimated glomerular filtration rate (eGFR) measurements. Common carotid intima-media thickness (CIMT) and presence of carotid plaque were assessed at baseline. Rapid renal function decline was defined as an eGFR decline >3.3% per year.ResultsOver a median follow-up of 6 years, 158 participants (16.3%) developed rapid renal function decline. While there was no difference in CIMT, the presence of carotid plaque in rapid decliners was significantly higher than in non-decliners (23.2% vs. 12.2%, P<0.001). In multivariable logistic regression analysis, presence of carotid plaque was an independent predictor of rapid renal function decline (odds ratio, 2.33; 95% confidence interval, 1.48 to 3.68; P<0.0001) after adjustment for established risk factors. The model including the carotid plaque had better performance for discrimination of rapid renal function decline than the model without carotid plaque (area under the receiver operating characteristic curve 0.772 vs. 0.744, P=0.016).ConclusionClose monitoring of renal function and early intensive management may be beneficial in patients with type 2 diabetes mellitus and carotid plaques.

Epidemiology of chronic kidney disease in Australian general practice: National Prescribing Service MedicineWise MedicineInsight dataset.

ABSTRACTAimTo describe sociodemographic characteristics and comorbidities of a large cohort of Australian general practice‐based patients identified as having chronic kidney disease (CKD), using data from National Prescribing Service (NPS) MedicineWise's MedicineInsight dataset, and compare this dataset to the 2011–2012 Australian Health Survey's (AHS) CKD prevalence estimates.MethodsThis was a cohort study using deidentified, longitudinal, electronic health record data collected from 329 practices and 1 483 416 patients distributed across Australia, from 1 June 2013 until 1 June 2016. Two methods were used to calculate the CKD prevalence. One used the same method as used by the 2011–2012 AHS, based on one estimate of the estimated glomerular filtration rate (eGFR) or albumin/creatinine ratios (ACR). The other defined CKD more rigorously using eGFR or ACR results at least 90 days apart.ResultsIn 2016, of 1 310 602 active patients, 710 674 (54.2%) did not have an eGFR or ACR test, while 524 961 (40.1%) had an eGFR or ACR test but did not meet AHS criteria for CKD. Age–sex adjusted rates of CKD (compared to AHS) were CKD 1–0.45% (3.9%), CKD 2–0.62% (2.5%), CKD 3a: 3.1% (2.7%), CKD 3b: 1.14% (0.6%), CKD 4–5: 0.41% (0.3%). The CKD cohort defined more rigorously using eGFR and ACR measures >90 days apart, had comorbidities of atrial fibrillation (30.5%), cardiovascular disease (25.0%), diabetes mellitus (17.1%) and hypertension (14.8%).ConclusionThe MedicineInsight dataset contains valuable and timely information about Australian patients with CKD, and provides prevalence estimates similar to those from AHS data.

Rapid Decline in Kidney Function in Sickle Cell Disease

Introduction:Chronic kidney disease (CKD) is common in sickle cell disease (SCD). We have recently reported on the progression of CKD in SCD and factors associated with it (Ciccone EJ et al, ASH, 2016). The purpose of this study was to evaluate the prevalence of rapid decline in kidney function, factors associated with such decline, and the association of rapid decline in kidney function with mortality in adult patients with SCD.Methods: We conducted a retrospective study of patients seen between July 2004 and December 2013 at an adult Sickle Cell Clinic. Patients had confirmed diagnoses of SCD, were at least 18 years old, and were in non-crisis state. We excluded patients with histories of HIV, hepatitis B and C, or systemic lupus erythematosus. Clinical and laboratory variables were obtained from medical records. Estimated glomerular filtration rate (eGFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration equation. Rapid decline of kidney function was defined as eGFR loss of >3.0 ml/min/1.73 m2per year during the observation period.Logistic regression was used to model the association of rapid eGFR decline with clinical and laboratory variables, adjusting for age and sex. Multivariable analysis with variable selection was performed with backward elimination from the following initial variables - hemoglobin, reticulocyte count, lactate dehydrogenase, baseline eGFR, history of stroke, hydroxyurea therapy, systolic blood pressure, use of ACE inhibitors/angiotensin receptor blockers (ACE-I/ARB) and history of diabetes. Since proteinuria measures were missing for many patients, we performed sensitivity analyses with 1) exclusion of proteinuria, 2) inclusion of only patients with available values, 3) assignment of no proteinuria to those missing values, or 4) assignment of proteinuria to those missing values. Age- and sex- adjusted Cox proportional hazards models were used to evaluate the association of the slope of eGFR (continuous variable) or rapid decline in eGFR (binary variable) with mortality. The slope of eGFR was estimated by linear regression modeling of eGFR over time. Kaplan-Meier estimates of survival probabilities for rapid and non-rapid decline groups were obtained, and the log-rank test was used to compare the survival probabilities for the two groups.Results: Three hundred and thirty-one SCD patients with at least two eGFR measurements(SS = 218, SC = 67, Sβ0= 18, Sβ+= 22, SE = 2, SD = 2, SHPFH = 2), median age of 29 years (IQR: 20 - 41 years) were evaluated and followed for a median of 4.01 years (IQR: 1.66, 7.19). Rapid decline of eGFR (>3.0 ml/min/1.73 m2per year) was noted in 103 (31.1%) patients; 80 (33.9%) with severe genotype (HbSS/HbSβ0thalassemia) and 21 (23.6%) with mild genotype (HbSC/HbSβ+thalassemia).Baseline laboratory factors significantly associated with rapid decline in eGFR were hemoglobin (p = 0.007), ferritin (p = 0.01), and baseline eGFR (p = 0.01) (Table 1). There was a trend towards an association (p = 0.06) with baseline proteinuria (at least 1+ on dipstick urinalysis). Clinical variables significantly associated with eGFR decline were history of stroke (p = 0.002) and use of ACE-I/ARB (p = 0.006). In multivariable analysis, history of stroke (estimate: 1.07, p = 0.01) and use of ACE-I/ARB (estimate: 1.15, p = 0.01) were associated with rapid eGFR decline when proteinuria was excluded from the model or proteinuria status was assigned to those with missing values. When we limited the dataset to those with available values for proteinuria, only history of stroke (estimate: 2.00, p = 0.007) was associated with rapid decline in eGFR. Finally, we observed an association of the slope of eGFR change over time with mortality (hazard ratio [HR]: 0.99, p = 0.0002). Rapid decline in eGFR was significantly associated with increased mortality compared with eGFR decline of ≤ 3 ml/min/1.73 m2per year (HR: 2.40, p = 0.005). Kaplan-Meier estimates also showed significantly lower survival probabilities for patients with rapid eGFR decline (log-rank test; p = 0.0002) (Figure 1).Conclusion:Rapid decline in eGFR is common in SCD. Use of ACE-I/ARB and history of stroke are associated with rapid decline in renal function. Rapid decline in eGFR is associated with an increased risk of death in SCD. Long-term studies are required to determine if therapies that may reduce loss of kidney function may decrease mortality in SCD. [Display omitted] DisclosuresAtaga:Pfizer: Research Funding; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Honoraria; Modus Therapeutics: Honoraria; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Is there a correlation between an eGFR slope measured over a 5-year period and incident cardiovascular events in the following 5 years among a Flemish general practice population: a retrospective cohort study

ObjectivesTo examine if the estimated glomerular filtration rate (eGFR) slope over a 5-year period is related to incident cardiovascular (CV) events in the following 5 years.DesignRetrospective cohort study.SettingPrimary care.ParticipantsAll patients...

Dose-Dependent Effect of Enzyme Replacement Therapy on Neutralizing Antidrug Antibody Titers and Clinical Outcome in Patients with Fabry Disease.

Use of enzyme replacement therapy (ERT) to treat Fabry disease, caused by deficient lysosomal α-galactosidase A activity, can lead to formation of neutralizing antidrug antibodies (ADAs). These antibodies are associated with increased accumulation of plasma globotriaosylceramide (Gb3) and disease progression. Because agalsidase ERT can saturate ADA-binding sites during infusions (achieving agalsidase/antibody equilibrium), we investigated in this open cohort study whether saturated patients (who have excess agalsidase after infusions) experience better clinical outcomes compared with not saturated patients (who have excess ADAs after infusions). We isolated ADAs from sera of 26 men with Fabry disease receiving ERT (for a median of 94 months) and determined the amount of agalsidase necessary for antibody saturation. Clinical and biochemical outcomes included measurements of eGFR, interventricular septum thickness, and lyso-Gb3. ADA titers decreased significantly in all patients during infusion. Agalsidase-α and agalsidase-β had similar ADA-binding capacity and comparable ADA saturation frequency. Fourteen patients with saturated ADAs presented with mild (but significant) loss of eGFR, stable septum thickness, and significantly decreased lyso-Gb3 levels. The 12 not saturated patients had a more pronounced and significant loss of eGFR, increased septum thickness, and a smaller, nonsignificant reduction in lyso-Gb3, over time. In three patients, dose escalation resulted in partially elevated ADA titers, but importantly, also in reduced lyso-Gb3 levels. A not saturated ADA status during infusion is associated with progressive loss of eGFR and ongoing cardiac hypertrophy. Dose escalation can result in saturation of ADAs and decreasing lyso-Gb3 levels, but may lead to increased ADA titers.