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Background COVID-19 is associated with increased risk of post-acute sequelae involving pulmonary and extrapulmonary organ systems-referred to as long COVID. However, a detailed assessment of kidney outcomes in long COVID is not yet available. Methods We built a cohort of 1,726,683 US Veterans identified from March 1, 2020 to March 15, 2021, including 89,216 patients who were 30-day survivors of COVID-19 and 1,637,467 non-infected controls. We examined risks of AKI, eGFR decline, ESKD, and major adverse kidney events (MAKE). MAKE was defined as eGFR decline ≥50%, ESKD, or all-cause mortality. We used inverse probability-weighted survival regression, adjusting for predefined demographic and health characteristics, and algorithmically selected high-dimensional covariates, including diagnoses, medications, and laboratory tests. Linear mixed models characterized intra-individual eGFR trajectory. Results Beyond the acute illness, 30-day survivors of COVID-19 exhibited a higher risk of AKI (aHR, 1.94; 95% CI, 1.86 to 2.04), eGFR decline ≥30% (aHR, 1.25; 95% CI, 1.14 to 1.37), eGFR decline ≥40% (aHR, 1.44; 95% CI, 1.37 to 1.51), eGFR decline ≥50% (aHR, 1.62; 95% CI, 1.51 to 1.74), ESKD (aHR, 2.96; 95% CI, 2.49 to 3.51), and MAKE (aHR, 1.66; 95% CI, 1.58 to 1.74). Increase in risks of post-acute kidney outcomes was graded according to the severity of the acute infection (whether patients were non-hospitalized, hospitalized, or admitted to intensive care). Compared with non-infected controls, 30-day survivors of COVID-19 exhibited excess eGFR decline (95% CI) of -3.26 (-3.58 to -2.94), -5.20 (-6.24 to -4.16), and -7.69 (-8.27 to -7.12) ml/min per 1.73 m2 per year, respectively, in non-hospitalized, hospitalized, and those admitted to intensive care during the acute phase of COVID-19 infection. Conclusions Patients who survived COVID-19 exhibited increased risk of kidney outcomes in the post-acute phase of the disease. Post-acute COVID-19 care should include attention to kidney disease.

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RATIONALE & AIMS: Healthy dietary patterns have been associated with a lower risk of chronic kidney disease (CKD). We aimed to investigate the association of a fully food-based diet quality score assessed by the Lifelines Diet Score (LLDS) with either incident CKD or eGFR decline in the general population.METHODS: For this study, data from a prospective general population-based Lifelines cohort in the Northern Netherlands was used. Diet was assessed with a 110-item food frequency questionnaire at baseline. The LLDS, based on international evidence for diet-disease relations at the food group level, was calculated to assess diet quality. For the analysis, the score was divided into tertiles. Logistic regression was performed to evaluate the association of the LLDS at baseline with either incident CKD (eGFR RESULTS: A total of 78 346 participants free of CKD at baseline were included. During a mean (SD) follow-up of 3.6 ± 0.9 years, 2071 (2.6%) participants developed CKD and 7611 (9.7%) had a ≥20% eGFR decline. Participants in the highest tertile of LLDS had a lower risk of incident CKD (fully adjusted OR 0.83, [95% CI: 0.72-0.96]) and ≥20% eGFR decline (fully adjusted OR 0.80, [95% CI: 0.75-0.86]), compared with those in the lowest tertile. Similar dose-response associations were observed in continuous LLDS.CONCLUSIONS: Higher adherence to a high-quality diet was associated with a lower risk of incident CKD or ≥20% eGFR decline in the general population.

Aims/Introduction The aim of this study was to elucidate whether sodium–glucose cotransporter 2 inhibitors (SGLT2is) treatment has any renoprotective effect for type 2 diabetes mellitus patients with an estimated glomerular filtration rate (eGFR) of, Administration of sodium–glucose cotransporter 2 inhibitors slowed the annual estimated glomerular filtration rate decline in type 2 diabetes patients with an estimated glomerular filtration rate of

BackgroundChronic kidney disease (CKD) is known to increase the risk of atrial fibrillation (AF) development, but the relationship between AF and subsequent renal function decline in patients with CKD is not well understood. In this study, we explored the role of AF on renal outcomes among patients with CKD.MethodsIn a retrospective hospital-based cohort study, we identified patients with CKD aged ≥20 years from 1 January 2008 to 31 December 2018. The patients were divided into AF and non-AF groups. We matched each patient with CKD and AF to two non-AF CKD controls according to propensity scores. The outcomes of interest included estimated glomerular filtration rate (eGFR) decline of ≥20%, ≥30%, ≥40% and ≥50%, and end-stage renal disease (ESRD).ResultsAfter propensity score matching, 6731 patients with AF and 13 462 matched controls were included in the analyses. Compared with the non-AF group, the AF group exhibited greater risks of eGFR decline ≥20% (HR 1.43; 95% CI 1.33 to 1.53), ≥30% (HR 1.50; 95% CI 1.36 to 1.66), ≥40% (HR 1.62; 95% CI 1.41 to 1.85) and ≥50% (HR 1.82; 95% CI 1.50 to 2.20), and ESRD (HR 1.22; 95% CI 1.12 to 1.34). Higher CHA2DS2-VASc scores were associated with greater risks of eGFR decline and ESRD.ConclusionsIn patients with CKD, AF was associated with greater risks of subsequent renal function decline. CHA2DS2-VASc scores may be a useful risk stratification scheme for predicting the risk of renal function decline.

ObjectiveCommunity-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk show conflicting results. The aim of this study is to investigate the links among kidney function, kidney function decline, and dementia incidence.MethodsWe analyzed the association of eGFR with the risk of dementia (defined as a new dementia diagnosis or initiation of dementia treatments) among 329,822 residents of Stockholm who accessed health care during 2006 to 2011, were ≥65 years of age, had no history of dementia, or underwent kidney replacement therapy. We also estimated the rate of eGFR decline among 205,622 residents with repeated eGFR measurements during the first year of observation and investigated its association with subsequent dementia risk.ResultsWe detected 18,983 cases of dementia (5.8% of participants) over a median follow-up of 5 years. Dementia incidence rates were progressively higher with lower eGFR: from 6.56/1,000 person-years in those with eGFR of 90 to 104 mL/min to 30.28/1,000 person-years in those with eGFR 2 mL/min/1.73 m2/y) within 1 year was associated with higher dementia risk. Risk magnitudes were stronger for vascular dementia than for Alzheimer dementia. As many as 10% (95% CI 6%–14%) of dementia cases could be attributed to eGFR 2, a proportion higher than that attributed to other dementia risk factors such as cardiovascular disease and diabetes.ConclusionsBoth lower kidney function and steeper kidney function decline are associated with the development of dementia.

Background: Progression of kidney disease is a deceptively simple word for a complex bio-clinical process, evidenced by the number of definitions in the literature. This has led to confusion and differences in interpretation of studies. Methods: We describe different patterns of progression, the performance of different definitions of progression and factors associated with chronic kidney disease (CKD) progression in a public renal service in Australia, in a study of patients enrolled in the CKD.QLD Registry with a minimum of 2 years' follow up. Results: Nine patterns of changing estimated glomerular filtration rate (eGFR) over two consecutive 12-month periods were identified. Most common was a stable eGFR over 2 years (30%), and the least was a sustainable improvement of eGFR over both periods (2.1%). There was a lack of congruence between the several definitions of progression of CKD evaluated. More people progressed using the definition of decline of eGFR of >5 mL/min/1.73 m/year (year 1 = 30.2%, year 2 = 20.7%) and the least using development of end-stage renal disease (year 1 = 5.4%, year 2 = 9.9%). Age (40–59, ≥80 years), degree of proteinuria at baseline (nephrotic range) and CKD aetiology (renal vascular disease, diabetic nephropathy) were significantly associated with eGFR decline over 2 years. Conclusions: This is one of the first demonstrations of the great variations among and within individuals in the progression of CKD over even a period as short as 2 years. Findings suggest considerable potential for renal function recovery and stability while demonstrating the importance of using identical definitions for comparisons across datasets from different sources.

The trajectory of glomerular filtration rate (GFR) in relation to glomerular hyperfiltration (GHF) has been unknown. It was evaluated retrospectively in 23,982 GHF-free health examinees who were followed for 2−10 yr (mean: 5.1 yr). GFR was estimated by the serum creatinine concentration, and GHF was defined as age- and sex-specific estimated GFR (eGFR) ≥ 95% of the Japanese general population. The temporal profile of eGFR was plotted in a GHF-centered way, which was fitted to a random coefficient linear mixed model. Of the 23,982 subjects, 797 and 23,185 subjects developed or did not develop GHF, respectively, so that they were termed as the GHF(+)and GHF(−)groups. At baseline, median eGFR was significantly elevated in the GHF(+)group compared with in the GHF(−)group: 94.1 versus 77.3 mL/min/1.73 m2( P < 0.001). Elevation of basal eGFR lasted for a mean (SD) of 3.3 (1.9) yr in the GHF(+)group; mean eGFR then rose to the GHF range, which was 108.5 mL/min/1.73 m2. The eGFR decline after the peak was steeper in the GHF(+)group than in the GHF(−)group: −0.984 versus −0.497 mL/min/1.73 m2/yr ( P < 0.001). Baseline eGFR, but no other variable, well predicted incident GHF, with an area under the receiver operating characteristic curve of 0.87 (95% confidence interval: 0.86–0.88). In conclusion, GHF occurs as a chronic, multiphasic phenomenon: initially with a sustained GFR elevation for years, followed by a GFR surge to the GHF range, which was accompanied by accelerated GFR declining.

Objectives To evaluate the association between excised parenchymal mass (EPM) and postoperative renal function (eGFR) following robotic-assisted partial nephrectomy (RAPN). EPM is the amount of healthy renal parenchyma excised during partial nephrectomy in order to achieve safe surgical margins. Methods We evaluated 406 consecutive RAPN performed by a single surgeon to eliminate variations in technique as a factor in EPM. EPM (mL) = (specimen volume * π/6) - (tumor volume * π/6). RENAL score was categorized as easy (4-6), moderate (7-9), or hard (10-12). EPM was grouped into four categories: ≤ 3.9 mL, 4.0-9.9 mL, 10.0-17.7 mL, and >17.7 mL. eGFR was evaluated preoperatively, postoperative day 1 (POD1), 1 month, and 6 months postoperatively. Results Median age was 63 years (22-84 years), 252 (62.1%) were male, and median EPM was 9.9 mL (interquartile range 3.9 to 17.7 mL). The median EPM and interquartile range for each RENAL category was 3.7 mL (2.0, 7.9), 12 mL (5.7, 19.4), and 16.2 mL (7.9, 24.3), respectively. Higher EPM was associated with worse changes in eGFR at POD1 (P = 0.005) and 1 month after RAPN (P = 0.002) but was not statistically significant at the 6-month time period (P = 0.35) Conclusion Increased tumor complexity is associated with an increase in EPM during RAPN. Increased EPM is associated with eGFR decline at POD1 and 1 month post RAPN but not at 6 months postoperatively.

BACKGROUND: Traditionally, clinical trials evaluating effects of a new therapy with creatinine-based renal end points use doubling of serum creatinine (equivalent to a 57% eGFR reduction), requiring large sample sizes.METHODS: To assess whether eGFR declines RESULTS: Among the 10,142 participants, 93 (0.9%), 161 (1.6%), 352 (3.5%), and 800 (7.9%) participants recorded renal outcomes on the basis of 57%, 50%, 40%, or 30% eGFR reduction, respectively, during a mean follow-up of 188 weeks. Compared with a 57% eGFR reduction (risk ratio [RR], 0.51; 95% confidence interval [95% CI], 0.34 to 0.77), the effect sizes were progressively attenuated when using 50% (RR, 0.61; 95% CI, 0.45 to 0.83), 40% (RR, 0.70; 95% CI, 0.57 to 0.86), or 30% (RR, 0.81; 95% CI, 0.71 to 0.93) eGFR reductions. In analyses that controlled for the acute hemodynamic fall in eGFR, effect sizes were comparable, regardless of whether a 57%, 50%, 40%, or 30% eGFR reduction was used. Estimated sample sizes for studies on the basis of lesser eGFR reductions were much reduced by controlling for this early hemodynamic effect.CONCLUSIONS: Declines in eGFR CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: CANagliflozin cardioVascular Assessment Study (CANVAS), NCT01032629 and CANVAS-R, NCT01989754.

BACKGROUND: The Mayo Clinic imaging classification of autosomal dominant polycystic kidney disease (ADPKD) uses height-adjusted total kidney volume (htTKV) and age to identify patients at highest risk for disease progression. However, this classification applies only to patients with typical diffuse cystic disease (class 1). Because htTKV poorly predicts eGFR decline for the 5%–10% of patients with atypical morphology (class 2), imaging-based risk modeling remains unresolved. METHODS: Of 558 adults with ADPKD in the HALT-A study, we identified 25 patients of class 2A with prominent exophytic cysts (class 2Ae) and 43 patients of class 1 with prominent exophytic cysts; we recalculated their htTKVs to exclude exophytic cysts. Using original and recalculated htTKVs in association with imaging classification in logistic and mixed linear models, we compared predictions for developing CKD stage 3 and for eGFR trajectory. RESULTS: Using recalculated htTKVs increased specificity for developing CKD stage 3 in all participants from 82.6% to 84.2% after adjustment for baseline age, eGFR, BMI, sex, and race. The predicted proportion of class 2Ae patients developing CKD stage 3 using a cutoff of 0.5 for predicting case status was better calibrated to the observed value of 13.0% with recalculated htTKVs (45.5%) versus original htTKVs (63.6%). Using recalculated htTKVs reduced the mean paired difference between predicted and observed eGFR from 17.6 (using original htTKVs) to 4.0 ml/min per 1.73 m(2) for class 2Ae, and from −1.7 (using original htTKVs) to 0.1 ml/min per 1.73 m(2) for class 1. CONCLUSIONS: Use of a recalculated htTKV measure that excludes prominent exophytic cysts facilitates inclusion of class 2 patients and reclassification of class 1 patients in the Mayo classification model.

Clinicians must consider renal function when administering anticoagulants for atrial fibrillation (AF). Determination of risk factors for renal function decline may enable identification of patients who require closer monitoring. We investigated the characteristics associated with renal function decline in patients with AF. The study cohort consisted of 631 AF patients who had at least one readmission during the follow-up period and stages 1-3 chronic kidney disease (CKD). The primary outcome measure was large renal function decline (≥30% decrease from baseline estimated glomerular filtration rate [eGFR]). The secondary outcome measure was a final eGFR < 60 mL/minute/1.73 m2 for those with a baseline eGFR above this level. The mean eGFR was 74.4 ± 18.5 mL/minute/1.73 m2, and the mean follow-up time was 30.2 ± 13.2 months. The primary outcome occurred in 155 patients (24.6%) and was associated with congestive heart failure (CHF), proteinuria, type of AF, and left atrial diameter (LAD) ≥ 45 mm. Among 478 patients with a baseline eGFR ≥ 60 mL/minute/1.73 m2, 137 (28.7%) progressed to renal failure (eGFR < 60 mL/minute/1.73 m2). A decreasing eGFR was associated with age ≥ 75 years, CHF, lower baseline eGFR, and LAD ≥ 45 mm. CHF, proteinuria, type of AF, and LAD ≥ 45 mm were associated with eGFR decline ≥ 30% in AF patients with CKD stages 1-3. Advanced age, CHF, lower baseline eGFR, and LAD ≥ 45 mm were associated with progression to renal insufficiency. These results should be considered when identifying patients who require more frequent monitoring of eGFR.

Disease-specific trajectories of renal function in advanced chronic kidney disease (CKD) are not well defined. Here, we compared these trajectories in the estimated glomerular filtration rate (eGFR) by CKD stages. Patients with multiple eGFR measurements during the 5-year preregistration period of the REACH-J study were enrolled. Mean annual eGFR declines were calculated from linear mixed effect models with the adjustment variables of baseline CKD stage, age, sex and the current CKD stage and the level of proteinuria (CKDA1-3). Among 1,969 eligible patients with CKDG3b-5, the adjusted eGFR decline (ml/min/1.73 m2/year) was significantly faster in diabetic kidney disease (DKD) patients and polycystic kidney disease (PKD) patients than in patients with other kidney diseases (DKD, − 2.96 ± 0.13; PKD, − 2.82 ± 0.17; and others, − 1.95 ± 0.05, p

Background There is controversial evidence on whether arteriovenous access (AVA) placement may protect renal function and hence should be considered in the timing of access placement. This study aimed to investigate the association between AVA placement and estimated glomerular filtration rate (eGFR) decline as compared with the placement of a peritoneal dialysis catheter (PDC) at a similar time point. Methods We studied a cohort of 744 pre-dialysis patients in Stockholm, Sweden, who underwent surgery for AVA or PDC between 2006 and 2012. Data on comorbidity, medication and laboratory measures were collected 100 days before and after surgery. Patients were followed until dialysis start, death or 100 days, whichever came first. The primary outcome was difference in eGFR decline after AVA surgery compared with PDC. Decline in eGFR was estimated through linear mixed models with random intercept and slope, before and after surgery. Results There were 435 AVA and 309 PDC patients. The AVA patients had higher eGFR (8.1 mL/min/1.73 m2 versus 7.0 mL/min/1.73 m2) and less rapid eGFR decline before surgery (−5.6 mL/min/1.73 m2/year compared with −6.7 mL/min/1.73 m2/year for PDC). We found no difference in eGFR decline after surgery in AVA patients compared with PDC patients [AVA progressed 0.26 (95% confidence interval −0.88 to 0.35) mL/min/1.73 m2/year faster after surgery compared with PDC]. Conclusions There was no significant difference in eGFR decline after placement of an AVA compared with a PDC. Both forms of access were associated with reduced eGFR decline in our population. The need for dialysis remains the main determinant for timing of access surgery.

OBJECTIVES: To investigate pre- and post-operative renal global function and renal parenchymal volume (RPV) in both partial nephrectomy (PN) and radical nephrectomy (RN) utilizing film-based technology. PATIENTS AND METHODS: The patient cohort consisted of 81 and 82 cases with T1 tumors (≤ 7 cm) treated by PN and RN, respectively. Renal global function was assessed using the estimated glomerular filtration rate (eGFR), and RPV was measured using a Synapse Vincent volumetric analyzer which creates a reconstructed image from a computed tomography scan. Renal global function and RPV were evaluated pre-operatively and 6 months post-operatively. RESULTS: The percent eGFR decline of PN cases was significantly reduced compared with RN cases (p < 0.0001). Post-operative RPV of the contralateral side was significantly increased compared with pre-operative RPV (p < 0.0001) in RN cases. The percent change of the contralat-eral side RPV was slightly increased in RN compared with PN cases (p = 0.1881). A strong positive correlation was noted between post-operative eGFR and post-operative total RPV (r = 0.69, p < 0.0001), and a strong negative correlation was noted between percent eGFR decline and post-operative total RPV (r = −0.63, p < 0.0001). CONCLUSIONS: Prominent compensatory renal hypertrophy occurred within 6 months after RN. Post-operative renal functional outcome was closely correlated with the post-operative total RPV. In addition to RPV, further studies to unravel post-operative renal function from multifactorial aspects including surgical factors and intrinsic medical disease should be performed in the future.

Background Serum uric acid (SUA) has been shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized SUA {i.e, SUA/creatinine (Cr) ratio} is a predictor of decreased renal function among diabetic patients. Methods The subjects comprised 185 men aged 72 ± 11 (mean ± standard deviation) years and 175 women aged 77 ± 10 years from a rural hospital. We examined the relationship between SUA/creatinine (Cr) ratio and renal function evaluated by estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease Study Group equation. Results Annual eGFR decline rate was significantly increased with increased tertile of baseline SUA/Cr ratio (p = 0.011), and prevalence of the rapid progression types (≥3.0 ml/min/1.73 m2/year) was significantly higher in the second and third tertile (≥7,21) of baseline SUA/Cr ratio than the first tertile ( Conclusion Our data demonstrated that baseline SUA/Cr ratio was independently and significantly associated with future renal function decline among diabetic patients.

AIMS: Relationship between baseline eGFR and the rate of decline in eGFR was investigated in diabetic kidney disease. MATERIALS AND METHODS: Patients with type 2 diabetes with microalbuminuria (MI) (n = 124) or macroalbuminuria (MA) (n = 81) received team-based medical care to prevent the development of diabetic kidney disease. The decline in eGFR over 4 years, divided into the first year and subsequent 3 years, was estimated by linear-mixed modeling. RESULTS: The eGFR showed a rapid decline during the first year, followed by a slower decline. On multiple regression analysis, the baseline eGFR was positively correlated with HbA1c in MI and negatively correlated with carotid plaque in MI and in MA. Subsequent eGFR decline following 1-year intervention was negatively correlated with the baseline eGFR and HbA1c level at 1 year in MI, whereas it was positively correlated with baseline eGFR and negatively correlated with the amount of proteinuria at 1 year in MA. Even in maintained baseline eGFR(≧ 60 ml/min/1.73 m(2)) at the first year, when HbA1c ≧ 7.5%, eGFR reduction rate and years to ESKD were much faster and shorter, compared to the group of HbA1c

The association between rate of kidney function decline and age-of-onset or duration of diabetes has not been well investigated. We aimed to examine whether rates of estimated glomerular filtration rate (eGFR) decline differ by age-of-onset or duration in people with type 2 diabetes. Using the Action to Control Cardiovascular Risk in Diabetes study which included those with HbA1c ≥ 7.5% and who were at high risk of cardiovascular events,, rates of eGFR decline were calculated and were compared among groups defined by the known age-of-onset (0–39, 40–49, 50–59, 60–69 and > 70 years) and 5-year diabetes duration intervals. Changes in renal function were evaluated using median of 6 (interquartile range 3–10) eGFR measurements per person. eGFR decline was the slowest in those with known age-at-diagnosis of 50–59 years or those with duration of diabetes 20 years compared to those diagnosed at 50–59 or those with duration of diabetes

BACKGROUND Donor-derived cell-free DNA (dd-cfDNA) is a marker of allograft injury in transplant recipients; however, the relationship between dd-cfDNA and other clinical parameters associated with adverse allograft outcomes is not well-characterized. METHODS We performed a retrospective analysis of kidney transplant recipients from the DART cohort (ClinicalTrials.gov Identifier: NCT02424227) to evaluate the associations between eGFR decline, de novo donor-specific antibodies (dnDSA), and dd-cfDNA. RESULTS Both elevated dd-cfDNA (≥1%) and dd-cfDNA variability (≥.34%) in the first post-transplant year were associated with decline in eGFR ≥25% in the second year (21.4% vs. 4.1%, P = .005; 25% vs. 3.6%, P = .002, respectively). Compared to samples from DSA negative patients, samples from patients with concurrent de novo HLA DSAs had higher dd-cfDNA levels (P

Purpose: To evaluate the association between the eGFR trajectory and cardiovascular/renal outcomes in SGLT2i users. Methods: Cardiovascular and Renal Outcome Trials of SGLT2i with reports of eGFR change were included. Random-effect model was used. Results: In all, 7 RCTs were included. Meta-analysis showed that the risk of all-cause mortality was only reduced in SGLT2i users with eGFR change rate >-1ml/min/1.73m2 per year (RR=0.87, 95%CI, 0.77 to 0.99). Consistent risk reductions were observed in SGLT2i users in terms of heart failure, 3P-MACE (MI, stroke, CV death), 4P-MACE (3P-MACE and heart failure) and composite renal endpoints (sustained decline in eGFR, renal replacement treatment and renal death), regardless of eGFR change rate. Conclusions: The preserved eGFR decline may confer reduced risk of all-cause mortality but did not influence the benefits in cardiovascular and renal outcomes in SGLT2i users. Disclosure C. Lin: None. X. Cai: None. L. Ji: None. Funding Beijing Natural Science Foundation (7202216); National Natural Science Foundation of China (81970698, 81970708)

Microalbuminuria is thought to be a risk factor for progression to macroalbuminuria, an indicator of renal functional decline in patients with type 1 or 2 diabetes. However, it remains unknown which renal histological factors predict the onset of macroalbuminuria or eGFR Conclusions: Aggravated arteriolar hyalinosis is a histological risk factor for renal functional decline and predicts the onset of macroalbuminuria and CKD in patients with type 2 diabetes, normo-microalbuminuria, and normal renal function regardless of microalbuminuria grade. This finding might reflect initial changes in early diabetic nephropathy. Disclosure T. Moriya: None. A. Hayashi: None. A. Suzuki: None. M. Matsubara: None. M. Ouchi: None.

This study aimed at determining the feasibility of conducting a large-scale pragmatic effectiveness study on the implementation of multidisciplinary care (MDC) program for patients with advanced chronic kidney disease (CKD). This is a single-arm pre-post intervention design pilot study over 12 months. Participants with an estimated glomerular filtration rate (eGFR) between 11 and 20 ml/min/1.73m2 were screened and recruited at the initial MDC clinic visit and followed for 12 months. Clinical parameters, KDQOL™-36, questionnaires, and interviews were collected, administered, and analysed for enrolment and completion rates, baseline characteristics, implementation fidelity, adherence to CKD interventions, eGFR decline, CKD complications, health-related quality of life, and participants’ acceptability of the program. The study enrolment and completion rates were 43.1% (50/116 screened) and 66.0% (33/50 recruited) respectively. The participants had a mean age of 68.5 years (SD9.0) and a mean eGFR of 15.4 ml/min/1.73m2(3.2). After 12 months of MDC program, there was increased adherence to CKD interventions (difference − 0.6(1.0), 95%CI − 1.1, − 0.1, p = 0.02). There was good participants’ acceptability of the program with participants being more satisfied with the waiting time and having a better understanding of kidney failure after attending the program. No difference in the eGFR decline noted (difference 0.0 ml/min/1.73m2(5.3), 95%CI − 1.9, 1.9, p = 1.00). Our pilot data suggest increased adherence to CKD interventions and good acceptability to MDC program, albeit no difference in eGFR decline probably because of the small sample size. However, reasons for overall low enrolment and completion rates need to be explored and addressed while designing a future large-scale randomised controlled trial.

Background Chronic kidney disease (CKD) progression is presumably related to inflammatory response. The modified Glasgow prognostic score (mGPS), based on combination between albumin and C-reactive protein, has been derived from oncology and validated in multiple diseases. Aims We aimed to evaluate the relationship between the mGPS and CKD progression. Methods The present retrospective unicentric cohort study included 547 CKD patients (age 60.2 years, 53% male, eGFR 42.0 mL/min, mean change -2 mL/min/year) admitted between January 1, 2007 and December 31, 2012. Patients records were reviewed from the CKD diagnosis to one of the four outcomes: end-stage kidney disease (ESKD), death, loss to follow-up, or until July 31, 2017. Results The mGPS score was 0 for 420 (78%), 1 for 110 (19%), and 2 for 17 (3%) patients. More patients with rapid CKD progression were found in the group with the highest mGPS (p=0.05). mGPS was negatively correlated with baseline eGFR and positively with albuminuria. In the multivariate analysis, mGPS was associated with the eGFR slope. During the study period, 130 patients (24%) died and 109 (20%) reached ESKD. The mean kidney survival time was 8.1 (95%CI 7.9 to 8.4) years. Patients with zero mGPS had better kidney survival than those with the score of one and two (Kaplan-Meier, p=0.02). However, the kidney survival differences were not present after adjusting for CKD progression risk factors. Conclusion The inflammation-based mGPS score was associated with eGFR decline in CKD patients. Therefore, could prove useful in improving risk stratification of CKD patients. This article is protected by copyright. All rights reserved.

Aims Nephropathy is a complication of type 2 diabetes, with increased albuminuria and reduced glomerular filtration rate (GFR) as biomarkers. Rates of progression to end-stage-renal disease are variable among patients. In this study we have examined the GFR decline in newly diagnosed T2DM. Methods A cohort of 410 patients with newly diagnosed T2DM and with at least four serum creatinine during the follow-up period were recruited. A linear model was used to calculate the decline in eGFR. A multivariable logistic model was used to identify independent predictors of rapid eGFR decline. Results Average follow-up was 12.4 years. The eGFR change was −0.80 ± 2.23 ml/min/1.73 m2 per year. Patients were arbitrarily stratified into rapid decliners (≤-3.0 ml/min/1.73 m2 per year), moderate decliners (-2.9/-1 ml/min/1.73 m2 per year) and slow/no decliners (>-1.0 ml/min/1.73 m2 per year). Subjects in the 3 categories were 11.4%, 27.3%, and 61.3%, respectively. Albuminuria was the stronger predictor of rapid eGFR decline. Conclusions A rapid decline in eGFR occurs in approximately 1 out of 10 newly diagnosed subjects. This rapid decline can be predicted by widely accessible clinical features, such as albuminuria. Identification of rapid decliners may help to reduce progression toward advanced stages of nephropathy.

Protective effects of tolvaptan against worsening renal function in acute heart failure have been shown. However, long-term effects of its agent on renal function remain to be elucidated. The present study investigated retrospectively whether long-term treatment with tolvaptan exerts renoprotective effects in patients with chronic heart failure, by comparing serial changes in estimated glomerular filtration rate (eGFR) for years before and after tolvaptan administration. From 63 outpatients with chronic heart failure taking diuretics including tolvaptan, 34 patients whose eGFR levels were continuously measured for more than 6 months both before and after administration of tolvaptan (average dose, 7.8 mg/day at the end of the follow-up period) were selected as eligible for the present analyses. All eGFR values were separately plotted before and after the initiation of treatment with tolvaptan (except hospitalization periods) along the time course axis and the slope of the linear regression curve was calculated as an annual change in eGFR. The mean follow-up periods before and after tolvaptan administration were 1197 and 784 days (3.3 and 2.1 years), respectively. Changing rates of eGFR per year were significantly ameliorated after treatment with tolvaptan (mean ± SD, − 8.02 ± 9.35 to − 1.62 ± 5.09 mL/min/1.73m2 /year, P = 0.001). In echocardiographic parameters, inferior vena cava (IVC) diameter significantly decreased after tolvaptan administration, and the decrease in IVC diameter was correlated with the improvement of eGFR decline slope after administration of tolvaptan (P = 0.0075). This longitudinal observational study indicated that long-term treatment with tolvaptan ameliorated annual decline in eGFR in outpatients with chronic heart failure. Our findings suggest that tolvaptan has a protective effect against chronically worsening renal function in heart failure patients.

Background Although young adulthood is associated with transplant loss, many studies do not examine eGFR decline. We aimed to establish clinical risk factors to identify where early intervention might prevent subsequent adverse transplant outcomes. Methods Retrospective cohort study using UK Renal Registry and UK Transplant Registry data, including patients aged Results The cohort (n = 5121, of whom n = 371 received another transplant) was 61% male, 80% White and 36% had structural disease. Live donation occurred in 48%. There were 1371 graft failures and 145 deaths with a functioning graft over a 39,541-year risk period. Median follow-up was 7 years. Fifteen-year graft survival was 60.2% (95% CI 58.1, 62.3). Risk associations observed in both graft loss and eGFR decline analyses included female sex, glomerular diseases, Black ethnicity and young adulthood (15–19-year and 20–24-year age groups, compared to 25–29 years). A higher initial eGFR was associated with less risk of graft loss but faster eGFR decline. For each additional 10 mL/min/1.73m2 initial eGFR, the hazard ratio for graft loss was 0.82 (95% CI 0.79, 0.86), p 2, higher initial eGFR was associated with faster eGFR decline (> 90 mL/min/1.73m2; − 3.55 mL/min/1.73m2/year (95% CI -4.37, − 2.72), p Conclusions In conclusion, young adulthood is a key risk factor for transplant loss and eGFR decline for UK children and young adults. This study has an extended follow-up period and confirms common risk associations for graft loss and eGFR decline, including female sex, Black ethnicity and glomerular diseases. A higher initial eGFR was associated with less risk of graft loss but faster rate of eGFR decline. Identification of children at risk of faster rate of eGFR decline may enable early intervention to prolong graft survival.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) improve kidney and cardiovascular outcomes. SLGT2i initiation is accompanied by an acute decline in glomerular filtration rate. However, the clinical significance of this acute change remains unclear. In this issue of Kidney International, Kraus et al. examined the factors associated with an initial decline in estimated glomerular filtration rate after starting empagliflozin or placebo, subsequent kidney function trajectory, and the associations of odds of initial estimated glomerular filtration rate dip with long-term cardiovascular and kidney outcomes.

Background: Determination of risks for progression in chronic kidney disease (CKD) would improve strategies to reduce progression to ESKD. The eGFR study recruited and followed a cohort of adult Aboriginal and Torres Strait Islander people (Indigenous Australians) from Northern Queensland, Northern Territory and Western Australia, with the aim to address the heavy CKD burden experienced within these communities.Methods: Using data from the eGFR study, we explored the association of baseline liver function tests (LFTs) (alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), bilirubin and albumin) and full blood count (FBC) indices (white blood cell and red blood cell counts and haemoglobin) with annual eGFR decline and renal outcomes (first of 30% decline in eGFR with a follow-up eGFR 2, initiation of renal replacement therapy, or renal death). Comparisons of baseline variables across eGFR categories were calculated using analysis of variance and logistic regression as appropriate. Linear and multivariable regression models were used to estimate the annual change in eGFR for changes in FBC indices and LFTs. Cox proportional hazard models were used to estimate the hazard ratio for developing renal outcome for changes in baseline FBC indices and LFTs.Results: Of 547 participants, 540 had at least one baseline measure of LFTs and FBC indices. The mean age was 46.1 (14.7) years and 63.6% were female. The median follow-up was 3.1 (IQR 2.8-3.6) years. Annual decline in eGFR was associated with low serum albumin (pConclusions: GGT, ALP, bilirubin, albumin and haemoglobin independently associate with renal outcomes. Contrary to findings from other studies, no association was found between renal outcomes and other FBC indices. These findings may help focus strategies to prevent disease progression in this high-risk population.

Artificial intelligence is increasingly being adopted in medical fields to predict various outcomes. In particular, chronic kidney disease (CKD) is problematic because it often progresses to end-stage kidney disease. However, the trajectories of kidney function depend on individual patients. In this study, we propose a machine learning-based model to predict the rapid decline in kidney function among CKD patients by using a big hospital database constructed from the information of 118,584 patients derived from the electronic medical records system. The database included the estimated glomerular filtration rate (eGFR) of each patient, recorded at least twice over a period of 90 days. The data of 19,894 patients (16.8%) were observed to satisfy the CKD criteria. We characterized the rapid decline of kidney function by a decline of 30% or more in the eGFR within a period of two years and classified the available patients into two groups-those exhibiting rapid eGFR decline and those exhibiting non-rapid eGFR decline. Following this, we constructed predictive models based on two machine learning algorithms. Longitudinal laboratory data including urine protein, blood pressure, and hemoglobin were used as covariates. We used longitudinal statistics with a baseline corresponding to 90-, 180-, and 360-day windows prior to the baseline point. The longitudinal statistics included the exponentially smoothed average (ESA), where the weight was defined to be 0.9*(t/b), where t denotes the number of days prior to the baseline point and b denotes the decay parameter. In this study, b was taken to be 7 (7-day ESA). We used logistic regression (LR) and random forest (RF) algorithms based on Python code with scikit-learn library (https://scikit-learn.org/) for model creation. The areas under the curve for LR and RF were 0.71 and 0.73, respectively. The 7-day ESA of urine protein ranked within the first two places in terms of importance according to both models. Further, other features related to urine protein were likely to rank higher than the rest. The LR and RF models revealed that the degree of urine protein, especially if it exhibited an increasing tendency, served as a prominent risk factor associated with rapid eGFR decline.

PURPOSE OF REVIEW: Acute declines in estimated glomerular filtration rate (eGFR) are often observed during intensive blood pressure (BP) lowering. This review focuses on identifying the various mechanisms of eGFR decline associated with intensive BP lowering and evaluates the evidence linking BP control with kidney and cardiovascular (CV) outcomes. RECENT FINDINGS: In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) began recommending treatment of all individuals to a BP target of

In EMPA-REG OUTCOME, empagliflozin (EMPA) reduced the risk of CV death by 38% in T2D patients (pts) with CV disease. EMPA induces an initial, reversible dip in estimated glomerular filtration rate (eGFR). We investigated whether this transient initial renal hemodynamic effect was influenced by baseline characteristics or had an impact on the EMPA-induced risk reduction in CV death. In a post-hoc analysis, among the 6,668 pts randomized to EMPA 10 mg, 25 mg or placebo [PBO] with eGFR available, 28.3% of EMPA pts vs. 13.4% PBO experienced an initial eGFR decline >10% from baseline to Week 4 (odds ratio [OR; 95% CI]: 2.7 [2.3-3.0]). Multivariate logistic regression was used to identify baseline characteristics predictive of eGFR dip >10%. The impact of an eGFR dip >10% on the risk reduction in CV death was assessed using Cox regression. Diuretic use and higher KDIGO (Kidney Disease: Improving Global Outcomes) risk category at baseline were predictive of an eGFR dip >10% with EMPA vs. PBO. Serious adverse events were generally lower or similar in EMPA vs. PBO, regardless of predictive baseline factors. EMPA-induced CV death risk reduction was consistent across subgroups below vs. above average eGFR dipping OR (Panel A) and not affected by eGFR dip >10% (Panel B). T2D pts with more advanced kidney disease and/or on diuretic therapy were more likely to experience an eGFR dip >10% with EMPA. EMPA reduced CV death, regardless of an initial eGFR dip >10%. Disclosure S.E. Inzucchi: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Abbott, Merck & Co., Inc., vTv Therapeutics. B.J. Kraus: Research Support; Self; Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. M.R. Weir: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Scientific Affairs, LLC., Merck & Co., Inc. G. Bakris: Consultant; Self; Alnylam, Merck & Co., Inc., Relypsa, Inc., Teijin Pharma Limited. Other Relationship; Self; Bayer AG, Novo Nordisk Inc., Vascular Dynamics. M. Mattheus: None. D. Cherney: Research Support; Self; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. Other Relationship; Self; from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS and Novo-Nordisk. N. Sattar: Advisory Panel; Self; Amgen, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Sanofi. Research Support; Self; Boehringer Ingelheim Pharmaceuticals, Inc. H.L. Heerspink: Consultant; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim International GmbH, CSL Behring, Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mundipharma International, Retrophin, Inc. I. Ritter: Employee; Self; Boehringer Ingelheim International GmbH. M. von Eynatten: Other Relationship; Self; Boehringer Ingelheim International GmbH. B. Zinman: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. C. Wanner: Advisory Panel; Self; Eli Lilly and Company, Merck & Co., Inc., Mundipharma International. Consultant; Self; Boehringer Ingelheim (Canada) Ltd., Sanofi Genzyme. Speaker’s Bureau; Self; AstraZeneca. Other Relationship; Self; Boehringer Ingelheim International GmbH. A. Koitka-Weber: Employee; Self; Boehringer Ingelheim International GmbH.

In participants with type 2 diabetes (T2D) in the REWIND trial, dulaglutide (DU) use for median follow-up of 5.4 years was associated with reduced composite renal outcomes, defined as the first occurrence of new macroalbuminuria, sustained decline in estimated glomerular filtration rate (eGFR) of ≥30%, or chronic renal replacement therapy. The objective of this post-hoc analysis was to evaluate the effect of dulaglutide on renal outcomes related to kidney function that are typically used in renal outcomes studies, defined as the composite endpoint of sustained eGFR decline ≥40%, end-stage renal disease (ESRD), or all-cause death. Participants with T2D at cardiovascular (CV) risk were randomized (1:1) to DU 1.5 mg once-weekly or placebo. This post-hoc analysis used Cox proportional hazards modeling for time to first event to determine the risk of renal outcomes. Sensitivity analyses were conducted by replacing the all-cause death component with CV or renal death, or renal death. At baseline, treatment groups had similar eGFR (mean±SD: DU=77.2±22.7; placebo=76.6±22.8). The incidence rate of the composite endpoint was significantly lower for the DU group compared with placebo (Table). Treatment with DU 1.5 mg was associated with a 17% risk reduction in kidney function-related outcomes, suggesting potential delay in progression of diabetic kidney disease in patients with T2D at CV risk. Disclosure J.E. Shaw: Advisory Panel; Self; AstraZeneca, Merck Sharp & Dohme Corp., Mylan, Sanofi. Research Support; Self; AstraZeneca. Speaker’s Bureau; Self; Eli Lilly and Company, Mylan. F.T. Botros: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. R. Malik: Employee; Self; Eli Lilly and Company. Stock/Shareholder; Self; Eli Lilly and Company. C. Atisso: Employee; Self; Eli Lilly and Company. H.M. Colhoun: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk Inc., Novo Nordisk Inc., Pfizer Inc., Regeneron Pharmaceuticals, Sanofi-Aventis. Speaker’s Bureau; Self; Eli Lilly and Company, Regeneron Pharmaceuticals, Sanofi. Stock/Shareholder; Self; Bayer AG, Roche Pharma. Other Relationship; Self; Eli Lilly and Company, Sanofi. H.C. Gerstein: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Self; Kowa Pharmaceuticals America, Inc. Research Support; Self; AstraZeneca, Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Other Relationship; Self; Boehringer Ingelheim (Canada) Ltd., Eli Lilly and Company, Sanofi. Funding Eli Lilly and Company

Objective: In type 2 diabetes(T2D), prevalence of chronic kidney disease (CKD) with normoalbuminuria is increasing. We assessed the annual eGFR decline rate (slope) in Japanese patients with T2D with CKD treated by sodium glucose transporter 2 inhibitor (SGLT2i). Methods: A total of 75 patients with T2D with CKD (eGFR Results: 1) Average initial (first month) eGFR drop values are as follows, in Norm/Micro (51.2 to 47.9ml/min/1.73m2: P10 ml/min/1.73m2/year) existed in 12.8% (5/39) and in 25.0% (9/36) respectively. Mean eGFR slopes in these rapid decliner were all improved and as follow, -12.2±2.1 to +1.2±3.4ml/min/1.73m2/year; P Conclusion: SGLT2i could still have a remarkable renal benefit in Norm/Micro diabetic kidney disease. Slope analysis might be useful for safety and detecting rapid eGFR decliner. Disclosure K. Kashima: None. H. Shimizu: None. M. Yamada: None.

No specific dietary patterns have been established that are linked with loss of kidney function. We aimed to identify an estimated glomerular filtration rate-based dietary pattern (eGFR-DP) and to evaluate its association with eGFR decline and chronic kidney disease (CKD) incidence in the general population. We included 78,335 participants from the Lifelines cohort in the Northern Netherlands. All participants had an eGFR &gt, 60 mL/min/1.73 m2 at baseline and completed a second visit five years later. The eGFR-DP was constructed at baseline using a 110-item food frequency questionnaire by reduced rank regression, stratified by sex. Logistic regression was performed to evaluated the association between the eGFR-DP score and either a &ge, 20% eGFR decline or incident CKD. Among women, eGFR-DP were characterized by high consumption of egg, cheese, and legumes and low consumption of sweets, white meat, and commercially prepared dishes. In men, eGFR-DP were characterized by high consumption of cheese, bread, milk, fruits, vegetables, and beer and low consumption of white and red meat. A higher eGFR-DP score was associated with a lower risk of a &ge, 20% eGFR decline (OR 4th vs. 1st quartile, women: 0.79 [95% CI: 0.73&ndash, 0.87], men: 0.67 [0.59&ndash, 0.76]). The association between the eGFR-DP score and CKD incidence was lost upon adjustment for baseline eGFR. Our results provide support for dietary interventions to prevent kidney function decline in the general population.

Background Higher serum sodium concentration has been reported to be a risk factor for the development of incident chronic kidney disease (CKD), but its relationship with the progression of established CKD has not been investigated. We hypothesised that increased serum sodium concentration is a risk factor for estimated glomerular filtration rate (eGFR) decline in CKD. Methods This was a retrospective cohort study using data collected over a 6-year period, with baseline data obtained during the first 2 years. We included patients known to our renal service who had had a minimum of three blood tests every 2 years and an eGFR of

Aim Evaluate legacy effect on renal outcomes after the end of a multifactorial-multidisciplinary intervention in patients with advanced diabetic nephropathy (ADN trial) CKD 3–4. Methods A retrospective electronic review was conducted of 72 patients who completed the ADN trial ESRD-free with subsequent follow-up of two years or until ESRD development. Results At baseline, reflecting ADN trial end, 38 post-intervention and 34 post-control patients were similar except for lower HbA1c, SBP and age in the post-intervention group. In post-trial follow-up, ESRD developed in both groups at similar rates (23 vs 20%). ESRD occurred mainly in baseline CKD 4 (75%). In CKD 3, only those in post-control developed ESRD (28.6%, p = 0.067). A significant decline in eGFR occurred within both groups. In multivariate analyses, ESRD was associated with baseline yearly eGFR decline. Greater yearly eGFR decline was associated with higher albumin/creatinine ratio at follow-up, lower age, and baseline SBP not being at target (p = 0.005, with an R2 of 0.197). Conclusions There was no significant post-intervention effect on ESRD progression in the two groups. Minimal legacy effect was observed in less advanced nephropathy (CKD 3). These renal and risk outcomes emphasize the importance and potential benefits of continuous and long-term multifactorial care.

In healthy individuals, glomerular filtration rate decreases by 1 mL/min/y after a peak level of 125.0 mL/min has been reached in adulthood. Any reduction greater than this is a progressive slope (slope more negative than -1 mL/min/y, stable [-1 to +1]), or an improvable slope if it shows more of an increase, that is, greater than +1.0 mL/min/y). The aim of the study was to determine the factors affecting estimated glomerular filtration rate (eGFR) slope during the first 2 years of renal transplant in patients with negative pretransplant panel-reactive antibody.The characteristics of 59 renal transplant patients, such as age, sex, etiology, and 2 years of laboratory data, were collected retrospectively. For each patient, the eGFR decline rate (slope) (mL/min-1/1.73 mOf 59 patients, 7 (11.8%) had a progressive slope, 22 (37.2%) had a stable slope, and 30 (50.8%) had an improvable slope. The first-year mean tacrolimus level was lower in patients with progressive slope than in the patients with stable slope and improvable slope (P .022). The determinants of eGFR slope in multiple regression analysis were post-transplant hypertension (β = -0.393; P = .002) and the first-year mean tacrolimus level (β = 0.320; P = .01), whereas age, serum albumin, and 2-year mean tacrolimus level did not reach the level of significance.Keeping tacrolimus levels high in the first year to prevent eGFR declining is important.

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.

Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n =19; 14%) or low-risk (one or zero risk alleles; n =117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m 2 ; P =0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m 2 ; P =0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m 2 per year, P =0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline ( P =0.39) or any statistical interaction by APOL1 status ( P =0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.

Background This study assessed the incidence and impact of acute kidney injury (AKI) on renal prognosis in patients who underwent robot-assisted laparoscopic radical prostatectomy (RARP). Methods Medical records of 305 patients treated with RARP were retrospectively reviewed. The patients with postoperative AKIs were dichotomized into early AKI (immediately after surgery) and late AKI (1-7 days after surgery). The impact of AKIs and their risk factors were statistically assessed. Results Early and late AKI were observed in 143 (46.9%) and 12 (3.9%) patients, respectively. Hypertension and console time were independent risk factors for early AKI. Among the patients with preoperative eGFR ≥60 mL/min, the eGFR decline 12 months after surgery was significantly greater in patients with early AKI than that without early AKI (-6.8 vs -3.2 mL/min, P = .02). Conclusions Approximately half of patients developed early AKI after RARP. The patients with early AKI had reduced renal function 12 months after surgery.

Whether the visceral-to-subcutaneous fat ratio (V/S ratio) is associated with renal prognosis in patients with chronic kidney disease (CKD) remains unclear. Furthermore, little is known about the effect of sex and the absolute amount of visceral fat accumulation such as visceral fat area (VFA) ≥100 cm2on the V/S ratio in relation to renal prognosis. In this study, 200 patients with CKD were evaluated for renal prognosis. Survival analyses and logistic regression analyses were conducted, generating time-series pseudo-R2values. The mean and percent change of the pseudo-R2values from the 6thyear to the 10thyear (6Y–10Y Mean and 6Y–10Y Change, respectively) were calculated for determining the cut-off points for the medium-term renal prognosis. Multivariate Cox regression analysis revealed that the V/S ratio was significantly associated with renal outcomes and that the VFA category (VFA ≥ 100 cm2) had significant interactions with the V/S ratio regarding renal prognosis. The hazard ratio (HR) of the V/S ratio was higher in the sub-cohort of VFA<100 cm2than in the sub-cohort of VFA ≥ 100 cm2(HR: 6.42 vs. 1.00). Regarding sex differences, a strong association was noted between the V/S ratio and renal prognosis in women but not in men (HR: 2.40 vs. 1.10). On the other hand, 6Y–10Y Mean of the pseudo-R2values indicated differences in the cut-off points of the V/S ratio between men and women (V/S ratio: 0.75 vs. 0.5). Our findings indicate that it may be clinically meaningful to consider the differences in sex and the amount of VFA ≥100 cm2for the V/S ratio in relation to renal outcomes in patients with CKD. The 6Y–10Y Mean of the pseudo-R2values contributed to determining the cut-off points of the V/S ratio according to the sex difference.

Background Chronic kidney disease (CKD) is a major public health concern. Baseline serum uric acid (SUA) levels were independently associated with incident renal dysfunction, but whether baseline and changes in SUA produce an interactive effect on renal dysfunction remains unclear. Methods The subjects comprised 460 men aged 68 ± 10 (mean ± standard deviation) years and 635 women aged 68 ± 9 years from a rural village. We have found participants who underwent a similar examination 3 years later, and analyzed the relationship between baseline SUA, changes in SUA, and a 3‐year follow‐up renal function evaluated by estimated glomerular filtration rate (eGFR). Results A total of 93 (20.2%) men and 76 (12.0%) women had hyperuricemia (men: SUA ≥ 7.0 mg/dL and women: SUA ≥ 6.0 mg/dL) at baseline. Multiple regression analysis using changes in eGFR as objective variable, adjusted for risk factors as explanatory variables, showed that the baseline SUA and changes in SUA were linearly associated with changes in eGFR (β = －0.115, P

SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) improve cardiovascular (CV) and renal outcomes through distinct mechanisms. However, evidence is lacking on clinical outcomes in patients treated with both classes. EXSCEL, the cardiovascular outcomes trial for the GLP-1 RA exenatide, provides an opportunity to explore CV and renal outcomes with dual GLP-1RA and SGLT2i treatment, as ∼10% of participants had an SGLT2i added to their glycemic management during follow-up. Cohorts of SGLT2i users in the exenatide arm were propensity-matched to: 1) users of exenatide but not SGLT2i; 2) placebo arm participants that did not take SGLT2i, based on last measured characteristics before SGLT2i initiation. Subsequent time-to-first adjudicated major adverse cardiovascular event (MACE) and all-cause mortality (ACM) were compared using Cox regression analyses. eGFR decline was quantified in the matched cohorts using a mixed model repeated measurement (MMRM) analysis. Exenatide plus SGLT2i use numerically decreased the MACE hazard ratio and significantly reduced ACM risk, compared with exenatide alone and with placebo. The combination also significantly improved eGFR slope in both comparisons. This post hoc analysis offers support for the hypothesis that combinatorial exenatide and SGLT2i use may provide benefit on renal function and all-cause mortality. Disclosure L.E. Clegg: Employee; Self; AstraZeneca. R.C. Penland: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca, Novartis AG. D.W. Boulton: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca, Bristol-Myers Squibb Company. S. Bachina: Employee; Self; AstraZeneca. M. Thuresson: Consultant; Self; AstraZeneca. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. S. Gustavson: Employee; Self; AstraZeneca. Employee; Spouse/Partner; AstraZeneca. C. Sjöström: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. J.A. Ruggles: Employee; Self; AstraZeneca. Stock/Shareholder; Self; Apple, AstraZeneca. A.F. Hernandez: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. Research Support; Self; AstraZeneca, GlaxoSmithKline plc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc. R.J. Mentz: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; GlaxoSmithKline plc. Other Relationship; Self; Amgen Inc., AstraZeneca, Bayer AG, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation. R.R. Holman: Advisory Panel; Self; Bayer AG, Novartis AG, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Bayer AG, Merck Sharp & Dohme Corp. Other Relationship; Self; AstraZeneca, Bayer AG, GlaxoSmithKline plc., Janssen Pharmaceuticals, Inc.

Background: DECLARE-TIMI 58 showed that dapagliflozin (dapa) a sodium glucose co-transporter 2 inhibitor (SGLT2i), reduced the rate of cardiovascular death or hospitalization for heart failure in patients with T2DM with or at high risk of atherosclerotic cardiovascular disease. SGLT2is have been shown to have a beneficial effect on renal outcomes. Methods: DECLARE-TIMI 58 pre-specified primary composite renal outcome (PCRO) included sustained 40% eGFR decline to < 60 ml/min/1.73m2, end-stage renal disease (defined as dialysis ≥90 days or kidney transplantation, confirmed sustained eGFR Results: A total of 17,160 subjects were enrolled, including 8,162 (47.6%) with eGFR ≥90, 7,732 (45.1%) with eGFR 60- Conclusion: In a large and broad population of patients with T2DM and mostly preserved renal function, dapa was associated with reduced progression of kidney disease and lower rates of clinically relevant renal events than was placebo. Disclosure O. Mosenzon: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Research Support; Self; AstraZeneca, Novo Nordisk Inc. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis. S.D. Wiviott: Consultant; Self; Aegerion Pharmaceuticals, Allergan, Angel Medical Systems, Inc., Arena Pharmaceuticals, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Boston Clinical Research Institute, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eisai Inc., Eli Lilly and Company, Icon Clinical, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Servier, St. Jude Medical, XOMA Corporation. Employee; Spouse/Partner; Merck & Co., Inc. Research Support; Self; Amgen Inc., Arena Pharmaceuticals, AstraZeneca, Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Eisai Inc., Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck & Co., Inc., Sanofi-Aventis. T.A. Zelniker: None. H.L. Heerspink: Consultant; Self; AbbVie Inc., Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Fresenius Medical Care, Gilead Sciences, Inc., Janssen Research & Development, Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation. J.P. Dwyer: Consultant; Self; Akcea Therapeutics, AstraZeneca, Bird Rock Bio, Eisai Inc., Goldfinch Bio, Sanofi-Aventis. A. Cahn: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, GlucoMe Ltd., Novo Nordisk A/S, Sanofi. Speaker's Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S. Stock/Shareholder; Self; GlucoMe Ltd. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. M.S. Sabatine: Consultant; Self; Amgen Inc., AstraZeneca, Bristol-Myers Squibb Company, CVS/Caremark, Dyrnamix, Esperion, Intarcia Therapeutics, Inc., Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis. Research Support; Self; Amgen Inc., AstraZeneca, Daiichi Sankyo Company, Limited, Eisai Co., Ltd., GlaxoSmithKline plc., Intarcia Therapeutics, Inc., Janssen Research and Development, Medicines Company, MedImmune, Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Pfizer Inc., Takeda. I. Raz: Advisory Panel; Self; AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Consultant; Self; AstraZeneca, BOL, Bristol-Myers Squibb Company, CameraEyes Ltd, DarioHealth, Diabot, Exscopia, GlucoMe Ltd., Insuline Medical, Medial EarlySign, Orgenesis Ltd. Speaker's Bureau; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk Inc., Sanofi. Stock/Shareholder; Self; BOL, CameraEyes Ltd, DarioHealth, Diabot, GlucoMe Ltd., Orgenesis Ltd. Funding AstraZeneca

Objective: The slope of eGFR decline is collecting attentions for earlier recognition of eGFR decliner. We analyzed the predictive value of maximum 1-year eGFR decline rate for the renal endpoint in prospective cohort. Research Design and Methods: We analyzed the data from EMPATHY trial which was the multicenter randomized control trial to assess the benefits of intensive statin therapy for patients with hypercholesterolemia and diabetic retinopathy. We calculated 1-year eGFR decline rate in every 6 months and analyzed its relation to the renal endpoint defined as initiation of chronic dialysis or increase in serum creatinine level by at least twofold. Results: The renal endpoint developed in 101 subjects out of 5,042 patients in mean follow-up 37 ± 13 months. The AUC of maximum 1-year eGFR decline rate by ROC was 0.960, that of albuminuria at baseline was 0.913, and that of eGFR at baseline was 0.809. When we defined the cut-off value of maximum 1-year eGFR decline rate as 20%, its sensitivity was 97.8% and its specificity was 80.2%. Time until the renal endpoint from the first demonstration of 1-year eGFR decline rate more than 20% was 353.1 ± 31.9 days. Conclusions: One-year eGFR decline more than 20% was highly associated with the renal endpoint. The renal endpoint was predominantly observed in the subjects with albuminuria. Disclosure S. Meguro: Research Support; Self; Novartis Pharmaceuticals Corporation. Speaker's Bureau; Self; Abbott, Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kyowa Hakko Kirin Co., Ltd., Merck & Co., Inc., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., NIPRO Medical Corporation, Novo Nordisk A/S, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited, Terumo Medical Corporation. Y. Sato: None. H. Itoh: None.

Early initiation of insulin therapy often remains contentious due to various patient and physician-related barriers. Insulin is delayed by several years despite high A1c and is the foremost reason for costly future complications. In addition, the problem of early aggressive use of insulin depleting drugs causes β-cell fatigue leading to "brittle diabetes" and higher insulin dose requirements. In this observational cohort study, a comparison has been made between early insulin initiators (EII) (within 7-8 years of diabetes onset) and late insulin initiators (LII) (>8 years of onset), in terms of progression of CKD (eGFR decline), if any. A total of 200 subjects in each arm were matched at baseline for T2DM duration (16.78±4.32 year), BP, BMI, HbA1c and presence of co-morbid illnesses. Both groups were closely followed-up through our Diabetes Tele Management System based health care model that have previously shown to be successful in safely achieving glycemic targets compared to conventional models of care. A paired t test was done for analyzing the eGFR decline within each arm. EII arm required a significantly lower total daily dose of insulin (TDD) (average of 9 units/day) to maintain glycemic control throughout than the LII arm (average of 30 units/day). The decline in eGFR was significant in the LII arm, whereas in the EII arm, eGFR was maintained throughout. Change in A1c was also significant. Disclosure J. Kesavadev: None. R. Warrier: None. L. Ramachandran: None. A. Shankar: None. A. David: None. N.A. Ajai: None. G. Sanal: None. K. Thampiraj: None. G. Krishnan: None. S. Jothydev: None.