Chronic Glomerulonephritis Group Research Articles

Alterations in urinary ceramides, sphingoid bases, and their phosphates among patients with kidney disease.

To avoid an invasive renal biopsy, noninvasive laboratory testing for the differential diagnosis of kidney diseases is a desirable goal. As sphingolipids are demonstrated to be involved in the pathogenesis of various kidney diseases, we investigated the possible usefulness of the simultaneous measurement of urinary sphingolipids for differentiating kidney diseases. Residual urine specimens were collected from patients who had been clinically diagnosed with chronic glomerulonephritis (CGN), diabetic mellitus (DM), systemic lupus erythematosus (SLE), and arterial hypertension (AH). The urinary sphingolipids-CERs C16:0, C18:0, C18:1, C20:0, C22:0, and C24:0; sphingosine [Sph]; dihydrosphingosine; sphingosine 1-phosphate [S1P]; and dihydroS1P [dhS1P]-were measured by liquid chromatography-tandem mass spectrometry. Based on the results, machine learning models were constructed to differentiate the various kidney diseases. The urinary S1P was higher in patients with DM than in other participants (P < 0.05), whereas dhS1P was lower in the CGN and AH groups compared with control participants (P < 0.05). Sph and dhSph were higher in patients with CGN, AH, and SLE than in those with control participants (P < 0.05). The urinary CERs were significantly higher in patients with CGN, AH, and SLE than in those with control participants (P < 0.05). As a results of constructing a machine learning model discriminating kidney diseases, the resulting diagnostic accuracy and precision were improved from 94.03% and 66.96% to 96.10% and 78.26% respectively, when the urinary CERs, Sph, dhSph, S1P, dhS1P, and their ratios were added to the models. The urinary CERs, sphingoid bases, and their phosphates show alterations among kidney diseases, suggesting their potential involvement in the development of kidney injury.

#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.

Effects of electroacupuncture at KI3 and ST36 on the hypothalamic paraventricular nucleus in a rat model of chronic glomerulonephritis.

The hypothalamic paraventricular nucleus (PVN) acts as a critical integrating center of endocrine/autonomic responses and regulates visceral functional activities. However, its involvement in electroacupuncture (EA) treatment of chronic glomerulonephritis (CGN) remains unclear. Over four experiments, we randomized 111 rats into: control, untreated model (CGN) or EA-treated model (CGN + EA) groups, a model group receiving EA after PVN damage (CGN + EA + Lesion) or untreated model groups injected with adeno-associated viral vectors encoding human M4 muscarinic receptor (CGN + hM4D) or enhanced green fluorescent protein (CGN + EGFP). CGN was modeled by intraperitoneal injection of bovine serum albumin for 2 weeks. Rats in the CGN + EA and CGN + EA + Lesion groups received EA at bilateral ST36 and KI3 for 14 days. Urine/serum samples were collected to evaluate inflammatory factors and changes in renal function. EA inhibited the release of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1β, and decreased urine protein (PRO), creatinine (Cre) and blood urea nitrogen (BUN) levels. PVN damage influenced the effect of EA on the levels of these parameters. EA appeared to inhibit the firing frequency and spectral energy of PVN neurons. In the viral vector experiment, levels of PRO, Cre, IL-6, IL-1β and TNF-α in the CGN group were increased in CGN versus control groups (p < 0.0001), decreased in CGN + hM4D versus CGN groups (p < 0.05) and did not differ between CGN + EGFP and control groups (p > 0.05). Our findings indicate that EA at ST36 and KI3 improves CGN in this rat model by weakening the activity of PVN neurons, alleviating impairment of renal function impairment and restricting the release of inflammatory factors.

Rhein Inhibits NF-κB Signaling Pathway to Alleviate Inflammatory Response and Oxidative Stress of Rats with Chronic Glomerulonephritis.

Objective To explore the effect and mechanism of rhein on chronic glomerulonephritis (CGN). Method Twenty-four eight-week-old male SD rats were randomly divided into following 4 groups (6 rats in each group): control group, CGN group, rhein group, and benazepril (Ben) group. And 5 mg/mL of cationization-bovine serum albumin (C-BSA) was mixed with an equal volume of Freund's incomplete adjuvant for the preparation of 2.5 mg/mL of C-BSA solution. The rat model of CGN was established by injection of C-BSA for six weeks. Calculation of the renal index in rats was conducted. Biochemical detection was performed to measure the level of 24 h urinary protein, blood urea nitrogen (BUN), serum creatinine (SCr), and serum albumin (ALB) of the rats, as well as the level of malondiadehyde (MDA), superoxide (SOD), and glutathione peroxidase (GSH-Px) in the kidney tissue. Hematoxylin and eosin (H&E) staining was utilized to measure histological changes in the kidney of the rats. The level of TNF-α, IL-1β, IL-6, and ICAM-1 in rat kidney tissues was determined by enzyme-linked immunosorbent assay (ELISA). Western blot was applied to check the expression of NF-κB in the nucleus and cytoplasm as well as the expression of IκBα and p-IκBα in rat kidney tissues. Results Rhein could decline urinary protein, restore blood biochemical parameters, and protect renal tissue in rats with CGN. Besides, rhein could inhibit the activity of the NF-κB signaling pathway in rats with CGN and could alleviate the inflammatory response and oxidative stress level at the same time. Conclusion Rhein alleviates inflammatory responses and oxidative stress in rats with CGN. It also provides a theoretical basis and data support for the therapeutic drugs for CGN.

MO254PREGNANCY OUTCOMES AND COMPLICATIONS IN PATIENTS WITH CHRONIC GLOMERULONEPHRITIS*

Abstract Background and Aims Pregnancy in patients with chronic glomerulonephritis (CGN) is associated with higher risk of complications and unfavorable outcomes compared to the general population. The aim of the study was to determine the incidence of pregnancy complications and outcomes in patients with preexisting CGN. Method 126 pregnancies in 119 women with CGN and CKD 1-4 stages: 1 st. – 86 patients, 2 st. – 17, 3 st. – 20, 4 st. – 3 and 20 pregnancies in 20 age-matching healthy women were included. Patients with secondary CGN, multiple pregnancy, pregnancy after IVF were excluded. A kidney biopsy was performed in 18 of 119 (15.1%) women: 15 – before conception and 3 – after delivery. IgA-nephropathy was detected in 11 of 18 (61.1%) patients, MCD/FSGS – in 4 (22.2%), MPGN – in 3 (16.7%). The incidence of unfavorable pregnancy outcome, preeclampsia (PE), preterm delivery, cesarean section (CS), low birth weight (LBW &amp;lt; 2500 g), small for gestational age (SGA) newborn (birth weight &amp;lt; 10th percentile), mean term of delivery, mean birth weight, frequency of treatment in neonatal intensive care unit (NICU) and achieving of end-stage kidney disease in mothers after delivery were evaluated. Results CKD was first diagnosed during pregnancy in 34.1% women with CGN. The incidence of adverse pregnancy outcomes, preterm delivery, LBW, SGA, and treatment in the NICU did not differ between groups, while the frequency of PE and CS were higher, and mean gestational age at delivery, birth weight were lower in the CGN group compared to the healthy control (Table). Severe PE was observed in 6 of 32 (18.7%) patients with PE and CGN. The incidence of PE increased in advanced stages of CKD, but the differences were not significant: 19.8% - in CKD1, 35.3% - CKD2, 35% - CKD3, 66.7% - CKD4, p=0.112. The frequency of PE depended on the presence of baseline nephrotic-range proteinuria (NPU) and chronic arterial hypertension (AH): PE was observed in women w/o NPU and w/o AH in 8.3% cases, w/o NPU and with AH – in 39%, with NPU and w/o AH – in 44,4%, with NPU and with AH – in 43.8%, p=0.00048. Preterm delivery, CS and LBW were more common in women with chronic renal failure, and their frequency increased with increasing severity of CKD: CKD1 – 3.5%, 21.2%, 3.5% resp.; CKD2 – 6.7%, 53.3%, 20%; CKD3 – 40%, 70%, 40%; CKD4 – 100%, 100%, 100% (p&amp;lt;0.0001, for all characteristics). We found differences in gestational age at delivery depending on the stages of CKD: in CKD1 it was 38.9 ± 1.3 wks, CKD2 – 38.2 ± 2.1 wks, CKD3 – 36.3 ± 3.5 wks, CKD4 – 32.4 wks (one child), p=0.00013. The proportion of newborns requiring intensive care was higher in mothers with CKD3 (30%) and CKD4 (100%) compared with CKD1 (0%) and CKD2 (13.3%), p&amp;lt;0.0001. Five of 126 (4%) patients in CGN group achieved stage 5 CKD with average postpartum follow-up period of 92.6 ± 20.5 months; 4 women had CKD3 during pregnancy, one – CKD1. Now 2 patients are treated with regular hemodialysis, 3 - live with kidney transplant. Conclusion Chronic glomerulonephritis has a negative effect on pregnancy course, increasing the incidence of PE and CS and contributing to reduce gestational age and birth weight. Incidence of preterm delivery, CS, LBW and proportion of newborns treated in NICU were highest in patients with CKD 3-4.

Impact of high mortality in incident dialysis patients due to hypertensive nephrosclerosis: a multicenter prospective cohort study in Aichi, Japan.

An increasing number of patients worldwide require dialysis as a result of hypertensive nephrosclerosis (HTN). However, in Japan, mortality in patients with end-stage renal disease (ESRD) has not been well by primary kidney disease including HTN and diabetic nephropathy (DN). Hence, we examined the differences in mortality among the primary kidney diseases of incident dialysis patients. The study was a multicenter prospective cohort analysis including 1520 incident dialysis patients in Aichi prefecture, Japan. We classified patients into three groups according to the primary kidney disease [i.e., a HTN group, n = 384, a DN group n = 658, and a chronic glomerulonephritis (CGN) group, n = 224]. In addition, we classified patients into the HTN group and the DN group using propensity score matching. We compared outcomes including all-cause and infection-related mortality. The mortality rates of the HTN, the DN, and the CGN group, were 135.9, 64.2, and 34.8 per 1000 patient years, respectively. All-cause mortality and infection-related mortality rates in the HTN group were as high as those in the DN group after adjustment for age, gender, history of cardiovascular disease, and estimated glomerular filtration rate. No significant difference of all-cause mortality was observed after propensity score matching between the two groups (Logrank test: p = 0.523). The present study was Japan's first large-scale prospective cohort to demonstrate that HTN is the second most common cause of ESRD. In addition, the prognosis of patients with HTN was as poor as that of patients with DN.

Fetal Risks and Maternal Renal Complications in Pregnancy with Preexisting Chronic Glomerulonephritis.

BackgroundAnalysis the maternal and fetal risk predictors in pregnancy in conjunction with chronic glomerulonephritis (CGN) patients are helpful to understand the influence of kidney diseases on pregnancy and the effects of pregnancy on kidney diseases. The aim of this study was to determine the predictors of adverse maternal and fetal outcomes in CGN patients.Material/MethodsMaternal and fetal outcomes in 64 pregnancies of CGN patients were retrospectively analyzed. We randomly selected 100 low-risk-pregnancy women without chronic kidney disease (CKD) at the same time as the control group. Clinical manifestations, laboratory data, medication, and outcomes during pregnancies of these patients were analyzed by univariate and logistic regression.ResultsCGN patients were associated with higher adverse pregnancy outcomes versus general pregnancies. The gestational ages are shorter, and the incidence of preeclampsia, gestational hypertension, and abortion were increased. The rates of premature delivery, low birth weights, and intrauterine growth restriction were higher in the CGN group. Prenatal proteinuria and blood pressure were significantly increased compared with pre-pregnancy stage. Proteinuria (0.9±0.6 g/d vs. 0.5±0.3 g/d, P=0.032) and hypertension (6.9% vs. 3.4%, P=0.021) at 6 months after delivery were aggravated. Prenatal proteinuria ≥3.5 g/d (OR 12.22, 95%CI 3.16~47.32, P=0.001) was the maternal risk predictor in pregnancy. Prenatal blood pressure ≥160/110 mmHg (OR 8.97, 95%CI 1.69~47.53, P=0.010) and uric acid ≥363 μmol/L (OR 7.35, 95%CI 1.88~28.76, P=0.004) were the fetal risk predictors in pregnancy in conjunction with CGN patients.ConclusionsMaternal-fetal risks are increased in pregnancies in conjunction with CGN patients. Prenatal proteinuria ≥3.5 g/d, BP ≥160/110 mmHg, and uric acid ≥363 μmol/L were the maternal and fetal risk predictors in pregnancy.

Posttransplant Urinary Tract Infection Rates and Graft Outcome in Kidney Transplantation for End-Stage Renal Disease Due to Reflux Nephropathy Versus Chronic Glomerulonephritis.

The goal of this study was to evaluate posttransplant urinary tract infection (UTI) rates and graft outcome in kidney transplantation for end-stage renal disease (ESRD) due to vesicoureteral reflux (VUR)-related reflux nephropathy (RN) versus chronic glomerulonephritis (CGN). A total of 62 patients with ESRD who underwent kidney transplantation for VUR-related RN (VUR-RN group, n= 31; mean ± standard deviation age, 34.1 ± 6.0 years; 58.1% female) or CGN (CGN group, n= 31; mean age, 34.2 ± 6.8 years; 71.0% male) at our unit between January 1996 and January 2011 were included in this retrospective study. Baseline recipient and donor characteristics, renal replacement therapy, posttransplant data on serum creatinine levels, graft outcome, and UTIs were recorded. Posttransplant UTIs and graft outcome were compared between the VUR-RN and CGN groups, as well as between patients with and without pretransplant nephrectomy in the VUR-RN group. The frequency of overall (72 vs 18 of 90; P= .05) UTI episodes was significantly higher in the VUR-RN group than in the CGN group; Escherichia coli (64.2%) was the most common pathogen. The VUR-RN and CGN groups were similar in terms of 1-year (100.0% for each), 5-year (95.8% vs 96.8%), and 10-year (82.0% vs 96.8%) graft survival. VUR-RN patients with and without nephrectomy were similar in terms of 1-year (100.0% for each), 5-year (91.7% vs 85.7%), and 10-year (81.5% vs 85.7%) graft survival. Our findings indicate kidney transplantation is a safe and effective option in ESRD patients with RN secondary to VUR. It resulted in high 1-year, 5-year, and 10-year graft survival rates.

Synchrotron radiation (SR) diffraction enhanced imaging (DEI) of chronic glomerulonephritis (CGN) mode.

The aim of this study is to investigate microstructural changes in chronic glomerulonephritis (CGN) rabbit model under diffraction enhanced imaging (DEI) technology of synchrotron radiation (SR). The chronic glomerulonephritis (CGN) models were obtained within two months after 5 New Zealand white rabbits were treated with doxorubicin hydrochloride. Blood exams, urine tests and kidney histological studies were carried out after the 5 rabbits were humanely sacrificed by hyperanesthesia. The kidney tissues were fixed in 4% formalin for one week before DEI experiment, with another 5 normal rabbits used as the control group. The experiment was performed at Beijing Synchrotron Radiation Facility (BSRF) with a 4W1A beam line (beam energy was 14keV). On routine scanning process, the rocking curve was detected, and slope position on the curve was selected to make a 360° spatial CT scan; DEI reconstruction software was used to generate a 3-dimensional image, from which the difference in grey value between the chronic glomerulonephritis (CGN) group and the control group was measured and analyzed using MATLAB and SPSS. Without radio-contrast, DEI provided clear visibility of the microstructures including artery, vein, straight collecting ducts, papillary tubules, glomeruli in both the chronic glomerulonephritis (CGN) group and the control group, with a spatial resolution as low as 10μm. MATLAB grey value extraction and SPSS analysis showed that cortex of CGN group (91 to 112) lost more gray value compared to the control group (121 to 141), T tests P < 0.05. Equivalant cortical ROI (data points 450×80) quantitative analysis showed that gross grey value of CGN group (ranking from 55 to 160) was smaller than the control group (ranking from 75 to 175). DEI images correlated well with pathologic images. Morphological changes in the microstructure of contstartabstractCGN kidney was revealed, due to the advantage of phase-contrast imaging (PCI) mechanism, and the diagnostic value of CGN by synchrotron radiation (SR) phase-contrast imaging (PCI) technology was evaluated. Synchrotron radiation (SR) diffraction enhanced imaging (DEI) experiment makes non-contrast CGN diagnosis possible in the rabbit model studied. With improvement of laboratory equipment and image analyzer in clinical practice, diffraction enhanced imaging (DEI) could fundamentally become a new diagnostic method for CGN.

Oral health in patients on haemodialysis for diabetic nephropathy and chronic glomerulonephritis

The objective of this study was to clarify differences in oral health status between patients who needed haemodialysis (HD) owing to diabetic nephropathy (DN) and chronic glomerulonephritis (CGN). Ninety-eight HD patients who were 50-70 years old were selected as the study subjects [DN group (29 subjects) and CGN group (69 subjects)] to compare with 106 control subjects (control group) not undergoing HD. All HD subjects underwent oral- and systemic-related examination just before HD therapy. The mean number of teeth present in the DN group was significantly less than in the CGN and control groups. The mean percentage of sites with bleeding on probing in the DN group was greater than in the CGN and control groups. The mean salivary flow rate in the DN and CGN groups was significantly lower compared with the control group. The patients undergoing HD for DN were found to have fewer teeth and worse periodontal health compared with those undergoing HD for CGN and with the control subjects not undergoing HD. Furthermore, the dental and periodontal health of the patients undergoing HD for CGN was comparable to that of the controls. For effective measures of prevention and improvement of oral health in HD patients, clinicians should be aware of the differences in the characteristics of the oral health between patients undergoing HD for DN and CGN.

Von Willebrand factor, ADAMTS13 activity, TNF-α and their relationships in patients with chronic kidney disease

Patients with chronic kidney disease (CKD) often exhibit associated endothelial dysfunction and inflammation. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. In this study, we assessed the relationships among endothelial dysfunction, a disintegrin-like and metalloprotease with thrombospondin type 1 repeats 13 (ADAMTS13) activity and levels of inflammatory cytokines in CKD patients. CKD patients were classified into three groups: The chronic glomerulonephritis group (CGN; n=31), the idiopathic nephritic syndrome group (NS; n=32) and the lupus nephritis group (LN; n=41). We measured the plasma levels of tumor necrosis factor-α (TNF-α), von Willebrand factor (VWF) antigen (VWF:Ag) and ADAMTS13 activity using an ELISA-based method in CKD patients (n=104) and normal controls (n=32). The ratio of the VWF:Ag levels to ADAMTS13 activity was calculated. The VWF:Ag levels were significantly higher and the ADAMTS13 activities were significantly lower in the disease groups compared to the controls (P<0.01). ADAMTS13 activity was lower in the NS group compared to the CGN and LN groups (P<0.05). The TNF-α levels were higher in the CKD group compared to the control group (P<0.01). TNF-α was positively correlated with the VWF:Ag levels (r=0.242, P=0.013) and negatively correlated with the glomerular filtration rate (GFR) (r=-0.193, P=0.049). ADAMTS13 activity was negatively correlated with the cholesterol levels in CKD patients (r=-0.2, P= 0.042). TNF-α levels in CKD were positively correlated with the VWF:Ag levels and negatively correlated with GFR, which indicates that inflammation may be a major cause of endothelial dysfunction and an index of renal function. The VWF:Ag levels increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state.

Von Willebrand Factor, ADAMTS13 Activity, TNF-Alpha, and Their Relationships in Patients with Chronic Kidney Disease

Abstract 5312Patients with chronic kidney disease (CKD) have increased risks of endothelial dysfunction and thrombosis. Systemic inflammation may contribute to the endothelial dysfunction and accelerated thrombosis observed in CKD patients. von Willebrand factor (VWF), a well-known index of endothelial damage, has been reported to increase both in CKD and inflammatory states. ADAMTS13 is a specific VWF-cleaving protease, and some reports suggested that the ratio of VWF and ADAMTS13 maybe more useful in the diagnosis and treatment evaluation of patients in the prothrombotic state. So we assessed the relationships among endothelial dysfunction, ADAMTS13 activity, and levels of inflammatory cytokines in CKD patients. CKD patients were classified into 3 groups: chronic glomerulonephritis group (CGN, n = 31), idiopathic nephritic syndrome group (NS, n = 32), and lupus nephritis group (LN, n = 41). We measured the plasma levels of TNF-α, VWF antigen (VWF:Ag), and ADAMTS13 activity by using an ELISA-based method in CKD patients (n = 104) and normal controls (n = 32). The ratio of the VWF:Ag level to ADAMTS13 activity was calculated. The VWF:Ag level was significantly higher and the ADAMTS13 activity was significantly lower in all the disease groups than in the controls (P < 0.01). ADAMTS13 activity was lower in the NS group than in the CGN and LN groups (P < 0.05) (Table 1). The TNF-α (pg/mL) level was higher in the CKD group than in the control group (CGN: 3.19 ± 1.01; NS: 3.26 ± 1.18; LN: 3.24 ± 1.24; Control: 2.27 ± 1.23; P < 0.01; P < 0.01). TNF-α was positively correlated with the VWF:Ag level (r = 0.242, P = 0.013) and negatively correlated with the glomerular filtration rate (GFR) (r = −0.193, P = 0.049). ADAMTS13 activity was negatively correlated with the cholesterol level in CKD patients (r = −0.2, P = 0.042). TNF-α level in CKD was positively correlated with the VWF:Ag level and negatively correlated with GFR, which suggests that inflammation might be a major cause of endothelial dysfunction and an index for renal function. The VWF:Ag level increased and ADAMTS13 activity decreased in CKD patients, which indicates that CKD leads to a prothrombotic state.Table 1The plasma VWF:Ag level, ADAMTS13 activity, and the VWF/ADAMTS13 ratio in the CGN, NS, LN, and control groupsNVWF (%)ADAMTS13 (%)VWF/ADAMTS13CGN31198.25 ± 140.20**61.93 ± 22.47**,#3.83 ± 3.29**NS32149.94 ± 74.50**48.87 ± 18.63**3.42 ± 1.59**LN41234.75 ± 134.91**,##67.81 ± 22.30**,##3.79 ± 2.52**CONTROL3299.55 ± 21.3794.37 ± 23.661.12 ± 0.37vs. CONTROL**P < 0.01; vs. NS##p < 0.01,#P < 0.05 Disclosures:No relevant conflicts of interest to declare.

Reevaluation of glomerular charge selective protein-sieving function

Recently, disorders of the slit diaphragm have been considered as major causes of proteinuria in renal disease and the charge barrier function of the glomerular capillary wall has been given less attention. We evaluated the charge selectivity index (CSI) in 40 patients with podocyte disease (PD), 75 with chronic glomerulonephritis (CGN), and 8 with Dent disease, to reexamine the charge barrier function. We evaluated CSI in Dent disease because the urinary protein profile in Dent disease was assumed to be a concentrate of a normal glomerular filtrate. CSI was defined as the renal clearance ratio between IgA and IgG. CSI values (mean +/- SD) in the CGN and PD groups and in Dent disease were 1.12 +/- 0.25, 0.42 +/- 0.31, and 0.16 +/- 0.06, respectively, suggesting that the charge barrier function was defective in the CGN group and of reduced capacity in the PD group. The results suggest that functional interactions between the slit diaphragm and the glomerular basement membrane exist, and that a slit diaphragm disorder is accompanied by a decrease in the charge barrier function in PD, as argued by the conventional hypothesis.

Useful indicators for performing renal biopsy in adult patients with isolated microscopic haematuria

Among adult patients with isolated microscopic haematuria (IMH) which is defined as persistent microscopic haematuria but without proteinura, hypertension, renal insufficiency, urinary tract infection or structural abnormality of the urinary tract, some patients have chronic glomerulonephritis (CGN), in whom early diagnosis by renal biopsy is beneficial to timely intervention. Nevertheless, a considerable number of patients with optimistic prognosis [e.g. thin basement membrane nephropathy (TBMN)] undergo invasive and needless renal biopsy. Indicators for weighing the necessity of renal biopsy would be clinically significant. To investigate the value of urinary albumin/creatinine ratio (UACR), serum IgA level, serum C3 level and serum IgA to C3 ratio in predicting the necessity of renal biopsy for adult patients with IMH, 216 patients were studied retrospectively. Patients were divided into: (CGN group, n=137), (TBMN group, n=56) and normal biopsy (normal group, n=23). Of all patients, 131 (61%) evidenced microalbuminuria (UACR=30-299 mg/g) and 85 (39%) had normoalbuminuria (UACR<30 mg/g). The mean value of UACR in CGN group was higher (96+/-17 mg/g) compared with that in TBMN (20+/-4 mg/g, p<0.01) or normal (18+/-3 mg/g, p<0.01) group. The mean values of serum IgA and serum IgA/C3 ratio in patients with IgA nephropathy (IgAN) were significantly higher than those with non-IgAN (380+/-103:217+/-99 mg/dl, p<0.01; 4.5+/-1.2 : 2.4+/-0.9, p<0.01). The odds ratio for distinguishing IgAN from non-IgAN was significantly correlated with serum IgA level and serum IgA to C3 ratio. For adult patients with IMH, UACR, serum IgA level and serum IgA to C3 ratio are non-invasive markers for predicting the necessity of renal biopsy.

Functional Polymorphism of the Myeloperoxidase Gene in Hypertensive Nephrosclerosis Dialysis Patients

Myeloperoxidase (MPO) may play an important role not only in host defense reactions but also in local inflammations, especially in atherosclerotic diseases such as hypertensive nephrosclerosis (HN). Paradoxically, MPO-deficient mice have been reported to show increased atherosclerosis compared with wild mice, although higher MPO levels are thought to exacerbate atherosclerotic disease. To clarify the genetic role of MPO in HN, we examined the function and distribution of the -463G/A polymorphism located in the promoter region of the MPO gene with ex vivo flow cytometry analysis and a study in end-stage renal disease patients, respectively. This polymorphism has been reported to have a functional significance in vitro, with the A allele being associated with lower MPO expression. In the present study, we also found significantly higher reactive oxygen species (ROS) production with peripheral neutrophils isolated from subjects with the GG genotype compared with those from subjects with other genotypes by flow cytometry assay with 2-[6-(4'-amino) phenoxy-3H-xanthen-3-on-9-yl] benzoic acid (APF), which shows higher sensitivity with hypochlorite (OCl(-)). Genotyping the -463G/A polymorphism in HN, chronic glomerulonephritis (CGN) and diabetic nephropathy (DM) patients who were under hemodialysis treatment demonstrated that the GG genotype was more frequent in the HN group than in the CGN and DM groups. However, the distribution of the GG genotype in the HN group was similar to that in healthy individuals. Although the -463G/A polymorphism is associated with ROS production, careful interpretation may be required to conclude that the -463G/A polymorphism can serve as a useful marker of atherosclerosis and cardiovascular events in dialysis patients.

Clinical outcomes of systemic lupus erythematosus patients undergoing continuous ambulatory peritoneal dialysis

The purpose of this study was to evaluate the outcome of systemic lupus erythematosus (SLE) patients on continuous ambulatory peritoneal dialysis (CAPD). Eighteen SLE patients who had been undergoing CAPD for at least 3 months in our unit were compared with 36 other age- and gender-matched non-diabetic CAPD patients with an underlying primary chronic glomerulonephritis (CGn). The clinical outcome, infective complications, lupus activities, biochemical parameters, haemoglobin level and the use of erythropoietin were reviewed. The duration of dialysis of the two studied groups was not different, with a mean of 35.4 months for the SLE group and 36.7 months for the CGn group. Before dialysis, SLE patients had a significantly lower albumin level (30.4+/-6.6 vs 35.4+/-5.59 g/dl, P<0.01), while the mean haemoglobin levels of the two groups were similar (8.5+/-1.8 g/dl for SLE vs 9.0+/-1.9 g/dl for the control group). However, the weekly dose of erythropoietin (EPO) used was significantly higher in the SLE group (6000 vs 3818 U/week, P<0.01) to maintain a similar haemoglobin level during dialysis. Regarding the infective complications, the SLE group had a higher peritonitis rate (5.7 episodes/100 patient-months vs 2.4 episodes/100 patient-months, P<0.05), and an increase in the non catheter related infection rate (6.67 episodes/100 patient-months vs 1.1 episodes/100 patient-months, P<0.001). However, no significant difference could be demonstrated in the Tenckhoff catheter exit site infection rate (2 episodes/100 vs 1.7 episode/100 patient-months). The number of patients who received a kidney transplant or required a change of mode to haemodialysis was similar among the two groups. Seven patients died during the follow-up period, and the overall mortality rate was much higher in the SLE group than in the control group (0.83/100 vs 0.15/100 patient-months, P<0.05). SLE patients on CAPD have a significantly lower pre-dialysis serum albumin level and use a higher dose of Epo to achieve a comparable haemoglobin level than other non-diabetic CGn CAPD patients. They also have a poorer prognosis in terms of infective complications and mortality rate.

Left ventricular diastolic dysfunction in patients with chronic renal failure: impact of diabetes mellitus

Left ventricular (LV) hypertrophy and LV diastolic dysfunction are cardiac changes commonly observed in patients with chronic renal failure (CRF) as well as hypertension. Although the impairment of LV diastolic function in patients with diabetes mellitus has been shown, little is known about the specific effect of diabetes on LV diastolic function in patients with CRF. The present study was designed to investigate the impact of diabetic nephropathy on LV diastolic dysfunction, independent of LV hypertrophy, in CRF patients. In 67 patients with non-dialysis CRF as a result of chronic glomerulonephritis (n = 33) or diabetic nephropathy (n = 34), and 134 hypertensive patients with normal renal function, two-dimensional and Doppler echocardiographic examinations were performed, and LV dimension, mass, systolic function, and diastolic function were evaluated. LV mass was increased and LV diastolic dysfunction was advanced in subjects with CRF compared with hypertensive controls. In the comparison of echocardiographic parameters between the two groups of CRF patients, i.e. chronic glomerulonephritis and diabetic nephropathy groups, all indices of LV diastolic function were more deteriorated in the diabetic nephropathy group than in the chronic glomerulonephritis group, although LV structure including hypertrophy and systolic function did not differ between the groups. In a multiple regression analysis, the presence of diabetes (i.e. diabetic nephropathy group) was a significant predictor of LV diastolic dysfunction in CRF subjects, independent of other influencing factors such as age, blood pressure, renal function, anaemia and LV hypertrophy. The present findings suggest that LV diastolic dysfunction, independent of LV hypertrophy, is specifically and markedly progressed in patients with CRF as a result of diabetic nephropathy.

Significance of Urinary Fibrin/Fibrinogen Degradation Products in Renal Diseases Measured by a Highly Sensitive ELISA

The urinary fibrin/fibrinogen degradation products (FDP), as sensitive indicators of various renal disorders, have been measured by several methods. For their determination, a new and highly sensitive enzyme-linked immunosorbent assay not requiring the urine concentration has been developed. The study comprised 42 patients with nonnephrotic chronic glomerulonephritis (CGN), 23 patients with primary nephrotic syndrome (NS), and 29 healthy adults. The results were as follows: (1) the content of urinary FDP in normal subjects was 10.30 +/- 9.08 ng/ml; (2) the mean level of urinary FDP in both CGN and NS groups was significantly higher than in normal subjects; (3) in the CGN group itself there was a tendency for an increase of urinary FDP during more active forms of the disease, and (4) there was a significant correlation between urinary FDP and urinary protein in the CGN group, whereas no correlation was observed in the NS group. These results suggest that the major part of urinary FDP in the CGN group derives from the increased filtration, while its origin in the NS group is not related to increased filtration only, but may also have involved intraglomerular coagulation abnormalities. The newly developed enzyme-linked immunosorbent assay can detect urinary FDP levels lower than 3.9 ng/ml. Therefore, this method can be of great value in determining the degree of abnormalities of intraglomerular coagulation and fibrinolysis in renal diseases.

Pathophysiology in malignant hypertension: with special reference to the renin-angiotensin system.

Pathophysiology of malignant hypertension, of which underlying disease was essential hypertension (EHT) in 33 cases and chronic glomerulonephritis (CGN) in 26 cases, was studied with reference to the renin-angiotensin system. Plasma renin activity (PRA) was significantly higher in the EHT than in the CGN group, and angiotensin II antagonist [Sar1, Ile8]angiotensin II (AIIA) induced a significant lowering of blood pressure only in the former group. PRA was linearly correlated with both pretreatment mean blood pressure (MBP, r = 0.474, n = 29, p less than 0.01) and serum creatinine (r = 0.540, n = 29, p less than 0.01) in the EHT group but not in CGN patients, although there was an inverse correlation between PRA and serum sodium in both groups. Multiple regression analysis revealed that PRA was independently related to MBP, serum creatinine, and serum sodium in the EHT group, but not in the CGN group. These results suggest that the renin-angiotensin system plays a significant role in elevating blood pressure and deteriorating renal function in malignant hypertension derived from EHT, but it is less important in CGN related hypertension.

A simple radioimmunoassay determination of urinary aldosterone using 125I-labeled ligand [ALDOCTK-125KIT] and its clinical application

A method of radioimmunoassay for urinary aldosterone excretion (AER) using 125I-labeled ligand [ALDOCTK-125KIT] is described. The sensitivity, specificity, reproducibility and accuracy of this method were compared with the 3H-RIA method previously reported. Since the extraction method using ALDOCTK-125KIT was considered to be preferable to the direct method, the former method was applied to the present study. An excellent correlation was found between the values determined by the 3H-RIA method and the extraction method (r = 0.935, p less than 0.001, Y = 0.89X + 0.80, n = 146). The within-assay and the between-assay coefficient of variation was 7.7--15.0% and 9.7--12.2%, respectively. As a clinical application, the circadian variation of AER was investigated in 5 control subjects and groups of essential hypertension (EHT), primary aldosteronism (PA), chronic glomerulonephritis (CGN) and Cushing's syndrome, each of which consisted of 5 patients, all of which had serum creatinine concentrations of less than 1.2 mg/dl. Under a control diet containing 10 g of salt per day, urine was collected in 4-hour pools starting at 8:00 for the ensuing 24 hours, and AER was determined by means of both 3H-RIA and the extraction method. The difference of the values between the peak and the nadir in each subject was statistically significant, and marked and identical circadian variations of AER with the peak and the nadir at the period of 4:00 to 12:00 and 20:00 to 4:00 were observed in the control, EHT, PA and CGN groups. In the Cushing group, however, the circadian variation of AER was different from the other 4 groups: the peak and the nadir of AER occurred at the period of 20:00 to 24:00 and 4:00 to 8:00, respectively. The circadian variation of AER became more obvious in all groups including the Cushing, when each value was expressed in the percentage of the mean. AER under the control diet was 9.38 +/- 2.04 micrograms/day in the control subjects. In PA and CGN, AER was significantly higher, and in the Cushing group, it was significantly lower than that observed in the control. However, no difference was found in AER between the control and EHT. AERs in both 4-hour and 24-hour urine specimens measured by ALDOCTK-125KIT were consistent with those by the 3H-RIA method.