Advanced Stages Of CKD Research Articles

Assessment of Bone Mineral Density (BMD) In Children with Advanced CKD (Stage 3 To 5): Experience from Tertiary Care Center, Dhaka, Bangladesh

Assessment of Bone Mineral Density (BMD) In Children with Advanced CKD (Stage 3 To 5): Experience from Tertiary Care Center, Dhaka, Bangladesh

The rate of chronic kidney disease progression in advanced stages and the dynamics of the uremic syndrome parameters

Background. The current practice of patients with advanced CKD stages management is not optimal, as it leads to the risk of an emergency dialysis start with an unfavorable prognosis, does not utilize all the possibilities of nephroprotective therapy and does not provide optimal correction of the most important uremic syndromes before starting dialysis, which worsens the per spectives of long-term patient-oriented dialysis treatment. THE AIM. The obtained features of the standard practice will provide the possibility to assemble group carefully matched with intensive management group to compare outcomes in future prospective study and to assess the significance of the proposed program components of the intensive management of patients with advanced stages of chronic kidney disease in the "transition center". PATIENTS AND METHODS. A group with regular (at least 6 visits per year) follow-up of 540 patients with baseline CKD3B was retrospectively formed from the city nephrology center database (which included 7696 patients with CKD3 and higher) and was traced to the need for renal replacement therapy or to death. As part of the follow-up, patients underwent regular clinical and laboratory evaluation and received nephroprotective therapy, which were recorded in the database. RESULTS. The dynamics of an accelerating decrease in eGFR (according to CKD-EPICr) from median of -2.76 (-3.26÷-2.36) to -4.34 (-5.01÷-3.46) and further to -6.01 (-7.11÷-5.23) ml/min/1.73 m2/ year for the stages of CKD3B→CKD4→CKD5 in parallel with the dynamics of blood levels of hemoglobin (and iron), phosphate (and calcium), albumin, as well as proteinuria is described – factors that turned out to be significant in the multiple regression model with a dependent variable – the rate of eGFR reduction (the significance of the model F=2.864; p=0.015). CONCLUSION. The obtained detailed description of the progression of CKD in a typical regional population under standard management conditions will provide the possiblity to form a group from a cohort of regular monitoring in a nephrocenter, carefully compared with an intensive management group in the prototype of a transition center based on a large inpatient dialysis center to assess the significance of the components of the proposed control and interventions program.

National Projections for Clinical Implications of Race-Free Creatinine-Based GFR Estimating Equations.

The National Kidney Foundation and American Society of Nephrology Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease recently recommended a new race-free creatinine-based equation for eGFR. The effect on recommended clinical care across race and ethnicity groups is unknown. We analyzed nationally representative cross-sectional questionnaires and medical examinations from 44,360 participants collected between 2001 and 2018 by the National Health and Nutrition Examination Survey. We quantified the number and proportion of Black, White, Hispanic, and Asian/Other adults with guideline-recommended changes in care. The new equation, if applied nationally, could assign new CKD diagnoses to 434,000 (95% confidence interval [CI], 350,000 to 517,000) Black adults, reclassify 584,000 (95% CI, 508,000 to 667,000) to more advanced stages of CKD, restrict kidney donation eligibility for 246,000 (95% CI, 189,000 to 303,000), expand nephrologist referrals for 41,800 (95% CI, 19,800 to 63,800), and reduce medication dosing for 222,000 (95% CI, 169,000 to 275,000). Among non-Black adults, these changes may undo CKD diagnoses for 5.51 million (95% CI, 4.86 million to 6.16 million), reclassify 4.59 million (95% CI, 4.28 million to 4.92 million) to less advanced stages of CKD, expand kidney donation eligibility for 3.96 million (95% CI, 3.46 million to 4.46 million), reverse nephrologist referral for 75,800 (95% CI, 35,400 to 116,000), and reverse medication dose reductions for 1.47 million (95% CI, 1.22 million to 1.73 million). The racial and ethnic mix of the populations used to develop eGFR equations has a substantial effect on potential care changes. The newly recommended 2021 CKD-EPI creatinine-based eGFR equation may result in substantial changes to recommended care for US patients of all racial and ethnic groups.

A Nomogram to Identify Hyperkalemia Risk in Patients with Advanced CKD.

Hyperkalemia is a common and life-threatening complication of CKD. We aimed to develop and validate a nomogram that could identify the risk of hyperkalemia (≥5.5 mmol/L) in patients with CKD. A retrospective cohort study was performed in adult patients with predialysis advanced CKD (stages ≥3) in 2020-2021 for the outcome of hyperkalemia within 6 months. The training set was used to identify risk factors of hyperkalemia. Then a nomogram was developed by multivariable logistic regression analysis. C-statistics, calibration curves, and decision curve analysis (DCA) were used, and the model was validated in the internal and two external validation sets. In total, 847 patients with advanced CKD were included. In 6 months, 28% of patients had hyperkalemia (234 out of 847). Independent risk factors were: age ≥75 years, higher CKD stages, previous event of serum potassium ≥5.0 mmol/L within 3 months, and comorbidities with heart failure, diabetes, or metabolic acidosis. Then the nomogram on the basis of the risk factors adding the use of renin-angiotensin-aldosterone system inhibitors was constructed. The C-statistic of the model was 0.76 (95% CI, 0.70 to 0.78), and was stable in both the internal validation set (0.73; 95% CI, 0.63 to 0.82) and external validation sets (0.88; 95% CI, 0.84 to 0.95 and 0.82; 95% CI, 0.72 to 0.92). Calibration curves and DCA analysis both found good performances of the nomogram. A feasible nomogram and online calculator were developed and validated to evaluate the risk of hyperkalemia within 6 months in patients with advanced CKD. Patients with CKD and a high risk of hyperkalemia may benefit from intensive monitoring and early triage.

Prevalence of Apparent Treatment-Resistant Hypertension in Chronic Kidney Disease in Two Large US Health Care Systems.

More intensive BP goals have been recommended for patients with CKD. We estimated the prevalence of apparent treatment-resistant hypertension among patients with CKD according to the 2017 American College of Cardiology/American Heart Association (ACC/AHA; BP goal <130/80 mm Hg) and 2021 Kidney Disease Improving Global Outcomes (KDIGO; systolic BP <120 mm Hg) guidelines in two US health care systems. We included adults with CKD (an eGFR <60 ml/min per 1.73 m2) and treated hypertension from Kaiser Permanente Southern California and the Veterans Health Administration. Using electronic health records, we identified apparent treatment-resistant hypertension on the basis of (1) BP above the goal while prescribed three or more classes of antihypertensive medications or (2) prescribed four or more classes of antihypertensive medications regardless of BP. In a sensitivity analysis, we required diuretic use to be classified as apparent treatment-resistant hypertension. We estimated the prevalence of apparent treatment-resistant hypertension per clinical guideline and by CKD stage. Among 44,543 Kaiser Permanente Southern California and 241,465 Veterans Health Administration patients with CKD and treated hypertension, the prevalence rates of apparent treatment-resistant hypertension were 39% (Kaiser Permanente Southern California) and 35% (Veterans Health Administration) per the 2017 ACC/AHA guideline and 48% (Kaiser Permanente Southern California) and 55% (Veterans Health Administration) per the 2021 KDIGO guideline. By requiring a diuretic as a criterion for apparent treatment-resistant hypertension, the prevalence rates of apparent treatment-resistant hypertension were lowered to 31% (Kaiser Permanente Southern California) and 23% (Veterans Health Administration) per the 2017 ACC/AHA guideline. The prevalence rates of apparent treatment-resistant hypertension were progressively higher at more advanced stages of CKD (34%/33%, 42%/36%, 52%/41%, and 60%/37% for Kaiser Permanente Southern California/Veterans Health Administration eGFR 45-59, 30-44, 15-29, and <15 ml/min per 1.73 m2, respectively) per the 2017 ACC/AHA guideline. Depending on the CKD stage, up to a half of patients with CKD met apparent treatment-resistant hypertension criteria.

Treatment of secondary hyperparathyroidism in non-dialysis CKD: an appraisal 2022s.

The situation of secondary hyperparathyroidism (SHPT) in chronic kidney disease patients not on dialysis (ND-CKD) is probably best characterised by the Kidney Disease: Improving Global Outcomes Chronic Kidney Disease-Mineral and Bone Disorder Update 2017 guideline 4.2.1 stating that the optimal parathyroid hormone levels are not known in these stages. Furthermore, new caution became recommended with regard to the routine use of active vitamin D analogues in early CKD stages and moderate SHPT phenotypes, due to their potential risks for hypercalcaemia and hyperphosphataemia aggravation. Nevertheless, there is still a substantial clinical need to prevent the development of parathyroid gland autonomy, with its associated consequences of bone and vascular damage, including fracture risks and cardiovascular events. Therefore we now attempt to review the current guideline-based and clinical practice management of SHPT in ND-CKD, including their strengths and weaknesses, favouring individualised approaches respecting calcium and phosphate homeostasis. We further comment on extended-release calcifediol (ERC) as a new differential therapeutic option now also available in Europe and on a potentially novel understanding of a required vitamin D saturation in more advanced CKD stages. There is no doubt, however, that knowledge gaps will remain unless powerful randomised controlled trials with hard and meaningful endpoints are performed.

Prescribing Nirmatrelvir/Ritonavir for COVID-19 in Advanced CKD.

Prescribing Nirmatrelvir/Ritonavir for COVID-19 in Advanced CKD.

Healthcare resource utilisation and related costs of patients with CKD from the UK: a report from the DISCOVER CKD retrospective cohort.

Chronic kidney disease (CKD) is widely reported to decrease quality of life, increase morbidity and mortality and cause increased healthcare resource utilisation (HCRU) as the disease progresses. However, there is a relative paucity of accurate and recent estimates of HCRU in this patient population. Our aim was to address this evidence gap by reporting HCRU and related costs in patients with CKD from the UK primary and secondary care settings. HCRU and cost estimates of CKD were derived for UK patients included in the DISCOVER CKD cohort study using clinical records from the Clinical Practice Research Datalink linked to external databases. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using the urinary albumin:creatinine ratio (UACR) and estimated glomerular filtration rate. Hospitalisation rates more than tripled between low (A1) and high (A3) UACR categories and the mean annual per-patient costs ranged from £4966 (A1) to £9196 (A3) and from £4997 (G2) to £7595 (G5), demonstrating that a large healthcare burden can be attributed to a relatively small number of patients with later stage CKD, including those with kidney failure and/or albuminuria. HCRU and costs associated with CKD impose a substantial burden on the healthcare system, particularly in the more advanced stages of CKD. New interventions that can delay the progression of CKD to kidney failure may not only prolong the patient's life, but would also provide significant resource and cost savings to healthcare providers.

Importance of Metabolic Acidosis as a Health Risk in Chronic Kidney Disease.

Human kidneys are well adapted to excrete the daily acid load from diet and metabolism in order to maintain homeostasis. In approximately 30% of patients with more advanced stages of CKD, these homeostatic processes are no longer adequate, resulting in metabolic acidosis. Potential deleterious effects of chronic metabolic acidosis in CKD, including muscle wasting, bone demineralization, hyperkalemia, and more rapid progression of CKD, have been well cataloged. Based primarily upon concerns related to nutrition and bone disease, early Kidney Disease Outcomes Quality Initiative guidelines recommended treating metabolic acidosis with alkali therapy targeting a serum bicarbonate ≥22 mEq/L. More recent guidelines have suggested similar targets based upon potential slowing of CKD progression. However, appropriately powered, long-term, randomized controlled trials to study efficacy and safety of alkali therapy for these outcomes are largely lacking. As a result, practice among physicians varies, underscoring the complexity of treatment of chronic metabolic acidosis in real-world CKD practice. Novel treatment approaches and rigorous phase 3 trials may resolve some of this controversy in the coming years. Metabolic acidosis is an important complication of CKD, and where it "falls" in the priority schema of CKD care will depend upon the generation of strong clinical evidence.

PARAMETERS OF LIPID METABOLISM IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND THYROID DYSFUNCTION

BACKGROUND . In CKD lipid metabolism disorders are associated with a high incidence of adverse outcomes. Dyslipidemia in patients with CKD is characterized by a decrease in HDL cholesterol, high triglyceride levels, and normal total cholesterol and LDL cholesterol levels. In CKD, a decrease in the functional activity of the thyroid gland (subclinical hypothyroidism) is often detected. THE AIM : to study the parameters of the lipid spectrum of blood in patients with different stages of chronic kidney disease and thyroid dysfunction. PATIENTS AND METHODS . A one-stage cross-sectional study of 457 patients with glomerulopathies without clinically significant diseases of the cardiovascular system with preserved ejection fraction (&gt; 55% according to Simpson method) according to echocardiography was carried out. To identify thyroid dysfunction, a screening determination of the level of TSH, free T4 was assessed. The parameters of the blood lipid spectrum and GFR were assessed in all patients. Parametric and nonparametric methods of statistical analysis were used. RESULTS . Advanced stages of CKD are characterized by the formation of atherogenic dyslipidemias. 13.1% of patients received statin therapy, the target values of the blood lipid spectrum on statin therapy were not achieved. In the group of patients with nephrotic syndrome, the parameters of the blood lipid spectrum were significantly worse. Most of the patients with CKD were outside the target values of the blood lipid spectrum. In patients with TSH&gt; 7.0 mIU / L, the content of TC, LDL, non-HDL was significantly higher than in the group of patients with normal thyroid function. CONCLUSION . Subclinical hypothyroidism contributes to the formation of atherogenic dyslipidemias in patients with CKD.

878-P: Maximize Benefits of SGLT2 Inhibitors in People with Advanced CKD Stages with Type 2 Diabetes

Objective: SGLT2 inhibitor (SGLT2i) should be considered for people with CKD with type 2 diabetes (T2D) . Since eGFR declining speed and responsiveness to SGLT2i are different in each person, we assessed renal protective effects by individual eGFR slope analysis. Methods: A total of 75 patients with T2D with advanced CKD stage 3-4, treated by SGLT2i (empagliflozin 65% and others) were analyzed. The duration of diabetes at the time of recruitment were as follows: stage 3a (n=29) ; 11.9±5.4, stage 3b (n=28) ; 19.9±12.1, and stage 4 (n=18) ; 13.8±8.5 years. The mean of age was 70.3±12.2 year-old. GLP-1RAs was used in 41%, 64% and 44% respectively. Most rapid baseline eGFR slopes were calculated from 45.7±19.9 months before using SGLT2i, and slopes after adding SGLT2i were calculated from 39.2±11.4 months. Results: 1) In total, the initiation of SGLT2i decreased eGFR from 46.1±14.1 to 43.6±13.5ml/min/1.73m2 (P&amp;lt;0.001) on the first month. 2) In total, averaged individualized eGFR slopes were improved from -6.4±9.1 to -1.5±3.2ml/min/1.73m2/year (P&amp;lt;0.001) . The rate of responders (responder: defined as slope are attenuated vs. baseline) in each stage were as follows: stage 3a; (22/29) , stage 3b; (22/28) , stage 4; (16/18) . Slopes in responders (60/75) were improved as follows, -7.5±9.8 to -0.8±3.0 ml/min/1.73m2/year (P&amp;lt;0.001) . Slopes in non-responders (15/75) were worsened as follows, -2.0±2.0 to -4.0±3.2ml/min/1.73m2/year (P&amp;lt;0.001) . Although no clear background differences could be found, responders were more rapid eGFR decliners and highly had macro-albuminuria (53% vs. 33%) . 3) Slopes were improved in all stages, stage 3a: -4.1±3.7 to -1.2±3.2 (P&amp;lt;0.001) and stage 3b; -4.9±3.7 to -1.3±3.1 (P&amp;lt;0.001) , and stage 4; -12.4±16.3 to -2.0±3.6ml/min/1.73m2/year (P&amp;lt;0.01) . In stage 4, nephrosis highly existed in 28% at the baseline. Conclusion: To pursuit the renal benefits safely, especially starting SGLT2i in lower eGFR level in people with advanced CKD stages, individualized slope analysis is needed. Disclosure K.Kashima: None. H.Shimizu: None. M.Yamada: None.

MO029: Urinary biomarkers in the progression of autosomal dominant polycystic kidney disease

Abstract BACKGROUND AND AIMS Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary disease characterized by the formation and growth of renal cysts, affecting the decrease of renal function, which may lead to end-stage renal disease (ESRD). Due to the enormous intrafamilial phenotypic variability of ADPKD and since serum creatinine and glomerular filtration rate (GFR) have a limited ability to assess the disease and predict its progression at earlier stages, there is a need to find new biomarkers to predict disease progression. The α-glutathione s-transferase (GST-α) and haptoglobin (Hp) are produced mainly by the proximal convoluted tubule, and these enzymes are released into the urinary lumen in direct response to tubular damage. This study aims to evaluate the urine concentration of α-GST and Hp biomarkers at different stages of ADPKD progression and correlate the levels of urinary biomarkers α-GST and Hp with traditional markers of renal dysfunction. METHOD Twenty-five patients with ADPKD, mean age of 41.57 ± 14.43 years, mostly female (56.0%), diagnosed according to the Ravine criteria and with a follow-up of at least 60 months. Demographic, hemodynamic, urinary creatinine (UCr) and serum creatinine (SCr) data were collected in baseline (T0) and at the end of the follow-up period (T1). GFR was determined using the CKD-EPI formula, grouping patients into early stages (CKD1 and CKD2) and advanced stages (CKD3 to CKD5). Biomarkers were determined by the ELISA method and indexed to UCr in T1. In addition, α-GST was determinate in a control sample composed of 17 individuals without diagnosed kidney disease. Statistical analysis was performed by SPSS version 26 with a significant value of P &amp;lt; 0.05. RESULTS Comparing the means of SCr and GFR between T0 and T1 were observed a decrease of renal function during the follow-up period (P = 0.013 and P = .017, respectively). About 14.4% of patients were in an advanced stage of kidney disease in T1, compared with 4.8% in T0. ADPKD patients had increased values of α-GST in relation to the control group (P &amp;lt; 0.001), but no difference in the SCr was found. We also found a trend for higher levels of HP in advanced stages of CKD (P = 0.071). In ADPKD patients, direct correlations were observed between the variation of SCr during the follow-up with α-GST and Hp (r = 0.606, P = 0.048 and r = 0.738, P = 0.037, respectively). A trend to correlation was found between the levels of Hp and the Scr in T1 (r = P = 0.058). CONCLUSION The levels of α-GST and Hp are associated with renal damage and may be helpful in the early identification of the decline in renal function in ADPKD patients.

MO380: Bio-Conductivity Measurement for Electrical Impedance Tomography (EIT) in Chronic Kidney Disease—A Non-Invasive and Portable Monitoring Approach

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) is an escalating global health concern, and non-invasive means for early CKD detection is eagerly awaited. Kidneys are water- and electrolytes-rich organs with good bio-conductivity. Kidney fibrosis and tubular atrophy are characteristic pathological changes in CKD [1], and is associated with restricted blood perfusion, fluid diffusion [2,3] and hence reduced bio-conductivity. Electrical impedance tomography (EIT) emerges as a non-invasive, ionizing radiation-free imaging technique measuring dielectric properties of the body parts [4]. This study investigated the relationship of EIT indices and renal function in patients with various stages of CKD. METHOD We prospectively recruited 98 patients with different stages of CKD (Stage 1, n = 16; Stage 2, n = 15; Stage 3, n = 20, Stage 4, n = 36 and Stage 5, n = 11). EIT measurements were performed at two frequencies (33.6 and 100 kHz) using a portable EIT device with an electrode belt consisting of 16 gel electrodes. EIT data was pre-processed and reconstructed as mean conductivity maps. Frequency differencing was then performed between conductivity maps at two frequencies. Kidney-related dielectric parameters were extracted around the kidney region located at lower one-third of the frequency differencing conductivity map. Conductivity changes between frequencies were then computed and further regressed with individual biometrics. Predicted eGFR values was then computed and compared with the standard eGFR scores to evaluate its effectiveness on classifying CDK stages. RESULTS The detected mean bio-conductivity changes were −3.9, −67.5, −133.5, −212.6 and −294.7 (a.u.) in patients with CKD Stage 1, 2, 3, 4 and 5, respectively (Fig. 1A). Patients with more advanced stages of CKD tend to show more reduction in bio-conductivity, and eGFR correlated positively with reduction in bio-conductivity (R2 = 0.37, P &amp;lt; 0.001) (Fig. 1B). EIT-predicted eGFR (eGFREIT) was further computed by the captured conductivity changes and individual biometrics (Fig. 2). eGFREIT showed significant correlation with eGFR measured by blood tests (R2 = 0.54, P &amp;lt; 0.001). CONCLUSION EIT showed good correlation with renal function changes in CKD patients, and thus holds promise to be developed into a non-invasive and portable device for early CKD detection in both clinical and community settings.

FC032: Copeptin as a Potential Biomarker in Patients with Autosomal-Dominant Polycystic Kidney Disease (ADPKD)—Update from the AD(H)PKD Study

Abstract BACKGROUND Prediction of disease progression is one of the main challenges in the treatment of Autosomal-Dominant Polycystic Kidney Disease (ADPKD). In addition to already established biomarkers such as total kidney volume (TKV), further biomarkers that are feasible and easy to collect would be important to allow conclusions on prognosis as well as, in the best case, on long-term treatment response. Post-hoc analyses of the TEMPO 3:4 study showed that copeptin could serve as such a biomarker [1, 2]. In this study, we investigated copeptin over a multi-year course in participants of the AD(H)PKD study. METHOD Copeptin was measure from serum samples of 486 patients in the AD(H)PKD study at both initial and follow-up presentations. A total of 95 patients were on tolvaptan therapy at least at one of the measurement time points. We examined the measured values with respect to their distribution in different patient groups (e.g. age, Mayo class) and their changes on tolvaptan administration. Baseline eGFR values were developed using historic creatinine measurements up to 8000 days prior and 1500 days after copeptin measurements. For each patient with at least 5 creatinine measurements an eGFR slope was calculated. The models were developed using a robust linear modelling approach. Slopes were extracted to be the parameter associated to date and multiplied by 365 to retrieve an annual eGFR slope. eGFRs predicted for the specific dates at which copeptin has been measured were then calculated and used in subsequent modelling approaches. To develop a model predictive of eGFR, we used a stepwise regression approach, removing insignificant coefficients at each step. RESULTS As expected, copeptin was significantly lower in 391 tolvaptan naive patients than in 95 patients on therapy (9.95 pmol/L versus 19.78 pmol/L; P &amp;lt; 0.0001). More advanced CKD stages showed higher copeptin levels, both with and without tolvaptan, than at lower stages. Independent from kidney function, copeptin levels were consistently higher on tolvaptan than without therapy. Also, larger TKV showed higher copeptin levels in both groups. In 40 patients, copeptin measurements before the start of tolvaptan therapy and follow-up measurements under tolvaptan at the target dose (90/30 mg) were available, and a significant increase in copeptin levels on tolvaptan (copeptin before tolvaptan therapy: 9.798 pmol/L, copeptin on tolvaptan 23.83 pmol/L; P &amp;lt; 0.0001) could be traced during the course. Linear regression models showed that copeptin is an independent variable for the prediction of eGFR slope when added to age, height-adjusted total kidney volume (htTKV) and baseline eGFR. Besides, correlation of predicted future eGFR based on Mayo Classification is slightly but significantly improved by adding copeptin to the model (R2 Mayo 0.9244 and R2 Mayo + copeptin 0.9446). CONCLUSION Our data obtained from the real-life setting should again be reconciled with the results from the TEMPO 3:4 cohort. Our findings show that copeptin levels are both associated with kidney function and with future eGFR loss. Adding copeptin to the model of the Mayo Classification indeed improves the prediction of future eGFR. However, it is not clear yet whether this mild effect will have an impact in routine clinical care. Copeptin has the potential to facilitate prognostic assessment as a biomarker and thus could be helpful in deciding on therapy initiation and possibly more patient-specific dosing. Future analyses of outcome in relation to copeptin will provide further data and might enable implementation in clinical practice.

Role of Mineralocorticoid Receptor Antagonists in Diabetic Kidney Disease

Diabetic kidney disease (DKD) represents a major public health issue, currently posing an important burden on healthcare systems. Renin–angiotensin system (RAS) blockers are considered the cornerstone of treatment of albuminuric DKD. However, a high residual risk of progression to more advanced CKD stages under RAS blockade still remains, while relevant studies did not show significant declines in cardiovascular events with these agents in patients with DKD. Among several other pharmacological classes, mineralocorticoid receptor antagonists (MRAs) have received increasing interest, due to a growing body of high-quality evidence showing that spironolactone and eplerenone can significantly lower blood pressure and albuminuria in patients with CKD. Furthermore, finerenone, a novel nonsteroidal MRA with unique physicochemical properties, was shown to effectively reduce cardiovascular events and death, as well as the incidence of end-stage kidney disease in patients with type 2 diabetes. This review discusses previous and recent clinical evidence on the issue of nephroprotection and cardioprotection in DKD offered by mineralocorticoid receptor antagonism, aiming to aid clinicians in their treatment decisions for diabetic patients.

Delay in Permanent Vascular Access Formation and Referral to a Nephrologist in Incident Hemodialysis Patients: A Single Center Experience.

Objective: This study assessed the factors associated with delayed referral to a nephrologist and delay in formation of a permanent vascular access in incident hemodialysis (HD) patients.Methods: This prospective cross-sectional study was conducted from February 2021 to July 2021 on end stage renal disease (ESRD) patients receiving maintenance hemodialysis (MHD) at our center. Data were collected at the bedside during the HD session about a referral to a nephrologist, about when they were asked for permanent vascular access formation and the reason for the delay in its formation. Results: Out of 296 patients recruited in our study, 168 (56.8%) were male and 128 (43.2) were female. The mean age was 53.5±15 years (minimum of 19 years and maximum of 90 years). The most common reason for refusal of making permanent vascular access [arterio-venous fistula (AVF) or arterio-venous graft (AVG)] was fear of pain in our patients 65 (43.3%) followed by the denial of the disease 32 (21.3%). Among the study subjects, 231 (78%) patients were referred to the nephrologist immediately or within one month of their diagnosis. Some 152 (51.4%) of the patients were not in favor of making AVF whereas 151 (51%) refused for starting HD, hence most of our patients 181 (61.1%) initiated HD in emergency by a central venous catheter (CVC).Conclusion: Early referral should be done by primary care physicians (PCPs) for the timely management of CKD patients. As CKD is a progressive disease, it requires special attention by a nephrologist for adjustment of patient’s medications, timely follow-up, counseling, the early formation of AVF for HD, and planning for renal transplant. In our study, the majority of our patients initiated their HD via CVC because of the delayed visit to a nephrologist. Most patients were asked for AVF formation on the same day of presentation to our nephrology unit as they had advanced CKD (Stage 5) 134 (51.4%). Most patients in our study delayed AVF formation 152 (51.4%). With timely referral to a nephrologist, the nephrologist will be able to do better and repeated counseling about the disease, its progression, and the need for permanent vascular access for initiation of HD while patients and their families will get more time to make decisions.

Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease.

Abnormalities in lipid metabolism, accumulation of uremic toxins and advanced glycation end products may contribute to worsening atherosclerosis. This study characterized the glycation and carbamoylation profile of serum albumin isolated from individuals with diabetic kidney disease and its influence on cholesterol efflux. 49 patients with type 2 diabetes (T2DM) and different eGFR evaluated glycation and carbamoylation profile by measurement of carboxymethyl lysine (CML) and carbamoylated proteins (CBL) in plasma by ELISA, homocitrulline (HCit) in plasma by colorimetry. In the isolated albumins, we quantified CBL (ELISA) and total AGE and pentosidine by fluorescence. Macrophages were treated with albumin isolated, and 14C-Cholesterol efflux mediated by HDL2 or HDL3 was measured. Kruskal-Wallis test, Jonckheere-Terpstra test and Brunner's posttest were used for comparisons among groups. Determination of CML, HCit, CBL in plasma, as total AGE and pentosidine in albumins, did not differ between groups; however, CBL in the isolated albumins was higher in the more advanced stages of CKD (p=0.0414). There was reduction in the 14C-cholesterol efflux after treatment for 18h with albumin isolated from patients with eGFR<60mL/min/1.73m2 compared with control group mediated by HDL2 (p=0.0288) and HDL3 (p<0.0001), as well as when compared with eGFR ≥60mL/min/1.73m2 per HDL2 (p=0.0001) and HDL3 (p<0.0001). Treatment for 48h showed that eGFR<15mL/min/1.73m2 had a lower percentage of 14C-cholesterol efflux mediated by HDL2 compared to control and other CKD groups (p=0.0274). Albumins isolated from individuals with T2DM and eGFR<60mL/min/1.73m2 suffer greater carbamoylation, and they impair the cholesterol efflux mediated by HDL2 and HDL3. In turn, this could promote lipids accumulation in macrophages and disorders in reverse cholesterol transport.

The Influence of Dietary Interventions on Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

Chronic kidney disease is a health problem whose prevalence is increasing worldwide. The kidney plays an important role in the metabolism of minerals and bone health and therefore, even at the early stages of CKD, disturbances in bone metabolism are observed. In the course of CKD, various bone turnover or mineralization disturbances can develop including adynamic hyperparathyroid, mixed renal bone disease, osteomalacia. The increased risk of fragility fractures is present at any age in these patients. Nutritional treatment of patients with advanced stages of CKD is aiming at prevention or correction of signs, symptoms of renal failure, avoidance of protein-energy wasting (PEW), delaying or prevention of the occurrence of mineral/bone disturbances, and delaying the start of dialysis. The results of studies suggest that progressive protein restriction is beneficial with the progression of renal insufficiency; however, other aspects of dietary management of CKD patients, including changes in sodium, phosphorus, and energy intake, as well as the source of protein and lipids (animal or plant origin) should also be considered carefully. Energy intake must cover patients’ energy requirement, in order to enable correct metabolic adaptation in the course of protein-restricted regimens and prevent negative nitrogen balance and protein-energy wasting.

787-P: Individualized Estimated GFR Slope Analysis Is Needed to Preserve Renal Function by SGLT2 Inhibitors in Patients with DKD

Objective: SGLT2 inhibitor (SGLT2i) should be considered for patients with type 2 diabetes (T2D) with CKD. Since eGFR declining speed is different in each patient, we assessed renal protective effects by individual eGFR slope analysis. Methods: A total of 75 patients with T2D with advanced CKD stage 3-4, treated by SGLT2i (empagliflozin 65% and others) were analyzed. The duration of diabetes at the time of recruitment were as follows: stage 3a (n=29); 11.9±5.4 yrs, stage 3b (n=28); 19.9±12.1 yrs, and stage 4 (n=18); 13.8±8.5 yrs. The mean of age was 70.3±12.2 yrs old. GLP-1RA (Liraglutide; n=36, Duraglutide; n=1) was used in 41%, 64% and 44% respectively. Most rapid baseline slopes were calculated from 46±20 months before using SGLT2i, and slopes after adding SGLT2i were calculated from 31±9 months. Results: 1) In total, the initiation of SGLT2i decreased eGFR from 46.1±14.1 to 43.6±13.5ml/min/1.73m2 (P&amp;lt;0.001) on first month. 2) Individualized most rapid slopes were improved from -6.4±9.1 to -1.6±3.3ml/min/1.73m2/year (P&amp;lt;0.001). 3) Slopes were improved in all stages, stage 3a: -4.1±3.7 to -1.1±3.4 (P&amp;lt;0.001) and stage 3b; -4.9±3.7 to -1.6±2.9 (P&amp;lt;0.001), and stage 4; -12.4±16.3 to -2.2±3.7ml/min/1.73m2/year (P&amp;lt;0.03). 3) The proportion of responders (defined as their ratios of slopes are reduced &amp;lt; 1.0 after addition of SGLT2i) in each stage were as follows: stage 3a; (22/29), stage 3b; (22/28), stage 4; (16/18). Slopes in responders (61/75) were improved as follows, -7.4±9.8 to -1.0±2.9ml/min/1.73m2/year (P&amp;lt;0.0001). Slopes in non-responders (14/75) were worsened as follows, -2.0±2.0 to -4.1±3.5ml/min/1.73m2/year (P&amp;lt;0.001). 4) Slopes in rapid decliners (13/75) were remarkably improved from -18.9±16.4 to -1.5±3.6ml/min/1.73m2/year (P&amp;lt;0.01) with combined use of GLP-1RA (11/13), who had macro-albuminuria (9/13) and nephrosis (7/13). Conclusion: To pursuit the renal benefits of SGLT2i, individualized slope analysis is needed for patient-centered care. Disclosure K. Kashima: None. H. Shimizu: None. M. Yamada: None.

MO254PREGNANCY OUTCOMES AND COMPLICATIONS IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS*

Abstract Background and Aims Pregnancy in patients with chronic glomerulonephritis (CGN) is associated with higher risk of complications and unfavorable outcomes compared to the general population. The aim of the study was to determine the incidence of pregnancy complications and outcomes in patients with preexisting CGN. Method 126 pregnancies in 119 women with CGN and CKD 1-4 stages: 1 st. – 86 patients, 2 st. – 17, 3 st. – 20, 4 st. – 3 and 20 pregnancies in 20 age-matching healthy women were included. Patients with secondary CGN, multiple pregnancy, pregnancy after IVF were excluded. A kidney biopsy was performed in 18 of 119 (15.1%) women: 15 – before conception and 3 – after delivery. IgA-nephropathy was detected in 11 of 18 (61.1%) patients, MCD/FSGS – in 4 (22.2%), MPGN – in 3 (16.7%). The incidence of unfavorable pregnancy outcome, preeclampsia (PE), preterm delivery, cesarean section (CS), low birth weight (LBW &amp;lt; 2500 g), small for gestational age (SGA) newborn (birth weight &amp;lt; 10th percentile), mean term of delivery, mean birth weight, frequency of treatment in neonatal intensive care unit (NICU) and achieving of end-stage kidney disease in mothers after delivery were evaluated. Results CKD was first diagnosed during pregnancy in 34.1% women with CGN. The incidence of adverse pregnancy outcomes, preterm delivery, LBW, SGA, and treatment in the NICU did not differ between groups, while the frequency of PE and CS were higher, and mean gestational age at delivery, birth weight were lower in the CGN group compared to the healthy control (Table). Severe PE was observed in 6 of 32 (18.7%) patients with PE and CGN. The incidence of PE increased in advanced stages of CKD, but the differences were not significant: 19.8% - in CKD1, 35.3% - CKD2, 35% - CKD3, 66.7% - CKD4, p=0.112. The frequency of PE depended on the presence of baseline nephrotic-range proteinuria (NPU) and chronic arterial hypertension (AH): PE was observed in women w/o NPU and w/o AH in 8.3% cases, w/o NPU and with AH – in 39%, with NPU and w/o AH – in 44,4%, with NPU and with AH – in 43.8%, p=0.00048. Preterm delivery, CS and LBW were more common in women with chronic renal failure, and their frequency increased with increasing severity of CKD: CKD1 – 3.5%, 21.2%, 3.5% resp.; CKD2 – 6.7%, 53.3%, 20%; CKD3 – 40%, 70%, 40%; CKD4 – 100%, 100%, 100% (p&amp;lt;0.0001, for all characteristics). We found differences in gestational age at delivery depending on the stages of CKD: in CKD1 it was 38.9 ± 1.3 wks, CKD2 – 38.2 ± 2.1 wks, CKD3 – 36.3 ± 3.5 wks, CKD4 – 32.4 wks (one child), p=0.00013. The proportion of newborns requiring intensive care was higher in mothers with CKD3 (30%) and CKD4 (100%) compared with CKD1 (0%) and CKD2 (13.3%), p&amp;lt;0.0001. Five of 126 (4%) patients in CGN group achieved stage 5 CKD with average postpartum follow-up period of 92.6 ± 20.5 months; 4 women had CKD3 during pregnancy, one – CKD1. Now 2 patients are treated with regular hemodialysis, 3 - live with kidney transplant. Conclusion Chronic glomerulonephritis has a negative effect on pregnancy course, increasing the incidence of PE and CS and contributing to reduce gestational age and birth weight. Incidence of preterm delivery, CS, LBW and proportion of newborns treated in NICU were highest in patients with CKD 3-4.