Onset Of Renal Disease Research Articles

Provision of transplant education for patients starting dialysis: Disparities persist

BackgroundAll patients starting dialysis should be informed of kidney transplant as a renal replacement therapy option. Prior research has shown disparities in provision of this information. In this study, we aimed to identify patient sociodemographic and dialysis facility characteristics associated with not receiving transplant information at the time of dialysis initiation. We additionally sought to determine the association of receiving transplant information with waitlist and transplant outcomes. MethodsWe retrospectively analyzed CMS-2728 forms filed from 2007 to 2019. The primary outcome was report of provision of information about transplant on the Centers for Medicare and Medicaid Services Form CMS-2728. For patients not informed at the time of dialysis, we collected the reported reason for not being informed (medically unfit, declined information, unsuitable due to age, psychologically unfit, not assessed, or other). Cox proportional-hazards model estimates were used to study determinants of addition to the waitlist and transplant (secondary outcomes). ResultsFifteen percent of patients did not receive information about transplant (N = 133,414). Non-informed patients were more likely to be older, female, white, and on Medicare. Patients informed about transplant had a shorter time between end-stage renal disease onset and addition to the waitlist; they also spent a shorter time on the waitlist before receiving a transplant. Patients at chain dialysis facilities were more likely to receive information, but this did not translate into higher waitlist or transplant rates. Patients at independent facilities acquired by chains were more likely to be informed but less likely to be added to the waitlist post acquisition. ConclusionsDisparities continue to persist in providing information about transplant at initiation of dialysis. Patients who are not informed have reduced access to the transplant waitlist and transplant. Maximizing the number of patients informed could increase the number of patients referred to transplant centers, and ultimately transplanted. However, policy actions should account for differences in protocols stemming from facility ownership.

Protective Effect of Probiotic Against Progression of Chronic Kidney Disease: A Randomized Clinical Study

Abstract Background: Chronic kidney disease (CKD) is a gradual, irreversible disease with severe global health implications. By raising the level of urea toxins in the body, gut microbiota dysbiosis may hasten the onset of chronic renal disease. Probiotics have been recognized to keep the intestinal microbiota’s physiological equilibrium. In an effort to develop alternatives to chronic hemodialysis, much research has been carried out, especially for elderly patients who face psychological challenges. Objectives: The goal of this study is to assess the therapeutic benefits of probiotics on CKD patients. Materials and Methods: This randomized clinical trial was carried out at the Dialysis Center of Al-Diwaniyah Medical Hospital in Diwaniyah Governorate. Forty-two patients with end-stage renal disease on regular hemodialysis were enrolled, with 21 patients receiving oral probiotic supplementation in addition to standard care, and 21 patients receiving only standard care. Blood samples were collected at the baseline and after eight weeks, and several biomarkers were measured, including estimated glomerular filtration rate, creatinine, urea, phosphorus, albumin, and indoxyl sulfate. Results: The results showed that there was a significant difference in the mean difference of blood urea (P = 0.008) and serum phosphorus (P = 0.004) among groups, and the significant level was attributed to the probiotic group. However, the other biomarkers were not affected by the treatment. Conclusion: The use of oral probiotics for 8 weeks in Iraqi patients on hemodialysis can improve urea and phosphorus levels and safeguard the intestinal epithelial barrier in CKD patients.

#1305 Analysis of clinicopathological characteristics of membranous nephropathy with concomitant malignancy and literature review

Abstract Background and Aims In recent years, the incidence of membranous nephropathy (MN) with malignancy has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Method Patients diagnosed with renal biopsy-proven MN and comorbid malignancy detected within 5 years before and after MN diagnosis were included. The control group were diagnosed with renal biopsy-proven IMN with no malignancy and no other clear secondary cause for MN. We present a comprehensive analysis of MN with concomitant malignancy in our cohort and literature review. Results A total of 19 MN patients with concomitant malignancy were evaluated at our center; among them, 13 (68.4%) were male, and the median age was 57.0 (45.0, 69.0) years. Malignancy occurred after the onset of renal disease in 61.1% of patients, with digestive system malignancy (36.8%) ranking as the predominant type. 8 (8/11) patients achieved either PR or CR during the follow-up period. Most patients had pathology typical of IMN. IF showed strong positivity for IgG (100%), whereas only 13 (68.4%) patients were positive for C3. IEM showed electron-dense deposits predominantly located in subepithelial. Specific MN antigen staining of renal tissues from 19 patients showed that the highest percentage was 68.4% (13/19) for PLA2R-only positivity followed by 15.8% (3/19) for THSD7A-only positivity. Specific MN antigen staining of malignant tissue was performed in 5 patients whose tumor samples were available. Only 2 patients expressed the same antigen on kidney and tumor. Screening 17 articles encompassing a total of 21 patients in whom MN-specific antigen staining was performed on both renal and tumor tissues simultaneously. Among these patients, 71.4% (15/21) were male, with a median age of 61.0 years (56.3, 72.8). In this cohort, malignancy was diagnosed before or simultaneously with MN in 15 patients (75.0%), with digestive system malignancy constituting the most prevalent comorbid malignancy, at 33.3%. Notably, THSD7A accounted for the highest proportion of MN antigens, at 66.7% (14/21); among these patients, 78.6% (11/14) also exhibited positive tumor THSD7A staining. Of the 21 patients, 72.2% (13/18) achieved CR or PR. No significant difference between the baseline characteristics was observed between the 19 patients from our center and 21 patients documented in the literature. Therefore, the clinicopathological data of these 40 patients were pooled and compared with 101 IMN patients without malignancy at our center. Compared to patients without malignancy, MN patients with malignancy were older at the time of renal biopsy (P = 0.017), had a lower eGFR (P = 0.035) and demonstrated a lower rate of CR or PR after treatment (P < 0.001). The rate of PLA2R positivity in the glomeruli of MN patients with concomitant malignancy was significantly lower (40.0% vs. 92.1%, P < 0.001), while the rate of THSD7A positivity was significantly higher (42.5% vs. 2.0%, P < 0.001). Renal tissue IgG subclass staining showed that the rate of IgG4 positivity was significantly decreased compared with that in IMN patients (59.3% vs. 90.1%, P < 0.001), and the rate of IgG2 positivity was significantly increased (36.0% vs. 16.5%, P = 0.033). Conclusion To conclude, malignancy screening should be more actively performed for MN patients presenting with the above characteristics.

Dynamic rubidium-82 PET/CT as a novel tool for quantifying hemodynamic differences in renal blood flow using a one-tissue compartment model.

Assessing renal perfusion in-vivo is challenging and quantitative information regarding renal hemodynamics is hardly incorporated in medical decision-making while abnormal renal hemodynamics might play a crucial role in the onset and progression of renal disease. Combining physiological stimuli with rubidium-82 positron emission tomography/computed tomography (82Rb PET/CT) offers opportunities to test the kidney perfusion under various conditions. The aim of this study is: (1) to investigate the application of a one-tissue compartment model for measuring renal hemodynamics with dynamic 82Rb PET/CT imaging, and (2) to evaluate whether dynamic PET/CT is sensitive to detect differences in renal hemodynamics in stress conditions compared to resting state. A one-tissue compartment model for the kidney was applied to cardiac 82Rb PET/CT scans that were obtained for ischemia detection as part of clinical care. Retrospective data, collected from 17 patients undergoing dynamic myocardial 82Rb PET/CT imaging in rest, were used to evaluate various CT-based volumes of interest (VOIs) of the kidney. Subsequently, retrospective data, collected from 10 patients (five impaired kidney functions and five controls) undergoing dynamic myocardial 82Rb PET/CT imaging, were used to evaluate image-derived input functions (IDIFs), PET-based VOIs of the kidney, extraction fractions, and whether dynamic 82Rb PET/CT can measure renal hemodynamics differences using the renal blood flow (RBF) values in rest and after exposure to adenosine pharmacological stress. The delivery rate (K1) values showed no significant (p=0.14) difference between the mean standard deviation (SD) K1 values using one CT-based VOI and the use of two, three, and four CT-based VOIs, respectively 2.01(0.32), 1.90(0.40), 1.93(0.39), and 1.94(0.40) mL/min/mL. The ratio between RBF in rest and RBF in pharmacological stress for the controls were overall significantly lower compared to the impaired kidney function group for both PET-based delineation methods (region growing and iso-contouring), with the smallest median interquartile range (IQR) of 0.40(0.28-0.66) and 0.96(0.62-1.15), respectively (p<0.05). The K1 of the impaired kidney function group were close to 1.0mL/min/mL. This study demonstrated that obtaining renal K1 and RBF values using 82Rb PET/CT was feasible using a one-tissue compartment model. Applying iso-contouring as the PET-based VOI of the kidney and using AA as an IDIF is suggested for consideration in further studies. Dynamic 82Rb PET/CT imaging showed significant differences in renal hemodynamics in rest compared to when exposed to adenosine. This indicates that dynamic 82Rb PET/CT has potential to detect differences in renal hemodynamics in stress conditions compared to the resting state, and might be useful as a novel diagnostic tool for assessing renal perfusion.

Sex and Age Differentially Regulate Epigenetic Modifications and Renal Injury Markers in Mice

Elucidation of epigenetic mechanism associated with aging renal physiology may reveal potential biomarkers and therapeutic targets for reversing aging renal pathologies. There is a sex difference in the age of onset of renal and cardiac disease, where females are protected against age related changes, including hypertension and fibrosis, until menopause. We hypothesized that sex and age would differentially regulate epigenetic modifications and renal physiology. To test this hypothesis, we examined kidney tissue and serum from 4-month (4M), 12-month (12M), and 24-month (24M)-old male and female C57BL/6JN mice (National Institute of Aging). Renal histone deacetylase (HDAC) and histone acetyltransferase (HAT) activities (ELISA) were significantly higher in all male mice groups compared with age-matched females. However, HAT activity decreased significantly in 24M males compared with 4M males and exhibited sex differences with 24M males having higher (p &lt; 0.05) activity that 24M females. Levels of histone 3 (H3) acetylation at lysine (K) 9 and 27 and methylation at K9 were comparable in all male and female groups. Nonetheless, age and sex differences were observed in H3K27 methylation levels with 24M males having significantly higher (p &lt; 0.05) levels as compared with 24M female mice. Serum creatinine (sCr) levels exhibited significant interaction between age and sex (p &lt; 0.0001). Aging significantly increased sCr levels in 24M mice compared with 4M mice in both sexes. However, sex-differences were evident in sCr levels with 24M female mice having higher levels compared with their age matched male counterparts. Of note, serum levels of kidney injury molecule-1 (KIM-1), a tubule injury biomarker were significantly higher in 24M mice compared with 4M and 12M sex-matched mice (male 24M, 410.1 ± 94.6 vs. 12M, 53.6 ± 17.2 and 4M, 27.9 ± 2.0; pg/ml, p &lt; 0.001; female 24M, 358.3 ± 56.1 vs. 12M, 63.8 ± 13.3 and 4M, 28.2 ± 5.0; pg/ml, p &lt; 0.001). Histones are released in the extracellular space during disease state, act as damage-associated molecular pattern molecules and activate inflammatory pathways. In the serum, circulating histone H3 levels showed significant interaction with age and sex (p &lt; 0.05) and increased significantly with age in both sexes. The data demonstrate that aged female mice exhibited higher levels of serum Cr and KIM-1 whereas aged males have higher KIM-1 levels as compared to sex matched young mice. Sex differences were observed in HDAC and HAT activity with males having higher enzymatic activity as compared to females. These findings will have important implications in age-related renal injury as aging is a primary risk factor for hypertension and related renal disease in men and women. Supported by the NIH grant R03AG075396. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Assessment of mental health and impact of patient counselling on quality of life of dialysis patients

Chronic renal disease patients undergoing hemodialysis may face several problems that increase their chance of developing psychological suffering as hemodialysis is a time-consuming process. This study was conducted to assess the prevalence of psychiatric illness and to evaluate the impact of patient counselling on the quality of life. A total of 135 patients undergoing hemodialysis for more than 3 months were enrolled in the study. Patients who were exposed to hospitalization, recent trauma, or major surgeries, and who were on antipsychotic drugs before onset of renal disease were excluded. The Depression, Anxiety, and Stress Scale was used to assess the prevalence and level of depression, anxiety, and stress in hemodialysis patients. From the study population, 62.9% of patients had depression, 39.2% had stress, and 22.2% had anxiety. The patients with depression, anxiety, and stress had worse scores on all domains of the QoL questionnaire. Depression, anxiety, and stress were negatively correlated with quality of life.

Global attention based GNN with Bayesian collaborative learning for glomerular lesion recognition

Background:Glomerular lesions reflect the onset and progression of renal disease. Pathological diagnoses are widely regarded as the definitive method for recognizing these lesions, as the deviations in histopathological structures closely correlate with impairments in renal function. Methods:Deep learning plays a crucial role in streamlining the laborious, challenging, and subjective task of recognizing glomerular lesions by pathologists. However, the current methods treat pathology images as data in regular Euclidean space, limiting their ability to efficiently represent the complex local features and global connections. In response to this challenge, this paper proposes a graph neural network (GNN) that utilizes global attention pooling (GAP) to more effectively extract high-level semantic features from glomerular images. The model incorporates Bayesian collaborative learning (BCL), enhancing node feature fine-tuning and fusion during training. In addition, this paper adds a soft classification head to mitigate the semantic ambiguity associated with a purely hard classification. Results:This paper conducted extensive experiments on four glomerular datasets, comprising a total of 491 whole slide images (WSIs) and 9030 images. The results demonstrate that the proposed model achieves impressive F1 scores of 81.37%, 90.12%, 87.72%, and 98.68% on four private datasets for glomerular lesion recognition. These scores surpass the performance of the other models used for comparison. Furthermore, this paper employed a publicly available BReAst Carcinoma Subtyping (BRACS) dataset with an 85.61% F1 score to further prove the superiority of the proposed model. Conclusion:The proposed model not only facilitates precise recognition of glomerular lesions but also serves as a potent tool for diagnosing kidney diseases effectively. Furthermore, the framework and training methodology of the GNN can be adeptly applied to address various pathology image classification challenges.

Primary hyperoxaluria: Description of a new oral finding and review of literature.

Oro-dental manifestations of hyperoxaluria and dental management of affected patients are rarely reported in the literature. We describe a new oral presentation of primary hyperoxaluria (PH) and review relevant literature about oro-dental manifestations and management of dental complications of hyperoxaluria. A case report of a 44-year-old female who presented with symptoms of temporomandibular joint dysfunction due to hyperoxaluria was described according to the CARE guidelines. In addition, an extensive search of biomedical databases (PubMed, Medline, Google Scholar, and Embase) for articles describing oro-dental manifestations and/or dental management in patients with hyperoxaluria was performed using the key words ("oral" and/or "hyperoxaluria" and/or "dental" and/or "oxalosis"). Included articles were reviewed and data about patient demographics, disease type and stage, oral and dental manifestations, and dental treatment outcome were retrieved and analyzed. A total of 14 articles describing the oral and dental manifestations in 15 patients with hyperoxaluria were included. Tooth mobility, root resorption, and radiographic alterations were consistently described in all cases. Oral manifestations were described mainly in PH at late stages, and only after the onset of chronic renal disease. Dental management in all reported cases was palliative and aimed to relive pain and treat periodontal infection. Tooth loss due to extraction or uncontrolled mobility was the ultimate outcome in almost all reported cases. Oral and dental manifestations in hyperoxaluria are rarely reported in the literature. Management of tooth mobility and root resorption in hyperoxaluria is challenging and clinical guidelines and evidence-based recommendations are lacking. Early diagnosis and treatment of hyperoxaluria might be the only effective approach to prevent dental and periodontal complications of the disease.

Diagnosis of Chronic Kidney Disease Using Machine Learning Algorithm

A large percentage of people globally suffer from chronic kidney disease (CKD), a serious health concern. Effective diagnosis, treatment, and referral of CKD depend heavily on early identification and prediction of the disease. However, it is difficult to evaluate and derive significant insights from health data due to its vast and complicated nature. Engineers and medical researchers are using data mining techniques and machine learning algorithms to create predictive models for chronic kidney disease (CKD) in an effort to address this issue. The goal of this research is to create and validate predictive models for chronic kidney disease (CKD) based on a variety of clinical factors, including albuminuria, age, diet, eGFR, and pre-existing medical problems. The objective is to estimate the likelihood of renal failure, which may necessitate kidney dialysis or a transplant, and to evaluate the degree of kidney disease. With the use of this knowledge, patients and healthcare providers should be able to make well-informed decisions about diagnosis, treatment, and lifestyle changes. Patterns in the gathered data can be found, and future incidence of CKD or other related diseases can be predicted, by utilising MLT such as ANN and data mining techniques. Finding novel characteristics linked to the onset of renal disease and adding more trustworthy data from CKD patients. The best algorithm to categorise the data as CKD or NOT_CKD is chosen throughout the design process, and the data is then classified according to this differentiation. Estimated glomerular filtration rate (eGFR), which offers important details about the patient's current kidney function, is used to classify cases of chronic kidney disease. By combining complete patient data with machine learning algorithms, this research advances the diagnosis of chronic kidney disease (CKD) and improves patient outcomes.

Errata: Volume 10; Issue 4, 2022

The following items published in the International Journal of Medical Students (IJMS) Volume 10, Issue 4 of 2022 were corrected on February 20, 2023: "A Cross-Sectional Study of p66Shc Gene Expression in Liquid Biopsy of Diabetic Patients. Is it Possible to Predict the Onset of Renal Disease?" was corrected for capitalization errors in the title.1 "Elective Courses in Global Surgery for Undergraduate Medical Students: A Narrative Review and a Proposal for European Universities" contained an error in the DOI on the footer of page 395. The correct DOI is: 10.5195/ijms.2022.1598.2 "Why the Furor about Polio?" was corrected for a spacing error in the title in the PDF version.3 In the article entitled "Research Experience of Medical Students Collaborating in an International Peer Research Mentorship Program", there were errors in the fourth and fifth authors’ names. The correct names are: Aysha Zulfiqar and Tejaswini Ashok.4 "‘First, Do No Harm'… A Call to Re-evaluate the Wellbeing of Healthcare Staff" was corrected for a spacing error in the title.5

A Cross-Sectional Study of p66Shc Gene Expression in Liquid Biopsy of Diabetic Patients. Is it Possible to Predict the Onset of Renal Disease?

Background: Diabetic nephropathy (DN) is a disorder affecting glomerular function that, histologically, is due to the presence of glomerulosclerosis accompanied with endothelial dysfunction of the afferent and efferent renal arterioles. Insulin resistance in diabetic patients is known to be one of the causes of endothelial dysfunction because it increases oxidative stress, and one of the main genes regulating the production pathways of reactive oxygen species is p66Shc. The aim of this study was to evaluate the p66Shc gene expression as a precocious biomarker of renal dysfunction in diabetic patients, using liquids samples of urine sediment and peripheral blood. Methods: 29 diabetic patients and 37 healthy donors were recruited from the Centro Universitário FMABC outpatient clinic. The RT-gPCR technique was applied to evaluate p66Shc gene expression in urine and peripheral blood samples from diabetic patients, which were compared with healthy donors. Results: There was no significant expression of p66Shc gene in samples from diabetic patients compared with healthy donors. However, p66Shc expression in the blood samples of diabetics (0.02417±0.078652-ΔCT, n=29) was 3.6 times higher than in healthy participants (0.00689±0.01758, n=37) while in the urine samples, it was 1.48 times higher in diabetics group (0.02761±0.05412-ΔCT) than in CTL group (0.0186±0.02199). Conclusion: There was no significant p66Shc gene expression in peripheral blood and urine samples of diabetic patients without kidney injury compared with healthy donors, although there is a tendency for this gene to participate in the oxidative imbalance present in diabetes.

An ecological study regarding the association between paraquat exposure and end stage renal disease

BackgroundPersons who experience paraquat poisoning rapidly develop damage to a variety of organ systems including acute kidney injury (AKI), the occurrence of which is associated with an increased risk of death. However, little is known about the effects of chronic paraquat exposure on renal function and the onset of chronic renal disease. The objective of the current study is to assess the association between paraquat exposure and the incidence of end stage renal disease (ESRD) in the United States.MethodsData on the incidence of ESRD for the period 2010 through 2017 and kilograms of paraquat use per square mile for each county in the conterminous United States was obtained from the United States Renal Data System (USRDS) and the National Water Quality Assessment (NAWQA) Program, respectively. Negative binomial regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for the association between quartiles of paraquat exposure and the incidence of ESRD.ResultsThe incidence of ESRD increased with increasing paraquat density. Based on a 20-year exposure lag, those in the highest paraquat density quartile had a 21% higher rate of ESRD compared to the lowest quartile whereas for a 15-year lag the increase was 26%. Adjusted associations were attenuated though still followed an increasing linear trend across quintiles.ConclusionsThe results of this study are consistent with a large number of studies documenting a high incidence of AKI and a small number of studies chronic renal disease following acute and chronic paraquat exposure, respectively. While the pathophysiological mechanisms underlying kidney injury following paraquat poisoning are well understood, more research is necessary to understand the natural history of chronic kidney disease due to chronic paraquat exposure.

Overexpression of Human TLR8 Causes Fatal Anemia in SLE-Prone Mice By Altering the Bone Marrow Erythropoietic Niche

Anemia is a common hematologic abnormality in patients with active systemic lupus erythematosus (SLE), a disease characterized by innate immune system activation by nucleic acid containing immune complexes and cell debris. Work in mouse models has shown that overactivation of several cytoplasmic innate immune sensors by either self-DNA or self-RNA specifically leads to erythroid cell death in the fetal liver while sparing other hematopoietic cell lineages.The endosomal receptors TLR7 and TLR8 both recognize ssRNA in humans. TLR7 overexpression in mice causes a lupus syndrome that includes the development of mild to moderate anemia (Hb >10) and thrombocytopenia and is associated with spleen histiocytosis, autoimmune hemolysis, erythrophagocytosis and compensatory stress erythropoiesis in the spleen. A recent study demonstrated that patients with TLR8 gain of function mutations present with immunodeficiency, inflammation and bone marrow failure. However the role of TLR8 in SLE has been difficult to study in mice because it has a 5 amino acid deletion that attenuates its RNA binding capacity.To address the role of TLR8 in SLE, we overexpressed human TLR8 in a lupus mouse model (huTLR8tg.Sle1.Yaa) using a BAC transgene. 50% of homozygous huTLR8tg.Sle1.Yaa mice developed severe anemia (Hb<9) resulting in early mortality starting at 3-4.5 months of age. This phenotype required both the Sle1 and Yaa loci that promote the formation of high titer anti-chromatin and anti-RNA antibodies and onset of nephritis at >6 months of age. There was no difference in autoantibody titers between Sle1.Yaa wt and huTLR8tg mice and early death was not due to premature onset of renal disease. All mice had normal RBC indices prior to 10 weeks of age. Anemia was associated with an increase in bone marrow (BM) trabecular bone and a decrease in erythroblastic islands (EBI) in the BM with compensatory stress erythropoiesis leading to reticulocytosis and vast splenomegaly. RBC half-life was normal even after the development of reticulocytosis, but decreased in severely anemic mice as a pre-terminal event. Using CFSE labeling of RBCs we showed that hemophagocytosis occurred in vivo as a result of expansion of phagocytic red pulp macrophages.Flow cytometry of BMs from transgenic mice showed normal erythroid progenitors but a block at the late CFU-E/early proerythroblast stage leading to overall decreased terminal erythroid differentiation. Single cell RNAseq of EBIs isolated from transgenic BMs confirmed the block in erythropoiesis. The erythroblast cluster proximal to the block had a signature of mitochondrial stress and decreased proliferation. Spleen EBIs from transgenic mice were characterized by a low frequency of early erythroblasts compared with BM EBIs. We found 6 related clusters of EBI central macrophages in the BMs of both wt and transgenic mice. In transgenic mice, most of these displayed an inflammatory and Type 1 IFN signature. One cluster (M2) expressed all the classical central macrophage phenotypic markers in wt mice but was characterized in transgenic mice by downregulation of multiple phagocytic receptors and a 5-fold decrease of VCAM1 expression. Loss of VCAM1 and downregulation of CD169 in central macrophages of transgenic BMs was confirmed by flow cytometry. By contrast spleen central macrophages from transgenic mice retained VCAM and CD169 expression.Together, these results suggest that failure of BM erythropoiesis in huTLR8 transgenic SLE.Yaa lupus-prone mice, in which the acquisition of anti-nucleic acid autoantibodies drives excess innate stimulus through TLR7 and huTLR8, is due to a block in differentiation from CFU-E to the early proerythroblast stage; this is associated with an inflammatory phenotype specifically in BM erythroblastic island central macrophages and down regulation of adhesion and phagocytic receptors. Stress erythropoiesis in the spleens is associated with vast expansion of red pulp macrophages with phagocytic properties and fatal anemia is associated with a decrease in red blood cell half-life, suggesting that excessive RBC phagocytosis, coupled with insufficient erythroblast progenitors, eventually exceeds the capability of stress erythropoiesis to replace the RBC mass. DisclosuresKalfa: Agios Pharmaceuticals, Inc.: Other: Steering Committee, Research Funding; FORMA Therapeutics, Inc: Research Funding. Paulson: Forma Therapeutics: Consultancy. Blanc: Keros Therapeutics, Inc.: Consultancy.

MP59-02 PURELY-OFF CLAMP VS ON-CLAMP IMPERATIVE MINIMALLY-INVASIVE PARTIAL NEPHRECTOMY: RESULTS OF A MULTI-INSTITUTIONAL COLLABORATIVE SERIES

MP59-02 PURELY-OFF CLAMP VS ON-CLAMP IMPERATIVE MINIMALLY-INVASIVE PARTIAL NEPHRECTOMY: RESULTS OF A MULTI-INSTITUTIONAL COLLABORATIVE SERIES

MO193EFFICACY AND SAFETY OF SINGLE DOSE RITUXIMAB IN STEROID-DEPENDENT OR FREQUENTLY RELAPSING MINIMAL CHANGE DISEASE IN A CHINESE MEDICAL CENTER

Abstract Background and Aims The purpose of our study was to evaluate efficacy and safety of single dose rituximab in steroid-dependent or frequently relapsing minimal change disease during one-year follow-up. Method Twenty patients with corticosteroid-dependent (n=12) or frequently relapsing (n=8) idiopathic minimal-change diseases were hospitalized between August 2018 and July 2019 in the tertiary hospital. They received a single-dose rituximab (1g) concomitantly with their corticosteroid and immunosuppressors. The side effects of RTX were also recorded. Results We included 20 patients (15 males and 5 females). The mean age of onset renal disease was 21±9 years old. The included patients were steroid dependent, of whom 8 patients were frequently relapse. All patients had been received steroid in the past. 14 patients had been treated with calcineurin inhibitors (n=13, 65%) or mycophenolate mofetil (n=1, 5%). The baseline serum albumin was 33±10g/L, and serum creatinine was 76±38μmol/L, and 24-hour urine protein was 0.22 (0.06, 6.07) g/d. B-cell depletion (CD19+B cell&amp;lt;5/μL) was achieved after RTX infusion within one week. The average frequency of administered RTX was 1.47 times per person per year. We observed B cell reconstitution (CD19+B cell&amp;gt;20/μL) in 8 cases (35%) after the first dose of RTX. During follow-up (15.5±7.0 months), 19 patients achieved complete remission, while one patient was resistant to treatment. However, five relapse episodes were recorded during tapering steroids or after stopping steroids. Compared with the year before rituximab treatment, the per-patient average number of relapses decreased from 1.4±0.6 to 0.4±0.7 during 1 year of follow-up. After rituximab, the per-patient prednisone maintenance median dose decreased from 0.28 mg/kg (0.17, 0.46) to 0mg/kg (0, 0.07) (P&amp;lt;0.001). Furthermore, the mean estimated GFR was stable (from 117±26 to 120±17 ml/min per 1.73m2, P&amp;gt;0.05). There were three cases of mild infusion reaction (manifested as skin itching and rash) and two cases of infection (one case each of pneumocystis pneumonia and skin infection caused by actinomycetes). Conclusion Single-dose of RTX effectively prevented relapse and reduced the need for steroid in steroid-dependent or frequently relapsing minimal change disease.

Patient Outcomes Associated With Utilization of Education, Case Management, and Advanced Practice Pharmacy Services by American Indian and Alaska Native Peoples With Diabetes.

The burden of diabetes is exceptionally high among American Indian and Alaska Native (AI/AN) peoples. The Indian Health Service (IHS) and Tribal health programs provide education, case management, and advanced practice pharmacy (ECP) services for AI/ANs with diabetes to improve their health outcomes. The objective of this study was to evaluate patient outcomes associated with ECP use by AI/AN adults with diabetes. This observational study included the analysis of IHS data for fiscal years (FY) 2011-2013. Using propensity score models, we assessed FY2013 patient outcomes associated with FY2012 ECP use, controlling for FY2011 baseline characteristics. AI/AN adults with diabetes who used IHS and Tribal health services (n=28,578). We compared health status and hospital utilization outcomes for ECP users and nonusers. Among adults with diabetes, ECP users, compared with nonusers, had lower odds of high systolic blood pressure [odds ratio (OR)=0.85, P<0.001] and high low-density lipoprotein cholesterol (OR=0.89, P<0.01). Among adults with diabetes absent cardiovascular disease (CVD) at baseline, 3 or more ECP visits, compared with no visits, was associated with lower odds of CVD onset (OR=0.79, P<0.05). Among adults with diabetes and CVD, any ECP use was associated with lower odds of end-stage renal disease onset (OR=0.60, P<0.05). ECP users had lower odds of 1 or more hospitalizations (OR=0.80, P<0.001). Findings on positive patient outcomes associated with ECP use by adults with diabetes may inform IHS and Tribal policies, funding, and enhancements to ECP services to reduce disparities between AI/ANs and other populations in diabetes-related morbidity and mortality.

Association of platelet-to-lymphocyte ratio with kidney clinicopathologic features and renal outcomes in patients with diabetic kidney disease

BackgroundGrowing evidence points to the pivotal role of inflammation in the pathogenesis of diabetic kidney disease (DKD). However, as an inflammation-based prognostic score, the significance of platelet-to-lymphocyte ratio (PLR) in biopsy-proven DKD remains uncertain. Therefore, the current study aimed to evaluate the association of PLR with the clinicopathological features and the progression of DKD. MethodsIn total, 167 patients with biopsy-proven T2DKD were retrospectively recruited. Clinicopathological characteristics were compared according to the tertiles of baseline PLR. Pearson’s or Spearman correlations were used to examine the associations between PLR and baseline characteristics. Assessment of the prospective relationship of PLR with the kidney outcomes defined as a doubling of baseline serum creatinine or onset of end stage renal disease (ESRD), were investigated by Kaplan-Meier survival analysis. Moreover, a cubic spline curve was further calculated to explore the significance of PLR in DKD prognosis. On top of that, identification of the risk factors associated with DKD progression was executed by a model of Cox proportional hazards. ResultsMedian follow-up period was 23.77 months, during which 92 (55.1%) patients confronted DKD progression. Pearson’s correlation indicated that urinary protein increased along with PLR rising (r = 0.193, P = 0.012). Kaplan–Meier survival curves revealed a significantly increased probability of event-free survival in the lowest tertile of PLR compared to those in the highest tertile (P = 0.018). A statistical linear correlation between PLR and DKD development was demonstrated by a restricted cubic spline analysis (P for nonlinear = 0.784). In addition, the analyses of multivariate Cox regression indicated that elevated PLR had an association with a greater risk of DKD progression (HR 1.004, 95%CI [1.000–1.008], P = 0.035), which was verified to be an independent risk factor for renal outcomes. ConclusionsOur findings demonstrated that the PLR was associated with proteinuria and prognosis in DKD patients. It was an independent risk factor for kidney progression in biopsy-proven DKD.

Triglyceride as a Biomaker for Predicting Systemic Lupus Erythematosus With Kidney Injury

Backgroud: Kidney injury of systemic lupus erythematosus (SLE) contributes to major mortality of SLE. To explore biomarkers is necessary for diagnosing and supervising SLE-related kidney injury. However, few effective biomarkers can be used for it. Methods: Apriori algorithm of association rules was employed to identify laboratory biomarkers related to SLE-related kidney injury. Logistic regression analysis was conducted to identify its risk factors, and spearman correlation analysis was used to evaluate the correlation between biomarkers and disease activity of SLE-related kidney injury. Finding: Ten biomarkers were identified by association rule mining. Among them, triglyceride, lactic dehydrogenase and α-hydroxybutyrate dehydrogenase were significantly higher, and hemoglobin and hematocrit were significantly lower in the patients of SLE with kidney injury compared to that without kidney injury. Furthermore, triglyceride was an independent risk factor for SLE-related kidney injury. Triglyceride level was positively correlated with urine protein and P-CAST and it was negatively correlated with albumin and IgG. The area under the receiver operating characteristic analysis for triglyceride was 0.72 in SLE-related kidney injury. The cutoff value of triglyceride for diagnosing SLE-related kidney injury was 1.84mmol/L. In addition, higher levels of triglyceride were found at the time of onset of renal disease (p=0.048). Conclusion: Triglyceride may be a biomarker for diagnosing SLE-related kidney injury. Funding Statement: This work was supported by the National Nature Science Foundations of China (grant number 81960388), Longyuan Youth Innovation and Entrepreneurship Talents (grant number No. 9, 2020, Organization Department of Gansu Province). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: The study protocol was approved by the Research Ethics Committee of the First Hospital of Lanzhou University (No. LDYYLL201731).

Outcome of biopsy-proven lupus nephritis with low glomerular filtration rate at presentation.

Currently, there is limited data regarding the outcomes of lupus nephritis (LN) with moderate to severe renal failure at presentation (defined by low glomerular filtration rate; GFR <30mL/min). Sixty-four patients with biopsy-proven LN and estimated GFR (eGFR) <30mL/min were prospectively analyzed. Outcome measure of persistently low eGFR, end-stage renal disease (ESRD) or death at 365days were grouped as Major Adverse Kidney Events (MAKE365). Diagnosis of lupus was simultaneous with onset of renal disease in 60% of cases. Histologically, 82.3% (n=51) were class IV, the median serum creatinine was 4mg/dL (interquartile range [IQR] 3.1-5.9mg/dL), median eGFR was 13.75mL/min (IQR 9.25-19mL/min) and 42.2% (n=27) required dialysis at presentation. Induction regimens included National Institute of Health (68.2%), Eurolupus protocol (10.9%) and mycophenolate mofetil (8%). Over 365days, 23 (37.5%) subjects died, while 41 (62.5%) survived. The majority of deaths were due to infection and sepsis (14/23). Among the survivors, 70.7% had good renal outcome, 12.1% had persistently low GFR (<30mL/min), while 17% developed ESRD. In this group, treatment response rate was 84.6% (complete response 25.6%, partial response 59%). Those with a better renal function at presentation had a good treatment response (100% vs. 40%). Altogether, n=35 (54.6%) were included in the MAKE365 category. Between the renal survival group (n=29) versus the MAKE365 group (n=35) there was no difference in clinical or histological parameters. The current treatment protocols had a good response rate in patients with LN even with severe kidney injury at presentation. However, the risk of serious infections and subsequent mortality was high.

P0484CLINICAL FEATURES AND OUTCOME OF LUPUS NEPHRITIS IN MOROCCO: A SINGLE CENTER STUDY OF 207 CASES

Abstract Background and Aims renal involvement is a common and potentially severe complication of systemic lupus erythematosus (SLE). Few data for Lupus nephritis (LN) exist on North Africans, especially those from Morocco. The aim of our study was to report the long-term renal outcome of a cohort of Moroccan patients with LN. Methods the records of 207 patients (191 females, 16 males) with LN (American College of Rheumatology criteria) admitted to the departments of nephrology and internal medicine of Marrakesh University Hospital were reviewed and included in a retrospective analysis. Results the mean age at the time of renal biopsy was 31,7 ± 15,9 years. Time between diagnosis of SLE and the onset of renal disease was 29 ± 10 months. Renal involvement was observed concomitantly with the onset of SLE in 39 patients (18,8%). At presentation, 65 patients (31,4%) had hypertension. Hematuria was seen in 158 patients (76,3%), nephrotic syndrome in 82 patients ( 39,6%) and renal failure in 76 patients (36,7%). The most frequent extarenal manifestations were skin and joint manifestations in 89,3% and 83,6% respectively. The most common histological finding was type IV LN in 96 patients, followed by type III LN in 51 patients. 191patients (92,3%) received corticosteroids as initial therapy followed by immunosuppressive therapy in 127 patients (61,3%). During the follow-up period, partial or total remission was obtained in 56,5% of cases while 61 patients (29,4%) progressed to end stage renal disease (ESRD) and 29 patients (14%) died. Logistic regression detected that hypertension, high serum creatinine at admission and proliferative histological classes were the main risk factors for poor renal outcome. Conclusion Our results showed that LN was particularly severe in our population compared with other published data with predominance of proliferative forms.