Chronic Glomerulonephritis Patients Research Articles

Chronic Kidney Disease in a Tertiary Care Hospital in Nepal

Introduction: Chronic kidney disease (CKD) is an increasingly recognized major public health problem globally and in Nepal. It has a high prevalence in the population and is associated with high morbidity, mortality and health care costs. Here, we aimed to study the socio-demographic profiles, etiologies of CKD and associated co-morbidities in patients attending a referral hospital. Methods: We conducted a hospital based, descriptive, observational, cross-sectional study among adult patients with CKD attending Tribhuvan University Teaching Hospital (TUTH), Kathmandu. Patients younger than 16 years and renal allograft recipients were excluded from the study. A diagnosis of CKD was established by the treating nephrologist based on KDIGO 2012 clinical practice guideline. Prior informed consent was taken. Data was collected on clinical features, socio-demographic profiles, major co-morbidities, presumed etiology of CKD and hematological and biochemical parameters of the patients. SPSS version 24 (Chicago, IL, USA) was used for the analysis of data. The study protocol was approved by the Institutional Review Board (IRB) of Institute of Medicine (IOM). Results: A total of 401 patients with CKD were included in the study. The mean age of the patient was 50.92 years (SD=17.98), male to female ratio was 1.8:1. Among these patients, 86% were Hindu, 24.4% were farmers, 57% were from the Hilly region of Nepal, 51% were active smokers, and 51.6% were alcohol consumers. Chronic glomerulonephritis (CGN) (36.2%; n= 145), diabetes mellitus (31.9%; n= 128) and hypertension (21.7%; n=87) were the three most common identified causes of CKD. Among the biopsy proven CGN patients, IgA nephropathy was the most common cause. In a large proportion of patients (68.3%) cause of CGN was not known. Most of the patients were in CKD stage 5 (27%), and stage 5D (55.8%). Coronary artery disease (CAD) (in 7% patients), heart failure (in 2.7%) and stroke (in 2.2%) were the most common comorbidities. Anemia was prevalent in CKD from stage 3 onwards, the severity increased with increasing stage (p <0.001). Hemodialysis was the predominant mode of renal replacement therapy (RRT) used by 98.2% of CKD 5D patients. Conclusion: Nepalese patients of CKD are younger; males are more affected than females. CGN, diabetes and hypertension are three most common causes of CKD; IgA nephropathy is the most common cause of biopsy proven CGN leading to CKD. Anemia is common from CKD stage 3 onwards. The most common associated co-morbidity is CAD.

#409 Correlation between ha factor concentration and urinary syndrome in patients with chronic glomerulonephritis when using rivaroxaban

Abstract Background and Aims Considering the pathogenetic role of factor X of the coagulation system in the formation and progression of chronic glomerulonephritis (CGN), as well as the mechanism of action of rivaroxaban, this study examined the concentration of coagulation factor X in peripheral blood. Aim of our study to reveal the pathogenetic relationship between the concentration of Xa factor and the severity of urinary syndrome in patients with CGN on the background of basic therapy with the inclusion of rivaroxaban. Method 108 CGN patients, on the background of 3-month baseline therapy with inclusion of rivaroxaban (AC+ group, 55 patients) and without anticoagulant (AC- group, 53 patients). Initially and after 3 months of the study the concentration of coagulation factor Xa in peripheral blood was studied. Results In CGN patients the concentration of Xa factor was significantly higher than in CG (122.17 ± 2.23% vs. 104.28 ± 6.54% in CG, p < 0.05). On the background of 3-month therapy including antiaggregant, corticosteroid hormone and cytostatic, the concentration of Xa factor decreased by 18.82 ± 0.64% (p < 0.001 reliability of difference with initial data). The use of rivaroxaban, as expected, was associated with a more significant decrease in Xa factor level—by 38.76 ± 1.40% (p < 0.001 significance of difference with baseline data; significance of difference in relative dynamics of Xa factor concentration between groups depending on anticoagulant use, p < 0.001). Correlation analysis revealed a significant positive strong correlation between the initial concentration of Xa factor in peripheral blood of CGN patients and the severity of hematuria (r = 0.83, p < 0.01) and a positive weak correlation between the concentration of Xa factor and cylindruria as a manifestation of proteinuria (r = 0.30, p < 0.01), as well as a positive weak correlation between the concentration of Xa factor and cylindruria at the end of the 3rd month of observation (r = 0.33, p < 0.01). There was also found a significant negative weak correlation between the initial concentration of Xa factor and the relative dynamics of hematuria (r = −0.48, p < 0.01) and cylindruria (r = −0.33, p < 0.01). Conclusion The study confirmed the pathogenetic relationship between the concentration of Xa factor and the severity of urinary syndrome in CGN patients. It was also found that initially high concentration of Xa factor is associated with less positive dynamics of urinary syndrome parameters.

#326 Features of intrarenal hemodynamics in patients with chronic glomerulonephritis on the background of taking anticoagulants

Abstract Background and Aims Chronic glomerulonephritis (CGN)-glomerular, autoimmune kidney disease, where baseline therapy is clinically proven to be successful. The study evaluates hemodynamic disorders of renal blood flow in patients with CGN on the background of baseline treatment with the inclusion of rivaroxaban. Method We researched108 patients CGN against the background of 3-month basic therapy with the inclusion of rivaroxaban (group AC+, 55 patients) and without anticoagulant (group AC-, 53 patients). Initial and after 3 months evaluation in the mode of color Doppler mapping and pulse-wave doppler. Results In the course of 3-month therapy, the performance of dopplerography of renal arteries in patients with CGN did not change reliably. But there was a credible and clinically significant increase in the systolic blood flow rate at the level of the Interregional Artery (IA), both compared to the baseline data and towards the end of hospitalization (by 9.27 2.58% p < 0.001 the validity of the difference with the raw data, by 8.60 2.53%, p < 0.01 with the 10th day of therapy), remaining reliably lower than in control group (p < 0.001). The speed at the arc artery (АА) also increased slightly (by 2.46 1.03%, p < 0.05 reliability of the difference with the original data and the end of hospitalization), but although statistical reliability was achieved, the dynamics was clinically insignificant and was less than 2.5%. The resistivity index (RI) at both IA and AA levels did not change reliably. Conclusion In CGN patients, intrarenal hemodynamics change with decreased blood flow rates in IA and AA. In the future, against the background of 3-month basic HGH therapy, there was some improvement in blood flow at the IA level but not AA, but no qualitative changes in intrarenal hemodynamics were achieved. The supplementation of long-term anticoagulation therapy with rivaroxaban has increased the effect of therapy on hemodynamic rates, resulting in some improvement in blood flow at both IA and AA levels, but no qualitative improvement has been achieved, possible due to pronounced structural remodeling of kidney vessels in patients with CGN.

RNA sequencing reveals the mechanism of FTO in inhibiting inflammation and excessive proliferation of lipopolysaccharide-induced human glomerular mesangial cells.

Chronic glomerulonephritis (CGN) is a leading cause of end-stage renal disease in China; thus, there is an urgent need for effective therapeutic targets and strategies for CGN treatment. However, studies on CGN pathogenesis are limited. In this study, we found that the fat mass and obesity-associated protein (FTO) was significantly decreased in the lipopolysaccharide (LPS)-induced human glomerular mesangial cells (HGMCs) (P < 0.01) and kidney tissues of CGN patients (P < 0.05). Moreover, double-labeling immunofluorescence and flow cytometry assays demonstrated that the overexpression of FTO could inhibit inflammation and excessive proliferation of HGMCs. Furthermore, RNA-sequencing (RNA-seq) and real-time quantitative polymerase chain reaction (RT-qPCR) analyses revealed that FTO overexpression induced differential expression of 269 genes (absolute fold change ≥ 2 and P-value < 0.05), including 143 upregulated and 126 downregulated genes. Further functional analysis of these differentially expressed genes by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested that FTO possibly mediates its inhibitory function by regulating the mammalian target of rapamycin (mTOR) signaling pathway and substance metabolism. Lastly, analysis of the PPI network and further identification of the top 10 hub genes (RPS15, RPS18, RPL18A, GNB2L1, RPL19, EEF1A1, RPS25, FAU, UBA52, and RPS6) indicated that FTO mediates its function by affecting the ribosomal proteins. Therefore, in this study, we elucidated the important role of FTO in the regulation of inflammation and excessive proliferation of HGMCs, suggesting FTO administration as a suitable therapeutic intervention for CGN.

#4624 VISCOELASTICITY MEASUREMENT- A NEW ULTRASOUND-BASED ELASTOGRAPHY METHOD IN THE ASSESSMENT OF THE KIDNEY

Abstract Background and Aims Viscoelasticity is the result of the tissue's combined viscous and elastic response to stress. This characteristic can reveal details about the function of the kidney and is essential for comprehending how it responds to deformation. Hologic Aixplorer Mach 30 ultrasound system comes with new and improved software that indirectly assesses the viscosity of the renal tissue by measuring tissue shear wave dispersion. Method Over the course of 2022 we performed a cross-sectional study by including 50 healthy participants, 50 kidney-transplanted patients, and 40 patients with chronic glomerulonephritis (before being referred for renal biopsy). Viscosity plane-wave ultrasound (Vi PLUS) measurements were performed on each participant, and the mean value of five distinct evaluations for each kidney was correlated with their demographic, biological, and clinical parameters. Results The mean viscosity value for the healthy group was 2.44 ± 0.57 Pascal.second (Pa.s), correlated with age (r = -0.4251, p = 0.0021), estimated glomerular filtration rate (eGFR) (r = 0.4057, p = 0.0038) but it did not correlate with C reactive protein (CRP), the mean value for Vi PLUS in the kidney-transplanted group was 2.82± 0.59 Pa.s, correlated with eGFR (r = 0.3335, p = 0.0180), but not with age or CRP, and the mean value for the patients with chronic glomerulonephritis group was 2.39 ± 0.73 Pa.s, did not correlate with age, but correlated with eGFR (r = 0.3637, p &amp;lt; 0.0211) and CRP (r = -0.3695, P = 0.0189) and we also found for a cut-off value of &amp;lt;2.8 Pa.s for detecting the presence of tubulointerstitial fibrosis with an AUC of 0.792, p &amp;lt; 0.001 with 94% sensitivity, and 60% specificity. Results of one-way ANOVA (p = 0.001), used to test the differences in the variables among the three groups, showed statistically significant higher values for the viscoelasticity in renal transplant patients compared to the other two groups, but no differences between the healthy and chronic glomerulonephritis groups. Conclusion Our results show that this novel ultrasound technique correlates with renal function and inflammation (in chronic glomerulonephritis patients) and it is also capable of discriminating between patients with and without tubulointerstitial fibrosis, but further research is needed for it to be implemented into routine clinical practice.

Intrarenal renin–angiotensin system activation and macrophage infiltrations in pediatric chronic glomerulonephritis

BackgroundThe current study tested the hypothesis that urinary angiotensinogen (UAGT) and urinary monocyte chemoattractant protein-1 (UMCP-1) levels provide a specific index of intrarenal renin–angiotensin system (RAS) status and the degree of infiltration of macrophages associated with RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis.MethodsWe measured baseline UAGT and UMCP-1 levels to examine the correlation between glomerular injury in 48 pediatric chronic glomerulonephritis patients before treatment. Furthermore, we performed immunohistochemical analysis of angiotensinogen (AGT) and CD68 in 27 pediatric chronic glomerulonephritis patients treated with RAS blockades and immunosuppressants for 2 years. Finally, we examined the effects of angiotensin II (Ang II) on monocyte chemoattractant protein-1 (MCP-1) expression in cultured human mesangial cells (MCs).ResultsBaseline UAGT and UMCP-1 levels positively correlated with urinary protein levels, scores for mesangial hypercellularity, rate of crescentic formation, and expression levels of AGT and CD68 in renal tissues (p < 0.05). UAGT and UMCP-1 levels were significantly decreased after RAS blockade and immunosuppressant treatment (p < 0.01), which was accompanied by AGT and CD68 (p < 0.01), as well as the magnitude of glomerular injury. Cultured human MCs showed increased MCP-1 messenger ribonucleic acid and protein levels after Ang II treatment (p < 0.01).ConclusionsThe data indicates that UAGT and UMCP-1 are useful biomarkers of the degree of glomerular injury during RAS blockade and immunosuppressant treatment in pediatric patients with chronic glomerulonephritis.

Chronic glomerulonephritis and pregnancy: predictors of preterm birth

Background: Chronic kidney disease (CKD) in pregnant women, with one of its most important causes being chronic glomerulonephritis (CGN), increases the incidence of adverse perinatal outcomes and gestational complications, including preterm birth (PB). Being the main cause of infant morbidity and mortality, PB has serious medical and social significance.&#x0D; Aim: To identify clinical predictors and develop a predictive model of PB in pregnant women with CGN.&#x0D; Materials and methods: A retrospective/prospective study included 122 CGN patients, whose 128 pregnancies resulted in childbirth from January 2009 to November 2022. Eighty-eight pregnancies were in the patients with CKD stage 1, 15 in stage 2, 21 in stage 3a, 3 in stage 3b, and one in stage 4. One hundred and nine (109) patients (115 pregnancies) delivered on term (at least 37 weeks of gestation) and were included into the group of term deliveries, whereas 13 women with 13 pregnancies had PB within the range of 22 weeks to 36 weeks 6 days. In the patients of both groups, we assessed nephrological and obstetric history, proteinuria and arterial hypertension at baseline and during pregnancy, complications of the index pregnancy, such as preeclampsia (PE) and severe PE, anemia, urinary tract infections, acute kidney injury, placental insufficiency, and cervical insufficiency. Binary logistic regression was used for prediction modeling of PB in women with CGN.&#x0D; Results: The proportion of PB in total cohort of the CGN patients was 10.2%. PB was spontaneous only in 2/13 (15.4%) cases, while in the rest of 11 pregnancies (84.6%) the delivery was induced due to maternal and fetal indications. Six independent predictors of PB were identified: body mass index, CKD stage, history of non-developing pregnancies, proteinuria during pregnancy 1 g/day, PE and placental insufficiency. The predictive model had sensitivity of 76.9%, specificity 99.1%, diagnostic efficiency 96.9%, positive predictive value 90.9%, and negative predictive value 97.4%.&#x0D; Conclusion: Predicting PB and targeting modifiable factors associated with PB may improve pregnancy outcomes in patients with CGN.

Thrombodynamics as a tool for monitoring hemostatic disorders in patients with chronic glomerulonephritis complicated by nephrotic syndrome.

To assess hemostatic disorders in CGN patients complicated by NS using the thrombodynamics test. The study included 60 adult patients with chronic glomerulonephritis (CGN), mean age 37 years, 31 (52%) women, and 29 (48%) men. Among all patients, 53 % of patients had NS, 47 % had no sign of NS. Hemostasis was assessed using the thrombodynamics test. The results were compared with biochemical parameters, which are usually associated with NS and renal dysfunction. According to the thrombodynamics test, CGN patients with NS demonstrated a tendency to hypercoagulability: increased rates of V (rate of clot growth), increased D (clot density), and increased CS (clot size) after 30 minutes. A positive correlation of these parameters with the serum albumin, creatinine levels, and glomerular filtration rate (GFR) indicates the influence of severe NS and renal dysfunction on the hemostasis activation in CGN patients with NS. According to the thrombodynamics test, CGN patients with NS demonstrate increased rates of clot formation, increased clot size after 30 minutes, and increased clot density due to secondary hemostasis activation. These changes positively correlate with the severity of hypoalbuminemia, hypercholesterolemia, and renal dysfunction in NS patients.

Evaluation of hemostasis disorders using the thrombodynamic test in patients with chronic glomerulonephritis with nephrotic syndrome

Nephrotic syndrome (NS) is accompanied by a risk of thrombotic complications due to hypercoagulability. Routine laboratory tests are not sensitive enough to detect these disorders, and therefore the use of integral coagulation tests, including a new thrombodynamic test (TT) in patients with NS, is of high relevance. Using a TT to determine hemostasis disorders in patients with chronic glomerulonephritis (CGN) with NS. The study included 49 patients with CGN, mean age 37 years, of which 25 (51%) women and 24 (49%) men. Of all the examined patients, 20 (40.8%) of people had NS, 29 (59.2%) had no NS. The process of clot formation was assessed by TT. According to TT, 30% (6/20) of patients with NS and 13.7% (4/29) of patients without NS have hypercoagulation with changes in parameters that go beyond the reference values. In patients with NS, an increase in clot density (D), clot formation rate (V) and clot size (CS) was found, especially when albumin decreased below 25 g/l. Negative correlations were found between the levels of albumin, creatinine and clot density (D), which reflects the level of hyperfibrinogenemia, the rate of clot formation (V) and the integral index of coagulation (CS). The results indicate mainly the activation of the plasma hemostasis due to the internal coagulation pathway. However, the correlation of Tlag (delay time for the onset of clot formation after contact of blood plasma with the insert-activator) with serum cholesterol levels may also indicate activation of the extrinsic coagulation pathway. In CGN patients with NS, activation of the plasma hemostasis is noted, as evidenced by an increase in the rate of formation (V) and size of the clot (CS) after 30 minutes, as well as the density of the formed clot (D).

Native T1 Mapping in Assessing Kidney Fibrosis for Patients With Chronic Glomerulonephritis.

Purpose: To assess the utility of non-contrast enhanced native T1 mapping of the renal cortex in assessing renal fibrosis for patients with chronic glomerulonephritis (CGN).Methods: A total of 119 patients with CGN and 19 healthy volunteers (HVs) were recruited for this study. Among these patients, 43 had undergone kidney biopsy measurements. Clinical information and biopsy pathological scores were collected. According to the results of the renal biopsy, the patients were classified into the high (25–50%), low (<25%) and no renal interstitial fibrosis (IF) (0%) groups. The correlations between the T1 value in the renal cortex and each of the clinical parameters were separately analyzed. The relationships between each fibrosis group and the T1 value were also evaluated and compared between groups. Binary logistic regression analysis was further used to determine the relationship between the T1 value and renal fibrosis. Receiver operating characteristic (ROC) curves were plotted to analyze the diagnostic value of the T1 value for renal fibrosis.Results: Compared with those of the HVs, the T1 values were significantly higher in patients at all stages of chronic kidney disease (CKD) (all p < 0.05). Significant T1 differences were also revealed between patients with different stages of CKD (p < 0.05). Additionally, the T1 value correlated well with CKD stage (p < 0.05), except between CKD 2 and 3. In addition, the T1 value was positively correlated with cystatin C, neutrophil gelatinase-associated lipocalin, and serum creatinine and negatively correlated with hemoglobin, kidney length, estimated glomerular filtration rate and hematocrit (all p < 0.05). Compared with those of the no IF group, the T1 values were increased in the low- and high-IF groups (both p < 0.05). Logistic regression analysis showed that an elevated T1 value was an independent risk factor for renal fibrosis. ROC analysis suggested that the optimal critical value of T1 for predicting renal fibrosis was 1,695 ms, with a specificity of 0.778 and a sensitivity of 0.625.Conclusion: Native T1 mapping demonstrated good diagnostic performance in evaluating renal function and was an effective noninvasive method for detecting renal fibrosis in CGN patients.

Analysis of profibrogenic microRNAs (miRNAs) expression in urine and serum of chronic kidney disease (CKD) stage 1\u20134 patients and their relationship with proteinuria and kidney function

PurposeBesides conventional kidney diseases diagnostics, micro RNAs (miRNAs) assessment in urine and serum is considered to be a promising non-invasive method of diagnostics of renal parenchymal diseases and valuable therapeutic target also. The purpose of the study was to investigate the role of several miRNAs as a markers of kidney damage.MethodsAssessment of 45 chronic kidney disease (CKD) patients stage 1–4 and 17 healthy control. Sample of urine and blood was taken from each participant for molecular analysis using Real Time PCR method to identify such micro-RNAs as: hsa-miR-155-5p, hsa-miR-214-3p, hsa-miR-200a-5p, hsa-miR-29a-5p, hsa-miR-21-5p, hsa-miR-93-5p, and hsa-miR-196a-5p. Basic biochemical test was done. Analysis was performed in CKD patients group and subgroup with chronic glomerulonephritis (CGN) confirmed by kidney biopsy. Moreover, analysis was performed in subgroup with different estimated glomerular filtration rate (eGFR) (according to CKD–EPI equation: eGFR < 60 ml/min, eGFR > 60 ml/min) and different daily protein excretion (DPE): (DPE < 3.5 g; DPE > 3.5 g).ResultsIncreased relative expression of hsa-miR-29-5p, hsa-miR-21-5p, and hsa-miR-196a-5p and decreased expression of hsa-miR-155-5p, hsa-miR-214-5p, hsa-miR-200a-5p, and hsa-miR-93-5p was demonstrated in urine of analyzed CKD patients. In subpopulation of chronic glomerulonephritis (CGN) patients, there was higher level of expression in urine of hsa-miR-155-5p, hsa-miR 214-3p, hsa-miR-93-5p, and hsa-miR-196a-5p in CGN with DPE < 3.5 g. CGN patients with eGFR < 60 ml/min showed higher expression level of miRNAs such as hsa-miR-214-3p, hsa-miR-29-5p, hsa-miR-93-5p, and hsa-miR-196-5p in urine. There was increase in hsa-miR 155-5p, hsa-miR-214-3p, and hsa-miR-200a-5p serum expression level in CKD population and reduction of hsa-miR-29a-5p, hsa-miR-21-5p, and hsa-miR-93-5p expression. Increased level of expression of hsa-miR-155-5p; hsa-miR-214-3p, hsa-miR-200a-5p, and hsa-miR-29-5p was found in CGN patients with eGFR > 60 ml/min.ConclusionIncreased relative expression of profibrogenic miRNAs in urine or serum of CKD patients with eGFR > 60 ml/min and DPE < 3.5 g may indicate higher degree of fibrosis at early CKD stages.

Current status of COVID‐19 among hemodialysis patients in the East Azerbaijan Province of Iran

IntroductionManagement of vulnerable patients during the COVID‐19 pandemic requires careful precautions. Hemodialysis patients constitute a large group of at‐risk patients that not only suffer from a compromised immune system but also are at a higher risk due to frequent admission to healthcare units. Therefore, a better understanding on the pathogenesis and possible risk factors of COVID‐19 in hemodialysis patients is of high importance.MethodsA total of 670 maintained hemodialysis patients from all dialysis units of the East Azerbaijan Province of Iran, including 44 COVID‐19 patients were included in the present study. Possible associations between the backgrounds of patients and the incidence of COVID‐19 were assessed. Also, hemodialysis patients with COVID‐19 were compared to 211 nonhemodialysis COVID‐19 patients.FindingsChronic glomerulonephritis patients and those with blood group A demonstrated a higher incidence of COVID‐19. On the other hand, patients with blood group AB+ and those with hypertension etiology of kidney failure demonstrated a lower incidence of COVID‐19. Hemodialysis patients with COVID‐19 had higher counts of polymorphonuclears (PMNs) in their peripheral blood compared to other COVID‐19 patients.DiscussionA better comprehension on the risk factors associated with COVID‐19 in hemodialysis patients can improve our understanding on the pathogenesis of COVID‐19 in different situations and help the enhancement of current therapeutics for COVID‐19 in hemodialysis patients.

The balance of proinflammatory cytokines and Treg cells in chronic glomerulonephritis

To determine the clinical significance of the Th17, Th1, and Treg cytokines in urine to assess the activity and progression of chronic glomerulonephritis with nephrotic syndrome (NS). The study included 98 patients with CGN 37 women and 61 men. Patients were divided into two groups according to the degree of CGN activity. Group I consisted of 51 patients with NS. In 21 subjects, a decrease in GFR60 ml/min was revealed. Group II included 47 patients with proteinuria from 1 to 3 g/day without NS. GFR60 ml/min/1.73 m2 was observed in 26 patients. A kidney biopsy was performed in 65 patients and the hystological diagnosis was verified: 20 had mesangioproliferative GN, 16 had membranous nephropathy, 18 had focal segmental glomerulosclerosis, and 11 had membranoproliferative GN. The control group consisted of 15 healthy people. The levels of IL-6, IL-10, IL-17, tumor necrosis factor a (TNF-a) in the urine were determined using enzyme-linked immunosorbent assay. The number of FoxP3-positive cells in the inflammatory interstitial infiltrate of the cortical layer was determined in 39 patients (in a biopsy sample in a 1.5 mm2 area). In group of patients with CGN, there was an increase in the levels of Th17, Th1, and Treg cytokines in urine TNF-a and IL-10 compared with healthy individuals. An increase in the levels of IL-6 in the urine of patients with high clinical activity of CGN (with NS and renal dysfunction) was more pronounced than in patients with NS and normal renal function. There was a decrease in the number of Treg cells in the interstitium of the kidney and a decrease in the production of anti-inflammatory IL-10 in CGN patients with NS, compared with patients without NS. The most pronounced changes in the cytokine profile were observed in patients with FSGS with an increase in pro-inflammatory cytokines and a decrease in Treg in the kidney tissue/anti-inflammatory IL-10 in the urine. An imbalance of cytokines characterized by an increased levels of pro-inflammatory IL-17, IL-6, TNF-a, and a reduced levels of anti-inflammatory IL-10 and T-regulatory cells in the kidney tissue is noted in patients with NS, especially with FSGS. Imbalance of cytokines reflects the high activity of CGN and the risk of the progression of the disease.

P0432GAMMA DELTA T-CELLS PHENOTYPIC PROFILE IN PATIENTS WITH IGA-NEPHROPATHY

Abstract Background and Aims γδТ-lymphocytes are enigmatic minor nonconventional peripheral blood cells population responded to non-peptidic antigens and displayed functional diversity, from effector action to immunoregulation, depending on pathological conditions. Although γδТ-lymphocytes are known to play a key role in chronic inflammation, their phenotype and functions in patients with chronic kidney diseases (CKD) are relatively unknown. The aim of this study was to investigate a surface phenotype of γδТ-lymphocytes in patients with IgA-nephropathy (IgAN) compared to systemic lupus erythematosus (SLE) and chronic glomerulonephritis (CG) due to focal-segmental glomerulosclerosis and minimal change disease patients. Method The peripheral blood was obtained from 23 CKD patients (13 IgAN, 5 SLE and 5 GN patients) aged of 32.0 (26.7 ÷ 36.0) y.o., male/female ratio as 12/11. The number of γδТ-lymphocytes was determined using monoclonal antibodies γδТCR-PC5, CD3-PC7 as well as phenotypic profile – with CD45RO-ECD and CD27-PE, CD314-PE (NKG2D), CD8-FITC, CD56-PC7 and CD16-ECD and TLR4-FITC using flow cytometry analysis (Cytoflex, «Beckman Coulter», USA). Statistical analysis was done using Statistica 8.0. Results The increased number of γδТ-cells in peripheral blood of IgAN patients (4.85 (4.13÷8.87)%) compared to SLE patients (3.31 (2.88÷3.48)%; p=0.001) and CG patients (1.14 (0.94÷3.15)%; p=0.03) was established. More than half of γδТ-cells in IgAN patients expressed central memory phenotype (γδТCR+CD45RO+: 50.2 (31.6÷61.3)%; γδТCR+CD27+: 58.7 (55.5÷61.8)%) enhancing phosphoantigen-dependent activation, survival, proliferation, and secretion of pro-inflammatory cytokines. Terminally differentiated effector memory γδТCR+CD45RO-CD27- phenotype of γδТ-cells was dominated in GC patients (γδТCR+CD45RO+: 25.7 (24.0÷27.5)%; γδТCR+CD27+: 43.3 (30.4÷56.2)%; р=0.05) regarded as “exhausted senescent” T cells with poor proliferation and severe functional abnormalities. The cytotoxic properties of γδТ-cells in IgAN patients are characterized with significantly higher expression of killer recognition receptor NKG2D (γδТCR+CD314+: 91.7 (51.7÷93.0)%) as well as true effector cytotoxic CD56+ marker (γδТCR+CD56+: 44.4 (27.2÷58.6)%) but not CD16 or CD8 antigens compared the both SLE and CG (р=0.05). Moreover, the number of γδТCR+CD314+ and γδТCR+CD56+ as well as γδТCR+CD45RO+ inversely correlated with glomerular filtration rate (R=-0.6, р=0.05). The increase of pattern recognition receptor TLR4 expression on γδТ-cells was reported in all groups of CKD patients suggested the activated state of γδТ-cells and their important role in the control of infection. Conclusion In IgAN patients the phenotypic profile of γδТ-lymphocytes is characterized as central memory γδТCR+CD45RO+CD27+ cells with increased cytotoxic potential (CD314highCD56highCD16lowCD8low) what is functionally differed from ones in SLE and GC patients. The inverse correlation of γδТ-cells phenotype profile with glomerular filtration rate suggests their pathological role and possible contribution to the initiation of autoimmune inflammation in IgAN patients.

Interleukin‐17 in urine and serum of patients with nephritis

Recent evidence suggests that interleukin-17 (IL-17) is involved in the pathogenesis of systemic lupus erythematosus (SLE) and it is a promising marker of disease activity in lupus nephritis (LN).1 IL-17 induces the expression of various pro-inflammatory cytokines and chemokines, which increase the influx of various leukocyte subpopulations and thus, causes severe inflammation. These inflammatory mediators enhance the involvement of various leukocyte subpopulations, which ultimately leads to damage.2, 3 Nordin et al published interesting data about IL-17 levels in 120 patients with SLE.4 The authors showed an increase in the levels of IL-17 in the serum and urine of patients and their correlations with British Isles Lupus Assessment Group and SLE Disease Activity Index scores, which is consistent with other studies.5, 6 But IL-17 was not a sensitive or specific marker of SLE activity. In addition, there was no correlations of IL-17 levels in urine or serum with the histological classes of LN. We also studied the levels of IL-17 in the urine and serum of patients with chronic glomerulonephritis (CGN). The levels of IL-17 in serum did not significantly differ from the levels in healthy individuals and did not depend on the activity of nephritis. On the contrary, the levels of IL-17A in the urine of patients with CGN were significantly higher at 3.05 (2.98-3.1) pg/mg creatinine (Cr) than that in healthy individuals 2.93 (2.92-2.94) pg/mg Cr The urinary IL-17A levels were not correlated with proteinuria (R2 = 0.21, P = .29) and serum albumin (R2 = 0.24, P = .21). These results indicate a connection between IL-17 levels in urine and inflammation of renal tissue in CGN patients. Also, IL-17 levels in the urine were significantly higher in the CGN patients with advanced interstitial fibrosis and a renal dysfunction with glomerular filtration rate less than 60 mL/min/1.73 m2 (2.97 [2.96-2.99] pg/mg Cr vs. 2.99 [2.98-3.00] pg/mg Cr in normal renal function, P < .05) regardless of histological forms. Currently, the role of IL-17 in fibrotic accumulation has been discussed. Severe fibrosis in murine radiation-induced lung disease was more pronounced with regard to reduction in Th1 cells in the presence of increased number of Th17 cells and higher levels IL-17.7 IL-6 can induce glomerulosclerosis and interstitial fibrosis in the kidney directly or through activation of IL-17.8 Changes in the Th17/Treg ratio may contribute to the development of advanced tissue fibrosis by transforming growth factor-β signaling through the activation of mitogen-activated protein kinases.9 Therefore, future research is needed to compare IL-17 levels in the urine with activity and sclerosis scores in the renal tissue and renal outcomes in LN.

Heat shock protein 90 and NFkB levels in serum and urine in patients with chronic glomerulonephritis.

Heat shock proteins play an important role in immune inflammation and the formation and restoration of proteins. In recent years, the importance of heat shock protein 90 (Hsp90) in the activation of immune inflammation through nuclear factor kB (NFkB) has been discussed. To assess the activation of the Hsp90-NFkB system by measuring serum and urinary levels in patients with chronic glomerulonephritis (CGN). This study included 32 patients with active forms of CGN and 14 patients with Fabry nephropathy. The control group included 10 healthy individuals. Twenty-one out of 32 CGN patients had nephrotic syndrome (NS). Eleven out of 32 CGN patients had proteinuria levels from 1 to 3g/day without nephrotic syndrome. A total of 17 patients had renal dysfunction (estimated glomerular filtration rate < 60ml/min/1.73m2). Fourteen patients with Fabry nephropathy had proteinuria without nephrotic syndrome. Serum and urine HSP-90 and NFkB p65 levels were determined using an enzyme-linked immunosorbent assay. The levels of HSP-90 and NFkB in the serum of patients with CGN were significantly higher than in healthy individuals and patients with Fabry nephropathy. In patients with Fabry nephropathy, the HSP-90 and NFkB levels in the urine and serum did not significantly differ from those in the control subjects. Serum Hsp90 levels were significantly higher in the CGN patients with NS than in patients without NS, as well as in patients with normal renal function compared with patients with an eGFR < 60ml/min/1.73m2 and patients with tubulo-interstitial fibrosis. Higher levels of HSP-90 and NFkB in serum were observed in patients with nephrotic forms of CGN, including focal segmental glomerulosclerosis, minimal change disease and membranous nephropathy. There were no correlations between the clinical signs of CGN and urinary HSP90/NFkB levels. Activation of the HSP-90-NFkB system, which is directly involved in the development of immune inflammation in CGN, was found in patients with an active course of CGN, especially in those with nephrotic syndrome.

Effectiveness of cinacalcet treatment for secondary hyperparathyroidism on hospitalization: Results from the MBD-5D study.

ObjectivesTo elucidate the effect of cinacalcet use on all-cause and cause-specific hospitalization outcomes using a prospective cohort of maintenance hemodialysis patients.MethodsWe used data from a prospective cohort of Japanese hemodialysis patients with secondary hyperparathyroidism and examined baseline characteristics as well as longitudinal changes. All patients were cinacalcet-naïve at study enrollment. Further, we used a marginal structural model to account for time-varying confounders on cinacalcet initiation and hospitalization outcomes, and an Andersen-Gill–type recurrent event model to account for any recurring events of hospitalization in the outcome analysis using the weighted dataset.ResultsAmong the 3,276 patients, cinacalcet treatment was initiated in 1,384 patients during the entire follow-up. Cinacalcet users were slightly younger, included more patients with chronic glomerulonephritis and fewer patients with diabetes, were more likely to have a history of parathyroidectomy, and were more often used receiving vitamin D receptor activator, phosphate binders, and iron supplements. The overall hospitalization analysis yielded a hazard ratio (HR) of 0.97 (95% confidence interval [CI]: 0.80, 1.18). A trend toward a mild protective association was observed for cardiovascular-related hospitalizations (HR: 0.85; 95% CI: 0.64, 1.14). In the subgroup analysis, a protective association was seen due to cinacalcet use for infection-related hospitalizations in the lowest intact parathyroid hormone group (HR: 0.36; 95% CI: 0.14, 0.95).ConclusionsCinacalcet initiation in patients on maintenance hemodialysis had no effect on all-cause and cause-specific hospitalizations. Although the overall association was statistically not significant, cinacalcet may have a protective association on cardiovascular-related hospitalization in all patients and infection-related hospitalization in patient with low intact parathyroid hormone.

A Decade of Live Related Donor Kidney Transplant: Experience in a Tertiary Care Hospital of Bangladesh

Background: Kidney transplantation is the preferred treatment for end stage kidney disease (ESKD). Live related donor kidney transplant was started in BIRDEM General Hospital, Bangladesh, on 6th November 2004. The aim of this study was to share our last 10 years’ experience of live related donor kidney transplant.Methods: A questionnaire was formed and data were collected from the hospital records. We retrospectively evaluated patients’ clinical and laboratory findings.Results: A total of 111 live related donor kidney transplants were performed from 2004 to 2014. Male:female was 2.3:1. The mean age of the recipients was 37.45 ± 10.58 years. The causes of ESKD were chronic glomerulonephritis (CGN) (52, 46.9%), diabetes mellitus (DM) (31, 27.9%), hypertension (26, 23.4%), chronic pyelonephritis (1, 0.9%) and obstructive nephropathy (1, 0.9%). Pre-emptive transplantation was done in 4 (3.6%) patients. Patients on continuous ambulatory peritoneal dialysis and haemodialysis were 2 (1.8%) and 105 (94.6%) respectively. Most of the donors were siblings (55.9%). Majority (64.9%) had an uncomplicated recovery. The commonest complication during post-transplant hospital stay was infection (27.0%), mostly urinary tract infection (21.6%). Surgical failure was experienced in 1 (0.9%) and acute rejection was noted in 2 (1.8%) patients. Other complications were renal vein thrombosis (1, 0.9%), haemolytic uremic syndrome (1, 0.9%), acute tubular necrosis (1, 0.9%), peri-renal collection (1, 0.9%), pericardial effusion (1, 0.9%) and clot retention in urinary bladder (2, 1.8%). Mean post-transplant hospital stay was 12.39 ± 4.27 days. Mean duration from surgery to normalization of serum creatinine was 5.75 ± 4.15 days. During discharge, 71.2% patients had normal renal function (RF) with mean serum creatinine 1.03 ± 0.15 mg/dl and 26.1% patients had gradually improving RF with mean serum creatinine 2.01 ± 1.04 mg/dl. As induction, 61 (55%) patients received basiliximab and as maintenance therapy all patients received oral prednisolone, calcinurine inhibitor and mycophenolate. In the first year of transplant, 49.5% patients suffered from infections, of which urinary tract infection was the commonest (55.9%). Incidence of chronic allograft nephropathy in CGN, DM and hypertension patients were 25%, 19.4% and 23.1% respectively. Graft survival at 1 year, 3 years and 5 years was 94.06%, 85.88% and 77.27% respectively. Patient survival at 1 year, 3 years and 5 years was 98.1%, 88.24% and 84.09% respectively.Conclusions: Our results are comparable or in some aspects, even better in comparison to other centers of both developing and developed world. In a center of a developing country with limited facility and resource, these achievements are encouraging.Birdem Med J 2018; 8(3): 198-202

Heat shock protein 70 and anti-heat shock protein 70 antibodies in patients with chronic glomerulonephritis.

We evaluated the heat shock system 70 (HSP70) in patients with chronic glomerulonephritis (CGN). Seventy-six patients with CGN patients were included in our study. Ten patients with mild proteinuria (median 0.48 [0.16-0.78] g/24h) and ten healthy subjects served as positive and negative controls, respectively. Urinary levels of HSP70, interleukin-10, and serum levels of anti-HSP70 were measured by ELISA. The immunohistochemical peroxidase method was used to study the expression of HSP70 and Foxp3+ in kidney biopsies. TregFoxP3+ cells in the interstitium were determined morphometrically. Median urinary HSP70 levels in patients with nephrotic syndrome (NS) [6.57 (4.49-8.33) pg/mg] and subnephrotic range proteinuria [5.7 (4.12-6.9) pg/mg] were higher (p < 0.05) than in positive [3.7 (2.5-4.82) pg/mg] and negative [3.78 (2.89-4.84) pg/mg] controls. HSP70 expression index in tubular cells positively correlated with urinary HSP70 (Rs = 0.948, р < 0.05) and proteinuria (Rs = 0.362, p < 0.05). The number of TregFoxp3+ cells in the kidney interstitium and interleukin-10 excretion were lower in patients with NS. Anti-HSP70 antibody serum levels in patients with NS [21.1 (17.47-29.72) pg/ml] and subnephrotic range proteinuria [24.9 (18.86-30.92) pg/ml] were significantly higher than in positive [17.8 (12.95-23.03) pg/ml] and negative [18.9 (13.5-23.9) pg/ml] controls. In patients with CGN, increasing proteinuria was associated with higher HSP70 renal tissue and urinary levels. However, activation of HSP70 in patients with nephrotic syndrome did not lead to an increase in tissue levels of TregFoxp3+ cells or to the release of IL-10.

Current characteristics of dialysis therapy in Korea: 2016 registry data focusing on diabetic patients.

Diabetic nephropathy is the most frequent cause of end-stage renal disease worldwide. Dialysis patients with diabetes mellitus (DM) have more complications and shorter survival duration than non-DM dialysis patients, requiring more clinical attention and difficult management. The registry committee of the Korean Society of Nephrology has collected data about dialysis therapy in Korea through an on-line registry program and analyzed the characteristics of patients. A survey of dialysis patients in 2016 showed that 50.2% of new dialysis patients had DM nephropathy as the cause of end-stage renal disease. The proportion of patients receiving hemodialysis (HD) for more than 5 years was 38% in DM patients and 51% in non-DM patients. The mean pulse pressure in DM HD patients was 71.5 mmHg, compared with 62.6 mmHg in non-DM patients. The proportion of DM patients with native vessel arteriovenous fistula as vascular access for HD was lower than that of non-DM patients (73% vs. 78%). Mean serum creatinine of DM and non-DM dialysis patients was 8.4 mg/dL and 9.5 mg/dL respectively. As vascular access of the DM HD patients was poor, the dialysis adequacy of DM patients was slightly lower than that of non-DM patients. The 5-year survival rate for DM HD patients was 53.9%, which was much lower than that of chronic glomerulonephritis patients (78.2%). The proportion of patients with a full-time job was 17% for DM patients and 28% for non-DM patients.