Related Nephropathy Research Articles

The effect of uric acid and albumin ratio in undergoing lower extremity endovascular interventions for peripheral arterial disease related contrast induced nephropathy

Among patients undergoing percutaneous vascular intervention, contrast-induced nephropathy (CIN) is associated with increased morbidity and mortality. Serum uric acid/albumin ratio (UAR) has emerged as a new marker associated with poor cardiovascular outcomes. We aimed to evaluate the relationship between UAR and CIN occurrence in patients treated for peripheral artery disease. Patients underwent percutaneous intervention due to peripheral artery disease were enrolled. The primary endpoint was development of contrast related nephropathy. Patients were divided into 2 groups according to the CIN occurrence. A total of 663 patients were enrolled and mean age was 62±10years. After the intervention, 45 patients had CIN and 618 patients did not have CIN. Logistic regression analysis was performed to define the parameters of CIN. Male gender, diabetes, UAR, contrast volume, presence of coronary artery disease, and C-reactive protein levels were found significant in univariate analysis. However, only UAR was found significant in multivariate analysis (odds ratio 95% confidence interval: 3.426 (1.059-11.079), (P=0.040)).Therefore, it is the only independent predictor for occurrence of CIN. UAR is a reliable scoring system, which predicts CIN in such patient group. This score is not only cost-effective also simple, which can be easily applied into the clinical practice.

Glomerular Elasticity and Gene Expression Patterns Define Two Phases of Alport Nephropathy.

Early steps in glomerular injury are poorly understood in collagen IV nephropathies. We characterized structural, functional, and biophysical properties of glomerular capillaries and podocytes in Col4α3-/- mice and analyzed kidney cortex transcriptional profiles at various disease stages. We investigated the effects of TUDCA (suppresses ER stress) on these parameters and used human FSGS transcriptomic data to identify pathways rescued by TUDCA. In Col4α3-/- mice, podocyte injury develops by 3 months, with maximum glomerular deformability and 40% podocyte loss at 4 months. This period is followed is followed by glomerular capillary stiffening, proteinuria, reduced renal function, inflammatory infiltrates, and fibrosis. Bulk RNA sequencing at sequential time points revealed progressive increases in inflammatory and injury gene expression, and activation of the TNF pathway. Mapping Podocyte-enriched genes from FSGS patients to mice showed that TUDCA, which mitigated renal injury suppressed molecular pathways associated with podocyte stress, hypertrophy and tubulo-interstitial injury. Col4α3-/- nephropathy progresses in two phases. The first is characterized by podocytopathy, increased glomerular capillary deformability and accelerated podocyte loss, and the second by increased capillary wall stiffening and renal inflammatory and profibrotic pathway activation. The response of podocytes to TUDCA treatment provides insights into signaling pathways in Alport and related nephropathies.

#2336 Hepatitis-B virus related membranous nephropathy presenting as nephrotic syndrome treated with tenofovir

Abstract Background The prevalence of Hepatitis B virus (HBV) related nephropathy particularly membranous nephropathy follows geographic HBV prevalence patterns. Hepatitis B virus infection occurs throughout the world and is endemic in developing countries such as Africa, Eastern Europe, the Middle East, Central Asia, China, Southeast Asia, the Pacific islands and the Amazon basin of South America. Vertical transmission from mother to child often predominates in endemic areas. Membranous glomerulonephritis is the most common histological renal lesion associated with hepatitis B virus infection. Treatment options for renal patients with chronic HBV infection are complex, being dictated by the overall clinical picture and best conducted by multidisciplinary approach and thorough renal monitoring. Therapeutic guidelines are very limited, mostly case series are available in this setting. Anti-viral treatment is indicated in hepatitis B surface antigen (HBsAg)-positive patients with evidence of active liver disease based on aminotransferases and serum HBV DNA levels of 2000-20 000 IU/ml have been proposed as the threshold to start treatment Aim To present a case of young healthy male with chronic HBV infection with nephrotic syndrome and Membranous Nephropathy who developed reactivation after discontinuation of Tenofovir. Case A 32-year old man presented with generalized edema 5 months ago associated with dipstick proteinuria. The swelling has progressed and now associated with walking difficulty thus sought consult and was then admitted. His mother had been hypertensive for more than a decade and work up revealed that she is positive for anti-HBS and negative for HBsAg. His father is negative for HBsAg. His childhood and past medical history is unremarkable. He is a non-smoker, non alcoholic and no history of illicit drug use. He is monogamous and not promiscuous. He has 6 siblings and two of his brothers are hypertensives and found to have chronic Hepatitis B infection. His complement levels were low, ANA and ASO titers were negative. His creatinine was 1.06 mg/dl, BUN- 11.77 mg/dl, SGPT-161 U/L (NV: < 42 U/L), albumin- 1.50 g/dl (NV: 3.5-5.0 g/dl). Total cholesterol- 443.30 mg/dl, Triglycerides 330.46 mg/dl. Urine PCR-4,369 mg/g. Hepatitis profile revealed reactive for HBsAg and HBeAg. His HBV viral load was 170 000 000 IU/ml (989 400 000 copies/ml). His HIV screening was negative. A kidney biopsy was performed which revealed Membranous Glomerulonephritis. He was given Tenofovir 300 mg daily for 6 months. His repeat HBV viral load was < 20 IU/ml (< 116 copies/ml) and his 24 h urinary protein was 1,891 mg/24H. His albumin was 4.57 g/dl and his creatinine remained stable at 0.96 mg/dl while his SGPT went back to normal at 40 U/L. A repeat HBeAg revealed 0.55 which could be a possible seroconversion. Tenofovir was discontinued for 6 months however patient came back with persistent proteinuria associated with high HBV DNA titer. A repeat 24H-urine protein showed 1,182 mg/24H. Tenofovir was resumed and Enalapril was continued. Follow up check up 3 months after revealed urine PCR was 850 mg/g and his kidney function remained stable. He is advised to continue Tenofovir with frequent follow up until he becomes HBsAg-negative. Recommendation We recommend that antiviral treatment in this subset of population requires prolong treatment until persistent seroconversion of HBeAg and persistent undetectable HBV DNA level or have lost HBsAg even if the patient does not develop hepatitis B surface antibody. This recommendation of prolong treatment are still developing and requires further investigation.

WCN24-1802 Outcomes in patients with anticoagulant related nephropathy: from bad to worse

WCN24-1802 Outcomes in patients with anticoagulant related nephropathy: from bad to worse

Clinicopathological characteristics and outcomes of PLA2R related idiopathic membranous nephropathy in patients with seronegative PLA2R antibodies

Background Idiopathic membranous nephropathy (IMN) with deposits of phospholipase A2 receptor (PLA2R) antigen in glomerular tissue (GAg+) but no circulating serum PLA2R antibody (SAb−) has been reported. However, little is known about the clinicopathological characteristics and prognosis of this subtype. Methods A total of 74 IMN patients with GAg + identified by kidney biopsy were enrolled in this study. We categorized patients into two groups based on the presence or absence of serum PLA2R antibody. Data on clinical features, pathological features, and outcomes were collected. Kaplan–Meier analysis of complete remission (CR) and partial remission (PR) comparing SAb−/GAg + and SAb+/GAg + patients. Cox proportional hazards models was used to examine factors associated with CR and PR. Results Among 74 IMN patients, 14 were SAb−/GAg+. Compared with SAb+/GAg + patients, SAb−/GAg + patients presented with higher levels of albumin, lower levels of cholesterol and low density lipoprotein cholesterol (all p < .01), but similar pathological manifestations of kidney biopsy. Multivariate logistic analyses indicated that low albumin (0.79 [95%CI: 0.66–0.95], p = .01) and high cholesterol (1.81 [95%CI: 1.02–3.19], p = .04) were correlated with seropositivity of PLA2R antibody. SAb−/GAg + patients exhibited a significantly higher probability of CR (p = .03) than patients who were SAb+/GAg+. However, no difference was found in the PR rate. Cox regression analyses showed that compared to SAb+/GAg + patients, SAb−/GAg + was more predictive of complete remission (4.28 [95%CI: 1.01–18.17], p = .04). Conclusion IMN with PLA2R staining on kidney biopsy but without serum PLA2R antibody has milder clinical manifestations and a better prognosis.

Role of plasminogen activated inhibitor-1 in the pathogenesis of anticoagulant related nephropathy.

Anticoagulant related nephropathy (ARN) is the result of glomerular hemorrhage in patients on systemic anticoagulation therapy or underlying coagulopathy. Red blood cells (RBC) that passed through the glomerular filtration barrier form RBC casts in the tubules, increase oxidative stress and result in acute tubular necrosis (ATN). The mechanisms of ARN still not completely discovered. Plasminogen activator inhibitor-1 (PAI-1) plays a significant role in the maintenance of coagulation homeostasis. We developed an animal model to study ARN in 5/6 nephrectomy (5/6NE) rats. The aim of this study was to elucidate the role of PAI-1 in the ARN pathogenesis. 5/6NE rats were treated per os with warfarin (0.75 mg/kg/day) or dabigatran (150 mg/kg/day) alone or in combination with PAI-1 antagonist TM5441 (2.5, 5.0 and 10 mg/kg/day). TM5441 in a dose dependent manner ameliorated anticoagulant-induced increase in serum creatinine in 5/6NE rats. Anticoagulant-associated increase in hematuria was no affected by TM5441. The levels of reactive oxygen species (ROS) in the kidneys were in a dose-dependent manner decreased in 5/6NE rats treated with an anticoagulant and TM5441. Our data demonstrates that PAI-1 may reduce ARN by decreasing ROS in the kidneys. Glomerular hemorrhage is not affected by anti-PAI-1 treatment. These findings indicate that while symptoms of ARN can be reduced by PAI-1 inhibition, the main pathogenesis of ARN - glomerular hemorrhage - cannot be prevented.

IL-33/ST2L signaling alleviates diabetic nephropathy by regulating endoplasmic reticulum stress and apoptosis

ObjectiveDiabetic nephropathy (DN) is a serious chronic complication of diabetes mellitus (DM). Endoplasmic reticulum (ER) stress is an important factor in the regulation of pathological processes in DN, and excessive ER stress can lead to apoptosis. Although the IL-33/ST2 axis is known to be involved in diabetic kidney disease or related nephropathy, its role and molecular mechanisms remain poorly understood in terms of DN. The purpose of this study was to investigate the effects of IL-33/ST2 signaling on DN and to characterize the roles that ER stress and apoptosis play in DN.MethodsTo investigate this study, mice were randomly assigned into DN (induced by 0.1% STZ) and Control groups. Biochemical indices (FBG, BUN, UPR, UCE) were measured in serum and urine samples to reflect blood glucose and kidney damage. Quantitative real-time PCR, western blot, and immunofluorescence were used to assess gene and protein expression of the IL-33/ST2 axis and ER stress relative signaling molecule. Apoptosis was analyzed by flow cytometry.ResultsIL-33 levels are significantly increased in the kidneys of patients and mice with DN. Double immunofluorescence staining showed that IL-33 colocalized with CD31-positive endothelial cells. Treatment with IL-33 attenuated kidney injury in Streptozotocin (STZ)-treated mice. In vitro, we showed that IL-33 attenuated ER stress and apoptosis in glomerular endothelial cells. However, sST2 treatment significantly reversed these effects of IL-33.ConclusionTogether, these data suggest that IL-33/ST2 signaling mitigates STZ-induced renal damage, partly at least, by suppressing ER stress and apoptosis. Therefore, IL-33 may be an effective therapeutic target in DN.

Epigenetic roles in clonal hematopoiesis and aging kidney-related chronic kidney disease.

Accumulation of somatic hematopoietic stem cell mutations with aging has been revealed by the recent genome-wide analysis. Clonal expansion, known as clonal hematopoiesis of indeterminate potential (CHIP), is a premalignant condition of hematological cancers. It is defined as the absence of definitive morphological evidence of a hematological neoplasm and occurrence of ≥2% of mutant allele fraction in the peripheral blood. In CHIP, the most frequently mutated genes are epigenetic regulators such as DNMT3A, TET2, and ASXL1. CHIP induces inflammation. CHIP is shown to be associated with not only hematological malignancy but also non-malignant disorders such as atherosclerosis, cardiovascular diseases and chronic liver disease. In addition, recent several large clinical trials have shown that CHIP is also the risk factor for developing chronic kidney disease (CKD). In this review article, we proposed novel findings about CHIP and CHIP related kidney disease based on the recent basic and clinical research. The possible mechanism of the kidney injury in CHIP is supposed to be due to the clonal expansion in both myeloid and lymphoid cell lines. In myeloid cell lines, the mutated macrophages increase the inflammatory cytokine level and induce chronic inflammation. It leads to epigenetic downregulation of kidney and macrophage klotho level. In lymphoid cell lines, CHIP might be related to monoclonal gammopathy of renal significance (MGRS). It describes any B cell or plasma cell clonal disorder that does not fulfill the criteria for cancer yet produces a nephrotoxic monoclonal immunoglobulin that leads to kidney injury or disease. MGRS causes M-protein related nephropathy frequently observed among aged CKD patients. It is important to consider the CHIP-related complications such as hematological malignancy, cardiovascular diseases and metabolic disorders in managing the elderly CKD patients. There are no established therapies for CHIP and CHIP-related CKD yet. However, recent studies have supported the development of effective CHIP therapies, such as blocking the expansion of aberrant HSCs and inhibiting chronic inflammation. In addition, drugs targeting the epigenetic regulation of Klotho in the kidney and macrophages might be therapeutic targets of CHIP in the kidney.

#5788 MONOCLONAL GAMMOPATHY OF RENAL SIGNIFICANCE: A SINGLE CENTER EXPERIENCE

Abstract Background and Aims Monoclonal gammopathy of renal significance is an organ-threatening manifestation of paraproteinemia. It can be secondary to the clonal proliferation of either plasma cells or mature B-lymphocytes. The underlying clonal disorder does not meet the current hematologic criteria for immediate myeloma-specific therapy. With the advent of routine use of light chain detection by immunofluroscence technique in tissue biopsy, more cases of monoclonal gammopathy of renal significance are being diagnosed but there remains a therapeutic uncertainty. Data regarding the prognosis and outcomes of the various clinical manifestations of monoclonal gammopathy of renal significance is limited due to its rarity and under diagnosis. MGRS if left untreated can lead to end-stage renal disease and premature death. Method This is a retrospective study conducted at the Institute of Nephro-urology, Bangalore by retrieving the data from the digital medical records of our institute. Demographic and clinical details of the patients diagnosed with monoclonal gammopathy of renal significance from 1 st January 2018 to 31 st October 2022 were collected. Myeloma related light chain cast nephropathy was excluded from the study. Follow-up data were collected usingout patient data base, through telephone, and from the records at the cancer institute where the patient was referred post-diagnosis at our institute. The data collected was entered in excel and analyzed using SPSS software version 27.0. Results Fifty eight patients (n = 52) were diagnosed with the disease during the study period. MGRS contributed to 1.27% of all the renal biopsies conducted at our institute during the study period. The mean age of the study population was 52.1 with 95% CI [48.5 to 55.6] with a male: female ratio of 1.36:1 and 36.5% (n = 19) ofstudy cohort aged above 60 years. Among clinical presentations CKD (n = 23) was the main clinical presentation followed by AKI, Nephrotic syndrome, Nephritic syndrome and RPGN as the other presentations. Dialysis requirement was noted in 35% at initial presentation. Most common histiopathological presentation was Amyloidosis (n = 15) followed by Light chain deposition disease LCDD (n = 14), monoclonal non-amyloid deposition disease NADD (n = 6), Light chain proximal tubulopathy LCPT (n = 5), Proliferative glomerulonephritis with monoclonal immunoglobulin deposition disease PGNMIDD (n = 9) and others (n = 3). The patient survival at the time of analysis was 22.7% and death censored renal survival was 80%. Conclusion MGRS contributed to 1.27% of all the renal biopsies conducted at our institute during the study period. Because of its variable clincal presentation,one needs high degree of clinical suspicion for early diagnosis. MGRS unlike MGUS carries significant morbidity and mortality.

#4044 FOCAL SEGMENTAL GLOMERULOSCLEROSIS DUE TO A3243G POINT MUTATION IN THE MTDNA CODING FOR TRNALEU(UUR)

Abstract Background and Aims Mitochondrial Diseases represent a heterogeneous set of maternally inherited diseases that arise by mutations either of the mitochondrial DNA (mtDNA) or in genes of nuclear DNA (nDNA) linked to the cell mitochondrial cross-talk. Many mutations in mtDNA that code for different genes are linked to a wide spectrum of kidney manifestations ranging from focal segmental glomerulosclerosis (FSGS), tubule-interstitial disease (TIN), nephrotic syndrome (NS), and proximal or distal tubulopathy. Renal manifestations of mtDNA disorders are poorly recognized in clinical practice and often misdiagnosed for other conditions like FSGS, Alport Syndrome, steroid-resistant nephrotic syndrome. The guanine for adenine point mutation (A–&amp;gt;G) at position 3243 in the mtDNA has emerged as the most common mutation found in patient with FSGS often accompained by diabetes mellitus and deafness. Focal Segmental Glomerulosclerosis, (FSGS) is the prevalent histologic finding in patients with mtDNA point mutations. Epidemiologic studies have shown that about 1% of diabetic populations in Europe and Japan have this mutation. Method A 34-year-old man presented for evaluation with recently diagnosed Type II diabetes mellitus and serum creatinine of 3.9 mg/dL with nephrotic range proteinuria (3.2 gr/die). His family history included Type II diabetes mellitus, chronic kidney disease, coronary artery disease, and hypertension. The patient medical history included hypertension, dyslipidemia, and sensorineural hearing loss which had initially developed during adolescence. Serum creatinine was reportedly elevated years before this presentation, and urinalysis showed mild proteinuria with no microhematuria, white cells, or casts. Results On evaluation his blood pressure was 150/90 mmHg, presented mild peripheral leg edema. Laboratory results showed serum creatinine 3.4 mg/dl (eGFR 23 ml/min), HbA1c of 7.2%, albumin 2.8 gr/dL. Urinalysis showed protein (3+), glucose (+1) and no hematuria. Urinary protein-creatinine ratio was 3 mg/g. Serum C3 and C4, immunoglobulins, liver enzymes were normal; autoimmunity tested negative (ANCA, Anti-PLA2r, Anti nuclear antobodies). A kidney biopsy was performed. Light microscopy revealed glomeruli with segmental obliteration of glomerular capillaries by collagenous sclerosis (Fig. 1). Both the Jones methenamine silver stain and Masson's trichrome stain (Fig. 1B, C) showed segmental collagen deposition and sclerosis of glomerular capillaries. Tubular atrophy and fibrosis were also present. Immunofluorescence microscopy was negative. A diagnosis of not otherwise specified focal segmental glomerulosclerosis (NOS FSGS) was made. Interestingly electron microscopy showed mitochondrial abnormalities in the tubular cells. In particular, the cytoplasm of a tubular cell appears to be whiffed by mitochondria of enlarged size and altered shape (Fig. 2). Mithocondria appeared dysmorphic with extensive reduction of mitochondrial cristae (Fig. 2 arrows). The patient was screened for mtDNA mutations and guanine for adenine substitution (A–&amp;gt;G) at position 3243 was detected. The patient received a diagnosis of chronic kidney disease with histological features of FSGS due to an A3243G point mutation in the mtDNA with associated diabetes mellitus and sensorineural deafness. Conclusion This case underscores the role of electron microscopy in identifying mithocondrial related nephropathies. Even more important is to evaluate mtDNA mutations in cases with familial FSGS, sensorineural hearing loss, cardiomyopathy and diabetes.

Pathophysiology and clinical manifestations of immune complex vasculitides.

Immune complex (IC) vasculitides present inflammations of vessel walls associated with perivascular deposition of immunoglobulins (Igs), mostly ICs. They encompass systemic and skin-limited variants of IgA vasculitis (IgAV), cryoglobulinemic vasculitis (CV), rheumatoid, lupus, and hypocomplementemic vasculitides, serum sickness cutaneous IgM/IgG (non-IgA) vasculitis, and recurrent macular (hypergammaglobulinemic or exertion-induced) vasculitis. Serum sickness and CV fulfill the criteria of a type III hypersensitivity immune reaction as large lattices of the IC precipitate at vessel walls and activate polymorphonuclear neutrophils (PMNs). Immunoglobulin-A vasculitis differs with regard to the causes of perivascular deposition of ICs since here many IgA1 molecules are hypoglycosylated (Gd-IgA1), which appears to facilitate their perivascular deposition in skin and mesangium (via e.g. CD71). The reasons for increased generation of immunoglobulins or formation of IC and their perivascular deposition in either skin or systemic organs are different and not fully explored. A common denominator of OC vasculitides is the activation of PMNs near the vessel wall via Fcy or Fcα receptors. Acute episodes of IgAV additionally require PMNs to become preactivated by IgA1 or by IC already in circulation. This intravascular priming results in increased adherence and subsequently vessel-destructive NETosis when they encounter IgA deposited at the vessel walls. Binding of IgA1 to PMNs in blood stream is associated with increased serum levels of hypogalactosidated IgA1. The characteristic clinical picture of IgAV (and also of so-called IgG/IgM vasculitis) comprises palpable or retiform purpura with a clear predilection for lower legs, probably due to stasis-related reduction in blood velocity, while in other IC vasculitides, additional factors influence the sites of vasculitides. Our knowledge of distinct forms and different pathophysiological pathways of IC vasculitides may lead to in efficacious or targeted therapies. Antibodies to complement components or intestinal budesonide for IgAV are promising agents (the latter suppresses the pathophysiologically related IgA nephropathy by reducing the generation of mucosal IgA.

S3707 A Cautionary Side of the Widely Prescribed: A Case of PPI-Induced AIN

Introduction: Proton pump inhibitors (PPIs) are widely prescribed for the treatment of gastric acid-related disorders. While generally well-tolerated, PPIs are not without side effects, including acute kidney injury. Here we highlight a rare case of biopsy proven PPI-induced acute interstitial nephritis (AIN). Case Description/Methods: A 54-year-old male with history of rheumatoid arthritis presented with one week history of fever, fatigue, arthralgias, and weight loss. One month prior he was admitted with upper GI bleeding due to NSAID induced peptic ulcer disease and promptly stopped NSAIDs with strict adherence to PPI therapy. He took no additional medications or supplements. On admission labs were notable for recurrent anemia without melena and new acute kidney injury, creatinine 2.32 mg/dL from baseline of 1. Given recent GI bleed patient underwent repeat EGD which showed a clean based healing antral ulcer. Recurrent anemia was attributed to renal dysfunction, which continued to worsen despite supportive care with peak creatinine 3.8 mg/dL. Urine studies were unrevealing without evidence of obstruction on imaging, but incidentally noted narrowing of the celiac artery was concerning for vasculitis related nephropathy given history of autoimmune disease. Confirmatory contrast enhanced imaging however was negative for evidence of vasculitis with negative serologies. Renal biopsy was performed which showed interstitial inflammation and tubulitis consistent with AIN. Ultimate diagnosis of PPI-induced AIN was made as he took no alternative medications which could be implicated. Patient was started on steroids with notable improvement in renal function. He was switched to an H2 receptor blocker to complete treatment of gastric ulcer and discharged on a steroid taper with complete renal recovery (Figure 1). Discussion: Initially described in 1992, PPI-induced AIN is a well-recognized albeit rare complication. It is thought to arise due to a hypersensitivity reaction, which may explain the classic presenting triad of fever, rash, and eosinophilia. However, studies have shown that this clinical triad is only present in 10% of cases thereby highlighting the difficulties of diagnosing AIN, which may ultimately require renal biopsy for definitive diagnosis. Treatment requires removal of the offending agent as well as initiation of steroids. Even with treatment, 30-70% of patients may develop chronic kidney disease. As such, it is important for clinicians to be cognizant of this potentially life altering complication of PPI.Figure 1.: Kidney biopsy showing inflammatory changes predominantly in the interstitium.

Empagliflozin ameliorates type 2 diabetes mellitus-related diabetic nephropathy via altering the gut microbiota

BackgroundThe dysregulation of gut microbiota can be found in patients with type 2 diabetes mellitus (T2DM)-related diabetic nephropathy (DN). Inhibitors of sodium-glucose co-transporter 2 (SGLT2) were reported to affect gut microbiota. This study aimed to identify whether empagliflozin (EMPA) attenuated DN via regulating gut microbiota. Materials and methodsThe high-fat diet (HFD) combining streptozocin (STZ) injection was performed to induce DN in mice. The therapeutic effects of EMPA were observed by staining of renal tissues and urine albumin/creatinine ratio (UACR). Mouse feces were collected for 16S rRNA sequencing. Fecal short-chain fatty acids (SCFAs) and fecal and serum lipopolysaccharide (LPS) were determined. An antibiotic-ablated model was established to confirm the role of the gut microbiota in the actions of EMPA. ResultsEMPA reduced the elevation of blood glucose and UACR caused by HFD/STZ. It inhibited the thickening of the colonic crypt and restored goblet cells and the expressions of ZO-1 and Occludin. The 16S rRNA sequencing showed that the diversity of gut microbiota was reduced after HFD/STZ treatment, while it was restored after EMPA treatment. The LPS-producing bacteria, Oscillibacter, and the SCFA-producing bacteria, Bateroid and Odoribacter, were changed after EMPA administration. The therapeutic effects of EMPA on ABX-treated mice were reduced. Meanwhile, the level of fecal SCFAs was decreased, while the levels of fecal and serum LPS were elevated, in T2DM mice, and they were negated by the administration of EMPA. ConclusionEMPA ameliorates T2DM-related DN via altering the gut microbiota, especially reducing LPS-producing bacteria and increasing SCFA-producing bacteria.

Extract of Fermented and Non-Fermented Seeds of Parkia Biglobosa Attenuates Hyperglycaemia and Related Nephropathy in Type 2 Diabetes Mellitus Animals.

Background: Diabetes mellitus persists as a major global health challenge despite several interventions. Remedies from natural plant products such as Parkia biglobosa (PB) seeds promises to be an effective alternative with no or fewer side effects. This study sort to assess and compare the total protein, fatty acid profile, phytochemical, antioxidant and antihyperglycaemic effect of fermented (FSE) and non-fermented (NSE) seed extract of PB in streptozotocin-nicotinamide induced (STZ-N) diabetic rats. Methods: Proximate composition (total proteins and lipids), fatty acid composition (by Soxhlet extraction with petroleum ether followed GC-MS) as well as phytochemical constituent and radical scavenging activity were performed on FSE and NSE. Type 2 diabetes mellitus was induced in rats by a single intraperitoneal injection of STZ (65 mg/kg b.w) followed by nicotinamide (110 mg/kg b.w) 15 minutes afterwards. Diabetic rats were orally treated with FSE and NSE (at 100 mg/kg b.w and 250 mg/kg b.w) or glibenclamide daily for 28 days. The antihyperglycemic effect was evaluated using biochemical parameters such as fasting blood glucose levels (FBG), lipid profile and kidney function parameters. Result: Protein and crude fat levels in the fermented were higher than non-fermented (12.5% and 97.6%, respectively). Polyunsaturated fatty acids were present in both. NSE had higher phenolic content and antioxidant activity. The 250 mg/kg b.w of NSE and FSE reduced serum glucose levels by 53% and 42%, comparable to 39.5% of glibenclamide. total cholesterol, triglycerides, LDL and VLDL cholesterol levels were reduced, with increased HDL levels. Further improvement in kidney function parameters was observed compared to the diabetes control. Conclusion: This study showed that both non-fermented and fermented seed extract of PB exerted antihyperglycemic effects and had potent therapy for type 2 diabetes and related nephropathy.

Correlation of copeptin with osmolarity and electrolytes in diabetes Mellitus: A tertiary center outpatient experience.

Background: Arginine Vasopressin (AVP) plays a significant role in the pathophysiology of Diabetes Mellitus (DM) and its related nephropathy. Timely detection of copeptin, a surrogate biomarker of AVP, would help in minimizing the osmoregulatory complications secondary to DM. The study aimed to correlate serum copeptin levels with serum osmolarity and electrolytes in subjects with progressive stages of DM. Methodology: A total of 120 patients were recruited as controls, pre-diabetes, DM without nephropathy, and nephropathy. Serum copeptin levels were measured by Enzyme-Linked Immunosorbent Assay. At the same time, routine biochemical tests for diabetes and renal function were done from the affiliated diagnostic laboratory. Results: The mean copeptin and osmolarity levels were 207.74 ± 192.08 pg/ml and 302.29 ± 18.13 mOsm/kg, respectively. Both, the copeptin and osmolarity levels raises progressively from controls to various stages of DM and share significant positive correlation (r=0.214, p=0.019). Osmolarity was also correlated significantly with RBS (r=0.262), BUN (r=0.844), Na+ (r=0.210) and K+ (r=0.461). Conclusion: The significant correlation of copeptin with osmolarity highlights the importance of the AVP system in regulating body fluid equilibrium in diabetic patients progressing towards nephropathy. Timely detection of copeptin can play an important role in the early management of the disease.

MO252: Complement 3 Deposits on Renal Tubule and Glomeruli in Phospholipase A2 Receptor-Related Idiopathic Membranous Nephropathy

Abstract BACKGROUND AND AIMS Evidence shows galactose-deficient IgG4 is able to act complement system via lectin pathway in phospholipase A2 receptor (PLA2R) related idiopathic membranous nephropathy (IMN). However, the severity of PLA2R-related IMN runs parallel with neither the electron microscope stage nor the complement density in situ. We find positive complement factor 3 (C3) deposition on renal proximal tubule in some IMN patients and manage to analysis the relationship between it and the severity of the disease. METHOD We retrospectively involved 113 PLA2R related IMN patients from March 2017 to October 2019. The inclusion criteria were diagnosed by kidney biopsy with complete clinical and pathological data. The exclusion criteria were with any secondary causes such as lupus nephritis type V, Sjogren's syndrome, hepatitis B associated glomerulonephritis and atypical membranous nephropathy. We divided total patients into four subgroups according to the C3 deposition site. We defined no C3 deposition subgroup (40,35%) as C3 appeared in neither glomeruli nor tubule, C3 glomeruli deposition subgroup (32, 28%) as C3 deposited on glomeruli only, C3 tubule deposition subgroup (12, 11%) as C3 deposited on tubule only, C3 extensive deposition subgroup (29, 26%) as C3 deposited on both glomeruli and tubule. RESULTS Clinical data of four groups were as follows: Male/female ratio were 22/18, 23/9, 5/7, 16/13, P = .252; The median of age were 50 (33, 57), 51 (42, 57), 57 (49, 61), 51 (33, 57), P = .412; The median of were 24-h urine protein were 4.4 (2.0, 6.9), 5.0 (2.7, 8.3), 4.9 (2.5, 11.2), 5.5 (2.4, 10.2) g/L, P = .427. The average serum albumin were 28.6 ± 6.8, 27.2 ± 6.7, 24.6 ± 2.7, 25.5 ± 6.0 g/L, P = .046. The median of serum creatinine were 70 (57, 82), 77 (65, 92), 68 (57, 89), 69 (58, 80) μmol/L, P = .255. The median of serum C3 were 1.14 (1.0, 1.33), 1.17 (1.04, 1.36), 1.22 (1.0, 1.34), 1.11 (0.99, 1.23) g/L, P = .291. The median of anti-PLA2R antibody were 0 (0, 55), 29 (25, 33), 12 (0, 136), 35 (19, 131) RU/mL, P = .049. CONCLUSION There were differences in serum anti-PLA2R antibody and Alb in patients with different C3 deposition. Patients with extensive C3 deposition showed higher PLA2R antibody.

Case report: rivaroxaban related nephropathy

The characteristics of direct oral anticoagulants (DOACs) make them more appealing for prevention of thromboembolic events than vitamin K antagonists (VKA). Despite that, both classes have been a recognized as a cause of anticoagulant related nephropathy (ARN). Herein we describe a case of a 72-year-old man, with chronic kidney disease (CKD), medicated with rivaroxaban, who presented with acute kidney injury (AKI) and microscopic hematuria. The kidney biopsy revealed anticoagulant related-nephropathy. Rivaroxaban was suspended, the patient showed improvement of renal function and apixaban was prescribed. This case emphasizes the need for careful monitoring of serum creatinine when these drugs are prescribed, especially in high risk groups.

Fabry disease related nephropathy – case family report and literature review

Introduction and aim. Fabry disease (FD) is a ultrarare storage disorder which causes irreversible damage to the brain, heart, and kidneys in young patients. The aim of our study was to draw clinician’s attention to the need of considering FD in the differential diagnosis of kidney disorders. Description of the case. We present the case of a 45-year-old man who has been misdiagnosed for several years with arterial hypertension with organ complications. He was referred to the nephrological ward due to chronic advanced kidney disease of unclear etiology. After 2 months of thorough differential diagnostics, based on the clinical course (past stroke, membranoproliferative glomerulonephritis (MPGN), left ventricular hypertrophy, paroxysmal limb pain) and conducted genetic examination, FD was confirmed. Then, screening tests were performed among the patient’s family members, confirming the presence of the same mutation as in our patient in 4 women of which in 3 were diagnosed cardio-renal syndrome. The authors of other studies report glycolipid deposits in the kidney cells on a needle biopsy, usefulness assess podocyturia, globotriaosylceramide protein in the urine and renal parapelvic cysts in an ultrasound examination in diagnostic FD nephropathy. Conclusions. This is the first case report to describe membranoproliferative glomerulonephritis in a patient suffering from FD. In patients with FD and the same genotype, kidney damage has a different phenotype.

Period circadian clock 3 inhibits palmitic acid-induced oxidative stress and inflammatory factor secretion in podocytes.

High fat-induced podocyte injury is one of the important factors leading to obesity related nephropathy (ORG), but the mechanism is not clear. This study aims to explore the mechanism of period circadian clock 3 (PER3) in the oxidative stress and inflammation induced by palmitic acid (PA) in podocytes. The C57BL/6J mice were fed with chow and high-fat diet for 16 weeks. The PER3 expression in kidney tissues were detected in the normal body weight group and the obesity group. The PER3 mRNA and protein expression were detected after the podocytes were induced with different concentrations (0, 50, 150 and 300 μmol/L) of PA for 48 h. The PER3 mRNA and protein expression were detected after the podocytes were induced with 150 μmol/L PA for 0, 24, 36, and 48 h. Triglyceride (TG) levels were examined in the PA group, the adenovirus (ad)-PER3+PA group, and the siRNA-PER+PA group after the podocytes were transfected by Ad-PER3 or small interfering RNA (siRNA)-PER3 for 48 h and subsequently were induced with 150 μmol/L PA for 48 h. The differential gene expression was detected using RNA sequencing (RNA-seq) after podocytes were transfected by siRNA-PER3 (siRNA-PER3 group) and siRNA-control (siRNA-control group), respectively. The mRNA levels of nephrin, podocin, podocalyxin, podoplanin, superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPX1), catalase (CAT), and the levels of malondialdehyde (MDA), glutathione (GSH), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-2 (IL-2) were detected after podocytes were transfected with Ad-PER3 or Ad-control for 48 h and then they were induced by 150 μmol/L PA for 48 h. The PER3 was down-regulated in the obesity group compared with the normal body weight group (P<0.05), and the PER3 was significantly down-regulated after the podocytes were treated with 150 μmol/L for 48 h compared with 0, 24, and 36 h (all P<0.01). The TG contents were significantly decreased in the Ad-PER3+PA group compared with the PA group (P<0.05). On the contrary, TG contents were increased in the siRNA-PER3+PA group compared with the PA group (P<0.05). The RNA-seq results showed that: compared with the siRNA-control group, the differential genes in the siRNA-PER3 group were enriched in different pathways including oxidative phosphorylation, TNF signaling pathway, extracellular matrix receptor interaction, fatty acid metabolism, and fatty acid degradation (all P<0.05). The podocyte marker genes (nephrin, podocin, podocalyxin and podoplanin), oxidative stress (SOD1, GPX1, CAT and GSH), and inflammation factors (TNF-α, IL-6, IL-1β and IL-2) were significantly down-regulated in the Ad-PER3+PA group compared with the PA group (all P<0.05). PER3 can decrease the PA-induced oxidative stress and inflammatory factor secretion via inhibiting the lipogenesis in podocytes.

Myeloproliferative neoplasm related nephropathy

Primary Myelofibrosis associated Nephropathy is a recently described entity. Primary Myelofibrosis (PMF) is a Myeloproliferative Neoplasm (MPN) where the marrow space shows fibrosis with megakaryocyte dysplasia. We present a case of a 32 year old patient who was detected to have proteinuria, renal dysfunction and anemia ,on a routine health check up. Primary Myelofibrosis was confirmed by positive Jak 2 expression. Kidney biopsy showed focal segmental glomerulosclerosis along with thickened glomerular basement membrane. The histomorphological features of renal and bonemarrow biopsies are analysed and a detailed review of the literature is done.