Decline In GFR Research Articles

PS-C15-4: CARDIOVASCULAR COMPLICATIONS IN RESISTANT HYPERTENSIVE PATIENTS

Objective: To evaluate the incidence of cardiovascular (CV) complications and its predictors in treated resistant hypertensive (RH) patients. Design and Methods: We studied 117 RH patients and 114 controlled hypertensive (CH) patients on a triple fixed-dose combination of a blocker of the renin-angiotensin system / calcium channel blocker / thiazide or thiazide-like diuretic. Patients with RH treated with the same type of triple fixed-dose combination in maximally tolerated doses plus the individually defined most effective fourth-line agent (spironolactone/eplerenone 56.1%, torasemide 26.8 %, nebivolol 14.6 %, moxonidine 2.5 %); the fifth class of antihypertensive drug was added for 35.2 % of patients. A cardiovascular complications (CV death, myocardial infarction and/or revascularization, stroke, atrial fibrillation, peripheral arterial disease, kidney outcome (dialysis or GFR decline by 40 % or greater) were estimated after five years (5.1 ± 0.1). Results: The goal office and 24-h blood pressure (BP) were achieved at 49.6 and 34.2 % RH patients at the end of follow-up. The incidence of CV outcomes were in 4.4 times higher at RH patients compared to CH patients (composite CV events (30.8 vs 7.0 %, P = 0.001). According to univariate logistic regression analysis CV complications were associated with baseline TNF-a (β = 0.78; OR = 2.18; 95% CI: 1.15 - 4.13), cystatin C (β= 0.56; OR = 1.81; 95% CI: 1.22 - 2.68), citrulline plasma levels (β= 0.07; OR = 1.07; 95% CI: 1.03 - 1.10); 24-h albuminuria (β= 0.006; OR = 1.01; 95% CI: 1.0 - 1.01), CysC GFR (β= -0.44; OR = 0.96; 95% CI: 0.93 - 0.99), body mass index (β = 0.15; OR = 1.17; 95% CI: 1.03 - 1.32) and low initial adherence to treatment (β= 0.97; OR = 2.63; 95% CI: 1.11 - 6.21). Conclusions: A median follow-up time of 5 years, RH was associated with increased risk for incidence of CV outcomes. The markers of low-grade systemic inflammation, kidney function, body mass index, and initial adherence to treatment were associated with the composite CV endpoint.

2105. Early-onset and Late-onset BK Polyomavirus-associated Nephropathy: A 10-year Retrospective Analysis

Abstract Background Polyomavirus-associated nephropathy (BKVAN) is one of the serious causes of allograft dysfunction and allograft loss in kidney transplant (KT) patients. Most of the patients were diagnosed with BKVAN within the first year after transplantation but some more cases of BKVAN occur later. A study focused on the differentiation between early and late-onset BKVAN is needed. Methods We conducted a retrospective cohort study among KT recipients at Ramathibodi Hospital between January 2010 – December 2020. The incidence of early-onset (diagnosed within 1 year) and late-onset (diagnosed after 1 year) BKVAN, as well as composite kidney allograft outcomes, were compared. Results From 1032 KT recipients, 645 (62.5%) were screened for BK viral infection. BKVAN was diagnosed in 83 (12.8%) patients. Of those, 46 (55.4%) and 37 (44.6%) were diagnosed with early-onset and late-onset BKVAN, respectively. Composite kidney allograft outcomes of GFR decline≥ 40% from baseline, graft loss or death were greater in early-onset BKVAN compared to late-onset BKVAN (7.5 vs 5.52 per 1000 person-months; hazard ratio 0.47; 95%CI, 0.23-0.95; P=0.037). In multivariate analysis, female gender and living-related kidney transplantation (LRKT) were independently associated with late-onset BKVAN compared to early-onset BKVAN. The more advanced the BKVAN diagnosis, the worse the allograft outcome occurs, even with optimizing immunosuppressive drugs and adjunctive therapy. Conclusion BKVAN could occur later after one-year post-transplantation, although relatively better composite kidney outcomes were observed compared to early-onset BKVAN. Female individuals who underwent living-related KT should be considered for BK virus preemptive monitoring beyond one year to detect this late-onset BK virus infection. Disclosures All Authors: No reported disclosures.

Effect of Two Different Dietary Weight Loss Strategies on Risk Factors for Urinary Stone Formation and Cardiometabolic Risk Profile in Overweight Women

Overweight has been suggested to increase the risk of kidney stone formation. Although weight reduction might affect risk factors for urolithiasis, findings on the impact of different dietary weight loss strategies are limited. This randomized, controlled study evaluated the effect of a conventional energy-restricted modified diet with (MR group) or without meal replacement (C group) on risk factors for stone formation in overweight women without a history of urolithiasis. Of 105 participants, 78 were included into the per-protocol analysis. Anthropometric, clinical, biochemical, and 24 h urinary parameters were collected at baseline and after 12 weeks. Although both dietary interventions resulted in a significant weight reduction, relative weight loss and rate of responders were higher in the MR group. Weight loss improved cardiometabolic risk profile in both groups. Unfortunately, the benefit of decreased GPT activity in the C group was offset by a significant increase in homocysteine and a decline in GFR. While the relative supersaturation of calcium oxalate decreased significantly in both groups, a significant decline in serum uric acid concentration and relative supersaturation of uric acid was observed only in the MR group. Finally, the energy-restricted modified diet with meal replacement showed significant advantages over the energy-restricted modified diet alone.

Abstract 10533: Cardiorenal Effects of Sglt2 Inhibitors and Finerenone in Type 2 Diabetes and Chronic Kidney Disease. Single, Dual or Triple Therapy? A Network Meta-Analysis

Introduction: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and a non-steroidal mineralocorticoid receptor antagonist, finerenone, have demonstrated their efficacy in slowing CKD progression and preventing cardiovascular events in diabetic kidney disease (DKD). However, it is unclear which one is more effective or whether a combination could provide additional benefits. Methods: A network meta-analysis (NMA) was conducted on RCTs of DKD, which evaluated the cardiovascular and renal effects of SGLT2i and finerenone. The primary outcome was a cardiorenal outcome composed of GFR decline as defined in original RCTs, end-stage kidney disease (ESKD), heart failure hospitalization (HHF), and death from renal and cardiovascular causes. Results: This NMA comprised 4 RCTs and 61,609 patient-year with DKD. Dual therapy with SGLT2i+RAASi or finerenone+RAASi was more effective than single therapy with RAAS inhibition (RAASi) for the risk reduction of the cardiorenal composite HR 0.67 (95% CrI 0.60 - 0.74) and 0.81 (95% CrI 0.75 - 0.89), respectively. The dual therapy with SGLT2i+RAASi was superior to finerenone+RAASi HR 0.82 (95% CrI 0.72 - 0.94) for the reduction of cardiorenal events (Table 1). The triple therapy (SGLT2i+finerenone+RAASi) vs RAASi showed a 46% relative risk reduction (HR 0.54 95% CrI 0.5 - 0.58) for the cardiorenal composite. Finerenone+RAASi was most likely to lead to discontinuation of therapy due to hyperkalemia HR 2.83 (95% CrI 1.96 - 4.08) when compared to RAASi, however, it was not notice when compared to triple therapy HR 2.83 (95% CrI 0.83 - 9.62). All therapies reduced the risk of all-cause death as follows finerenone+RAASi (HR 0.88, 95% CrI 0.80 - 0.98), SGLT2i+RAASi HR 0.78 (95% CrI 0.66 - 0.91) and SGLT2i+finerenone+RAASi HR 0.69 (95% CrI 0.63 - 0.75). Conclusion: This NMA suggests that triple therapy with SGLT2i+finerenone+RAASi is superior in reducing cardiorenal events compared to single or dual therapy with a similar safety profile.

LBSUN291 Fournier's Gangrene In A Diabetic Male Taking Dapagliflozin

Abstract Background Fournier's gangrene (FG) is a form of necrotizing fasciitis characterized by polymicrobial infection of the perineal, perianal or genital areas; risk factors include diabetes mellitus and male gender. Dapagliflozin is one of four sodium-glucose cotransporter 2 (SGLT2) inhibitors FDA-approved for the treatment of Type 2 diabetes mellitus (T2DM). SGLT2 inhibitors decrease serum glucose and increase glycosuria by binding to renal tubular SGLT2 receptors, and inhibiting reabsorption of glucose from urine in the proximal convoluted tubule. Since their introduction in 2013, SGLT2 inhibitors have been shown to protect against decline in GFR, to improve LVEF in HFrEF, and to improve survival in T2DM. However, due to associated glycosuria, SGLT2 inhibitors are commonly associated with candidiasis, and are rarely associated with life-threatening adverse effects including FG, and euglycemic diabetic ketoacidosis. | Clinical case: A 57-year-old male with T2DM, diabetic neuropathy and hypertension presented to the ED with left testicular swelling, penile discharge and dysuria of several days duration. He was afebrile and vital signs were in normal ranges. Examination disclosed left-sided scrotal swelling surrounding a 1 cm black eschar, induration, erythema and discharge. WBC 15.1 with 79% neutrophils and HbA1c 10.4%. Dapagliflozin 4 mg daily had been added to insulin degludec one month earlier. He denied previous history of scrotal/genital infections. Ultrasound of the scrotum showed wall thickening on the left, a small hydrocele and heterogenous echogenicity suggesting an abscess. Pelvic CT scan with contrast revealed multiple small air bubbles in the scrotal wall. Findings were consistent with FG. He was treated promptly with IV piperacillin / tazobactam and vancomycin. Urological debridement of necrotic scrotal skin was carried out the morning after admission; cultures obtained at surgery grew Gram neg rods and Diphtheroids. Tissues within the scrotum were not gangrenous. Primary closure with a Penrose drain was attempted, but the skin surrounding the sutures necrosed and a second urological procedure was done to remove the sutures and allow the scrotal wall to heal by secondary intention. He was discharged after 5 days and I. V. ampicillin/sulbactam was continued for a total of 14 days with resolution of infection and healing of the skin. Conclusion SGLT2 inhibitors decrease mortality and increase quality of life in T2DM compared to older treatments with exogenous insulin and its secretagogues. Optimal utilization of SGLT2 inhibitors in the management of patients with T2DM will entail 1) quantifying risk specifically attributable to SGLT2 inhibitors since T2DM is a known risk factor for FG, and 2) routinely informing/reminding patients with T2DM to promptly report skin infections of the groin, perineum or perianal region. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

A Steep Slope: APOL1 High Risk Genotype and GFR Decline Among Black Patients With Membranous Nephropathy

A Steep Slope: APOL1 High Risk Genotype and GFR Decline Among Black Patients With Membranous Nephropathy

Renal Function Status in Patients with Diabetes Mellitus Having Diabetic Foot Infection and Role of Antibiotics

It has been shown that antibiotic therapy in diabetic foot ulcers has a toxic effect on renal function. Objective: To assess the renal function among patients with diabetes mellitus having diabetic foot infection. Methods: It was a cross-sectional retrospective study in the surgical Unit of DHQ Teaching Hospital KDA Kohat for six-month duration from January 2022 to June 2022. 130 patients with diabetic foot ulcers were selected for this study. The patients receiving antibiotic with a low renal toxicity risk were included in Group-A and patients receiving antibiotics with an increased renal toxicity risk were included in group B. GFR was calculated and measured from Cockcroft-Gault equation and serum creatinine levels. SPSS 20.0 was applied for data analysis with paired t-tests, t-test and chi-square tests. Results: In group A there were 65 (50%) participants and 65 (50%) in group B. GFR after and before antibiotic therapy was 58.30±31.13 cm3 / min and 65.98±35.76 cm3 / min (p = 0.004), correspondingly. The GFR in group B was reduced significantly after antibiotic therapy (p = 0.003). Conclusions: Conferring to this study, renal function decreased and nephrotoxicity was noted after antibiotic treatment, the percentage of decline in GFR being greater in patients who received higher nephrotoxic antibiotics.

Sex Differences in Age-Related Loss of Kidney Function.

CKD is more prevalent in women, but more men receive kidney replacement therapy for kidney failure. This apparent contradiction is not well understood. We investigated sex differences in the loss of kidney function and whether any sex disparities could be explained by comorbidity or CKD risk factors. In the Renal Iohexol Clearance Survey (RENIS) in northern Europe, we recruited 1837 persons (53% women, aged 50-62 years) representative of the general population and without self-reported diabetes, CKD, or cardiovascular disease. Participants' GFR was measured by plasma iohexol clearance in 2007-2009 (n=1627), 2013-2015 (n=1324), and 2018-2020 (n=1384). At each study visit, healthy persons were defined as having no major chronic diseases or risk factors for CKD. We used generalized additive mixed models to assess age- and sex-specific GFR decline rates. Women had a lower GFR than men at baseline (mean [SD], 90.0 [14.0] versus 98.0 [13.7] ml/min per 1.73 m2; P<0.001). The mean GFR change rate was -0.96 (95% confidence interval [CI], -0.88 to -1.04) ml/min per 1.73 m2 per year in women and -1.20 (95% confidence interval [CI], -1.12 to -1.28) in men. Although the relationship between age and GFR was very close to linear in women, it was curvilinear in men, with steeper GFR slopes at older ages (nonlinear effect; P<0.001). Healthy persons had a slower GFR decline, but health status did not explain the sex difference in the GFR decline. Among middle-aged and elderly individuals in the general population, decline in the mean GFR in women was slower than in men, independent of health status.

232.7: Elevated Donor-Derived Cell-Free DNA Associates With Subsequent Decline of Allograft Function

Introduction: Donor-derived cell-free DNA (dd-cfDNA) emerged as a candidate biomarker for detecting graft injury, particularly from antibody-mediated rejection, and is currently proposed to complement donor-specific antibodies (DSAs) as an alloimmune-mediated injury surveillance method. We sought to investigate the impact of an initial increase of dd-cfDNA level on subsequent decline in graft function. Materials: The study included all kidney transplant (KT) recipients that underwent dd-cfDNA testing as part of their clinical care between September 2017 and December 2019 at our center. Only patients with a follow-up of at least 12 months were included in this analysis. An elevated dd-cfDNA was defined as a level over 0.5%. Results: Of the 171 KT recipients tested for dd-cfDNA, 49 were followed for at least 12 months since initial testing. The study cohort had an initial serum creatinine and eGFR of 1.64 ± 0.58 mg/dl and 48 ± 21 ml/min/1.73m2, respectively. Overall, the absolute and percentual decline of eGFR were -0.12 ml/min/month (IQR, -0.43 to 0.56) and -4.26% (IQR, -20.5% to 17%), with 26.5% and 10.2% of patients having an eGFR decline of more than 15% and 30%, respectively. Fifteen patients (30.6%) had an elevated dd-cfDNA (over 0.5%) and had a similar baseline allograft function compared to those without an elevated dd-cfDNA level. After a median follow-up period of 15.3 months (IQR:13.6-19), patients with elevated dd-cfDNA had a faster decline of eGFR [absolute eGFR decline, -0.21 ml/min/month (IQR, -0.36 to 0.22); percentual GFR decline, -8.7% (IQR, -25% to 4.4%)], compared to those without elevated dd-cfDNA [absolute eGFR decline, +0.03 ml/min/month (IQR, -0.5 to 0.6); percentual GFR decline, +1.14% (IQR, -14% to 28%)](p=0.09)(Figure 1). Similarly, there was a tendency for a higher percentage of patients with elevated dd-cfDNA for a decline of eGFR greater than 15% (33.3% vs. 23.5%, p=0.5) or 30% (13.3% vs. 8.8%, p=0.6), respectively. In addition, patients with DSAs and an elevated dd-cfDNA showed a greater percentual eGFR decline (-9.1±16.5%), compared to those with DSAs and normal dd-cfDNA (+3.3±21.1%), or to those without DSAs and normal dd-cfDNA (+2.3±18.05%). In multivariable logistic regression analysis, an elevated dd-cfDNA level was independently associated with the subsequent percentual decline of eGFR (OR, 0.96; 95%CI, 0.93 to 1.00; p=0.05). Conclusion: We have shown that despite initial stable allograft function, a higher dd-cfDNA level associates with subsequent decline of eGFR. Thus, the initial identification of subclinical graft injury could associate with long-term graft outcomes, expanding the clinical utility of dd-cfDNA.

EVALUATION OF ANEMIA IN RENAL TRANSPLANT PATIENTS

ABSTRACT Background Post-renal transplant anaemia is a common complication among renal transplant patients. Graft dysfunction, medications, and IDA are the most common causes of PTA. Objectives To investigate further the prevalence of anaemia after kidney transplantation in Sulaimani city, determine the risk factors and the association of different socio-demographic characteristics with PTA, and identify the essential causes of anaemia Patients and Methods A cross-sectional descriptive study was conducted on two hundred renal transplant patients who visited Shar- hospital in Sulaimani city for their regular follow up between January/ 2020-January/ 2021. Results Among the total 200 patients involved in the study, 63% were males, 37% were females, mean age was 45.32±9.28. It demonstrated that PTA was remarkably high (40%). Iron deficiency anaemia is the most common cause of PTA 28.75%, especially in 1st six months after renal transplantation; GFR decline for any reason (rejection, ATN, viral infection) is significantly associated with anaemia; the lower the GFR, the higher number of anaemic patients (p=0.000). Conclusion Our findings showed that anaemia is widespread after renal transplantation. Iron deficiency anaemia is the most common cause of anaemia, followed by acute cellular rejection.

405-P: Glycemic Control Impacts Renal Function Decline among People with Type 1 Diabetes after the Onset of Diabetic Kidney Disease

While poor glycemic control increases the risk of diabetic kidney disease (DKD) , its impact on renal function decline among those with established DKD is unclear. To examine this, we tested the relationship between baseline HbA1c and renal outcomes in the 3-year Preventing Early Renal Loss (PERL) trial (n=530) , which included persons with type 1 diabetes (T1D) and early-to-moderate DKD (eGFR 40-100 ml/min/1.73m2 and persistent albuminuria and/or ongoing GFR decline) . In Cox regression models, baseline HbA1c was associated (p&amp;lt;0.0001) with a higher risk of progression to ESKD or serum creatinine doubling (HR 1.87 per HbA1c unit increment, 95% CI 1.42-2.47) , and in mixed-effects linear regression models, with 0.87 and 0.51 ml/min/1.73m2/year higher rates of estimated glomerular filtration rate (eGFR) and iohexol GFR decline (p&amp;lt;0.00for both) . Baseline albumin excretion rate (AER) was a modifier of the HbA1c-GFR slope relationships (p for interaction &amp;lt;0.05) , such that HbA1c was associated with a higher rate of GFR decline among those with AER≥200 μg/min than among those with AER&amp;lt;20 or 20≤AER&amp;lt;200 (Fig.1) . Thus, worse glycemic control in PERL was a major determinant of GFR decline and ESKD risk after DKD onset, especially in persons with overt proteinuria. Efforts to normalize HbA1c should continue among such persons. Disclosure H.Shah: None. J.B.Mcgill: Advisory Panel; Gilead Sciences, Inc., Lilly Diabetes, MannKind Corporation, Novo Nordisk A/S, Provention Bio, Inc., Salix Pharmaceuticals, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; Dexcom, Inc., Novo Nordisk. I.B.Hirsch: Consultant; Abbott Diabetes, Bigfoot Biomedical, Inc., GWave, Roche Diabetes Care, Research Support; Beta Bionics, Inc., Insulet Corporation, Medtronic. C.Wu: None. A.Galecki: None. M.Mauer: None. A.Doria: Research Support; Novo Nordisk Foundation. Perl consortium: n/a. Funding National Institutes of Health UC4DK101108Juvenile Diabetes Research Foundation 17-2012-377The Leona M. and Harry B. Helmsley Charitable Trust 2018PG-T1D014

398-P: KIM-1 and TNFR 1 and Associations with Early Diabetic Nephropathy Histology

Aim: GFR and urine albumin excretion (UAE) are prevailing measures used to detect and monitor diabetic nephropathy (DN) . We tested whether serum kidney injury molecule-1 (KIM-1) and tumor necrosis factor receptor-1 (TNFR1) , markers of DN progression, are associated with DN renal structural parameters in persons with TIDM. Methods: We measured KIM-1 and TFNR1 in 285 participants from the Renin Angiotensin System Study (RASS) . Participants had T1DM for 2-20 yrs and were free of any clinical DN. Baseline iGFR and kidney biopsies were obtained. We used linear regression to estimate cross-sectional associations of markers with renal structural measures. Results: Mean age was 30 ± yrs; mean iGFR was 125 ± 18 ml/min/1.73 m2; median UAE was 5 (IQR 4- 7) . Higher KIM-1 was associated with significantly greater mesangial fraction volume [Vv (Mes/glom) ] and the tubular atrophy (table 1) . Higher TNFR1 was associated with significantly higher Vv (Mes/glom) and glomerular basement membrane (GBM) width. Neither iGFR nor UAE were significantly associated with lesions. Conclusion: Serum KIM-1 and TNFR1 were associated with higher values for Vv (Mes/glom) , GBM, and tubular atrophy in persons with T1DM and normal kidney function, suggesting relevance as markers of early DN structural changes prior to UAE elevation or GFR decline. KIM-1 is specific to the tubules, highlighting the importance of characterizing the natural history of tubular functions in DN. Disclosure F.Tian: None. D.Prince: None. A.Doria: Research Support; Novo Nordisk Foundation. M.Mauer: None. B.Kestenbaum: Consultant; Reata Pharmaceuticals, Inc. Funding T32

CARDIOVASCULAR AND KIDNEY OUTCOMES IN TREATED RESISTANT HYPERTENSIVE PATIENTS

Objective: To evaluate the incidence of cardiovascular (CV) and kidney outcomes and its predictors in treated resistant hypertensive (rHTN) patients. Design and method: We studied 117 rHTN patients and 114 controlled hypertensives (cHTN) patients on a triple fixed-dose combination of RAAS blockers / CCB / thiazide or thiazide-like diuretic. Patients with rHTN treated with the same type of triple fixed-dose combination in maximally tolerated doses plus the individually defined most effective fourth-line agent (spironolactone/eplerenone 56.1%, torasemide 26.8%, nebivolol 14.6%, moxonidine 2.5%); the fifth class of antihypertensive drug was added for 35.2 % of patients. A composite CV (CV death, myocardial infarction and/or revascularization, stroke, atrial fibrillation, and peripheral arterial disease) and kidney outcome (dialysis or GFR decline by 40% or greater) were estimated after five years (a mean follow-up 5.1 ± 0.1). The combined endpoint was defined as total CV and renal outcome events. Results: The goal office and 24-h BP were achieved at 49.6 and 34.2 % rHTN patients by the end of 5-year follow-up. During follow-up the incidence of all outcomes were higher at rHTN patients compared to cHTN pts: composite CV events (26.5 % vs 7 %, P = 0.001), kidney outcomes (4.3 % vs 0.9 %, P = 0.01), and diabetes (3.4 % vs 0.9 %, P = 0.02). The independent predictors of combined end point identified by multivariant logistic regression analysis were initial 24-h systolic BP ( = 0.099; OR = 1.10; 95 % CI 1.03 – 1.18; P = 0.008), blood concentration of endothelial progenitor cells (CD45+/CD34+) ( = - 0.89; OR = 0.41; 95 % CI: 0.21 – 0.79), P = 0.007) and citrulline ( = - 0.89; OR = 1.13; 95 % CI: 1.07 – 1.20; P &lt; 0.001). Conclusions: Despite significant improvement in BP control the incidence of CV and renal outcomes in rHTN patients were higher than in cHTN patients. The independent predictors of combined CV and renal events were higher baseline systolic blood pressure, citrulline plasma level, and low concentration of endothelial progenitor cells.

Long-Term Complications After Nephrectomy for Living Donor Transplant

Living donor kidney transplant represents the best treatment option for patients with end-stage kidney disease; however, it has been associated with possible risks to the donor. Our aim was to evaluate the impact of kidney donation in the donor's estimated glomerular filtration rate (eGFR), blood pressure, and proteinuria and related risk factors. A single-center, retrospective study, including all living donors who underwent nephrectomy between January 2000 and December 2019, was performed. Demographic, clinical, and laboratory data were collected. Risk factors for a decrease in eGFR >30 mL/min/1.73 m2one year after donation were assessed. Eighty-six donors were included with a mean age of 46.7 ± 9.07 years. The mean follow-up was 105.6 ± 65.4 months, and 35 patients (41%) had more than 10 years of follow-up. No significant difference was found in proteinuria or body mass index (P > .1) before and after the donation. The prevalence of hypertension was higher after kidney donation (9.3% vs 22.1%; P < .001). A mean reduction in the eGFR in the first year of 37 ± 12 mL/min/1.73 m2, followed by stabilization in the following years, was observed. The only variable that was significantly associated with a decline in GFR >30 mL/min/1.73 m2 was a lower predonation eGFR, with a cutoff value established at 100 mL/min/1.73 m2 for our sample. Living donor nephrectomy appears to be an acceptably safe intervention. Predonation eGFR influences the adaptative response after nephrectomy; however, other variables did not have an impact on long-term outcome in our population.

MO512: Association of Urinary Biomarkers and Accelerated, Age-Related Decline in Measured Gfr

Abstract BACKGROUND AND AIMS Urinary albumin excretion (UAE) is considered as a risk marker for chronic kidney disease (CKD), but the exact pathophysiological mechanisms are not known. Studies have shown that urinary orosomucoid excretion (UOE) is associated with general endothelial dysfunction and atherosclerosis, and UOE is suggested to be a more sensitive marker of GFR decline than albuminuria. In this longitudinal study, we investigated the association between urinary markers (UAE and UOE) and accelerated decline in measured GFR in a middle-aged general population. METHOD The Tromsø study is a population-based study with repeated health surveys of inhabitants of Tromsø, Northern Norway. As a part of Tromsø 6, the Renal Iohexol Clearance Survey (RENIS-T6, 2007–9) included participants between 50–62 years old without previous coronary artery disease, diabetes mellitus or kidney disease. Follow-up studies were conducted in 2013–15 (RENIS-FU) and in 2018–2020 (RENIS-R3). GFR was measured by plasma clearance of iohexol. Urinary specimens from three consecutive days were analysed immediately for albumin and creatinine. Urinary orosomucoid was analysed later after freezing and thawing. Urinary albumin and orosomucoid were divided by the creatinine concentration (UACR: urinary albumin creatinine ratio, UOCR: urinary orosomucoid creatinine ratio) of the same specimen, and median log transformed values were used. The association between UOCR and GFR decline was assessed by linear mixed regression models. RESULTS A total of 786 women and 773 men (n = 1559) were included. The mean age was 58 years for both women and men, and mean GFR was 91.1(±12.3) mL/min/1.73 m² for women and 98.2(±13.1) mL/min/1.73m² for men. Men had higher blood pressure, BMI and lower cholesterol as well as higher median UOCR than women (men: 0.36 (IQR: 0.19–0.77) mg/g; women: 0.29 (IQR: 0.19–0.60) mg/g; P = .04), but median UACR was lower in men compared with women (men: 0.25 (IQR: 0.13–0.49) mg/mmol; women: 0.32 (IQR: 0.19–0.59) mg/mmol; P &amp;lt; .001). The median observation time was 5.5 years (IQR: 0–10.5). In the follow-up studies (RENIS-FU, RENIS-R3), we included participants with GFR measurements and urinary markers in 1271 and 1129 participants, respectively. Adjusted for age and sex, a doubling (log2) of baseline UOCR was associated with a lower GFR of 0.63 mL/min/1.73 m² {P = .002, [95% confidence interval (95% CI) –1.03 to –0.23]}, but no association was found between UACR and GFR (P = .670). Adjusted for the same variables, each log2 UOCR was associated with an accelerated annual GFR decline of 0.06 mL (P = .011, 95% CI –0.10 to –0.01) throughout the follow-up period. No association was found between log2UACR and accelerated annual GFR decline (P = .107, 95% CI –0.08–0.01). CONCLUSION In a population-based study of middle-aged to elderly, relatively healthy men and women with a mean observation time of 8.3 years, we found an association between UOCR and accelerated annual GFR decline adjusted for age and sex. We did not find the same association for UACR. The clinical relevance of this association needs to be studied further.

MO405: Leucine-Rich Alpha-2-Glycoprotein as a Potential Marker of Mesangial Cell Proliferation in Immunoglobulin a Nephropathy

Abstract BACKGROUND AND AIMS Leucine-rich alpha-2-glycoprotein (LRG1) is a novel proangiogenic factor involved in the abnormal angiogenesis and renal fibrosis in diabetic nephropathy by potentiating endothelial transforming growth factor-beta/activin receptor-like kinase 1 (TGF-β/ALK1) signalling [1]. TGF-β mediates mesangial matrix accumulation culminating in the development of glomerulosclerosis [2], which also occurs in immunoglobulin A nephropathy (IgAN) patients. Our study aims to evaluate LRG1 as a marker of mesangial cell proliferation in IgAN patients. METHODS: Adults with a morphologically confirmed IgAN by the presence of IgA deposits by immunofluorescence microscopy were included in the study. Diabetes mellitus, oncology, acute inflammation processes were exclusion criteria. Serum LRG1 was detected using ELISA. RESULTS A total of 73 patients with IgAN were included [mean age 41 years, interquartile range (IQR) 35–47; range, 21–65; 65.8% men]. The median estimated glomerular filtration rate (eGFR) was 44 (IQR 24–83, range 4–133) mL/min/1.73m2. Kidney biopsies were analyzed according to the Oxford classification: M0 in 10 (13,7%), M1 in 56 (76.7%) patients. The median serum LRG1 was 49 µg/mL (IQR 40.7–57.7, range 29–133.3). Bivariate analyses showed that plasma LRG1 was negatively associated with eGFR (rho = −0.342, P = 0.003). A linear model showed that GFR decline for 1 mL/min was associated with an increase of LRG1 for 0.194 µg/mL. In IgAN patients with an M1-score LRG1 was higher (P = 0027, Mann–Whitney U test), the area under the ROC curve value for serum LRG1 was 0.739. CONCLUSION Serum LRG1 increases with GFR decline in patients with IgAN and at the same time correlates with mesangial hypercellularity according to Oxford classification. Therefore, LRG1 might be a potential marker of advanced disease in IgAN.

MO329: Acute Kidney Injury (AKI) is Associated With Increased in-Hospital Mortality and With Impairment of Renal, Lung, Motor and Immune Function 1 Year After Discharge For COVID-19

BACKGROUND AND AIMSAKI is the most frequent complication after respiratory failure in COVID-19. AKI increases mortality risk, length of hospital stay and healthcare costs, with possible progression towards CKD. Study aims: (1) evaluation of AKI incidence in 1020 COVID-19 hospitalized patients; (2) comparison of AKI incidence in COVID-19 versus pre-pandemic period; (3) establishment of out-patient follow-up for monitoring kidney, lung, motor and immune function; (4) creation of a biobank for biomarker discovery studies.METHODAKI incidence was calculated matching laboratory and administrative data of 26 214 hospitalized patients in 2018–2019 and in 1020 COVID-19 patients in 2020–2021: KDIGO algorithms were applied for AKI grading. After 12 months from discharge, 232 COVID AKI patients and relative controls matched for age and gender were evaluated for kidney (eGFR, biomarkers of tubular damage NGAL, CCl-14, DKK-3), lung (DLCO, CT scan) and neuro-motor (SPPB, 2-min walking test, post-traumatic stress test-IES) function.RESULTSBefore the pandemic, in-hospital AKI incidence was 18% (10% KDIGO 1, 5% KDIGO 2, 3% KDIGO 3): median age of AKI patients was 69. In-hospital mortality was 3.5% in non-AKI group versus 15% in AKI group in accordance with KDIGO stages. In COVID patients, AKI incidence increased to 37% (20% KDIGO 1.11% KDIGO 2, 6% KDIGO 3): median age of patients was 54. In-hospital mortality was 31% in the AKI group; AKI is an independent risk factor for death. After 12 months from hospital discharge, COVID AKI patients showed a persistent reduction of respiratory function (severe DLCO impairment < 60%) related to the extent of CT scan abnormalities. AKI patients also presented the motor function impairment and a worse post-traumatic stress response. GFR reduction was 1.8 mL/min in non-AKI patients versus 9.7 mL/min in AKI COVID patients not related to age. Urinary DKK-3 and CCL-14 were also higher in the AKI group. Last, IgG response after SARS-CoV-2 vaccination was significantly lower in the AKI group.CONCLUSIONAKI incidence was significantly increased during COVID-19 in respect to the pre-pandemic period, with an association with higher mortality in class 2–3 KDIGO. In the post-COVID follow-up, AKI was associated with lung and neuro-motor function impairment, a defective antibody response and a sudden GFR decline concomitant to the persistence of tubular injury biomarkers. These results suggest the importance of nephrological and multidisciplinary follow-up of frail patients who developed AKI during hospitalization for COVID-19.Figure 1:Kaplan–Maier curves of survival for hospitalized COVID-19 patients on the basis of AKI-specific cut off of RPA.Table 1.Univariate and multivariate logistic regression analyses for AKI in hospitalized patients with COVID-19UNIVARIATE MODELMULTIVARIATE MODELOdds ratio95% CI P Odds ratio95% CI P Age, years1.000.97–1.03.9600.960.91–1.01.146Male gender0.870.32–2.33.7770.260.05–1.23.090Charlson index1.110.90–1.38.3251.160.89–1.53.266Hypertension2.791.13–6.88 .025 1.250.30–5.30.759Diabetes0.560.14–2.29.422Heart failure1.190.25–5.70.828Creatinine, mg/dL4.841.23–29.13 .026 50.74.62–556.01 .001 RPA < 24 HU2.220.86–5.74.1004.561.27–16.44 .020

Role of Proximal Tubule DPP4 in Inflammation and Kidney Disease Progression

Obesity and overweight leads to an entity called obesity related kidney disease (ORKD), which is a major risk factor for chronic kidney disease (CKD) progression to End Stage Renal Disease and/or dialysis. ORKD is characterized by proximal tubule brush border vacuolization and injury, basement membrane thickening, glomerular accumulation of fat globules and glomerulomegaly. We have developed a mouse model of Western diet (high fat and high sucrose)‐induced obesity that manifests all the features of ORKD. In addition, our lab observed that obese mice fed a Western diet, manifest early hyperfiltration (3 months into feeding). It is later followed by reduction in glomerular filtration rate (GFR, beginning at 18 months of age), and this pattern mimics human diabetic kidney disease progression. Our lab also observed that in ORKD, there is increased Dipeptidyl Peptidase 4 (DPP4) activity in the kidney, especially the proximal tubules and proximal tubule specific deletion of DPP4 improves the GFR. Lastly, our lab demonstrated that there is a major role for inflammation in the obese kidney and DPP4 inhibitors mitigate the inflammation. However, it is not known if and how proximal tubule DPP4 contributes to inflammation and pathophysiological changes in ORKD. Therefore, we hypothesized that proximal tubule DPP4 mediates inflammation and contributes to the pathophysiological changes in ORKD, thereby identifying DPP4 as a target to prevent CKD progression.MethodsProximal tubule specific DPP4fl/fl;SGLT2Cre+ (PT DPP4KO) and DPP4fl/fl;SGLT2Cre‐ (PT DPP4WT) mice were fed a WD and control chow (CD) for 6 mths, 15 mths and till sacrifice (18 to 27 mths). Inflammation was assessed both by flow cytometry assessment of kidney immune cells and expression of pro and anti‐inflammatory genes and proteins).ResultsThere were more pro‐inflammatory as well as DPP4 expressing macrophages in the WD‐fed WT group compared to the KO group (p&lt;0.05). There was also activation of the T‐cells in particular the CD8s which was suppressed in the KO group (p&lt;0.05). Deep sequencing of kidney mRNA revealed activation of pro‐inflammatory cytokines including Th1, Th17, M1 macrophage‐based cytokines and TLR4 and ICAM‐1. The KO group showed improvement in both TLR4 and ICAM‐1 (p&lt;0.05). At the protein level, there was an increase in pro‐fibrotic (Desmin) and pro‐inflammatory (ERK) proteins in the WD‐fed WT groups and phosphorylation of ERK was suppressed in the KO group (p&lt;0.05). When inflammation was assessed across the months it seemed that the earliest changes were in the growth pathways and beta‐oxidation of lipids, followed by the more inflammatory genes later in the course of the disease.ConclusionWD feeding led to hyperfiltration followed by a decline in GFR that was partly mitigated by PT deletion of DPP4 and this was associated with improved kidney histology and less fibrosis. WD feeding in WT mice was associated with increase in expression of several pro inflammatory genes and TLR4 and ICAM 1 were normalized in KO mice. DPP4 protein expression in kidney was associated with increased phosphorylation of ERK and this was suppressed in KO mice. Overall, these data suggest that suppression of early activation of DPP4 in ORKD may slow down the progression of CKD.

Efficacy and Safety of Novel Non-steroidal Mineralocorticoid Receptor Antagonist Finerenone in the Management of Diabetic Kidney Disease: A Meta-analysis.

Background:Data are scant on use of finerenone in diabetic kidney disease (DKD). We undertook this meta-analysis to address this knowledge gap.Methods:Electronic databases were searched for randomized controlled trials (RCTs) involving diabetes patients receiving finerenone compared to controls. The primary outcome was changes in urine albumin-creatinine ratio (UACR). Secondary outcomes were time to kidney failure (decline in GFR by >40% from baseline over 4 weeks), time to end-stage kidney disease, hospitalization for any cause, death and adverse events reported.Results:From initially screened 79 articles, data from 7 RCTs involving 13,783 patients were analyzed (3 in active control group [ACG] defined as having eplerenone/spironolactone as active comparator; 4 in passive control group [PCG] defined as having placebo as controls). Patients receiving finerenone had greater percentage lowering of UACR from baseline as compared to PCG [MD23.82% (95%CI: –24.87 to –22.77); P < 0.01; I2 = 96%] at 90 days, after 2 years [MD 37.9% (95%CI: –38.09 to –37.71); P < 0.01] and 4 years [MD 25.20%(95%CI: –25.63 to –24.77);P < 0.01] of treatment. Patients receiving finerenone has lower chance of >40% decline in GFR (OR 0.83 [95%CI: 0.75 to 0.92];P < 0.01; I2 = 0%). Patients receiving finerenone had lower occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for heart failure, as compared to placebo/eplerenone (OR0.86 [95%CI: 0.78 to 0.95]; P = 0.003; I2 = 0%). TAEs was similar (RR0.97 [95%CI: 0.88–1.07]; P = 0.56; I2 = 0%), but SAEs significantly lower (RR0.91 [95%CI: 0.84 to 0.97]; P < 0.01; I2 = 0%) in finerenone-group compared to controls.Conclusion:This meta-analysis provides reassuring data on beneficial impact of finerenone in reducing UACR and GFR decline as compared to placebo. We still lack head-to-head comparison of renal outcomes of finerenone vs eplerenone/spironolactone in DKD.

Modifiable Lifestyle Behaviors and CKD Progression: A Narrative Review.

Living a healthy lifestyle is one of the safest and most cost-effective ways to improve one's quality of life and prevent and/or manage chronic disease. As such, current CKD management guidelines recommend that patients adhere to a healthy diet, perform ≥150 minutes per week of physical activity, manage their body weight, abstain from tobacco use, and limit alcohol. However, there are limited studies that investigate the relationship between these lifestyle factors and the progression of CKD among people with established CKD. In this narrative review, we examine the reported frequencies of health lifestyle behavior engagement among individuals with non-dialysis-dependent CKD and the existing literature that examines the influences of diet, physical activity, weight management, alcohol consumption, and tobacco use on the progression of CKD, as measured by decline in GFR, incident ESKD, or elevated proteinuria or albuminuria in individuals with CKD. Many of the available studies are limited by length of follow-up and small sample sizes, and meta-analyses were limited because the studies were sparse and had heterogeneous classifications of behaviors and/or referent groups and of CKD progression. Further research should be done to determine optimal methods to assess behaviors to better understand the levels at which healthy lifestyle behaviors are needed to slow CKD progression, to investigate the effect of combining multiple lifestyle behaviors on important clinical outcomes in CKD, and to develop effective techniques for behavior change. Despite the lack of evidence of efficacy from large trials on the ability of lifestyle behaviors to slow CKD progression, maintaining a healthy lifestyle remains a cornerstone of CKD management given the undisputed benefits of healthy lifestyle behaviors on cardiovascular health, BP control, and survival.