egfr slope
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Diabetes Care ◽  
2022 ◽  
Author(s):  
Bruce A. Perkins ◽  
Ionut Bebu ◽  
Xiaoyu Gao ◽  
Amy B. Karger ◽  
Irl B. Hirsch ◽  
...  

OBJECTIVE Rapid loss of estimated glomerular filtration rate (eGFR) within its normal range has been proposed as a strong predictor of future kidney disease. We investigated this association of eGFR slope early in the course of type 1 diabetes with long-term incidence of kidney and cardiovascular complications. RESEARCH DESIGN AND METHODS The annual percentage change in eGFR (slope) was calculated during the Diabetes Control and Complications Trial (DCCT) for each of 1,441 participants over a mean of 6.5 years and dichotomized by the presence or absence of early rapid eGFR loss (slope ≤−3% per year) as the exposure of interest. Outcomes were incident reduced eGFR (eGFR <60 mL/min/1.73 m2), composite cardiovascular events, or major adverse cardiovascular events (MACE) during the subsequent 24 years post-DCCT closeout follow-up. RESULTS At DCCT closeout (the baseline for this analysis), diabetes duration was 12 ± 4.8 years, most participants (85.9%) had normoalbuminuria, mean eGFR was 117.0 ± 13.4 mL/min/1.73 m2, and 149 (10.4%) had experienced early rapid eGFR loss over the preceding trial phase. Over the 24-year subsequent follow-up, there were 187 reduced eGFR (6.3 per 1,000 person-years) and 113 MACE (3.6 per 1,000 person-years) events. Early rapid eGFR loss was associated with risk of reduced eGFR (hazard ratio [HR] 1.81, 95% CI 1.18–2.79, P = 0.0064), but not after adjustment for baseline eGFR level (HR 0.94, 95% CI 0.53–1.66, P = 0.84). There was no association with composite cardiovascular events or MACE. CONCLUSIONS In people with type 1 diabetes primarily with normal eGFR and normoalbuminuria, the preceding slope of eGFR confers no additional association with kidney or cardiovascular outcomes beyond knowledge of an individual’s current level.


2021 ◽  
Author(s):  
Tomomichi Iida ◽  
Michihiro Hosojima ◽  
Hideyuki Kabasawa ◽  
Keiko Kabasawa ◽  
Sawako Goto ◽  
...  

Abstract Background Urinary excretion of megalin, a proximal tubular endocytic receptor, may be associated with the development and progression of diabetic kidney disease (DKD). However, no studies have assessed whether the levels of the urinary ectodomain (A-megalin) and full-length (C-megalin) forms of megalin can predict DKD progression. Methods We evaluated the correlation of urinary A-megalin levels of 34 patients with type 2 diabetes as measured by novel reducing and previous methods. Then, we retrospectively analyzed 188 type 2 diabetes patients not taking sodium glucose cotransporter 2 (SGLT2) inhibitors in order to investigate whether urinary A- and C-megalin might be used as predictors of kidney outcomes. The median observation period was 3.96 years. The associations between the baseline urinary A-megalin measured by the novel method and/or C-megalin levels and the subsequent estimated glomerular filtration rate (eGFR) slope were analyzed using a generalized estimating equation. Patients were categorized into higher or lower groups based on the optimal cutoff values, obtained from a receiver operating characteristic (ROC) curve, of the two forms of urinary megalin. Results Urinary A-megalin levels measured by the two methods were strongly correlated. The eGFR slopes of the higher A-megalin and C-megalin groups were −0.904 (95% confidence interval [CI] −1.584, −0.224) and −0.749 (95% CI −1.312, −0.186) ml/min/1.73 m2 per year steeper than those of the lower groups, respectively. Moreover, the eGFR slope was −1.888 (95% CI −2.764, −1.011) ml/min/1.73 m2 per year steeper in the group with both higher A- and higher C-megalin than in the other groups. These results remained significant when adjusted for albuminuria or known tubular injury markers. Conclusions Our novel method allows urinary A-megalin measurements to be performed more easily. Baseline urinary megalin levels were associated with the subsequent eGFR slope independently of known biomarkers in type 2 diabetes patients not receiving SGLT2 inhibitors. These two forms of megalin may be distinct urinary biomarkers of the progression of DKD.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 122-122
Author(s):  
Santosh L. Saraf ◽  
Jin Han ◽  
Maria Armila Ruiz ◽  
Andrew Srisuwananukorn ◽  
David Shuey ◽  
...  

Abstract Chronic kidney disease is observed in up to 50% of adults with sickle cell disease (SCD) and is a consistent predictor for increased morbidity and early mortality. Progression of kidney disease can be manifested by a rapid decline in estimated glomerular filtration rate (eGFR). In retrospective studies, up to 38% of SCD patients have a rapid decline in kidney function, defined from the non-SCD literature as an eGFR slope < -3.0 mL/min/1.73m 2. Clinical and genetic predictors and the appropriate cutoff for rapid eGFR decline in SCD are unclear, but are paramount for guiding intervention studies in sickle cell nephropathy. We investigated 1) genetic, laboratory, and clinical risk factors for eGFR decline and 2) the rate of eGFR decline that best predicted mortality risk in a longitudinal cohort of SCD patients enrolled in a prospective registry at our institution. Between 10/2009 and 2/2018, 439 SCD patients were recruited. Blood samples, clinical and laboratory data were collected after obtaining consent at the time of enrolment during a clinic visit without the patient being in a vaso-occlusive crisis. 352 SCD patients with > 6 months of outpatient eGFR assessments were included in this analysis. The eGFR slope was calculated for each patient by linear regression of eGFR by time. Genotyping for the APOL1 G1 and G2 kidney risk variants and alpha thalassemia were performed by PCR. High-risk APOL1 status was defined as being either homozygous or compound heterozygous for the G1 and/or G2 variants. The statistical analyses for predictors of eGFR decline were conducted using linear regression, adjusting for age, sex, SCD genotype, hydroxyurea use, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use, and baseline eGFR. Median and interquartile ranges (IQR) are provided. The median age of the cohort was 32 years old (IQR, 24 - 43 years), 60% were female, 76% had Hb SS or Sβ 0-thalassemia genotype, 47% were on hydroxyurea, and 12% were on ACEi or ARB therapy. With a median follow up of 6.7 (IQR, 3.8 - 8.5) years, the median annual eGFR slope was -0.9 (IQR, -3.6 to 1.1) mL/min/1.73m 2. A faster rate of eGFR decline was observed in SCD patients with the Hb SS or Sβ 0-thalassemia genotype, with high-risk APOL1 status, and in those without coinheritance of α-thalassemia (Figure 1A). The urine albumin concentration, based on the average of two consecutive values from the time of enrolment, was significantly associated with a more rapid eGFR decline (β -0.63, P < 0.0001). An albuminuria cutoff of ≥ 100 mg/g creatinine was a stronger predictor for eGFR decline than cutoffs of ≥ 30 or ≥ 300 mg/g (Figure 1B). During the follow up period, we observed 26 deaths (7.4% mortality). An annual eGFR slope of < -6 mL/min/1.73m 2 was independently associated with a greater risk for mortality, after adjusting for age, sex, SCD genotype, hydroxyurea use, ACEi or ARB use, and baseline eGFR (Figure 1C). Using receiver operating curves, this cutoff was also associated with the largest area under the curve for predicting mortality. Our data highlights genetic risk factors and supports albuminuria as an independent predictor of eGFR decline in a longitudinal cohort of SCD patients. We also demonstrate that an annual eGFR slope of < -6 mL/min/1.73m 2 is the strongest predictor for mortality in our cohort. This threshold will need to be validated in other longitudinal SCD cohorts. The association of urine albumin ≥ 100 mg/g creatinine with eGFR decline supports using this cutoff as a clinical biomarker to identify high risk patients for kidney disease progression and for initiating disease modifying and reno-protective therapies. Figure 1 Figure 1. Disclosures Saraf: Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Gordeuk: Modus Therapeutics: Consultancy; Novartis: Research Funding; Incyte: Research Funding; Emmaus: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; CSL Behring: Consultancy.


2021 ◽  
Vol 11 (10) ◽  
pp. 972
Author(s):  
Pei-Yu Wu ◽  
Jiun-Chi Huang ◽  
Yi-Hsueh Liu ◽  
Ho-Ming Su ◽  
Szu-Chia Chen ◽  
...  

Patients with chronic kidney disease (CKD) often have cardiac functional and structural abnormalities which can lead to adverse cardiovascular outcomes. In this study, we investigated associations between diabetes mellitus (DM) and cardiac functional and structural parameters in patients with CKD focusing on aortic root diameter (ARD). We also investigated associations of renal outcomes with DM and cardiac functional and structural characteristics. We enrolled 419 patients with CKD stage 3–5 were enrolled. ARD was normalized to body surface area (BSA) (ARD/BSA), and the rate of decline in renal function was assessed by the estimated glomerular filtration rate (eGFR) slope (mL/min/1.73 m2/year). ARD/BSA ≥2.1 cm/m2 in men or ≥2.2 cm/m2 in women was defined as indicating aortic root dilatation. The patients with DM had lower ARD/BSA, higher left atrial dimension (LAD), lower left ventricular ejection fraction, lower ratio of peak early transmitral filling wave velocity to peak late transmitral filling wave velocity, and higher left ventricular relative wall thickness, than those without DM. After multivariable analysis, DM (vs. non-DM; coefficient β, −0.060; p = 0.018) was significantly associated with low ARD/BSA. Significantly fewer patients with DM had aortic root dilatation compared to those without DM (14.3% vs. 23.1%, p = 0.022). In the patients with DM, there were significant associations between a high left ventricular mass index (LVMI) (per 1 g/m2, β, −0.016; p = 0.040) and high LAD (per 1 cm; β, −1.965; p < 0.001) with a low eGFR slope. However, other parameters, including ARD/BSA, were not associated with eGFR slope. Furthermore, there were no associations between eGFR slope and any of the echocardiographic parameters in the patients without DM. Aortic root dilatation was attenuated in the patients with DM, but it was not associated with a decline in renal function. However, high LAD and LVMI were associated with rapid renal function decline in the CKD patients with DM.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lee-Moay Lim ◽  
Ming-Yen Lin ◽  
Shang-Jyh Hwang ◽  
Hung-Chun Chen ◽  
Yi-Wen Chiu

AbstractThe factors associated with the timely creation of distal vascular access for hemodialysis initiation are unclear. We aimed to explore the association between the slope of estimated glomerular filtration rate (eGFR) and the successful usage of vascular access upon hemodialysis initiation. This single center retrospective cohort study enrolled chronic kidney disease patients who undertook a multidisciplinary care program from 2003 to 2016. Using eGFR slope as predictor, we evaluated the vascular access created timely upon hemodialysis initiation. Among the 987 patients, vascular access was created at a median eGFR of 5.8 min/ml/1.73 m2, with a median duration of 3.1 months before hemodialysis. The proportions of vascular access created timely, created not timely (vascular access immature), and not created were 68.5%, 8.8%, and 22.7%, respectively. There was a significant negative association of eGFR upon vascular access creation with eGFR slope (r = − 0.182, P < 0.001). The fastest eGFR slope patients (the first quartile or < − 10 min/ml/1.73 m2/year) had the lowest percentage of vascular access created timely. In the multivariable logistic regression analysis, only higher eGFR upon vascular access creation (P = 0.001) and eGFR slope (P = 0.009) were significantly associated with vascular access created timely. The adjusted odds ratios of each quartile of eGFR slopes for vascular access created timely were 0.46 (95% confidence interval 0.27–0.86), 1.30 (0.62, 2.72), 1.00 (reference), and 0.95 (0.48–1.87), respectively. eGFR slope is associated with the timely creation of vascular access for the initiation of hemodialysis in a reverse-J-shaped pattern and may help determine the time of vascular access creation.


Author(s):  
David Cherney ◽  
Francesco Cosentino ◽  
Samuel Dagogo-Jack ◽  
Darren McGuire ◽  
Richard Pratley ◽  
...  

Background and objectives: A reduction in the rate of eGFR decline, with preservation of ≥0.75 ml/min/1.73 m2/year, has been proposed as a surrogate for kidney disease progression. We report results from prespecified analyses assessing effects of ertugliflozin versus placebo on eGFR slope from the VERTIS CV trial (NCT01986881). Design, setting, participants, and measurements: Patients with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease were randomized to placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg (1:1:1). The analyses compared the effect of ertugliflozin (pooled doses, n=5499) versus placebo (n=2747) on eGFR slope per week and per year by random coefficient models. Study periods (weeks 0-6 and weeks 6-52) and total and chronic slopes (week 0 or week 6 to weeks 104, 156, 208, and 260) were modeled separately and by baseline kidney function status. Results: In the overall population, from weeks 0-6, the least square mean eGFR slopes (ml/min/1.73m2/week [95% CI]) were −0.07 (−0.16, 0.03) and −0.54 (−0.61, −0.48) for the placebo and ertugliflozin groups respectively; the difference was −0.47 (−0.59, −0.36). During weeks 6-52, least square mean eGFR slopes (ml/min/1.73 m2/year [95% CI]) were −0.12 (−0.70, 0.46) and 1.62 (1.21, 2.02) for the placebo and ertugliflozin groups respectively; the difference was 1.74 (1.03, 2.45) For weeks 6-156, least square mean eGFR slopes (ml/min/1.73 m2/year [95% CI]) were −1.51 (−1.70,−1.32) and −0.32 (−0.45,−0.19) for the placebo and ertugliflozin groups respectively; the difference was 1.19 (0.95,1.42). During weeks 0-156, the placebo-adjusted least square mean slope was 1.06 (0.85, 1.27). These findings were consistent by baseline kidney function status. Conclusion: Ertugliflozin has a favorable placebo-adjusted eGFR slope >0.75 ml/min/1.73 m2/year, documenting the kidney function preservation underlying the clinical benefits of ertugliflozin on kidney disease progression in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Eleftherios Gkekas ◽  
Tsz Yau Tiffany Tang ◽  
Alan Green ◽  
Han Davidson ◽  
Rachel Fraser ◽  
...  

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is a cause of progressive chronic kidney failure (CKD) and end stage kidney disease (ESKD). Tolvaptan has been shown within clinical trials to slow down decline of kidney function in patients with ADPKD at risk of rapid progression. We performed a retrospective review of a cohort of ADPKD patients who had been established on tolvaptan therapy to determine its efficacy in a real- world clinic setting. Method Subjects who had a clinical diagnosis of ADPKD and who had been established on tolvaptan for a period of &gt;18 months were reviewed retrospectively in terms of their eGFR. Subjects were between the ages of 18-65 years old and both males and females were included in this study. Other inclusion criteria involved a pre-treatment slope of &lt;-2.5 ml/min/1.73m2 based on readings for a 3 year period, a pre-treatment eGFR of 30-90 ml/min/1.73m2 and ability to tolerate tolvaptan treatment and be maintained on treatment for at least12 months. We calculated based on eGFR slopes, predicted time to reach CKD stage 5 with and without tolvaptan therapy. Given this was a retrospective review, eGFR were estimated during clinic visits whilst on tolvaptan treatment, rather than after a drug washout period. Results The cohort of patients included 20 from Newcastle upon Tyne Hospitals and 2 from Sunderland Royal Infirmary. The mean rate of eGFR decline prior to treatment was -5.92 ml/min/1.73m2 per year for the cohort. Following tolvaptan treatment, the average decline in eGFR was reduced to -2.57 ml/min/1.73m2 per year. Therefore, tolvaptan lessened average eGFR decline within this cohort by 3.35 ml/min/1.73m2 per year, gaining 7 years and 9 months delay until CKD stage 5. The majority of patients (n=19) received full dose tolvaptan (90mg/30mg). At an individual level, 3 patients failed to respond at all to tolvaptan, with no improvement in decline of GFR and 2 others had a very mild improvement only (change in eGFR slope of &lt;0.5 ml/min/1.73m2 per year). 6 patients had a dramatic improvement in eGFR slope (&gt;5 ml/min/1.73m2 per year). Conclusion The real life use of tolvaptan seemed to give a dramatic improvement in eGFR slopes, much more than the previously reported clinical studies have shown. This may be in part due to patient selection and only including patients who tolerated therapy, a “tolvaptan clinic” effect where great personal care is given to these patients and to excellent compliance with medication. Reasons for both non-response and exaggerated response need to be evaluated carefully to determine how individualisation of tolvaptan therapy can be best used.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Derralynn Hughes ◽  
Gabriela Dostalova ◽  
Kathy Nicholls ◽  
Michael West ◽  
Camilla Tã¸ndel ◽  
...  

Abstract Background and Aims Females with Fabry disease (FD) often develop symptoms and disease complications later in life than males. However, they can experience significant health declines, including renal function impairment. Pegunigalsidase alfa is a novel PEGylated alpha-galactosidase A enzyme in development for the treatment of patients with FD with potential pharmacokinetic benefits. We previously reported that males with FD showed improvements in several parameters including median (minimum, maximum) estimated glomerular filtration rate (eGFR) slope from -4.6 (-20.5, 4.8) to -1.1 (-18.6, 14.2) mL/min/1.73m2/year after treatment with pegunigalsidase alfa.(Tondel et al. ASN 2020. PO0562. www.asn.scientificposters.com) Here we report a subgroup analysis of the safety and efficacy of pegunigalsidase alfa treatment in females with FD. Method BRIDGE (PB-102-F30; NCT03018730) is a phase 3, open-label, switch-over study designed to assess the safety and efficacy of pegunigalsidase alfa in adults with FD previously treated with agalsidase alfa for at least 2 years. Patients received intravenous pegunigalsidase alfa at 1 mg/kg every other week for 12 months. Results Twenty-two patients were enrolled in the study; of the 20 patients who completed 12 months of study treatment, 7 were female. Females had a mean age of 46.7 years (range: 26–59 years), and had the following median (minimum, maximum) baseline measurements: residual enzymatic activity in leucocytes of 23.7% (16, 46) of the normal laboratory mean; plasma lyso-Gb3 of 12.9 (7.4, 23.2) nmol/L; eGFR of 87.7 (55.3, 109.2) mL/min/1.73m2; and an annualized eGFR slope of −3.7 (-11.2, 1.5) mL/min/1.73m2/year. After 12 months of pegunigalsidase alfa treatment, the annualized eGFR slope was 1.4 (-6.3, 4.1) mL/min/1.73m2/year, indicating an improvement from baseline of 5.9 mL/min/1.73m2/year. In addition, plasma lyso-Gb3 had a reduction of 23.3% (-45.7, -17.3). Although all females had baseline mean residual enzyme activity &gt; 5% and were previously treated with agalsidase alfa, only 2 had stable kidney disease (eGFR slope ≥ -3 mL/min/1.73m2/year), while 2 had moderately progressing kidney disease (eGFR slope between ≥-5 and &lt; -3 mL/min/1.73m2/year), and 3 had fast progressing kidney disease (eGFR slope &lt; -5 mL/min/1.73 m²/year).( Wanner et al. 2018 Mol Genet Metab 124:189-203) After treatment all but 1 patient experienced categorical improvement or remained stable; this patient had a decline of &lt; 3 mL/min/1.73m2/year and remained in the fast progressing disease category. Mean left ventricular mass index in females increased from 66.9 g/m2 at baseline to 74.1 g/m2 at month 12, but remained within normal ranges(47–77 g/m2).(Kawel-Boehm et al. 2015 J Cardiovasc Magn Reson 17:29) All females had at least 1 treatment-emergent adverse event (TEAE), and all TEAEs were mild or moderate. The most common TEAEs reported in female were nasopharyngitis (n=2), oropharyngeal pain (n=2), and headache (n=2). None of these TEAEs were considered related to treatment. However, 2 females had injection site reactions and 2 developed transient, non-neutralizing anti-drug antibodies to pegunigalsidase alfa treatment. Conclusion The current study included females with symptoms of Fabry disease comparable to the disease presentation of males enrolled in this study. At baseline most females had eGFR decline characterizing progressive or rapidly progressive kidney disease. Most females showed improvements in disease status following 12 months of pegunigalsidase alfa treatment, as previously reported for males enrolled in this study. This long-term, controlled study suggests a potential benefit and a favorable safety profile for pegunigalsidase alfa on renal function in females with FD previously treated with agalsidase alfa. While this subgroup analysis should be interpreted with caution due to the small number of patients, these findings may provide valuable insight for future studies.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Edouard Fu ◽  
Marco Trevisan ◽  
Vivekananda Lanka ◽  
Catherine M Clase ◽  
Yang Xu ◽  
...  

Abstract Background and Aims While clinical trials have demonstrated the efficacy of SGLT2 inhibitors on preventing cardiovascular and renal damage, few studies have expanded this evidence to routine-care settings. Method We compared clinical outcomes of adults who started SGLT2i or DPP4i therapy in Stockholm, Sweden, during 2013-2019. The primary outcome was a composite of cardiovascular (CV) death and hospitalization for heart failure (HF). Secondary outcomes included major adverse cardiovascular events (MACE; composite of cardiovascular death, myocardial infarction, stroke), all-cause mortality and the rate of eGFR decline (eGFR slope). Propensity score weighted Cox regression was used to balance 55 variables and estimate intention-to-treat hazard ratios with 95% confidence intervals. Differences in eGFR slope were calculated with linear mixed models. Results We identified 7136 individuals starting SGLT2i and 13,618 starting DPP4i therapy. Median age was 64 years (37% women) and median eGFR 86 ml/min/1.73m2. During median follow-up of 2.1 years, 211 individuals developed the primary outcome, 269 experienced MACE and 178 died. After propensity score weighting, patients starting SGLT2i therapy were at lower risk for the composite of CV death/HF hospitalization (HR 0.71; 95% CI 0.53-0.94) compared with DPP4i, and showed a tendency towards lower MACE (0.84; 95% CI 0.67-1.04) and all-cause mortality (0.85; 95% CI 0.62-1.18). There were a median of 4 (interquartile range: 2-8) eGFR measurements during follow-up per patient to estimate their eGFR slopes. In adjusted models, new users of SGLT2i had a slower rate of kidney function decline compared with DPP4i (eGFR slope difference of 0.43 (95% CI 0.15-0.72) ml/min/1.73m2 per year). Results for the primary outcome were consistent across 7 pre-specified subgroups, including eGFR (eGFR ≥60: HR 0.79 [95% CI 0.57-1.08]; eGFR &lt;60: HR 0.62 [0.38-0.99], p-value for interaction 0.40). Conclusion In patients undergoing routine care, initiation of SGLT2i was associated with fewer cardiovascular outcomes and less rapid kidney function decline compared with DPP4i initiation.


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