MO394TWO POINT ESTIMATE OF KINETIC GFR IN ACUTE KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Frieder Keller

Abstract Background and Aims When anuria suddenly occurs, the rise in creatinine and consequently the decrease in the estimated glomerular filtration rate (eGFR) will always be delayed. Thus, the drug dose could be selected too high in the progressive phase whereas it could be adjusted too low in the restitution phase of acute kidney disease (AKD). Sheldon Chen proposed a solution for changing kidney function with the kinetic GFR (KeGFR). A simplified but also more general solution (kinetGFR) might even facilitate the automatic implementation into lab systems. Method Deterioration of kidney function is diagnosed when the creatinine increases within a definite time interval (Δ t) and the estimated eGFR declines (Δ eGFR). The new 2-point estimate of the kinetGFR can be derived when the prospective eGFRt+24 predicted for the next day (t+24) will be set equal to the present true GFR at critical day (t2). kinetGFR=eGFR2−eGFR1−eGFR2t2−t1⋅t+24 h The 24 h delay follows from anuria, the most extreme and most relevant case (GFR = 0). A zero GFR will be associated with a linear rise in creatinine according to the constant production rate by roughly 100 µmol/l every day. This rise leads to the corresponding bisection of the estimated eGFR nearly every day (100 => 50 => 25 => 13 => … ml/min). The curvilinear eGFR decline will never become zero even after > 2 weeks. The new kinetGFR can identify a complete anuria already after one day (24 h). kinetGFR=50−100−5024−0⋅24=0.0 ml/min This is already at the critical day (t2). Results The retrospective look at the anonymized data from 20 patients with AKD allowed for comparing the former KeGFR with the new two-point kinetGFR estimate. For worsening kidney function, the average eGFR2 was 18 ml/min (+ 12) and the KeGFR estimate was not different with 19 ml/min (+ 17). The new 2-point kinetGFR, however, was 13 ml/min (+ 11) and 28 % less than eGFR2 at the critical day (t2). For improving kidney function, the eGFR2 was 15 ml/min (+ 4) and the KeGFR was already much higher at 27 ml/min (+ 3). The new 2-point estimate of the kinetGFR was in between at 21 ml/min (+ 7). Conclusion In AKD, the difference between eGFR and presumably true GFR was the higher the more rapidly kidney function declined. The new kinetGFR estimate appears clinically more plausible than the former KeGFR estimates.

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 504
Author(s):  
Stefanos Roumeliotis ◽  
Panagiotis I. Georgianos ◽  
Athanasios Roumeliotis ◽  
Theodoros Eleftheriadis ◽  
Aikaterini Stamou ◽  
...  

Proteinuria is characterized by low accuracy for predicting onset and development of diabetic kidney disease (DKD) because it is not directly associated with molecular changes that promote DKD, but is a result of kidney damage. Oxidized low-density lipoprotein (ox-LDL) reflects oxidative stress and endothelial dysfunction, both underlying the development of proteinuria and loss of kidney function in DKD. We aimed to investigate whether ox-LDL modifies the association between proteinuria and progression of DKD in a cohort of 91 patients with proteinuric DKD and diabetic retinopathy, followed for 10 years. The primary endpoint was a combined kidney outcome of eGFR decline ≥30% or progression to end-stage kidney disease. After the end of the study, we considered the percentage change of eGFR over time as our secondary outcome. Proteinuria was associated with both outcomes, and ox-LDL amplified the magnitude of this link (p < 0.0001 for primary and p < 0.0001 for secondary outcome, respectively). After adjustment for duration of diabetes, history of cardiovascular disease and serum albumin, ox-LDL remained a significant effect modifier of the association between proteinuria and eGFR decline over time (p = 0.04). Our study shows that in proteinuric DKD, circulating ox-LDL levels amplified the magnitude of the association between proteinuria and progression of DKD.


2019 ◽  
Vol 50 (5) ◽  
pp. 401-410 ◽  
Author(s):  
Simon B. Ascher ◽  
Rebecca Scherzer ◽  
Michelle M. Estrella ◽  
Michael G. Shlipak ◽  
Derek K. Ng ◽  
...  

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV–) men. Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV– men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR. Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV– men. Among HIV+ men, the highest vs. lowest tertiles of albumin (–1.78 mL/min/1.73 m2/year, 95% CI –3.47 to –0.09) and α1m (–2.43 mL/min/1.73 m2/year, 95% CI –4.14 to –0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV– men, the highest vs. lowest tertile of α1m (–2.49 mL/min/1.73 m2/year, 95% CI –4.48 to –0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus. Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.


Author(s):  
Chris H L Thio ◽  
Sander K R van Zon ◽  
Peter J van der Most ◽  
Harold Snieder ◽  
Ute Bültmann ◽  
...  

Abstract Both genetic predisposition and low educational attainment (EA) are associated with higher risk of chronic kidney disease. We examined the interaction of EA and genetic risk in kidney function outcomes. We included 3,597 participants from the Prevention of REnal and Vascular ENd stage Disease Cohort Study, a longitudinal study in a community-based sample from Groningen, the Netherlands (median follow-up 11 years, 1997-2012). Kidney function was approximated by estimating glomerular filtration rate (eGFR) from serum creatinine and cystatin C. Individual longitudinal linear eGFR trajectories were derived from linear mixed models. Genotype data on 63 single nucleotide polymorphisms, with known associations to eGFR, were used to calculate an allele-weighted genetic score (WGS). EA was categorized into high, medium, and low. In ordinary least squares analysis, higher WGS and lower EA showed additive effects on reduced baseline eGFR; the interaction term was non-significant. In analysis of eGFR decline, the significant interaction term suggested amplification of genetic risk by low EA. Adjustment for known renal risk factors did not affect our results. This study presents the first evidence of gene-environment interaction between EA and a WGS on eGFR decline, and provides population-level insights into the mechanisms underlying socioeconomic disparities in chronic kidney disease.


2020 ◽  
Vol 33 (11) ◽  
pp. 1003-1010
Author(s):  
Seiji Itano ◽  
Yuichiro Yano ◽  
Hajime Nagasu ◽  
Hirofumi Tomiyama ◽  
Hiroshi Kanegae ◽  
...  

Abstract BACKGROUND Our aims were to assess whether arterial stiffness is associated with a higher risk for kidney dysfunction among persons without chronic kidney disease (CKD). METHODS We analyzed data from the national health checkup system in Japan; for our analyses, we selected records of individuals who completed assessments of cardio-ankle vascular index (CAVI) and kidney function from 2005 to 2016. We excluded participants who had CKD at baseline, defined as the presence of proteinuria or estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73 m2. We compared 2 groups of CAVI measurements—the highest quartile (≧8.1) and the combined lower 3 quartiles (&lt;8.1). We used Cox proportional hazards models to assess associations between these 2 groups and subsequent CKD events, proteinuria, eGFR &lt;60 ml/min/1.73 m2, and rapid eGFR decline (greater than or equal to −3 ml/min/1.73 m2 per year). RESULTS The mean age of the 24,297 included participants was 46.2 years, and 60% were female. Over a mean follow-up of 3.1 years, 1,435 CKD events occurred. In a multivariable analysis, the hazard ratios with 95% confidence intervals (CIs) for the highest vs. combined lower quartiles of CAVI measurements were 1.3 (1.1, 1.5) for CKD events, 1.3 (0.96, 1.62) for proteinuria, 1.4 (1.1, 1.7) for eGFR &lt;60 ml/min/1.73 m2, and the odds ratio with 95% CI was 1.3 (1.1, 1.4) for rapid eGFR decline. CONCLUSIONS Persons with CAVI measurements ≧8.1 had a higher risk for CKD events compared with their counterparts with CAVI measurements &lt;8.1. Greater arterial stiffness among adults without CKD may be associated with kidney dysfunction.


2016 ◽  
Vol 44 (5) ◽  
pp. 381-387 ◽  
Author(s):  
Casey M. Rebholz ◽  
Adrienne Tin ◽  
Yang Liu ◽  
Marie Fanelli Kuczmarski ◽  
Michele K. Evans ◽  
...  

Background: Prior studies suggest that certain aspects of the diet related to magnesium intake, such as dietary acid load, protein intake and dietary patterns rich in fruits and vegetables, may impact kidney disease risk. We hypothesized that lower dietary magnesium intake would be prospectively associated with more rapid kidney function decline. Methods: Among participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 at baseline (2004-2009), dietary magnesium intake was calculated from two 24-hour dietary recalls. Rapid decline was defined as ≥3% eGFR decline per year. Results: Median (25th-75th percentile) dietary magnesium intake was 116 (96-356) mg/1,000 kcal. Among 1,252 participants, those with lower dietary magnesium intake were younger, and were more likely to be African-American men. A total of 177 participants (14.1%) experienced rapid eGFR decline over a median follow-up of 5 years. Lower dietary magnesium intake was significantly associated with a greater odds of rapid eGFR decline (OR for tertile 1 vs. 3: 2.02, 95% CI 1.05-3.86, p value for trend across tertiles = 0.02) in analyses adjusted for sociodemographics (age, sex, race, education level, health insurance status, poverty status), kidney disease risk factors (smoking status, diabetes, hemoglobin A1c, hypertension, body mass index), baseline eGFR and dietary factors (total energy intake; diet quality; dietary intake of fiber, sodium, calcium, potassium and phosphorus). Conclusions: In this urban population, lower dietary magnesium intake was independently associated with greater odds of rapid kidney function decline.


BMJ Open ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. e051165
Author(s):  
Chun-Fu Lai ◽  
Jian-Jhong Wang ◽  
Ya-Chun Tu ◽  
Chia-Yu Hsu ◽  
Hon-Yen Wu ◽  
...  

ObjectivesTo examine whether urinary excretion of cysteine-rich protein 61 (Cyr61), an acknowledged proinflammatory factor in kidney pathologies, increases in chronic kidney disease (CKD) and is associated with subsequent rapid kidney function decline.DesignAn observational cohort study.SettingIn the nephrology outpatient clinics of a tertiary hospital in Taiwan.ParticipantsWe enrolled 138 adult CKD outpatients (n=12, 32, 18, 18, 29 and 29 in stages 1, 2, 3a, 3b, 4 and 5 CKD, respectively) between February and October 2014 and followed them for 1 year. Their mean age was 60.46±13.16 years, and 51 (37%) of them were women.Primary outcome measuresUrinary Cyr61 levels were measured by ELISA. Rapid kidney function decline was defined as an estimated glomerular filtration rate (eGFR) decline rate ≥ 4 mL/min/1.73 m2/year or developing end-stage renal disease during subsequent 3-month or 1-year follow-up period. Models were adjusted for demographic and clinical variables.ResultsThe urine Cyr61-to-creatinine ratio (UCyr61CR) increased significantly in patients with stage 4 or 5 CKD. Multivariable linear regression analysis showed that log(UCyr61CR) was positively correlated with log(urine protein-to-creatinine ratio) (p<0.001) but negatively correlated with baseline eGFR (p<0.001) and hypertension (p=0.007). Complete serum creatinine data during the follow-up were available for 112 patients (81.2%). Among them, multivariable logistic regression identified log(UCyr61CR) was independently associated with rapid kidney function decline (adjusted OR 2.29, 95% CI 1.27 to 4.15) during the subsequent 3 months. UCyr61CR improved the discriminative performance of clinical models to predict 3-month rapid kidney function decline. In contrast, log(UCyr61CR) was not associated with rapid eGFR decline during the entire 1-year follow-up.ConclusionsElevated urinary Cyr61 excretion is associated with rapid short-term kidney function deterioration in patients with CKD. Measuring urinary Cyr61 excretion is clinically valuable for monitoring disease trajectory and may guide treatment planning.


2021 ◽  
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  

<b>Objective: </b>Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. <p><b>Research Design and Methods: </b>Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. </p> <p><b>Results: </b>At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (p<sub>heterogeneity</sub> ≥0.35). </p> <p><b>Conclusions: </b>The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.</p>


2021 ◽  
Author(s):  
Hajime Nagasu ◽  
Yuichiro Yano ◽  
Hiroshi Kanegae ◽  
Hiddo J.L. Heerspink ◽  
Masaomi Nangaku ◽  
...  

<b>Objective: </b>Randomized controlled trials have shown kidney protective effects of sodium glucose transporter 2 (SGLT2) inhibitors, and clinical practice databases have suggested that these effects translate to clinical practice. However, long-term efficacy as well as whether the presence or absence of proteinuria and the rate of estimated glomerular filtration rates (eGFR) decline prior to SGLT2 inhibitors initiation modifies treatment efficacy among type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) patients is unknown. <p><b>Research Design and Methods: </b>Using the Japan Chronic Kidney Disease Database (J-CKD-DB), a nationwide multicenter CKD registry, we developed propensity scores for SGLT2 inhibitor initiation, with 1:1 matching with patients who were initiated on other glucose-lowering drugs. The primary outcome included rate of eGFR decline, and the secondary outcomes included a composite outcome of 50% eGFR decline or end-stage kidney disease. </p> <p><b>Results: </b>At baseline, mean age at initiation of the SGLT2 inhibitor (n=1,033) or other glucose-lowering drug (n=1,033) was 64.4 years; mean eGFR was 68.1 mL/min per 1.73 m²; and proteinuria was apparent in 578 (28.0%) of included patients. During follow-up, SGLT2 inhibitor initiation was associated with reduced eGFR decline (difference in slope for SGLT2 inhibitors vs other drugs 0.75 mL/min/1.73 m² per year (0.51 to 1.00). During a mean follow-up of 24 months, 103 c<a>omposite kidney outcomes </a>occurred: 30 (14 events per 1,000 patient-years) among the SGLT2 inhibitors group and 73 (36 events per 1,000 patient-years) among the other drugs group (hazard ratio 0.40, 95% CI 0.26 to 0.61). The benefit provided by SGLT2 inhibitors was consistent irrespective of proteinuria and rate of eGFR decline before initiating SGLT2 inhibitors (p<sub>heterogeneity</sub> ≥0.35). </p> <p><b>Conclusions: </b>The benefits of SGLT2 inhibitors on kidney function as observed in clinical trials translate to patients treated in clinical practice with no evidence that the effects are modified by the underlying rate of kidney function decline or the presence of proteinuria.</p>


2018 ◽  
Vol 314 (5) ◽  
pp. F985-F991 ◽  
Author(s):  
Nimrit Goraya ◽  
Jan Simoni ◽  
Lauren N. Sager ◽  
Jessica Pruszynski ◽  
Donald E. Wesson

Greater H+ retention in animal models of chronic kidney disease (CKD) mediates faster glomerular filtration rate (GFR) decline and dietary H+ reduction slows eGFR decline in CKD patients with reduced eGFR and H+ retention due to the high acid (H+) diets of developed societies. We examined if H+ retention in CKD is inversely associated with estimated GFR (eGFR) using cross-sectional and longitudinal analysis of individuals with CKD stage 1 (>90 ml·min− 1·1.73 m−2), CKD stage 2 (60–89 ml/min per 1.73 m2), and CKD stage 3 (30–59 ml·min− 1·1.73 m−2) eGFR. H+ retention was assessed using the difference between observed and expected plasma total CO2 2 h after 0.5 meq/kg body wt oral NaHCO3. H+ retention was higher in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.02) at baseline and 5 yr, and was higher in CKD 2 vs. CKD 1 ( P < 0.01) at 10 yr. All groups had lower eGFR at subsequent time points ( P < 0.01) but H+ retention was not different among the three time points for CKD 1. By contrast, eGFR decrease was associated with higher H+ retention in CKD 2 at 5 yr ( P = 0.04) and 10 yr ( P < 0.01) and with higher H+ retention in CKD 3 at 5 yr ( P < 0.01). Yearly eGFR decline rate was faster in CKD 2 vs. CKD 1 ( P < 0.01) and in CKD 3 vs. CKD 2 ( P < 0.01). The data show that H+ retention is inversely associated with eGFR, with faster eGFR decline, and support the need for greater dietary H+ reduction therapy for CKD individuals with lower eGFR.


2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chenyu Li ◽  
Long Zhao ◽  
Lingyu Xu ◽  
Chen Guan ◽  
Zhibo Zhao ◽  
...  

Abstract Background and Aims The current diagnostic criteria for acute kidney injury (AKI) predict the need for dialysis and early mortality, but are less useful to predict long-term outcomes. Acute kidney disease (AKD) defines patients with AKI or subacute loss of kidney function lasting for more than 7 days, which should predict better subsequent chronic kidney disease (CKD). The aim of this study was to investigate the risk factors and prognosis of AKD and to compare different types of acute/subacute renal impairment among Chinese inpatients. Method From a cohort of 450,000 patients consecutive admitted from June 1, 2012, to March 31, 2018 to five district hospitals, complete data were available from 71,041 inpatients. AKI and AKD were diagnosed based on the Acute Disease Quality Initiative Criteria 2017. Based on this diagnostic criterion of AKI and AKD, patients were classified as having (1) AKI Recover, if Scr back to baseline value within 7 days (renal impairment duration of less than 7 days or rapid recovery within 7 days), and (2) AKD with AKI, if a condition in which stage 1 or greater AKI was present ≥ 7 days after an AKI initiating event (continuous AKI progressing to AKD), (3) AKD without AKI, if Scr levels increased slowly but lasted more than 7 days (subacute AKD without meeting the AKI criterion). Results Of 71,041 inpatients, 16,098 (22.66%) patients developed AKI or AKD. 5,895 (8.30%) AKI patients recovered within 7 days (AKI Recover), 5,623 (7.91%) were followed by AKD and 4,580 (6.44%) patients developed AKD without AKI. Thus, AKI and AKD are frequent complications in Chinese inpatients (Fig 1). Compared to AKI recover or AKD without AKI, patients with AKI followed by AKD had higher hospital mortality (16.59% vs. 3.82% vs. 2.12%, P&lt;0.05) and more de novo CKD (8.95% vs. 7.29% vs. 5.48%, P&lt;0.05). Mortality was proportional to stages of AKI and AKD (P for trend &lt;0.05), while AKI followed by AKD was associated with a higher risk of long-term mortality (hazard ratio (HR) 4.51, 4.32-4.71, P&lt;0.05) as compared to AKD without AKI (HR 2.25, 2.13-2.39, P&lt;0.05) and AKI Recover (HR 1.18, 1.09-1.26, P&lt;0.05). The AKI criterion yielded a higher risk for overall survival and a lower risk for de novo CKD than the AKD criterion, indicating that both criteria imply persistent kidney damage but that a rapid decline in excretory kidney function implies higher mortality risks while a persistent decline may rather result in de novo CKD (Fig 2). Meanwhile, these associations between different kidney injury criteria and outcomes had good generalizability and were constant across different genders, surgeries, and comorbidities (Fig 2). The AKD criterion was robustly associated with overall survival (area under the receiver operating characteristic curve (AUROC) 0.71) and de novo CKD (AUROC 0.71), while AKI criterion showed a relatively lower ability to fitting risk of overall survival (AUROC 0.65, P&lt;0.05) and CKD (AUROC 0.63, P&lt;0.05). Moreover, combining AKI and AKD was strongly associated with long-term mortality (AUROC 0.725) and de novo CKD (AUROC 0.72) compared to each single criterion of AKI or AKD (Fig 3). Conclusion (1) Adding AKD as a definition for renal failure lasting &gt;7 days up to 90 days is of clinical importance in addition to the existing definitions for AKI and CKD. (2) These findings suggest research activities and clinical practice should also focus on AKD, which is far more accurate to predict subsequent de novo CKD.


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