Primary Chronic Glomerulonephritis Research Articles

Interleukin-6 and Epidermal Growth Factor as non-invasive biomarkers of progression in chronic glomerulonephritis.

Several cytokines and chemokines are involved in the pathogenesis and progressive injury of renal tissues in patients with primary chronic glomerulonephritis (CGN). The objective of this study was to determine whether the urinary excretion of interleukin-6 (IL-6), transforming growth factor β1 (TGFβ1), monocytes chemoattractant protein (MCP-1), soluble tumor necrosis factor receptor 1 (sTNFR1) and epidermal growth factor (EGF) in patients with newly recognized CGN can serve as prognostic biomarkers in patients with newly recognized CGN and whether they can be effective in predicting a progressive reduction of renal function in prospective observation. The study included 150 Caucasian patients. UIL-6, UTGFβ1, UMCP-1 and UsTNFR1 and UEGF were measured using ELISA methods (Quantikine R&D System). UIL-6, UTGFβ1, UMCP-1 and UsTNFR1 were significantly higher, yet UEGF excretion was significantly lower in nephrotic patients, in patients with estimated glomerular filtration rate (eGFR) < 60/min/1,73m2 at presentation, as well as in the progressor (PG) subgroup. In a multivariate regression analysis basal eGFR correlated with UsTNFR1, UIL-6 and UEGF excretion, although in the follow-up, ΔeGFR (delta estimated glomerular filtration rate) significantly correlated only with UEGF excretion. A logistic regression analysis showed that the most significant independent risk factors for the deterioration of renal function with time are initial high (>11.8 pg/mgCr) UIL-6 excretion, initial low (<15.5 ng/mgCr) urinary UEGF excretion and male gender. In patients with newly diagnosed CGN, UIL-6 and UEGF can serve as prognostic biomarkers for the progression of the disease.

Postpartum progression of chronic kidney disease in patients with chronic glomerulonephritis

Background: In the recent years, pregnancy outcomes in women with primary chronic glomerulonephritis (CGN) have been encouraging despite increased incidence of complications and preterm birth. However, the impact of pregnancy on CKD progression in glomerulonephritis remains understudied.&#x0D; Aim: To evaluate the effect of pregnancy on CKD progression in the postpartum period in patients with primary CGN.&#x0D; Materials and methods: This was an observational longitudinal study. The study group included 40 patients with CGN and CKD G1G3b, who had 40 deliveries from January 2009 to November 2022. The control group included 35 patients with CGN who had no pregnancies after CKD was diagnosed. Serum creatinine and estimated glomerular filtration rate (GFR) were assessed during the follow up, recording the development of CKD G5.&#x0D; Results: The annual rate of GFR decline in the study group was -4.6 [-8.0; -2.5] ml/min/1.73 m2, and in the control group -1.8 [-5.8; +1.5] ml/min/1.73 m2 (p = 0.056). After complicated pregnancy (preeclampsia, placental insufficiency, increase in proteinuria, worsening of arterial hypertension, acute kidney injury), the annual rate of GFR decline was -6.4 [-13.4; -3.5] ml/min/1.73 m2, which was higher than in the controls (p = 0.042). There were no significant differences in survival without GFR decrease by 30%, 50% and without CKD G5 between the study and the control groups. However, CKD G5-free survival in the patients with complicated pregnancy was lower than that in the controls (p = 0.022) and in those with uncomplicated pregnancies (p = 0.009).&#x0D; Eleven (11) of 40 patients in the main group and 3/35 in the control group reached CKD G5. The time from delivery to CKD G5 was 4.83 [2.08; 7.07] years. Among women who reached end-stage renal failure after childbirth, there were significantly more patients with CKD G3, proteinuria 1 g/day during pregnancy, arterial hypertension at baseline and during pregnancy, preeclampsia, acute kidney injury, delivery at less than 37 weeks of gestation, with neonates requiring treatment at intensive care unit, and unfavorable pregnancy outcomes.&#x0D; Conclusion: Renal survival in the women with primary CGN who had been pregnant was not significantly different from that in the women who did not have pregnancies; however, complicated pregnancy increased the rate of kidney function decline.

Microbiome and metabolome analysis to clarify the interaction between the urine microbiota and serum metabolites in Chinese patients with immunoglobulin A nephropathy

The bacterial and metabolic networks in immunoglobin A nephropathy (IgAN), the most common type of primary chronic glomerulonephritis worldwide, have not been extensively studied. To help develop better methods for the diagnosis, treatment, and prognosis of IgAN, we characterized the alterations of the urinary microbiome and serum metabolome in patients with IgAN. We analyzed serum and urine samples from Chinese patients with IgAN and healthy controls (HCs) using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and 16S ribosomal RNA gene sequencing. Patients with IgAN had a higher relative abundance of Actinomyces and a lower relative abundance of Lactobacillus. The elements of metabolism have been affected, including free amino acids, polyunsaturated fatty acids, and oligopeptides. We also identified the 9 metabolites that might be the core metabolites, including guanidinoacetic acid, apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)], and diethanolamine, which linked the metabolic networks between the urinary tract (UT) and blood. Other core metabolites, such as homocitrulline, apo-[3-methylcrotonoyl-CoA:carbon-dioxide ligase (ADP-forming)], butyrylcarnitine, formiminoglutamic acid (FIGLU), diethanolamine, and prolylhydroxyproline, were positively correlated with urinary mili-total protein (MTP). Conversely, Lactobacillus was negatively correlated with MTP. We verified the connection between the disruption of the microbiota and serum metabolites, along with the clinical parameters, in patients with IgAN, which may help provide a tool for IgAN interventions.

Cost Analysis of Screening for IgA Nephropathy Using Novel Biomarkers

ObjectivesIgA nephropathy (IgAN) is the most common primary chronic glomerulonephritis and a major cause of end-stage kidney disease worldwide. Novel biomarkers, including the aberrantly glycosylated IgA1 and glycan-specific antibodies, could be useful in the diagnosis of IgAN. The aim of this study was to assess the cost analysis of IgAN screening using novel biomarkers in addition to the conventional screening compared with conventional screening alone. MethodsTo estimate the medical expense of each strategy related to renal disease for 40 years, we developed an analytical decision model. The decision tree started at “40 years of age with first-time hematuria.” It simulated 2 clinical strategies: IgAN screening using the novel biomarkers (group N) and conventional screening (group C). The analysis results were presented as medical expenses from a societal perspective. Discounting was not conducted. ResultsThe expected medical expense per person for 40 years was ¥31.2 million (~$291 000) in group N and ¥33.4 million (~$312 000) in group C; hence, expense in group N was lower by ¥2.2 million (~$21 000). In group N, the expected value of IgAN increased by 5.67% points (N 48.44%, C 42.77%) and that of dialysis introduction decreased by 0.85% points (N 19.06%, C 19.91%). In the sensitivity analysis, expenses could be reduced in almost all cases except when renal biopsy using conventional screening was performed at the rate of 73% or higher. ConclusionScreening for IgAN using novel biomarkers would reduce renal disease–related expenses.

Role of MCP-1 in the development of tubulointerstitial fibrosis in patients with primary chronic glomerulonephritis

BACKGROUND. To date, the study of the factors involved in the glomerular-tubular pathological connections leading to damage to the tubulointerstitial tissue is one of the topical areas of nephrology. THE AIM: to study the effect of MCP-1 in the development of tubulointerstitial fibrosis as a factor in the irreversible progression of chronic renal failure. PATIENTS ANDMETHODS. Prospective observation and retrospective analysis of case histories were carried out, which included a total of 75 patients with primary chronic glomerulonephritis. RESULTS. The average age of the patients was 36.7 ± 12.3 years, of which 52 were males, 23 were women. The average length of service in a nephrological disease was 3.0 [1.0; 5.0] years. The calculated GFR values are 87.3 ± 31.2 ml / min / 1.73 m2. In the general population, the moderate degree of MCP-1 expression, estimated at 2 points, was 35 %, pronounced expression was found in 25 % of the respondents. In the mesangium of the glomeruli and in macrophages, the expressed degree of MCP-1 expression was 20 % and 16 %, respectively, which characterizes MCP-1 as a marker produced by resident cells. When studying the relationship of MCP-1 in blood with clinical parameters, a correlation was found with the values of total protein (Rs= –0.43; p &lt;0.05), with erythrocyturia (Rs= –0.28; p &lt;0.05), as well as with an albumin level (Rs= –0.5; p &lt;0.05), which indicates the role of MCP-1 in the development of nephritic forms of glomerulonephritis. Depending on the severity of MCP-1 expression in biopsy specimens, the incidence of focal tubulointerstitial fibrosis with MCP-1 expression estimated at 1 point was 13.3 %, 2 points – 14.3 %, 3 points – 44.0 %. The revealed significant correlation between the serum level of MCP-1 and the severity of tubulointerstitial fibrosis confirms the MCP-1-mediated mechanism of progression of CKD. CONCLUSION. The relationship of serum and tissue forms of MCP-1 with the progression of tubulointerstitial fibrosis in chronic glomerulonephritis has been demonstrated. MCP-1-induced mesangial cell plays a critical role in the development of renal tubular damage, and its increased expression is associated with progressive tubulointerstitial fibrosis and decreased renal function.

Immunohistological score of transcription factor 21 had a positive correlation with its urinary excretion and proteinuria in immunoglobulin A nephropathy.

Transcription factor 21 (TCF21) contributes to mammalian nephrogenesis, and especially to glomerular maturation. Our previous study suggested its influence on glomerular injury, showing that TCF21 expression in podocytes had a positive correlation with the urinary protein value and also with the urinary TCF21 concentration. We now focus on its influence on the clinical course of immunoglobulin A nephropathy (IgAN), as patients with IgAN constitute the largest population of individuals with primary chronic glomerulonephritis in the world. Twenty cases of IgAN were divided into two groups according to the immunohistological score (IHS) of glomerular TCF21 expression: group IHS1 (n=7) and group IHS2+3 (n=13). Sixteen of the 20 cases were followed up for 2 years. Group IHS2+3 had heavier urinary protein (p=0.03) and a greater urinary TCF21 level (p<0.001) compared to group IHS1 at baseline. None of the other factors including hematuria, estimated glomerular filtration rate (eGFR), or the Oxford classification showed a statistically significant difference between these two groups. At the 2-year follow-up, even though the rate of remission in urinary protein, hematuria and the eGFR decline were not statistically correlated to IHS, the IHS2+3 group had a slight tendency toward a steeper eGFR decline compared to IHS1 (p=0.31). The present study suggested that the higher IHS of TCF21 corresponded to heavier proteinuria and a higher urinary TCF21 level in IgAN. This could be the first step in determining the TCF21 value for predicting the prognosis for IgAN.

Prediction of remodeling of arteries of kidneys of small diameter in patients with chronic glomerulonephritis

Objective: to determine the significance of clinical, laboratory and morphometric indicators of structural restructuring of kidney tissue in the prognosis of remodeling of small-diameter kidney arteries in patients with primary chronic glomerulonephritis. Materials and methods: the study included 97 patients with primary chronic glomerulonephritis and indications for puncture nephrobiopsy. In all patients, anamnestic and clinical and laboratory risk factors were recorded, and nephrobiopsy was performed. When performing morphometric analysis of nephrobiopsy, the state of the tissue and vessels of the kidneys of small diameter was studied. To achieve this goal, all patients were divided into two groups, the ranking of which was carried out according to the median wall thickness of the interlobular artery. Results: Among all the risk factors studied, a statistically significant effect of an increase in the stages of hypertension (χ2 criterion = 4.24, p = 0.03) and a decrease in GFR (χ2 criterion = 5.92, p = 0.015) on the risk of increasing the thickness of the interlobular artery was found. The indicators of structural reconstruction of the renal tissue did not have a statistically significant effect on the likelihood of remodeling of the arterial wall. However, a direct correlation of weak strength was found between the severity of tubulointerstitial inflammation and the thickness of the wall of the interlobular artery (r = 0.23, p = 0.02). Conclusions: this work shows the paramount importance of hypertension, accompanied by damage to target organs, as a marker of remodeling of the vascular wall of the interlobular artery in patients with chronic glomerulonephritis.

Analysis of the influence of clinical and morphological parameters on the risk of small-diameter renal artery fibroelastosis in arterial hypertension and primary chronic glomerulonephritis

Abstract Introduction The study of remodeling of small-diameter renal arteries in hypertension (AH) and primary chronic glomerulonephritis (CGN) is promising. This is due to the high prevalence of CGN and the likelihood of developing chronic renal failure, as well as insufficient information about the process of remodeling the small arterial wall of the kidneys. Goal To evaluate the influence of clinical and morphological parameters on the risk of small-diameter renal artery fibroelastosis in patients with AH and CGN. Materials and methods The study included 105 patients with AH and CGN. One of the main criteria for inclusion in the study was the presence of indications for performing nephrobiopsy. All subjects underwent a standard clinical and laboratory study, with determination of serum creatinine, of glomerular filtration rate (GFR) (CKD-EPI), detection of daily proteinuria, systolic (SAD) and diastolic blood pressure (DAP), and the degree and stage of AH. That 66 patients had no signs of fibroelastosis of arteries (the first group), and 39 patients had fibroelastosis (the second group). The presence of tubulointerstitial fibrosis (TF) and inflammation (TI), the prevalence of fibrosis were recorded. Results In the first group of patients, the level of SAD, established at the stage of inclusion in the study, was 124.33±21.5mmHg, in the second group – 131.15±17.3mmHg. (p=0.09). DAP values were in the range of 81.97±11.2 and 83.08±9.15mmHg. respectively (p=0.59). When analyzing the degree and stage of AH, statistically significant differences were obtained - 1.29±1.05 and 1.82±0.9 degrees (p=0.009), 1.41±1.08 and 2.08±0.9 stages (p=0.002), respectively. The value of creatinine in the first group was 98.33±39.8mmol/l (1.11 mg/dl), in the second group – 131.49±54.4mmol/l (1.49 mg/dl) (p=0.03), GFR - 97.6±40.4 and 69.3±32.5 ml/min/1.73m2 (p=0.0001), respectively. There were no significant differences in the proteinuria of patients in the study groups (3.64±6.2 and 4.1±5.1 g/l, respectively, p=0.42). Analysis of data obtained during morphological examination allowed us to establish more pronounced changes in TF and TI in the study groups (44 and 35 cases of TF (p=0.009), 35 and 29 cases of TI (p=0.025), respectively, groups). In the first group of patients, the prevalence of TF fever was set at 14.1±19.4%, in the second group – 27.95±21.9% (p=0.001). Conclusions The leading reasons for remodeling the vascular bed of small-diameter kidneys in AH and CGN are hemodynamic factor and tissue changes in the kidneys. The presence of fibrosis and interstitial inflammation is associated not only with the effects of the main CGN process, but also with the presence of AH. Confirmation of this conclusion is obtained differences in the stages of AH. An result of the study is data indicating that there are no differences in the clinical sign of progression of CGN-proteinuria, that is, the main pathogenetic factor of CGN does not affect of remodeling of the arteries. Funding Acknowledgement Type of funding source: None

Клинико-морфологические варианты первичного хронического гломерулонефрита у пациентов нефрологического отделения Витебской областной клинической больницы

Клинико-морфологические варианты первичного хронического гломерулонефрита у пациентов нефрологического отделения Витебской областной клинической больницы

Prediction of small-diameter arterial fibrosis in patients with hypertension and primary chronic glomerulonephritis

Aim. To study clinical, laboratory, and morphological risk factors for small-diameter renal arterial fibrosis in patients with hypertension (HTN) and primary chronic glomerulonephritis (CGN).Material and methods. The study included 102 patients with primary CGN. The first group consisted of 62 patients with small-diameter renal arterial fibrosis according to renal biopsy; the second group included 40 patients without vascular fibrosis. All patients signed informed consent.Results. A comparative analysis revealed the most significant differences between groups 1 and 2: mean systolic blood pressure (SBP) — 131,85±17,56 mm Hg and 119,65±22,2 mm Hg, respectively (p=0,0008); mean diastolic blood pressure (DBP) — 84,11±10,7 and 79,63±9,7 mm Hg (p=0,03), respectively; peak SBP — 158,61±23,76 mm Hg and 144,25±23,56 mm Hg (p=0,002), respectively; peak DBP — 95,66±10,33 mm Hg and 90,63±10,74 mm Hg (p=0,02), respectively; HTN stage — 1,85 [1; 3] and 1,38 [1; 3] (p=0,03), respectively; HTN grade — 1,73 [1; 3] and 1,13 [1; 3] (p=0,004), respectively; left ventricular hypertrophy — 15 patients and 2 patients (p=0,006), respectively; blood urea nitrogen — 8,98±7,31 and 6,42±4,02 mmol/L (p=0,03), respectively. Significant morphological differences between first and second groups were as follows: tubulointerstitial fibrosis — 56% and 21% (p&lt;0,001), respectively; tubulointerstitial inflamemation — 44% and 16% (p=0,002), respectively; interstitial fibrosis — 24,9±20,5% and 9,89±19,8% (p=0,001), respectively.Conclusion. The presented analysis emphasizes a significant contribution of hemodynamics in small-diameter renal arterial fibrosis in patients with HTN and CGN. It manifested by a persistent increase of SBP and involvement of target organs. Systemic hemodynamic changes are fundamental in the development of small-diameter renal arterial fibrosis in patients with HTN and primary CGN, while the isolated progression of CGN does not significantly affect the structure of small-diameter renal arteries.

P0505COST ANALYSIS OF SCREENING FOR IGA NEPHROPATHY USING NOVEL BIOMARKERS

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary chronic glomerulonephritis and a major cause of end-stage kidney disease worldwide. Recently, novel biomarkers including aberrantly glycosylated IgA1 and the glycan-specific antibodies can be measured and will predict the IgAN. However, little is known about the cost-effectiveness of this screening method from the societal perspective. This is the cost analysis of additional novel biomarkers to the conventional IgAN screening strategy. Method Cost analysis was carried out to compare the two diagnostic strategies with or without biomarkers. We developed an analytical decision model to estimate the lifetime medical expense of each strategy. The decision tree was started at forty years old with first time hematuria, and simulated the clinical strategy after the screening using the novel biomarkers (Group N: N), and conventional strategy (Group C: C). The result of the analysis is presented as the lifetime medical expenses from societal perspective. Discount was not considered. Results Lifetime medical expenses per person during forty years were calculated as 31.6 million JPY (≈287,270 USD) for using the novel biomarkers, 33.9 million JPY (≈307,903 USD) for conventional strategy. They were lower by 2.3 million JPY (≈20,633 USD) in Group N. Moreover, by using the novel biomarkers, the expected value of IgAN led to increase by 5.67 percent points (N: 48.44%, C: 42.77%), and the expected value of the dialysis led to decrease by 0.85 percent points (N: 19.91%, C: 19.06%). One-way sensitive analysis showed that the prevalence of IgAN was the most influential variable. In the sensitivity analysis, the rate of tonsillectomy with steroid pulse therapy and achieved clinical remission was higher, the expected lifetime expenses were reduced by 3.3 million JPY (≈30,355 USD) and the expected value of the dialysis led to decrease by 1.76 percent points (N: 11.80%, C: 13.56%). Conclusion Screening for IgAN using novel biomarkers is expected to reduce the lifetime medical expenses.

SAT-414 CLINICO-PATHOLOGICAL BASED PREDICTORS OF END STAGE RENAL DISEASE IN IgA NEPHROPATHY - EXPERIENCE FROM A TERTIARY CARE CENTRE IN SOUTHERN INDIA

Immunoglobulin A nephropathy (IgAN) is the most prevalent form of primary chronic glomerulonephritis. Around 20–40% patients progress variably to end-stage renal disease (ESRD) within 20 years of onset. Histological classification is essential, however, there are limitations in predicting the prognosis based on this information alone. Currently there is no validated tool to predict disease progression. Therefore, we combined both clinical and histological parameters to risk stratify patients of IgAN. Patients with biopsy proven IgAN from 2014 January to June 2019 were included. Independent pathological variables like mesangial hypercellularity(m), endocapillary proliferation(e), segmental and global sclerosis(s&g), interstitial fibrosis, tubular atrophy(t), crescents(c) and vascular lesions(v) – intimal hyalinosis, luminal narrowing and endothelial prominence were taken into account and divided into four histological grades (HG). 24-hour urinary protein excretion (UPE) values and estimated glomerular filtration rate(eGFR) were applied to a prognostic-predictive equation - [threshold score (− 1.86) = 0.722 + 0.364 × UPE − 0.046 × eGFR] for clinical grading (CG). In addition to above, serum uric acid, hypertension at the time of biopsy and haematuria was also compared for their effect on progression to ESRD. Association between clinical and histological variables at the time of renal biopsy with the incidence of subsequent ESRD were analysed using univariate logistic regression analysis along with Chi square and Fischer exact test. We also analysed association of variables with ESRD by calculating odds ratio and 95% confidence interval. 69 IgAN patients were included in the study with a mean age of 33.83 +11.05 years and eGFR of 54.85ml/min per 1.73 m2 with majority being males (60.9%). Mean proteinuria was 4.26 + 2.86 g/d of which 37 (53.6%) were in nephrotic range, of which 19(51.4%) progressed to ESRD. Only 21.7%(n=15) received steroids and 62.3%(n=43) received renin-angiotensin system (RAAS) inhibitors, of which 6.7%(n=1) and 2.3%(n=1) progressed to ESRD respectively. Among pathological variables global glomerulosclerosis (p=0.003, OR=4.4) and vascular lesions (p=0.002, OR=3.25) had significant association with ESRD progression. Vascular lesions were seen in 33.3% patients who had 3.25 times risk of progressing to ESRD. Most of our patients belonged to CG3(42%) or 4(38%). 30.4% patients who developed ESRD were in CG4 at presentation. Renal biopsy findings classified patients into HG1(15.9%), HG2(13%) and HG3 & 4(71%). 16 patients in HG3 & 4 progressed to ESRD as compared to 4(19%) in HG2 and 1(4.8%) HG1. Our study concluded that chronic lesions like global glomerular sclerosis and vascular lesions showed significant association to progression to ESRD in IgAN patients rather than any of the classically described MEST-C scoring from oxford classification. Considering the fact that UPE and eGFR significantly predict progression to ESRD, our population needs different predictive prognostic equation derived from multicentre study for clinical grading and need to consider wider spectrum of histopathological lesions to predict risk groups and prognosis to ESRD in IgAN patients.

ANALYSIS OF THE RELATIONSHIP BETWEEN RENAL REMODELING AND VASCULAR ADHESION-1 PROTEIN (VAP-1) IN CHRONIC PRIMARY GLOMERULONEPHRITIS

Goal. Determination of the relationship between the concentration of VAP-1 and the clinical and morphological parameters of the structural reorganization of the renal tissue. Materials and methods. The study included 80 patients with primary chronic glomerulonephritis in the period of exacerbation. The predominant morphological variants were IgA-nephropathy (42 patients) and focal-segmental glomerulosclerosis (16 patients). All patients underwent general clinical examination, with the establishment of stages of CKD, and nephrobiopsy was performed. Based on the results of morphological analysis, the parameters of remodeling of renal tissue were taken into account. A blood sample was taken to study the concentration of Vascular Adhesion- 1 protein (VAP-1). Nine months after the patients were admitted to the study and treated according to standard therapy, several indicators were re-recorded. Results. It was found that the age, duration of the disease, urea, proteinuria of a single and a daily portion of urine were inversely proportional to the level of VAP-1. Moreover, a signifi cant difference was found between the groups of patients ranked by median VAP-1, by prevalence in the group of patients with higher VAP-1 concentration of nephritic syndrome, IgA nephropathy, cases with mesangium expansion, mesangial and endothelial hypercellularity, endothelial swelling, IgA immune deposits In mesangium and capillary loops. Conclusion. As a result of the study, the prognostic signifi cance of VAP-1 concentration in patients with chronic glomerulonephritis was demonstrated. The formulas and the table of risk stratifi cation for the development of morphological reconstruction of kidney tissue are presented. It was found that the concentration of VAP-1 is statistically signifi cantly increased in the early stages of glomerulonephritis, with the predominance of infl ammatory and proliferative changes. At the stage of fi brous restructuring of renal tissue, there was no reliable difference. When analyzing the material obtained, it was concluded that it is necessary to determine the level of VAP-1 in patients with chronic glomerulonephritis, especially IgA-nephropathy, in the early stages of the disease, in order to predict its course.

Proteinuria rebound in IgA nephropathy associated with obesity-related glomerulopathy.

IgA nephropathy (IgAN), the most prevalent primary chronic glomerulonephritis worldwide, has three major risk factors: hypertension, proteinuria >1g/day, and severe renal lesions. Obesity also portends a poor prognosis. A Japanese boy with IgAN showed nephrotic syndrome at presentation. Pathological features resembled those of membranoproliferative glomerulonephritis (MPGN), although IgA deposition differed from MPGN and IgAN. Combination therapy improved renal lesions, but rebound deterioration of proteinuria occurred in this patient, who had marked obesity and hypertension. Serial kidney biopsy specimens were compatible with obesity-related glomerulopathy (ORG). Rebound proteinuria was apparently attributable to ORG rather than relapse and flaring up of IgAN.

Prognostic significance of urinary NGAL in chronic kidney disease.

BackgroundChronic kidney disease (CKD) is a worldwide public health problem. Recently urinary NGAL (uNGAL) has been proven to be a useful (potentially ideal) biomarker for early detection of CKD. The aim of the present study was to examine the correlation of uNGAL with severity of renal impairment in CKD and to evaluate its prognostic value in these subjects.MethodsThis was a prospective study carried out over a period of 24 months in subjects with CKD due to primary chronic glomerulonephritis. New cases of CKD stage II, III, IV aged between 18 and 65 years were enrolled as per KDIGO (Kidney Disease: Improving Global Outcomes) guidelines 2012. A total of 90 subjects completed the study up to the end-point. The primary follow-up end-point was 18 months, or decreased glomerular filtration rate of less than 15 mL/min. Secondary follow-up end-point was the number of subjects who expired during this period.ResultsMultiple regression model of estimated glomerular filtration rate showed significant associations with log uNGAL (β=0.38, P<0.001), Ca×PO4 (β=0.60, P<0.001), hemoglobin (β=0.37, P<0.001), urine protein (β=0.34, P<0.001), serum albumin (β=0.48, P<0.001), and systolic blood pressure (β=0.76, P<0.001). Receiver operator curve for uNGAL considering the progression of CKD showed area under the curve for uNGAL was 0.878 (95% confidence interval: 0.68–0.96). Cut-off value for uNGAL was log 3.5 unit with a sensitivity of 93.08% and specificity of 71.43% for predicting the progression of CKD. Kaplan–Meier survival curve showed that patients with log uNGAL levels <3.51 unit had a survival rate of 71.4% while patients with NGAL level >3.51 unit had a renal survival rate of 14.7%.ConclusionOur study result showed that uNGAL has a positive correlation with disease severity which signifies the prognostic importance of uNGAL in CKD.

PP.13.18

Objective: Recent evidence suggests that renal vascular changes contribute to progressive renal disease and that alteration of vascular endothelial growth factor-A (VEGF-A) might play an important role in modulating microvascular loss of macrovascular remodeling in the kidney, as well as in the vessels. It remains controversial the mechanism by which VEGF works in the kidney, as well as in the vessels at least in the early stages of chronic kidney disease (CKD). Whether VEGF-A is detrimental in early stages of CKD or whether in other renal conditions has not yet been clearly answered. Tissue inhibitor of metalloproteinase -1 (TIMP-1) has been identified in humans and its expression is regulated during development and tissue remodeling. TIMP-1 overexpression in a mouse model of atherosclerosis showed a lesion reduction. The aim of the present study was to determine the serum levels of VEGF-A and TIMP-1 and to investigate their potential correlation with hypertension (HT), atherosclerotic markers and albuminuria in early stages of CKD and primary chronic glomerulonephritis (CGN). Design and method: CKD patients of stages 1 and 2 with CGN (n = 50) were included. As controls, there were healthy individuals (n = 40). Clearance of creatinine (Clcr) and albumin excretion were examined in the 24 h urine. VEGF-A and TIMP-1 levels were measured by an ELISA method. Intima media thickness (IMT) of carotid and femoral arteries and atheromatic plaque were evaluated by a high resolution ultrasonography. Results: There was a statistically significant difference between VEGF-A (200 ± 30, p < 0.0001), TIMP-1 (400 ± 20, p < 0.0001), HT (20 ± 5, p < 0.0001) and IMT (0.3 ± 0.09, p < 0.0001) in the patient group. There was a statistically significant negative strong correlation between levels of VEGF-A and TIMP-1 (r = -0.7, p < 0.0001), such as between TIMP-1 and IMT (r = -0.65, p < 0.0001). There was a statistically positive correlation between VEGF-A and IMT (r = 0.6, p < 0.0001). Further, VEGF-A and TIMP-1 levels were independently correlated with HT, IMT and atheromatic plaque. Conclusions: Our study suggests that serum levels of VEGF-A and TIMP-1 might present independent risk factors of hypertension, atherosclerosis and albuminuria, at least in the early stages of primary glomerulonephritis to the progression of CKD.

PP.41.17

Objective: Transforming growth factor β-1 (TGF-β1) is involved nowadays in atherosclerosis and proteinuria. Albuminuria is considered to be one of the most importantagents for the onset and progression of renal dysfunction in chronic kidney disease (CKD) and more recently, it has also been implicated in cardiovascular disease (CVD) and peripheral vascular disease. Conflicting studies cannot establish at present a clear role for TGF-β1 in the pathogenesis of diabetic albuminuria and atherosclerosis. This fibrogenic cytokine, stimulated by the diabetic state, induces diabetic renal hypertrophy, mesangial matrix expansion, and the development of renal insufficiency. Interleukine-6 (IL-6) is considered to be pro-inflammatory lipocytokine. The aim of the present study was to determine the serum levels of TGF-β1 and IL-6 and to investigate their potential correlation with hypertension, atherosclerotic markers and albuminuria in early stages of CKD and primary chronic glomerulonephritis (CGN). Design and method: CKD patients of stages 1 and 2 with CGN (n = 50) were included. As controls, there were healthy individuals (n = 40). Clearance of creatinine (Clcr) and albumin excretion were examined in the 24 h urine. TGF-β1 and IL-6 levels were measured by an ELISA method. Blood pressure (BP) was taken using a manual sphygmomanometer. Intima media thickness (IMT) of carotid and femoral arteries and atheromatic plaque were evaluated by a high resolution ultrasonography. Results: There was a statistically significant difference between TGF-β1 (10000 ± 1200, p < 0.0001), IL-6 (4 ± 0.5, p < 0.0001), BP (20 ± 5 p < 0.0001) and IMT (0.3 ± 0.09, p < 0.0001) between patients and controls. There was a statistically significant positive strong correlation between levels of TGF-β1 and IL-6 (r = 0.65, p < 0.0001), TGF-β1 and BP (r = 0.7, p < 0.0001), such as between TGF-β1 and IMT (r = 0.65, p < 0.0001) in the patient group. There was also a statistically positive correlation between IL-6 and IMT (r = 0.7, p < 0.0001) in the patient group. Further, TGF-β1 and IL-6 levels were independently correlated with BP, IMT and atheromatic plaque. Conclusions: Our study suggests that serum levels of TGF-β1 and IL-6 might present independent risk factors of blood pressure, atherosclerosis and albuminuria, at least in the early stages of CGN to the progression of CKD.

PP.25.21

Objective: Matrix metalloproteinase-2 (MMP-2) is considered to be the main enzyme that degrades collagen type-IV (col-IV) and has been implicated in chronic kidney disease (CKD) and cardiovascular disease (CVD). Tissue inhibitor of metalloproteinase-2 (TIMP-2) participates in nephron morphogenesis and inhibits endothelial cell growth induced by fibroblast growth factor, as well MMP-2. Conflicting studies cannot establish at present a clear role for TIMP-2 in the pathogenesis of albuminuria and atherosclerosis. The aim of the present study was to investigate the serum levels of TIMP-2 and MMP-2 and their potential role in hypertension, atherosclerosis and albuminuria in patients with early stages of CKD and primary chronic glomerulonephritis (CGN). Design and method: CKD patients of stages 1 and 2 with CGN (n = 50) were included. Patients with active inflammatory disease or malignancy were excluded. As controls, there were healthy individuals (n = 40). Clearance of creatinine (Clcr) and albumin excretion were examined in the 24 h urine. TIMP-2 and MMP-2 levels were measured by an ELISA method. Blood pressure (BP) was taken using a manual sphygmomanometer. Intima media thickness (IMT) of carotid and femoral arteries and atherosclerotic plaque were determined by a high resolution ultrasonography. Results: There was a statistically significant difference between MMP-2 (250 ± 10, p < 0.0001), TIMP-2 (100 ± 20, p < 0.0001), BP (25 ± 15, p < 0.0001) and IMT (0.15 ± 0.2, p < 0.0001) in the patient group. There was a statistically significant negative strong correlation between levels of MMP-2 and TIMP-2 (r = -0.7, p < 0.0001), such as between TIMP-2 and IMT (r = -0.62, p < 0.0001). There was a statistically positive correlation between MMP-2 and IMT (r = 0.75, p < 0.0001). Further, MMP-2 and TIMP-1 levels were independently correlated with BP, IMT and atheromatic plaque. Conclusions: This study suggests that serum levels of TIMP-2 and MMP- 2 were found to be independent risk factors of hypertension, atherosclerosis as well as of albuminuria in early stages of CKD and CGN.

Distribution of Streptococcus mutans strains with collagen-binding proteins in the oral cavity of IgA nephropathy patients

IgA nephropathy (IgAN) is the most common primary chronic glomerulonephritis; however, its precise initiating pathogenesis remains unclear. Streptococcus mutans is a major pathogen of human dental caries. S. mutans strains with the cnm gene encoding Cnm, a collagen-binding protein, have been reported to contribute to the development of systemic diseases. However, the contribution of S. mutans with Cnm in the development of IgAN has not been reported. The aim of this study was to investigate the prevalence of cnm-positive S. mutans in IgAN patients and clarify the effects of cnm-positive S. mutans on the histological pathology of IgAN. We identified the cnm gene in S. mutans isolated in saliva specimens, which were collected from IgAN patients (n = 53) and control subjects (n = 50). We evaluated the collagen-binding properties of S. mutans in IgAN patients and controls. The clinical parameters and histological scores were also assessed in IgAN patients. The rates of S. mutans isolation in IgAN and control groups were 84.0 and 84.9 %, respectively, not significantly dfferent. cnm-positive strains were significantly more prevalent in the IgAN group than in controls (32.1 vs. 14.0 %, p < 0.05). With regard to collagen-binding assays, the binding rates of cnm-positive strains were significantly higher in the IgAN group than in controls (96.6 vs. 30.0, p < 0.05). In addition, the segmental glomerulosclerosis scores were significantly higher in cnm-positive patients with IgAN than in cnm-negative patients with IgAN (0.94 vs. 0.57, p < 0.05). cnm-positive S. mutans strains are potentially associated with the pathogenesis of IgAN.

Implications of the changes in serum neutrophil gelatinase‐associated lipocalin and cystatin C in patients with chronic kidney disease

Early intervention in patients with chronic kidney disease (CKD) significantly improves the prognosis. The present widely used markers of renal function, such as serum creatinine (sCr), fail to reflect early renal damage and predict the progression of disease. The authors aimed to evaluate whether neutrophil gelatinase-associated lipocalin (NGAL), a novel specific biomarker of acute kidney injury, could predict the progression of CKD. We identified 92 patients with stage 2-4 CKD caused by primary chronic glomerulonephritis. The patients were followed for 2 years, the changes in NGAL levels in the progressive and non-progressive groups were compared. First, the serum NGAL levels of patients with stage 2-4 CKD were significantly increased compared with the control group. Second, based on Pearson correlation analysis, positive correlations existed between NGAL and cystatin C levels and between NGAL and sCr levels. Third, bounded by the progress of renal function, the area under the curve of serum NGAL was 0.872 (95% confidence interval, 0.786-0.933), which suggests a blood NGAL cut-off level of 246 ng/mL (sensitivity 85.19%, specificity 81.54%). Fourth, Kaplan-Meier survival curve analysis showed that the serum NGAL level was closely related to the end-point of renal function in patients with CKD. Fifth, Cox multivariate regression analysis showed that the estimated glomerular filtration rate and blood NGAL are associated with progression of CKD. Serum NGAL is an effective biomarker for detecting early-stage renal damage in CKD patients. Serum NGAL was significantly correlated with the severity of renal damage and the progression of renal function deterioration.