Cause Of Chronic Kidney Disease Research Articles

Diagnostic Yield and Benefits of Whole Exome Sequencing in CAKUT Patients Diagnosed in the First Thousand Days of Life

Congenital anomalies of the kidney and urinary tract (CAKUT) are the predominant cause of chronic kidney disease (CKD) and the need for kidney replacement therapy (KRT) in children. Although more than 60 genes are known to cause CAKUT if mutated, genetic etiology is detected, on average, in only 16% of unselected CAKUT cases, making genetic testing unproductive. Whole exome sequencing (WES) was performed in 100 patients with CAKUT diagnosed in the first 1000 days of life with CKD stages 1 to 5D/T. Variants in 58 established CAKUT-associated genes were extracted, classified according to the American College of Medical Genetics and Genomics guidelines, and their translational value was assessed. In 25% of these mostly sporadic patients with CAKUT, a rare likely pathogenic or pathogenic variant was identified in 1 or 2 of 15 CAKUT-associated genes, including GATA3, HNF1B, LIFR, PAX2, SALL1, and TBC1D1. Of the 27 variants detected, 52% were loss-of-function and 18.5% de novo variants. The diagnostic yield was significantly higher in patients requiring KRT before 3 years of age (43%, odds ratio 2.95) and in patients with extrarenal features (41%, odds ratio 3.5) compared with patients lacking these criteria. Considering that all affected genes were previously associated with extrarenal complications, including treatable conditions, such as diabetes, hyperuricemia, hypomagnesemia, and hypoparathyroidism, the genetic diagnosis allowed preventive measures and/or early treatment in 25% of patients. WES offers significant advantages for the diagnosis and management of patients with CAKUT diagnosed before 3 years of age, especially in patients who require KRT or have extrarenal anomalies.

Clustering-based spatial analysis (CluSA) framework through graph neural network for chronic kidney disease prediction using histopathology images

Machine learning applied to digital pathology has been increasingly used to assess kidney function and diagnose the underlying cause of chronic kidney disease (CKD). We developed a novel computational framework, clustering-based spatial analysis (CluSA), that leverages unsupervised learning to learn spatial relationships between local visual patterns in kidney tissue. This framework minimizes the need for time-consuming and impractical expert annotations. 107,471 histopathology images obtained from 172 biopsy cores were used in the clustering and in the deep learning model. To incorporate spatial information over the clustered image patterns on the biopsy sample, we spatially encoded clustered patterns with colors and performed spatial analysis through graph neural network. A random forest classifier with various groups of features were used to predict CKD. For predicting eGFR at the biopsy, we achieved a sensitivity of 0.97, specificity of 0.90, and accuracy of 0.95. AUC was 0.96. For predicting eGFR changes in one-year, we achieved a sensitivity of 0.83, specificity of 0.85, and accuracy of 0.84. AUC was 0.85. This study presents the first spatial analysis based on unsupervised machine learning algorithms. Without expert annotation, CluSA framework can not only accurately classify and predict the degree of kidney function at the biopsy and in one year, but also identify novel predictors of kidney function and renal prognosis.

Rate of Kidney Function Decline is Associated With Kidney and Heart Failure in Individuals With Type 1 Diabetes

Diabetes is the most common cause of chronic kidney disease (CKD). Urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) are commonly used to monitor the onset and progression of diabetic kidney disease (DKD). We studied if the preceding rate of kidney function decline, that is, the eGFR slope, is independently associated with incident clinical cardiorenal events. This study included longitudinal data for 2498 Finnish individuals with type 1 diabetes (T1D). The eGFR slope was calculated from 5 years preceding the study visit. Data on kidney failure, coronary heart disease (CHD), stroke, 3-point major adverse cardiovascular events (MACE), heart failure, and death were obtained from national registries. The associations between the eGFR slope and incident events were assessed with multivariable competing risk models during the average follow-up of 9.2 years. The eGFR slopes were associated (P≤ 0.001) with all outcomes when adjusted for age, sex, and HbA1c. However, eGFR slope remained associated only with the composite outcome of kidney failure or death when the albuminuria group and eGFR at the study visit were included in the model (P= 0.041). In addition, eGFR slope was independently associated with kidney failure in individuals without CKD (eGFR > 60 ml/min per 1.73 m2; P= 0.044), and with heart failure in those with CKD (P= 0.033). However, eGFR slope did not markedly improve the model C-index. The eGFR slope was independently associated with kidney failure in those without CKD, and with heart failure in those with CKD. However, it is unlikely to have major relevance for clinical practice when the current eGFR and albuminuria status are known.

Prioritization of Monogenic Congenital Anomalies of the Kidney and Urinary Tract Candidate Genes with Existing Single-Cell Transcriptomics Data of the Human Fetal Kidney

Introduction: Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in the first 3 decades of life. Over 40 genes have been identified as causative for isolated human CAKUT. However, many genes remain unknown, and the prioritization of potential CAKUT candidate genes is challenging. To develop an independent approach to prioritize CAKUT candidate genes, we hypothesized that monogenic CAKUT genes are most likely co-expressed along a temporal axis during kidney development and that genes with coinciding high expression may represent strong novel CAKUT candidate genes. Methods: We analyzed single-cell mRNA (sc-mRNA) transcriptomics data of human fetal kidney for temporal sc-mRNA co-expression of 40 known CAKUT genes. A maximum of high expression in consecutive timepoints of kidney development was found for four of the 40 genes (EYA1, SIX1, SIX2, and ITGA8) in nephron progenitor cells a, b, c, d (NPCa–d). We concluded that NPCa–d are relevant for CAKUT pathogenesis and intersected two lists of CAKUT candidate genes resulting from unbiased whole-exome sequencing (WES) with the 100 highest expressed genes in NPCa–d. Results: Intersection of the 100 highest expressed genes in NPCa–d with WES-derived CAKUT candidate genes identified an overlap with the candidate genes KIF19, TRIM36, USP35, CHTF18, in each of which a biallelic variant was detected in different families with CAKUT. Conclusion: Sc-mRNA expression data of human fetal kidney can be utilized to prioritize WES-derived CAKUT candidate genes. KIF19, TRIM36, USP35, and CHTF18 may represent strong novel candidate genes for CAKUT.

Urine myo-inositol as a novel prognostic biomarker for diabetic kidney disease: a targeted metabolomics study using nuclear magnetic resonance.

As a leading cause of chronic kidney disease, clinical demand for noninvasive biomarkers of diabetic kidney disease (DKD) beyond proteinuria is increasing. Metabolomics is a popular method to identify mechanisms and biomarkers. We investigated urinary targeted metabolomics in DKD patients. We conducted a targeted metabolomics study of 26 urinary metabolites in consecutive patients with DKD stage 1 to 5 (n = 208) and healthy controls (n = 26). The relationships between estimated glomerular filtration rate (eGFR) or urine protein-creatinine ratio (UPCR) and metabolites were evaluated. Multivariate Cox analysis was used to estimate relationships between urinary metabolites and the target outcome, end-stage renal disease (ESRD). C statistics and time-dependent receiver operating characteristics (ROC) were used to assess diagnostic validity. During a median 4.5 years of follow-up, 103 patients (44.0%) progressed to ESRD and 65 (27.8%) died. The median fold changes of nine metabolites belonged to monosaccharide and tricarboxylic acid (TCA) cycle metabolites tended to increase with DKD stage. Myo-inositol, choline, and citrates were correlated with eGFR and choline, while mannose and myo-inositol were correlated with UPCR. Elevated urinary monosaccharide and TCA cycle metabolites showed associations with increased morality and ESRD progression. The predictive power of ESRD progression was high, in the order of choline, myo-inositol, and citrate. Although urinary metabolites alone were less predictive than serum creatinine or UPCR, myo-inositol had additive effect with serum creatinine and UPCR. In time-dependent ROC, myo-inositol was more predictive than UPCR of 1-year ESRD progression prediction. Myo-inositol can be used as an additive biomarker of ESRD progression in DKD.

Triiodothyronine and Protein Malnutrition Could Influence Pulse Wave Velocity in Pre-Dialysis Chronic Kidney Disease Patients.

Cardiovascular diseases (CVD) are the first cause of chronic kidney disease (CKD) mortality. For personalized improved medicine, detecting correctable markers of CVD can be considered a priority. The aim of this study was the evaluation of the impact of nutritional, hormonal and inflammatory markers on brachial-ankle Pulse Wave Velocity (PWV) in pre-dialysis CKD patients. A cross-sectional observational study was conducted on 68 pre-dialysis CKD patients (median age of 69 years, 41.2% with diabetes mellitus, 52.9% male). Laboratory data were collected, including levels of prolactin, triiodothyronine, TGF α, IL-6, and IL-1β. The high values of brachial-ankle PWV were associated with reduced muscle mass (p = 0.001, r = -0.44), low levels of total cholesterol (p = 0.04, r = -0.26), triglycerides (p = 0.03, r = -0.31), triiodothyronine (p = 0.04, r = -0.24), and prolactin (p = 0.02, r = -0.27). High PWV was associated with advanced age (p < 0.001, r = 0.19). In the multivariate analysis, reduced muscle mass (p = 0.018), low levels of triiodothyronine (p = 0.002), and triglycerides (p = 0.049) were significant predictors of PWV, but age (p < 0.001) remained an important factor. In conclusion, reduced triiodothyronine together with markers of malnutrition and age were associated with PWV in pre-dialysis CKD patients.

The burden of diabetic nephropathy in India: Need for prevention

Abstract Diabetic nephropathy (DN) is a growing public health problem with a high economic burden. DN is the main cause of chronic kidney disease (CKD) and end-stage renal disease (ESRD). The pathogenesis and risk factors associated with DN must be assessed to better understand the disease and its complications. Therefore, the early identification and treatment of DN have been shown to slow, stop, or even reverse the progression of ESRD.

A novel homozygous missense variant in TBC1D31 in a consanguineous family with congenital anomalies of the kidney and urinary tract (CAKUT).

Congenital anomalies of the kidney and urinary tract (CAKUT) is the leading cause of chronic kidney disease in the first three decades of life. Until now, more than 180 monogenic causes of isolated or syndromic CAKUT have been described. In addition, copy number variants (CNV) have also been implicated, however, all of these causative factors only explain a small fraction of patients with CAKUT, suggesting that additional yet-to-be-discovered novel genes are present. Herein, we report three siblings (two of them are monozygotic twin) of a consanguineous family with CAKUT. Whole-exome sequencing identified a homozygous variant in TBC1D31. Three dimensional protein modeling as well as molecular dynamics simulations predicted it as pathogenic. We therefore showed for the first time an association between a homozygous TBC1D31 variant with CAKUT in humans, expanding its genetic spectrum.

Autosomal dominant polycystic kidney disease in Colombia

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common genetic cause of chronic kidney disease (CKD) that requires dialysis. Knowing geographical clusters can be critical for early diagnosis, progression control, and genetic counseling. The objective was to establish the prevalence, geographic location, and ethnic groups of patients with ADPKD who underwent dialysis or kidney transplant in Colombia between 2015 and 2019.MethodsWe did a cross-sectional study with data from the National Registry of Chronic Kidney Disease (NRCKD) managed by the High-Cost Diseases Fund (Cuenta de Alto Costo [CAC] in Spanish) between July 1, 2015, and June 30, 2019. We included Colombian population with CKD with or without renal replacement therapy (RRT) due to ADPKD. Crude and adjusted prevalence rates were estimated by state and city.Results3,339 patients with ADPKD were included, period prevalence was 9.81 per 100,000 population; there were 4.35 cases of RRT per 100,000 population, mean age of 52.58 years (± 13.21), and 52.78% women. Seventy-six patients were Afro-Colombians, six were indigenous, and one Roma people. A total of 46.07% began scheduled dialysis. The highest adjusted prevalence rate was in Valle del Cauca (6.55 cases per 100,000 population), followed by Risaralda, and La Guajira. Regarding cities, Cali had the highest prevalence rate (9.38 cases per 100,000 population), followed by Pasto, Medellin, and Bucaramanga.ConclusionsADPKD prevalence is lower compared to Europe and US; some states with higher prevalence could be objective to genetic prevalence study.

Glucocorticoids for the treatment of IgA nephropathy: pros and cons. Research data and own experience

IgA nephropathy is the most common pattern of primary glomerular diseases worldwide and remains a leading cause of chronic kidney disease and kidney failure. The incidence of IgA nephropathy is 2.5 per 100,000 population per year. Presentation ranges from isolated haematuria to significant proteinuria, acute kidney injury and even chronic kidney disease. The 10-year risk of progression to end stage kidney disease or halving of GFR is 26 %. The basis of management of IgA nephropathy is goal-directed supportive care in the form of rigorous blood pressure control, use of renin-angiotensin system blockers in the maximum tolerated dose, and a focus on life-style modification that includes smoking cessation, weight management, and restriction of sodium intake. Ho­wever, supportive therapy does not always achieve its goals and cannot affect the autoimmune pathogenesis of the disease, while the role of immunosuppressants and systemic glucocorticoids remains controversial. This review presents an analysis of clinical trials and our own experience regarding the role of steroids and supportive therapy in the treatment of IgA nephropathy.

Research progress on Cornus officinalis and its active compounds in the treatment of diabetic nephropathy.

Diabetic nephropathy (DN) is a kidney disorder secondary to diabetes and is one of the main diabetic microvascular complications. As the number of diabetic patients grows, DN has become the leading cause of chronic kidney disease in China. Unfortunately, no definitive cure currently exists for DN. Cornus officinalis (CO), frequently utilized in clinical settings for diabetes mellitus treatment, has proven vital in both preventing and treating DN. This article explores the pathogenesis of DN and how CO and its active compounds regulate glucose and lipid metabolism, exhibit anti-inflammatory properties, inhibit oxidative stress, regulate podocytes, and manage autophagy. The mechanism and role of and its active compounds in the treatment of DN are discussed.

Elevated serum trimethylamine oxide levels as potential biomarker for diabetic kidney disease

Diabetic kidney disease (DKD) has become a major cause of chronic kidney disease. However, early diagnosis of DKD is challenging. Trimethylamine oxide (TMAO) is an intestinal microbial metabolite which might be associated with diabetes complications. The aim of this study was to investigate the correlation between TMAO and DKD. A cross-sectional study was conducted. 108 T2DM patients and 33 healthy subjects were enrolled in this study. Multiple logistic regression analysis and area under receiver operating characteristic curve (AUROC) were performed to evaluate the correlation between serum TMAO and DKD. Serum TMAO levels were significantly higher in DKD patients than healthy control group and the NDKD (T2DM without combined DKD) group (P < 0.05). TMAO levels were negatively correlated with eGFR and positively correlated with urea nitrogen, ACR and DKD (P < 0.05). Logistic regression analysis indicated that serum TMAO was one of the independent risk factors for DKD patients (P < 0.05). In the diagnostic model, the AUROC of TMAO for the diagnosis of DKD was 0.691. Elevated levels of serum TMAO levels were positively associated with the risk of DKD in T2DM patients, which might be a potential biomarker for DKD.

The pathogenic role of intestinal flora metabolites in diabetic nephropathy.

With the increasing incidence of diabetes, diabetic kidney disease has become a major cause of chronic kidney disease. The role of the gut microbiota in diabetes and its related complications have been extensively investigated; the modulatory effect of the gut microbiota on the host depends on several gut microbial metabolites, particularly short-chain fatty acids, secondary bile acids, and trimethylamine N-oxide. In this review, we focused on the evidence related to the pathogenic role of each of the gut microbial metabolites in diabetic nephropathy. The main novel therapies targeting the gut microbiota include probiotics, dietary prebiotics, synbiotic supplements, and faecal microbiota transplants, although there is no standard treatment principle. Further research is therefore needed to elucidate the link between gut microbes and diabetic nephropathy, and more therapeutic targets should be explored to treat diabetic nephropathy with dysbiosis of the gut microbes.

Treatment patterns of antidiabetic and kidney protective therapies among patients with type 2 diabetes mellitus and chronic kidney disease in Colombia. The KDICO descriptive study

BackgroundType 2 diabetes mellitus is one of the most common causes of chronic kidney disease (CKD) worldwide and prevalence of 1.75 per 100 inhabitants in Colombia. The aim of this study was to describe the treatment patterns of a group of patients with type 2 diabetes mellitus and CKD in an outpatient setting from Colombia.MethodsA cross-sectional study in adult patients with type 2 diabetes mellitus and CKD identified in the Audifarma S.A. administrative healthcare database between April 2019 and March 2020 was performed. Sociodemographic, clinical and pharmacological variables were considered and analyzed.ResultsA total of 14,722 patients with type 2 diabetes mellitus and CKD were identified, predominantly male (51%), with a mean age of 74.7 years. The most common treatment patterns of type 2 diabetes mellitus included the use of metformin monotherapy (20.5%), followed by the combination of metformin + dipeptidyl peptidase-4 inhibitor (13.4%). Regarding the use of drugs with nephroprotective properties, the most prescribed treatments were angiotensin receptor blockers (67.2%), angiotensin converting enzyme inhibitors (15.8%), sodium glucose cotransporter 2 inhibitors (SGLT2i) (17.0%) and glucagon-like peptide-1 analogs (GLP1a) (5.2%).ConclusionIn Colombia, the majority of patients with type 2 diabetes mellitus and CKD identified in this study were treated with antidiabetic and protective medications to ensure adequate metabolic, cardiovascular, and renal control. The management of type 2 diabetes mellitus and CKD may be improved if the beneficial properties of new groups of antidiabetics (SGLT2i, GLP1a), as well as novel mineralocorticoid receptor antagonists, are considered.

The Renoprotective Effect of Shikonin in a Rat Model of Diabetic Kidney Disease

In diabetes mellitus, diabetic nephropathy (DN) is a typical complication and pivotal cause of chronic kidney disease. The DN disease burden is among the highest in the world and is associated with high morbidity, mortality, and disease burden. Safe and effective medications are urgently needed for the treatment of DN. Interest has been increasing in Shikonin, extracted from the naphthoquinone plant, particularly in determining its renal protective effect. In this study, we explored Shikonin's effects and potential mechanisms on a streptozotocin (STZ)-induced DN experimental model. An STZ-induced rat diabetic model was established, and the rats were treated with different doses of Shikonin (10/50 mg/kg) for 4 weeks. Blood, urine, and renal tissue samples were collected after the last administration. Renal tissues were examined to detect each group's physiologic, biochemical, histopathologic, and molecular changes. The results showed that Shikonin administration could significantly alleviate the STZ-induced elevation of blood urea nitrogen, serum creatinine, urinary protein content, and renal pathologic injury. Furthermore, Shikonin significantly decreased oxidative stress, inflammation, and Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor-κB expression levels in DN kidney tissues. Shikonin showed a dose-dependent effect, with the best outcome at 50 mg/kg. Shikonin could effectively alleviate DN-related nephropathy damage and reveal the underlying pharmacologic mechanism. Based on the results, a Shikonin combination can be used in clinical treatment.

Evaluation of the parenchymal distribution of renal steatosis in chronic kidney disease using chemical shift magnetic resonance imaging.

Renal steatosis is an abnormal accumulation of fat in the kidney and may cause chronic kidney disease (CKD) or CKD progression. This pilot study aimed to evaluate the quantitative measurability of the parenchymal distribution of lipid deposition in the renal cortex and medulla using chemical shift magnetic resonance imaging (MRI) and investigate its relationship with clinical stages in CKD patients. The study groups included CKD patients with diabetes (CKD-d) (n = 42), CKD patients without diabetes (CKD-nd) (n = 31) and control subjects (n = 15), all of whom underwent a 1.5T MRI of the abdomen using the Dixon two-point method. The fat fraction (FF) values in the renal cortex and medulla were calculated from measurements made on Dixon sequences, and then compared between the groups. The cortical FF value was higher than the medullary FF value in control (0.057 (0.053-0.064) compared to 0.045 (0.039-0.052)), CKD-nd (0.066 (0.059-0.071) compared to 0.063 (0.054-0.071)), and CKD-d (0.081 (0.071-0.091) compared to 0.069 (0.061-0.077)) groups (all p < 0.001). The CKD-d group cortical FF values were higher than those of the CKD-nd group (p < 0.001). The FF values began increasing at CKD stages 2 and 3, and reached statistical significance at stages 4 and 5 in CKD patients (p < 0.001). Renal parenchymal lipid deposition can be quantified separately in the cortex and medulla using chemical shift MRI. Fat accumulation occurred in cortical and medullary parenchyma in CKD patients, though predominantly in the cortex. This accumulation increased proportionally with the disease stage.

IgA nephropathy associated with Crohn's disease.

The relationship between IgA nephropathy (IgAN) and Crohn's disease was reported. IgAN is the most common primary glomerulonephritis and one of the leading causes of chronic kidney disease and end-stage renal failure, and up to 50% of cases progressed to end-stage renal disease within 25 years after IgAN diagnosis. However, specific and effective therapeutic strategies are still lacking. In this review, we discuss the possibility of the mechanism involved in IgAN associated with Crohn's disease based on the findings of basic and clinical studies. Although the etiology of IgAN associated with Crohn's disease is not permanent and various factors are thought to be involved, the stabilization of the disease condition of Crohn's disease is believed to help treat IgAN.

423-P: Urinary Extracellular Vesicles in African Americans with Chronic Kidney Disease With and Without Type 2 Diabetes Mellitus

Introduction: Type 2 diabetes (T2D) is the leading cause for chronic kidney disease (CKD). Novel biomarkers are critical in early detection of CKD. Methods: Healthy Eatonville Project (HEP) was a prospective study (n=300, females (F)=71%, T2D 32%, CKD 25%) in historically black community of Eatonville, FL. We characterized EVtrap®-isolated urinary extracellular vesicles (uEV) proteins from a balanced HEP cohort of 48 African Americans (mean age 62y, F=73%, BMI 32.2 kg/m2, T2D 46%) with CKD risk ranging from low, intermediate, to high-very high (H-VH), with and without T2D. Differential expression and coexpression network analyses were implemented. Results: We detected 5265 uEV proteins, 46 of which were significantly (fold change&amp;gt;1.5, P&amp;lt;0.05, FDR&amp;lt;0.1) differentially expressed (DE) in CKD risk groups. Of those, 24 were significantly upregulated in H-VH risk CKD (Figure Module Pr.1). A set of 15 DE proteins appeared to represent a protective pathway against CKD (Figure Module Pr.2). Key biomarkers of acute kidney injury IGFBP7, TIMP2, and IL18 had significant negative correlations with CKD risk (-0.59 ≤ r ≤ -0.44, P&amp;lt;0.002). Supporting our findings, several of these biomarkers had been previously reported in kidney disease studies. Conclusion: The uEV proteomic landscape is representative of kidney pathophysiology and suggests potential biomarkers of CKD in Africans Americans. Disclosure T.K.Thethi: Other Relationship; Bayer Inc., Novo Nordisk. A.Bilal: None. M.S.Zaino: None. A.Iliuk: None. R.E.Pratley: Other Relationship; Bayer Inc., Corcept Therapeutics, Dexcom, Inc., Gasherbrum Bio, Inc., Hanmi Pharm. Co., Ltd., Hengrui (USA) Ltd., Merck Sharp &amp; Dohme Corp., Novo Nordisk, Pfizer Inc., Rivus Pharmaceuticals Inc., Sanofi, Scohia Pharma Inc., Sun Pharmaceutical Industries Ltd. Y.O.Nunez lopez: None.

Epidemiology And Risk Factors Of Chronic Kidney Disease In Rural Areas 4 (Badin) Of Sind, Pakistan.

To evaluate the epidemiology of chronic kidney disease in a rural setting. The retrospective study was conducted at Indus Hospital, Badin, Sindh, Pakistan, and comprised data of patients of either gender regardless of age who visited the nephrology clinic between July 2019 and July 2020. Data was retrieved from the institutional health management information system. Data was analysed using SPSS 21. Of the 348 patients, 184(52.9%) were males and 164(47.1%) were females. The overall mean age was 40.4±19 years. Obstructive nephropathy was the most frequent cause of chronic kidney disease 108(31%), followed by chronic kidney disease of unknown aetiology 79(22.7%). The most prevalent comorbid was hypertension in 106(30.5%) patients, while 56(16.1%) were diabetic. The stone disease was found in 90(24.6%) patients. Age was strongly associated with chronic kidney disease (p<0.001). Among those with chronic kidney disease of unknown aetiology, 35(44.3%) patients were aged 31-50 years 35. The expected glomerular filtration rate in such patients was significantly associated with the cause of chronic kidney disease (p<0.001). Unknown aetiology and kidney stones were the leading causes of chronic kidney disease among the rural population studied.

#6624 EFFICACY AND SAFETY OF GLP1 ANALOGUES IN ADVANCED CKD PATIENTS: A POTENTIAL STRATEGY FOR WEIGHT LOSS AND INCLUSION IN RENAL TRANSPLANT WAITING LIST

Abstract Background and Aims Diabetes mellitus (DM) is one of the main causes of chronic kidney disease (CKD) and the need for renal replacement therapy. New antidiabetic drugs such as glucagon-like peptide type 1 receptor analogues (aGLP1) improve glycemic control and cardiovascular risk and promote weight loss. Our main objective was to analyze the efficacy and safety of aGLP1 agonists in patients with advanced chronic kidney disease (ACKD). Method Prospective cohort study of CKD (estimated glomerular filtration rate (eGFR) ≤30 ml/min) and DM2 patients who started treatment with aGLP1 between April 2018 and November 2022. We analyzed clinical and demographic variables. We collected aGLP1 type and dose, eGFR and weight at baseline and after 6 and 12 months of treatment. We analyzed glycemic and lipid control and blood pressure (BP). We documented adverse effects. Descriptive analysis was performed and we compared eGFR before and after aGLP1 initiation. Results During the period 36 patients with ACKD started treatment with aGLP1 in our center, 30 with a minimum follow-up of 6 months. 66.7% were male and the mean age was 67. 88.9% were hypertensive and 91.7% dyslipidemic. 33.3% had a history of ischemic heart disease, 11.1% heart failure, 41.7% peripheral arterial disease and 8.3% stroke. The mean eGFR at drug initiation was 20.7 mL/min. The most frequent cause of CKD was diabetic nephropathy (66.7%) followed by glomerulonephritis (11.1%). Mean weight was 92.7±9.7 kg and BMI 33.15±3.2 kg/m2. The most prescribed aGLP1 was Semaglutide (83.4%) followed by Liraglutide (13.9%) and Dulaglutide (2.8%). Maximum drug dose was reached in 69.4% of patients. After initiation, eGFR remained stable at 6 months and 1 year (p = .424). We observed a 12% reduction in weight at one year after treatment (94Kg vS 83Kg; p&amp;lt;.001). We found no differences in glycosylated hemoglobin, lipid control and BP at 6th month and first year. Two patients suffered gastrointestinal adverse effects and one discontinued the drug because of this. One patient died during follow-up of independent cause. Conclusion aGLP1 in patients with ACKD are safe. Adverse effects do not occur more frequently than in the non-CKD population. In addition to improving cardiovascular risk of patients, they can produce a weight loss that can independently help patients to be included in the waiting list for renal transplantation.