Final eGFR Research Articles

#2665 Acute kidney injury (AKI) and chronic kidney disease (CKD) in living kidney donors (LKD): time for a new “surgical” classification system?

Abstract Background and Aims Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD) represent two significant complications in patients who undergo radical (RN) nephrectomy in oncological patients. However, Living kidney donors (LKD) undergo a similar surgery, but kidney dysfunctions are rare. Our study aimed to investigate the incidence of AKI and CKD in a consecutive cohort of LKD. Method This multi-institutional study involved 256 kidney donors who performed RN between 2014 and 2021 in four tertiary care hospitals. Clinical and laboratory data were collected at baseline pre-surgery, six months after surgery, and then every 12 months for a five-year follow-up. eGFR was calculated with the CKD-EPI equation. Statistical analysis was performed using descriptive statistics and logistic regression. Results Descriptive analysis is reported in Table 1. Of note, the rate of AKI was high (85%), even though it was 100% of stage 1. At 12 months, LKD missed 27.9 ± 19.67 ml/min/1.73 m2, persisting stable at 60 months. 26% of patients developed CKD stage GIII, and 10% of patients lost about 30 ml/min/1.73 m2 from the baseline eGFR (Fig. 1 and Tables 1 and 2). The multivariate analysis (logistic regression) showed that age had a direct correlation with the risk of AKI (OR 1.057, p = 0.019), while the female sex was inversely correlated (OR 0.180, p = 0.006); on the other hand, age had a direct correlation with the risk of CKD (OR 1.15, p = 0.001), as well as eGFR before the surgery (OR 1,053, p = 0.027). Conclusion AKI and CKD affected a non-negligible percentage of LKD. However, it is remarkable that most LKD had a medium final eGFR >60 ml/min/1.73 m2 due to a healthy solitary kidney that worked properly, increasing its function by about 30% of its baseline capacity.

BIOM-16. LONGITUDINAL GLIOMA CEREBROSPINAL FLUID CELL-FREE DNA FOR MONITORING AND TREATMENT RESPONSE ASSESSMENT

Abstract Few methods exist via which to assess treatment response with high fidelity in gliomas. While CSF has previously been used as a source of cfDNA, it remains unknown how cfDNA abundance and sequencing changes throughout treatment and inevitable recurrence in gliomas. We utilized our biobank of longitudinal intracranial CSF specimens to determine the potential utility of CSF cfDNA as a monitoring tool for treatment response in patients with gliomas. Longitudinal CSF specimens were acquired via Ommaya reservoirs (NCT04692337) or ventriculoperitoneal shunts (NCT04692324) in patients with gliomas. cfDNA was extracted from 1-5 mL of CSF, and next-Generation sequencing or low-pass whole genome sequencing (LPWGS) was performed by Predicine, Inc. CSF acquired prior to versus after resection demonstrated an increase in quantified cfDNA (2.97x, range: 1.58-5.26x), consistent with the impact of increased parenchymal disruption and closer contact with CSF. Thereafter, CSF cfDNA continued to decrease throughout chemoradiation and adjuvant treatment and increased at recurrence, including in patients co-enrolled in immunotherapy trials for IL-7 agonists and pembrolizumab. Copy number burden (CNB) increased by the time of recurrence in three patients with known disease progression, and continued to decrease throughout immunotherapy treatment in one patient despite concerns of pseudoprogression. In one patient with a hypermutated glioblastoma, CSF cfDNA revealed over 59 genomic alterations, including MAP2K1, KIT, and PDGFRA, excluding even more variants of unknown significance, each of which had been detected in sequencing of the tissue acquired at resection and subsequently decreased with chemoradiation. In another patient with a known progressing EGFR-amplified GBM, over 200 new variants were identified by the patient’s final sample and EGFR copy number increased from 2 to over 30. In conclusion, cfDNA analysis over a patient’s disease course, including resection and treatment with standard-of-care and experimental therapies, may be of use for disease monitoring and treatment response.

African Caribbean Ethnicity Is an Independent Predictor of Significant Decline in Kidney Function in People With Type 1 Diabetes.

The aim of the study was to identify the demographic and clinical features in an urban cohort of people with type 1 diabetes who developed a ≥50% decline in estimated glomerular filtration rate (eGFR). We evaluated 5,261 people with type 1 diabetes (51% female, 13.4% African Caribbean) with baseline eGFR >45 mL/min/1.73 m2 between 2004 and 2018. The primary end point was an eGFR decline of ≥50% from baseline with a final eGFR <30 mL/min/1.73 m2. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the cohort, 263 (5%) reached the primary end point. These individuals were more likely to be of African Caribbean ethnicity, be older, have a longer duration of diabetes, have higher systolic blood pressure and HbA1c, have more prevalent retinopathy, and have higher albuminuria (all P < 0.05). In multivariable Cox regression models, African Caribbean ethnicity emerged as a significant risk factor for the primary end point (hazard ratio 1.57, 95% CI 1.19, 2.08) compared with other ethnicities and independent of established risk factors (P < 0.01). The incidence rate for the primary end point in African Caribbean people was double that in non-African Caribbean people (16 vs. 7.7 per 1000 patient-years, P < 0.001). A similar significant independent impact of African Caribbean ethnicity for secondary end points (≥40% and ≥30% fall in eGFR) was observed. We report a novel observation that African Caribbean ethnicity increased the risk of kidney function loss in people with type 1 diabetes, an effect that was independent of traditional risk factors. Further studies are needed to examine the associated pathophysiology that may explain this observation.

Impact of Arteriovenous Fistula Creation on Progression of Chronic Kidney Disease

Background: All guidelines recommend pre-emptive arteriovenous fistula (AVF) formation in late-stage chronic kidney disease (CKD) patients. New evidence shows that pre-emptive AVF can improve estimated glomerular filtration rate (eGFR) as well. Aim: To evaluate the beneficial effect of AVF on improvement of eGFR in pre dialysis patients of CKD stage 5 disease. Methodology: A total of one hundred CKD stage five pre-dialysis patients were included in this prospective cohort research from the Nephrology unit of Services Hospital Lahore (SHL). After receiving approval from the ethical review committee SHL, the study was performed from September 2021 to March 2022. Patients were separated into two groups. Fifty patients with arteriovenous fistula (AVF) were in Group AVF, whereas those in Group Non-AVF were only on conservative therapy as they opted for conservative treatment despite counseling about need for AVF and Renal Replacement Therapy (RRT) in future. Over the course of six months, both groups were monitored. The initial eGFR was measured immediately after the formation of AV fistula and monthly for next six months (Final eGFR). Results: The median age of the study population was 37 years in which the sixty percent of the males. The most common comorbid condition was hypertension (96%) and the main reason for late-stage renal disfunction was diabetic nephropathy (45%). We found statistically significant improved eGFR in AVF group as compared to the non-AVF group (p &lt; 0.01). Conclusion: From the results of our study, it can be concluded that the creation of AV fistula in the pre-dialysis patient has a beneficial effect on improvement of eGFR and delaying the progression CKD. Keywords: End Stage Renal Disease, AV fistula, Pre-Dialysis, e GFR, chronic kidney disease,

MO296: Seasonal Variations in AKI Incidence and Outcomes

Abstract BACKGROUND AND AIMS Kuwait enjoys a cool winter but suffers a very hot summer. We aim to evaluate the relationship between weather temperature and acute kidney injury (AKI) incidence and outcome. METHOD We prospectively collected demographic (age, sex and nationality), clinical (CKD status, cause of AKI and comorbidities), management (fluids, diuretics, inotropes, ventilatory support and dialysis) and 30-day patients and kidney outcome data for all adult nephrology consultations for AKI in seven major public hospitals in Kuwait during January, February and March/2021 and compared them to those of June, July and August/2021. RESULTS A total of 2038 patients with AKI were enrolled (mean age: 64; males: 59%, Kuwaitis: 58%; mean eGFR: 66.5; mean initial Hgb: 106). Of the cohort, 42% had baseline eGFR &amp;lt; 60 (with a mean eGFR of 37, a mean age of 68 and a mean Hgb of 102 versus a mean eGFR of 88, a mean age of 59 and a mean Hgb of 109 for the group with baseline eGFR &amp;gt; 60). Higher percentage of AKI cases took place in cooler months (63% versus 37%). Patients with AKI in cooler months were significantly older (65 versus 59), with lower baseline eGFR (63 versus 72.5) and more comorbidities (DM, HTN, CAD). There was no difference between the two groups in the use of IV fluids (saline, bicarbonate, blood products, etc.) or IV diuretics (loop, thiazide or potassium-sparing); however, IV vasopressors were used more often in cooler months in cases of AKI. Mechanical ventilation was more frequently used in the summer cases (44% of summer AKI cases versus 40% of winter AKI cases) but not statistically significant. Dialysis was needed for 44% of the entire cohort, 56% of dialysis cases were in cooler months (31% of winter AKI cases) and 44% in summer months (40% of summer AKI cases). Dialysis modality was continuous in 85% of all cases. At 30 days, 36.5% of the total cohort died; 72% of them died while on dialysis. Larger proportion of deaths in AKI cases in cooler months (58% of total deaths or 33% of the winter AKI cases versus 42% of the total death or 42% of the summer AKI cases), with more deaths while on dialysis seen in cooler months too (56% versus 44% of deaths while on dialysis). However, lower rates of complete recovery from AKI were seen in summer cases (33% versus 67%), with a mean final eGFR of 57 for the winter AKI cases versus 41 for the summer AKI cases. CONCLUSION AKI is more common in the cooler months of the year affecting an older group of patients with more comorbidities, and is associated with higher usage of dialysis and higher rates of death, but probably better chances of kidney recovery in those who survive.

Impact of Time-Zero Biopsy on the Outcome of Transplanted Kidneys

A low supply of donated organs led to the expansion of criteria for kidney transplantation (KT), and the impact on late glomerular function rates (eGFR) is still uncertain. This study aimed to correlate the histologic findings at time-zero biopsy (TzB) with the final eGFR, to identify criteria that could help achieve a more thorough preimplantation evaluation of the organ. Records from 395 adult deceased KTs were reviewed. TzBs were analyzed considering histologic criteria by compartment (vascular, interstitial, tubular, and inflammatory) and correlated with the eGFR after 1 year. Among donors, 56.9% were men (mean age 39 years), with the main causes of death being brain trauma (44.2%) and stroke (46.0%). Histologic analysis of TzB revealed 6.0% of glomerulosclerosis; 18.8% presenting vascular alterations; interstitial fibrosis in 54.6%; tubular changes in 76.9%, and nonspecific inflammatory infiltrate in 2.3%. Linear regression analysis showed that the main histologic findings that had impact in the eGFR were interstitial fibrosis (P=.000), followed by tubular alterations (P=.036) and glomerulosclerosis (P=.008). Histologic variables like interstitial fibrosis and tubular alterations show the most significant negative correlation with final eGFR. The effect of glomerulosclerosis may not be as important as formerly suggested in the literature.

Predicting Future Renal Function Decline in Patients with Autosomal Dominant Polycystic Kidney Disease Using Mayo Clinic Classification

Introduction: Mayo clinic classification (MCC) has been proposed in patients with autosomal dominant polycystic kidney disease (ADPKD) to identify who may experience a rapid decline of renal function. Our aim was to validate this predictive model in a population from southern Spain. Methods: ADPKD patients with measurements of height-adjusted total kidney volume (HtTKV) and baseline estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m² were selected. Last eGFR was estimated with Mayo Clinic (MC) equation and bias and accuracy were studied. We also analyzed predictive capacity of MCC classes using survival analysis and Cox regression models. Results: We included 134 patients with a mean follow-up of 82 months. While baseline eGFR was not different between classes, last eGFR decreased significantly with them. eGFR variation rate was different according to the MCC class with a more rapid decline in 1C, 1D, and 1E classes. Final eGFR predicted was not significantly different from the real one, with an absolute bias of 0.6 ± 17.0 mL/min/1.73 m². P10 accuracy was low ranging from 37.5 to 59.5% in classes 1C, 1D, and 1E. Using MC equation, the rate of eGFR decline was underestimated in 1C, 1D, and 1E classes. Cox regression analysis showed that MCC class is a predictor of renal survival after adjusting with baseline eGFR, age, sex, and HtTKV, with 1D and 1E classes having the worst prognosis. Conclusion: MCC classification is able to identify patients who will undergo a more rapid decline of renal function in a Spanish population. Prediction of future eGFR with MC equation is acceptable as a group, although it shows a loss of accuracy considering individual values. The rate of eGFR decline calculated using MC equation can underestimate the real rate presented by patients of 1C, 1D, and 1E classes.

MO128RETINOL BINDING PROTEIN (RBP) - NEW BIOMARKER OF KIDNEY INJURY IN MULTIPLE MYELOMA PATIENTS*

Abstract Background and Aims The aim of the study was to analyse the utility of retinol binding protein (RBP) in case of renal impairment in MM patients and investigate its relationship with acclaimed parameters of renal failure and markers of MM stages. Method We recruited 73 patients (35 women, 38 men, in age range of 29-90 years, mean 70 ± 10 years) with multiple myeloma (MM), including 6 (8%) with smoldering MM, 40 (55%) with International Staging System (ISS) stage I, 15 (21%) with ISS II and 12 (16%) with ISS III. The majority of patients (65, 89%) received at least one treatment scheme. Thirty patients (41%) received maintenance treatment at recruitment. Median eGFR based on serum creatinine (CKD-EPICr) equaled 67 (range 9 – 117) ml/min/1.73 m2. Results Significant correlation was observed between RBP and the ordered variable describing MM stage from smoldering myeloma to ISS III (R=0.36; p=0.002). There were no differences between patients in CR, PR, SD and PD at the time of samples’ collection. Patients who were on maintenance treatment at recruitment tended to have higher serum RBP (median 42.6 versus 37.7 mg/l), however, the difference was not statistically significant (p=0.068). The patients who received steroid treatment had significantly higher RBP concentrations. There were no such association with other medications. There was no association between RBP and the number of previous treatment lines (p=0.8). Serum RBP did not differ between men and women (p=0.7) and did not correlate with age (p=0.6). Significant correlations were found between RBP and serum creatinine, cystatin C and eGFR values calculated based on creatinine and/or cystatin C (Table 1). In multiple regression, serum creatinine or cystatin C and the treatment with steroids were associated with RBP independently of ISS stage (Table 2). Moreover, RBP correlated with β2-microglobulin, LDH, leukocyte count, α-klotho, FGF-23, GDF-15, uNGAL and uIGFBP-7, however, only the associations with β2-microglobulin and sTfR were independent of serum creatinine in multiple regression (Table 1). Baseline serum RBP concentration was significantly correlated with eGFR after a median of 19 months follow-up (range 1-24 months) (R=-0.35; p=0.003), however, the correlation was not independent of baseline serum creatinine ((beta ± SE: 0.06 ± 0.10; p=0.5). To the contrary, baseline serum cystatin C (beta ± SE: -0.36 ± 0.13; p=0.009) predicted final eGFR independently of baseline serum creatinine. Conclusion RBP may be useful marker in renal damage in patients with chronic kidney injury among patients with MM. This can lead to noninvasive biomarker-targeted diagnostic interventions and contribute to early beginning of treatment that may improve life expectancy quality of life in MM.

Quantitative levels of serum N-glycans in type 1 diabetes and their association with kidney disease.

We investigated associations of quantitative levels of N-glycans with hemoglobin A1c (HbA1c), renal function and renal function decline in type 1 diabetes. We measured 46 total N-glycan peaks (GPs) on 1565 serum samples from the Scottish Diabetes Research Network Type 1 Bioresource Study (SDRNT1BIO) and a pool of healthy donors. Quantitation of absolute abundance of each GP used 2AB-labeled mannose-3 as a standard. We studied cross-sectional associations of GPs and derived measures with HbA1c, albumin/creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR), and prospective associations with incident albuminuria and final eGFR. All GPs were 1.4 to 3.2 times more abundant in SDRTN1BIO than in the healthy samples. Absolute levels of all GPs were slightly higher with higher HbA1c, with strongest associations for triantennary trigalactosylated disialylated, triantennary trigalactosylated trisialylated structures with core or outer arm fucose, and tetraantennary tetragalactosylated trisialylated glycans. Most GPs showed increased abundance with worsening ACR. Lower eGFR was associated with higher absolute GP levels, most significantly with biantennary digalactosylated disialylated glycans with and without bisect, triantennary trigalactosylated trisialylated glycans with and without outer arm fucose, and core fucosylated biantennary monogalactosylated monosialylated glycans. Although several GPs were inversely associated prospectively with final eGFR, cross-validated multivariable models did not improve prediction beyond clinical covariates. Elevated HbA1c is associated with an altered N-glycan profile in type 1 diabetes. Although we could not establish GPs to be prognostic of future renal function decline independently of HbA1c, further studies to evaluate their impact in the pathogenesis of diabetic kidney disease are warranted.

Primary care referrals to nephrology in patients with advanced kidney disease.

Optimizing care for patients with advanced kidney disease requires close collaboration between primary care physicians (PCPs) and nephrologists. Factors associated with PCP referral to nephrology were assessed in patients with estimated glomerular filtration rates (eGFRs) less than 30 mL/min/1.73 m2. Electronic health record review at an integrated health care network. Factors associated with referral status were identified using Fisher's exact tests, t tests, and multivariable logistic regression. Of 133,913 patients regularly seeing PCPs between October 2017 and September 2019, 1119 had a final eGFR less than 30 mL/min/1.73 m2 and were not on renal replacement therapy. Care was provided by 185 PCPs (61 practices). Analyses were restricted to the 97.1% (n = 1087) of patients who were African American or European American. Of these, 54.6% had not been referred to nephrology. Nonreferred patients had higher numbers of PCP visits (P = .004). In contrast, referred patients were younger, were more often African American, and had PCPs at the academic medical center (all P < .0001). Referred patients had more complex medical histories with higher Charlson Comorbidity Index scores, more hospitalizations, and greater numbers of inpatient days (all P < .0001). Analyses restricted to patients with serum creatinine concentration of at least 2 mg/dL yielded similar results. Age, number of hospitalizations, ancestry, academic physician, diabetic end-organ damage, peripheral vascular disease, and tumor status were independent predictors of nephrology referral. Impediments to appropriately timed nephrology referrals persist in patients with high likelihoods of progression to end-stage kidney disease. Improved access to nephrology care should be rapidly addressed to meet targets in the 2019 Executive Order on Advancing American Kidney Health.

Biomarkers associated with early stages of kidney disease in adolescents with type 1 diabetes.

To identify biomarkers of renal disease in adolescents with type 1 diabetes (T1D) and to compare findings in adults with T1D. Twenty-five serum biomarkers were measured, using a Luminex platform, in 553 adolescents (median [interquartile range] age: 13.9 [12.6, 15.2] years), recruited to the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial. Associations with baseline and final estimated glomerular filtration rate (eGFR), rapid decliner and rapid increaser phenotypes (eGFR slopes <-3 and > 3 mL/min/1.73m2 /year, respectively), and albumin-creatinine ratio (ACR) were assessed. Results were also compared with those obtained in 859 adults (age: 55.5 [46.1, 64.4) years) from the Scottish Diabetes Research Network Type 1 Bioresource. In the adolescent cohort, baseline eGFR was negatively associated with trefoil factor-3, cystatin C, and beta-2 microglobulin (B2M) (B coefficient[95%CI]: -0.19 [-0.27, -0.12], P = 7.0 × 10-7 ; -0.18 [-0.26, -0.11], P = 5.1 × 10-6 ; -0.12 [-0.20, -0.05], P = 1.6 × 10-3 ), in addition to clinical covariates. Final eGFR was negatively associated with osteopontin (-0.21 [-0.28, -0.14], P = 2.3 × 10-8 ) and cystatin C (-0.16 [-0.22, -0.09], P = 1.6 × 10-6 ). Rapid decliner phenotype was associated with osteopontin (OR: 1.83 [1.42, 2.41], P = 7.3 × 10-6 ), whereas rapid increaser phenotype was associated with fibroblast growth factor-23 (FGF-23) (1.59 [1.23, 2.04], P = 2.6 × 10-4 ). ACR was not associated with any of the biomarkers. In the adult cohort similar associations with eGFR were found; however, several additional biomarkers were associated with eGFR and ACR. In this young population with T1D and high rates of hyperfiltration, osteopontin was the most consistent biomarker associated with prospective changes in eGFR. FGF-23 was associated with eGFR increases, whereas trefoil factor-3, cystatin C, and B2M were associated with baseline eGFR.

SO081LITHIUM EXPOSURE AND OCCURENCE OF CHRONIC KIDNEY DISEASE IN THE IRISH HEALTH SYSTEM: A COHORT STUDY

Abstract Background and Aims Lithium is implicated as a causative factor in the development and progression of chronic kidney disease (CKD). Few studies have assessed the independent impact of plasma levels and duration of lithium therapy on CKD progression. We examined the influence of lithium on CKD progression in the Irish health system. Method We utilised data from the Irish Kidney Disease Surveillance System (IKDSS) to explore associations of lithium levels and duration of exposure with kidney function in a regional cohort. A retrospective cohort study was conducted between 1999 to 2014 from the Midwest Region. All adult patients with lithium levels were identified and followed longitudinally. Kidney function was assessed at baseline and longitudinally using serum creatinine and estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI. Patients with &amp;lt; 2 lithium values, missing data on creatinine were excluded. The index date was the date of the first lithium blood test. Toxicity from lithium was defined as levels &amp;gt;1.2mmol/L as per NICE guidelines while duration of treatment was calculated based on patient –years of exposure as determined by positive blood lithium levels. Relationships between baseline kidney function, lithium levels, duration of exposure and each patients most recent eGFR value on follow up were assessed using multiple linear regression Results We identified 1,978 patients exposed to lithium from 1999-2014, mean age was 47.4 (15.6), 45.1% were men, eGFR [median (IQR)] at baseline was 84.4 (32.1) ml/min1.73m and the median duration of exposure was 3.0 years (IQR=4 years). Frequency of lithium testing increased from 1.77 in 1999 to 2.66 in 2014. In multiple linear regression, the final eGFR on follow-up was significantly lower in older patients (-0.48 ml/min/1.73m per year increase in age), P&amp;lt;0.001; in patients with elevated baseline lithium levels (-2.18 ml/min1.73m lower per unit increase), P&amp;lt;0.05, with long duration of exposure (-1.42 ml/min/1.73m lower for each year on lithium), P&amp;lt;0.001, and for patients with low GFR at baseline (P&amp;lt;0.001). Together these variables explained 58% of the variation in the final model. Conclusion Both the magnitude of and the duration of lithium exposure are both independently associated with CKD progression among lithium users in the Irish health system. Higher baseline lithium values had a more deleterious impact on kidney function. Continued efforts should be expended in minimising the risks of lithium induced nephrotoxicity through switching to alternatives and dose reduction when over possible. Funding This study is funded by the Health Research Board and the Midwest Research and Education Foundation (MKid).

Factors Associated with a Large Decline in Renal Function or Progression to Renal Insufficiency in Hospitalized Atrial Fibrillation Patients with Early-Stage CKD.

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.

Comparison of serum and urinary biomarker panels with albumin/creatinine ratio in the prediction of renal function decline in type 1 diabetes

Aims/hypothesisWe examined whether candidate biomarkers in serum or urine can improve the prediction of renal disease progression in type 1 diabetes beyond prior eGFR, comparing their performance with urinary albumin/creatinine ratio (ACR).MethodsFrom the population-representative Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) we sampled 50% and 25% of those with starting eGFR below and above 75 ml min−1 [1.73 m]−2, respectively (N = 1629), and with median 5.1 years of follow-up. Multiplexed ELISAs and single molecule array technology were used to measure nine serum biomarkers and 13 urine biomarkers based on our and others’ prior work using large discovery and candidate studies. Associations with final eGFR and with progression to <30 ml min−1 [1.73] m−2, both adjusted for baseline eGFR, were tested using linear and logistic regression models. Parsimonious biomarker panels were identified using a penalised Bayesian approach, and their performance was evaluated through tenfold cross-validation and compared with using urinary ACR and other clinical record data.ResultsSeven serum and seven urine biomarkers were strongly associated with either final eGFR or progression to <30 ml min−1 [1.73 m]−2, adjusting for baseline eGFR and other covariates (all at p<2.3 × 10−3). Of these, associations of four serum biomarkers were independent of ACR for both outcomes. The strongest associations with both final eGFR and progression to <30 ml min−1 [1.73 m]−2 were for serum TNF receptor 1, kidney injury molecule 1, CD27 antigen, α-1-microglobulin and syndecan-1. These serum associations were also significant in normoalbuminuric participants for both outcomes. On top of baseline covariates, the r2 for prediction of final eGFR increased from 0.702 to 0.743 for serum biomarkers, and from 0.702 to 0.721 for ACR alone. The area under the receiver operating characteristic curve for progression to <30 ml min−1 [1.73 m]−2 increased from 0.876 to 0.953 for serum biomarkers, and to 0.911 for ACR alone. Other urinary biomarkers did not outperform ACR.Conclusions/interpretationA parsimonious panel of serum biomarkers easily measurable along with serum creatinine may outperform ACR for predicting renal disease progression in type 1 diabetes, potentially obviating the need for urine testing.

Discontinuation of Proton Pump Inhibitors in Patients With Chronic Kidney Disease.

Purpose: Proton pump inhibitors (PPIs) are commonly used medications and are historically well tolerated. Recent studies have linked PPI use to the development of chronic kidney disease (CKD) and end-stage renal disease. This study investigated the impact of discontinuing PPIs on renal function in patients with CKD. Methods: We conducted a retrospective chart review of patients with established CKD, defined as 2 eGFR (estimated glomerular filtration rate) measurements of less than 60 mL/min/1.73 m2 at least 90 days apart, who were on a PPI from January 1, 2014 to December 31, 2014, with a medication possession ratio greater than or equal to 70%. We compared baseline eGFR to a final eGFR after at least 6 months of discontinuation or continuation of a PPI. After power analysis, we targeted an enrollment of 200 patients (100 in each group) to achieve a power of 0.80 and an alpha of 0.05. Summary: A total of 97 patients in the PPI discontinuation group and 100 patients in the PPI continuation group met the study inclusion criteria. Baseline eGFR in the PPI continuation group was 47.9 mL/min/1.73 m2 and 50.7 mL/min/1.73 m2 in the discontinuation group. Final eGFR in the PPI continuation group was significantly higher than baseline at 51.1 mL/min/1.73 m2 (+3.25 ± 12.8, P = .01). Final eGFR in the PPI discontinuation group was 51.8 mL/min/1.73 m2 (+1.09 ± 12.8, P = .3). The average time between baseline and final eGFRs was 270 days in the PPI continuation group and 301 days in the discontinuation group. There was no statistically significant difference in the change in eGFRs between groups (95% confidence interval [CI] = -5.48-2.03, P = .37). Conclusions: Proton pump inhibitor discontinuation after prolonged continuous use in patients with CKD was not associated with a significant change in renal function after 1 year.

Predicting renal disease progression in a large contemporary cohort with type 1 diabetes mellitus

Aims/hypothesisThe aim of this study was to provide data from a contemporary population-representative cohort on rates and predictors of renal decline in type 1 diabetes.MethodsWe used data from a cohort of 5777 people with type 1 diabetes aged 16 and older, diagnosed before the age of 50, and representative of the adult population with type 1 diabetes in Scotland (Scottish Diabetes Research Network Type 1 Bioresource; SDRNT1BIO). We measured serum creatinine and urinary albumin/creatinine ratio (ACR) at recruitment and linked the data to the national electronic healthcare records.ResultsMedian age was 44.1 years and diabetes duration 20.9 years. The prevalence of CKD stages G1, G2, G3 and G4 and end-stage renal disease (ESRD) was 64.0%, 29.3%, 5.4%, 0.6%, 0.7%, respectively. Micro/macroalbuminuria prevalence was 8.6% and 3.0%, respectively. The incidence rate of ESRD was 2.5 (95% CI 1.9, 3.2) per 1000 person-years. The majority (59%) of those with chronic kidney disease stages G3–G5 did not have albuminuria on the day of recruitment or previously. Over 11.6 years of observation, the median annual decline in eGFR was modest at −1.3 ml min−1 [1.73 m]−2 year−1 (interquartile range [IQR]: −2.2, −0.4). However, 14% experienced a more significant loss of at least 3 ml min−1 [1.73 m]−2. These decliners had more cardiovascular disease (OR 1.9, p = 5 × 10−5) and retinopathy (OR 1.3 p = 0.02). Adding HbA1c, prior cardiovascular disease, recent mean eGFR and prior trajectory of eGFR to a model with age, sex, diabetes duration, current eGFR and ACR maximised the prediction of final eGFR (r2 increment from 0.698 to 0.745, p < 10−16). Attempting to model nonlinearity in eGFR decline or to detect latent classes of decliners did not improve prediction.ConclusionsThese data show much lower levels of kidney disease than historical estimates. However, early identification of those destined to experience significant decline in eGFR remains challenging.

Diabetes and higher HbA1c levels are independently associated with adverse renal outcomes in inpatients following multiple hospital admissions

ObjectiveTo assess the association between glycaemic status prior to the first hospital presentation with developing adverse renal outcomes overtime in patients with multiple hospital re-admissions. DesignA prospective observational cohort study. ParticipantsAll inpatients aged ≥54 years admitted between 2013 and 16 to a tertiary hospital. Main outcomesWe prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013 and 16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30 ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR; (b) rapid decline in renal function (eGFR decline >5 mL/min/1·73m2/year) and (c) final eGFR<30 ml/min/1·73m2. ResultsOf 4126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR = 1·42;95% CI:1·18–1·70;p < 0·001); (b) rapid decline in renal function (OR = 1·40;95%CI:1·20–1·63;p < 0·001), and (c) reaching eGFR<30 ml/min/1.73m2 (OR = 1·25;95%CI:1·03–1·53;p < 0·05). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR = 1·07;95% CI:1·01–1·4;p < 0·05) and (b) rapid decline in renal function (OR = 1·11;95% CI:1·05–1·18;p < 0·001). ConclusionsIn patients with ≥two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

SAT-285 DIABETES AND HIGHER HbA1c LEVELS ARE INDEPENDENTLY ASSOCIATED WITH ADVERSE RENAL OUTCOMES OVERTIME IN INPATIENTS WITH MULTIPLE HOSPITAL ADMISSIONS

Patients with diabetes commonly have multiple hospital admissions which potentially increases the risk of developing diabetes related complications in the future. The association between glycaemic status prior to the first hospital presentation and developing adverse renal outcomes overtime in patients with multiple hospital re-admissions is unclear but likely important. We prospectively measured HbA1c levels in all inpatients aged ≥54 years admitted between 2013-16. Diabetes was defined as prior documented diagnosis of diabetes and/or HbA1c ≥6.5% (47·5 mmol/L). Included patients had ≥ two admissions (at least 90 days apart), baseline estimated glomerular filtration rate (eGFR) >30ml/min/1·73m2 and no history of renal replacement therapy. We assessed several renal outcomes: (a) 50% decline in eGFR using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation; (b) rapid decline in renal function (eGFR decline >5mL/min/1·73m²/year) and (c) final eGFR<30ml/min/1·73m². We used logistic regression analysis to assess the relationship between baseline glycaemic state and these outcomes. Of 4,126 inpatients with a median follow-up of 465 days (254, 740), 26% had diabetes. The presence of diabetes was associated with higher odds of (a) 50% decline in eGFR (OR=1·42;95% CI:1·18-1·70;p<0·0001); (b) rapid decline in renal function (OR=1·40;95%CI:1·20-1·63;p<0·0001), and (c) reaching eGFR<30ml/min/1·73m² (OR=1·25;95%CI:1·03-1·53;p=0·024). Every 1% (11 mmol/L) increase in baseline HbA1c was associated with significantly greater odds of (a) >50% decline in eGFR (OR=1·07;95% CI:1·01-1·4;p=0·029) and (b) rapid decline in renal function (OR=1·11;95% CI:1·05-1·18;p<0·0001).View Large Image Figure ViewerDownload Hi-res image Download (PPT) In patients with ≥ two admissions, the presence of diabetes and higher HbA1c levels were strongly and independently associated with adverse renal outcomes at follow up. Such patients are at high risk of relatively rapid deterioration in renal function and a logical target for structured preventive interventions.

Biomarker panels associated with progression of renal disease in type 1 diabetes

Aims/hypothesisWe aimed to identify a sparse panel of biomarkers for improving the prediction of renal disease progression in type 1 diabetes.MethodsWe considered 859 individuals recruited from the Scottish Diabetes Research Network Type 1 Bioresource (SDRNT1BIO) and 315 individuals from the Finnish Diabetic Nephropathy (FinnDiane) study. All had an entry eGFR between 30 and 75 ml min−1[1.73 m]−2, with those from FinnDiane being oversampled for albuminuria. A total of 297 circulating biomarkers (30 proteins, 121 metabolites, 146 tryptic peptides) were measured in non-fasting serum samples using the Luminex platform and LC electrospray tandem MS (LC-MS/MS). We investigated associations with final eGFR adjusted for baseline eGFR and with rapid progression (a loss of more than 3 ml min−1[1.73 m]−2 year−1) using linear and logistic regression models. Panels of biomarkers were identified using a penalised Bayesian approach, and their performance was evaluated through 10-fold cross-validation and compared with using clinical record data alone.ResultsFor final eGFR, 16 proteins and 30 metabolites or tryptic peptides showed significant association in SDRNT1BIO, and nine proteins and five metabolites or tryptic peptides in FinnDiane, beyond age, sex, diabetes duration, study day eGFR and length of follow-up (all at p < 10−4). The strongest associations were with CD27 antigen (CD27), kidney injury molecule 1 (KIM-1) and α1-microglobulin. Including the Luminex biomarkers on top of baseline covariates increased the r2 for prediction of final eGFR from 0.47 to 0.58 in SDRNT1BIO and from 0.33 to 0.48 in FinnDiane. At least 75% of the increment in r2 was attributable to CD27 and KIM-1. However, using the weighted average of historical eGFR gave similar performance to biomarkers. The LC-MS/MS platform performed less well.Conclusions/interpretationAmong a large set of associated biomarkers, a sparse panel of just CD27 and KIM-1 contains most of the predictive information for eGFR progression. The increment in prediction beyond clinical data was modest but potentially useful for oversampling individuals with rapid disease progression into clinical trials, especially where there is little information on prior eGFR trajectories.

546-P: Deep Learning Predictions of Diabetic Retinopathy Associated with Progression of Renal Disease in Type 1 Diabetes

Background and Aims: We considered if deep learning (DL) models trained to predict diabetic retinopathy (DR) are also useful for prediction of renal disease in people with type 1 diabetes. Materials and Methods: We used 35000 retinal images and associated ground truth DR grades from the online Kaggle dataset. These were used to train a Resnet convolutional neural network (CNN) to predict the ground truth DR grades. The CNN was then applied to retinal images for each patient in the SDRNT1BIO available from the national screening program generating 10 DL outputs corresponding to DR gradings for both eyes. Longitudinal eGFR readings and risk factor data were available for the SDRNT1BIO through linkage to clinical records. Univariate associations of DL outputs with final eGFR at follow-up was tested via linear regression models. A penalised Bayesian approach using 10-fold cross-validation was used to select the most predictive DL features and assess prediction performance. Results: We found 7 DL outputs had a significant univariate association with follow-up eGFR adjusting for age, sex, duration of diabetes, baseline eGFR, and length of follow-up at p&amp;lt;10-4. 4 DL outputs remained significant on adjusting for the screening program manual DR grading of the image (p ranging from 1.62x10-8 to 9.9x10-5). For predicting achieved eGFR we found that DL outputs improved test log-likelihood by 22.2 natural log units (equivalent to a p-value of &amp;lt; 10-9) increasing the R2, from 0.64 to 0.65. Conclusion: This small study demonstrates that retinal images contain information for predicting eGFR decline and that deep learning can extract this information. Future work on a larger dataset using DL to predict renal disease progression directly is therefore warranted. Disclosure J.C. Mellor: None. A.J. Storkey: None. H. Colhoun: Advisory Panel; Self; Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Sanofi-Aventis. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis. Speaker's Bureau; Self; Eli Lilly and Company, Regeneron Pharmaceuticals, Sanofi. Stock/Shareholder; Self; Bayer AG, Roche Pharma. P.M. McKeigue: Advisory Panel; Spouse/Partner; Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Sanofi. Research Support; Spouse/Partner; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk A/S, Pfizer Inc., Regeneron Pharmaceuticals, Roche Pharma, Sanofi-Aventis. Stock/Shareholder; Spouse/Partner; Bayer AG, Roche Pharma.