Sex differences in the evaluation of proteinuria using the urine dipstick test.

Background: The urine protein dipstick test is widely used, but false-positive and false-negative results may occur. This study aimed to compare the urine protein dipstick test with a urine protein quantification method. Methods: The data were extracted using the Abbott Diagnostic Support System, which analyzes the inspection results using multiple parameters. This study included 41,058 specimens tested using the urine dipstick test and protein creatinine ratio from patients aged ≥18 years. The proteinuria creatinine ratio was classified according to the Kidney Disease Outcomes Quality Initiative guidelines. Results: Urine protein on the dipstick test was negative in 15,548 samples (37.9%), trace in 6,422 samples (15.6%), and ≥1+ in 19,088 samples (46.5%). Among the trace proteinuria samples, A1 (<0.15 g/gCr), A2 (0.15-0.49 g/gCr), and A3 (≥0.5 g/gCr) category proteinuria accounted for 31.2, 44.8, and 24.0% of samples, respectively. All trace proteinuria specimens with a specific gravity of <1.010 were classified as A2 and A3 category proteinuria. In the trace proteinuria cases, women had a lower specific gravity and a higher percentage of A2 or A3 category proteinuria than men. The sensitivity in the "dipstick proteinuria" ≥ trace" group was higher than that in the "dipstick proteinuria ≥ 1+" group within the lower specific gravity group. The sensitivity in the "dipstick proteinuria ≥ 1+" group was higher for men than for women, and the sensitivity in the "dipstick proteinuria ≥ trace" group was higher than that in the "dipstick proteinuria ≥ 1+" group for women. Conclusion: Pathological proteinuria assessment requires caution; this study suggests that evaluating the specific gravity of urine specimens with trace proteinuria is essential. Particularly for women, the sensitivity of the urine dipstick test is low, and caution is needed even with trace specimens.

Variation in antibody titers determined by Abbott and Roche Elecsys SARS-CoV-2 assays in vaccinated healthcare workers.

SARS-CoV-2-specific antibody measurement is important for evaluating COVID-19 vaccine efficacy. We quantified and compared anti-spike (S) antibodies using different commercial immunoassays. We tested serum samples from 70 SARS-CoV-2-naive health care workers 2 weeks after vaccination with a single dose of BNT162b2, 2 and 4 weeks, and 3 months after the second dose of BNT162b2. The following quantitative assays were used: Roche Elecsys Anti-SARS-CoV-2 S (Roche-S), Abbott SARS-CoV-2 IgG II Quant [Abbott-IgG(S)], and Abbott SARS-CoV-2 IgM (Abbott-IgM). All samples tested positive for Roche-S and Abbott-IgG antibodies after the second dose, with 83.6% Abbott-IgM positive rate. Roche-S and Abbott-IgG(S) correlated significantly in all samples (r = 0.920, p < 0.0001), and the Roche-S and Abbott-IgG(S) assay showed a strong correlation with each other at each time point after vaccination. Roche-S and Abbott-IgG(S) antibody titers were correlated with age; their rate of decline was age-dependent in males but not in females. Abbott-IgG(S) antibody titers decreased from 2 weeks after the second dose. Roche-S antibody titers peaked 2 weeks after the second dose in 76.2% of the participants; the titers recovered 3 months post-vaccination after declining at week 4 in 40.7% of the participants. The concordance between Roche-S and Abbott-IgG(S) antibody titers over time was 47.5%. Most participants presented significantly high Roche-S and Abbott-IgG(S) antibody titers after immunization. Some measurements were inconsistent with titer changes between these assays, possibly because of differences in the immunoglobulin-specificity of the kits.

Monoclonal Autoantibody Against a Cryptic Epitope on Tissue-Adherent Low-Density Lipoprotein for Molecular Imaging in Atherosclerosis.

BACKGROUND: Antibody-based constructs for molecular imaging and therapeutic delivery provide promising opportunities for the diagnosis and treatment of atherosclerosis. OBJECTIVES: The authors aimed to generate and characterize immunoglobulin (Ig)G monoclonal autoantibodies in atherosclerosis for targeting of novel molecular determinants. METHODS: The authors created hybridomas from an unimmunized low-density lipoprotein (LDL) receptor-deficient (Ldlr-/-) mouse and selected an IgG2b isotype autoantibody, LO9, for further characterization. RESULTS: LO9 reacted well with native LDL bound to immobilized matrix components and less well to oxidized LDL. LO9 binding to immobilized native LDL was not neutralized by fluid-phase native LDL, indicating an adhesion-dependent epitope. The authors localized the epitope to a 20 amino-acid peptide sequence (P5) in the globular amino-terminus of apolipoprotein B. LO9 reacted with antigen in mouse atherosclerosis and in both human stable and ruptured coronary atherosclerosis. Furthermore, in vivo near-infrared fluorescence molecular tomographic imaging, and ex vivo confocal microscopy showed that intravenously injected LO9 localized beneath endothelium of the aortic arch in Ldlr-/- mice, in the vicinity of macrophages. CONCLUSIONS: The authors believe LO9 is the first example of an IgG autoantibody that reacts with a native LDL epitope revealed by adherence to tissue matrix. Antibodies against adherent native LDL have potential as molecular targeting agents for imaging of and therapeutic delivery to atherosclerosis.

A Novel Immunoassay for Malondialdehyde-Conjugated Low-Density Lipoprotein Measures Dynamic Changes in the Blood of Patients Undergoing Coronary Artery Bypass Graft Surgery.

Oxidized low-density lipoproteins play an important role in tissue pathology. In this study, we report a sensitive novel enzyme-linked immunosorbent assay for the detection of malondialdehyde-modified low-density lipoprotein (MDA-LDL), a key component of oxidized LDL. The assay is capable of measuring a variable presence of MDA-LDL within human plasma and serum. We demonstrate the robust nature of the assay on samples stored for over 20 months, as well as high inter-operator reproducibility (r = 0.74, p < 0.0001). The assay was capable of detecting dynamic changes in patient blood samples after coronary artery bypass graft surgery, indicating synthesis or release of MDA-LDL with the oxidative stress of surgery, followed by homeostatic clearance. This robust, sensitive and specific assay for circulating MDA-LDL will serve as a valuable translational tool for the improved detection of oxidative forms of LDL in response to a range of physiological or pathological stimuli, with potential clinical applicability.

High Serum Immunoglobulin G and M Levels Predict Freedom From Adverse Cardiovascular Events in Hypertension: A Nested Case-Control Substudy of the Anglo-Scandinavian Cardiac Outcomes Trial.

AIMS: We aimed to determine whether the levels of total serum IgM and IgG, together with specific antibodies against malondialdehyde-conjugated low-density lipoprotein (MDA-LDL), can improve cardiovascular risk discrimination. METHODS AND RESULTS: The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized 9098 patients in the UK and Ireland into the Blood Pressure-Lowering Arm. 485 patients that had cardiovascular (CV) events over 5.5years were age and sex matched with 1367 controls. Higher baseline total serum IgG, and to a lesser extent IgM, were associated with decreased risk of CV events (IgG odds ratio (OR) per one standard deviation (SD) 0.80 [95% confidence interval, CI 0.72,0.89], p<0.0001; IgM 0.83[0.75,0.93], p=0.001), and particularly events due to coronary heart disease (CHD) (IgG OR 0.66 (0.57,0.76); p<0.0001, IgM OR 0.81 (0.71,0.93); p=0.002). The association persisted after adjustment for a basic model with variables in the Framingham Risk Score (FRS) as well as following inclusion of C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NtProBNP). IgG and IgM antibodies against MDA-LDL were also associated with CV events but their significance was lost following adjustment for total serum IgG and IgM respectively. The area under the receiver operator curve for CV events was improved from the basic risk model when adding in total serum IgG, and there was improvement in continuous and categorical net reclassification (17.6% and 7.5% respectively) as well as in the integrated discrimination index. CONCLUSION: High total serum IgG levels are an independent predictor of freedom from adverse cardiovascular events, particularly those attributed to CHD, in patients with hypertension.

Combined IgG4κ and IgG1λ deposition in the glomerular and tubular basement membrane accompanied by autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP).

A 48-year-old male was admitted to our hospital with nephrotic syndrome. Light-microscopic examination of a renal biopsy specimen showed almost normal glomerular appearance, however, immunofluorescence examination revealed linear and granular IgG deposits on the glomerular basement membrane (GBM), accompanied by slight IgG deposition in the tubular basement membrane (TBM). Further investigation of the IgG subclass and light chain staining revealed that the glomerular deposits were composed of IgG1 and IgG4, with both κ and λ light chains, while the tubular deposits were composed of only IgG4 and κ light chains. The electron-microscopic findings of small granular deposits in the GBM and TBM closely resembled those of light and heavy chain deposition disease (LHCDD). Immunoelectron microscopy confirmed the presence of κ and λ chains in the GBM and TBM, however, only significant κ chain deposition was found in the TBM. There was no evidence of monoclonal gammopathy. Clinically, the patient subsequently developed neutropenia and thrombocytopenia associated with the presence of anti-neutrophil antibody and anti-GPIIb/IIIa antibody-producing B cells in the blood. Oral steroid administration was initiated, which led to amelioration of the neutropenia, thrombocytopenia and proteinuria. This may be a very rare case of combined IgG4κ and IgG1λ deposition disease accompanied by autoimmune neutropenia (AIN) and immune thrombocytopenia (ITP) suggestive of biclonal immunoglobulin deposition disease (BIDD). Investigation of the IgG subclass and of the light chains was useful for recognizing the clonality of the immunoglobulin deposits in the kidney.

Effect of single-dose rituximab on steroid-dependent minimal-change nephrotic syndrome in adults.

BACKGROUND: Steroid-dependent minimal-change nephrotic syndrome (MCNS) requires administration of prolonged courses of prednisolone (PSL); therefore, a paradigm shift from such toxic 'non-specific' therapies to selective immunomodulating regimens is necessary for these cases. METHODS: To assess the therapeutic effects of rituximab (an anti-CD20 antibody) in adult patients with steroid-dependent MCNS, we performed a prospective trial of the effects of a single dose of rituximab administered twice at an interval of 6 months in 25 MCNS patients. We evaluated the biochemical parameters and compared the clinical findings between the 12-month period before and 12-month period after the first rituximab infusion. RESULTS: A significant reduction in the number of relapses and the total dose and the maintenance dose of PSL administered was observed during the 12-month period after the first rituximab infusion when compared with the findings during the 12-month period before the first rituximab infusion [25 (100%) versus 4 (16%), P < 0.001; 8.2 versus 3.3 g, P < 0.001; 26.4 mg/day at baseline versus 1.1 mg/day at 12-month, P < 0.0001]. Complete remission was achieved/maintained in all patients undergoing B-cell depletion. Four of 17 patients with B-cell repletion developed relapse. CONCLUSIONS: Our results revealed that rituximab therapy was associated with a reduction in the number of relapses and in the total dose of PSL needed. Therefore, rituximab appears to be a useful therapeutic agent for adult patients with steroid-dependent MCNS. These results suggest that this treatment is rational and should be considered as an important option in the management of adult patients with steroid-dependent MCNS.

Serum complement C3 predicts renal arteriolosclerosis in non-diabetic chronic kidney disease.

AIM: Complement C3 (C3) is one of the major mediators of inflammation. Serum C3 has been shown to be correlated with the presence of atherosclerosis. We examined whether the serum C3 level might be correlated with the severity of renal arteriolosclerosis in patients with chronic kidney disease (CKD). METHODS: Non-diabetic CKD (stages 1-3) patients who underwent renal biopsy were enrolled in this study. Renal arteriolosclerosis was defined by the presence of hyaline changes and vessel wall thickening in the renal biopsy specimens. We examined whether the serum C3 level might be correlated with the severity of renal arteriolosclerosis in CKD patients. RESULTS: A total of 208 CKD patients (age 36.0±13.6 years; 94 male) who underwent renal biopsy were included. Univariate analysis showed that the serum C3 level was positively correlated with age, body mass index, blood pressure and the serum triglyceride, LDL cholesterol and CRP (p<0.001). The serum C3 level was also inversely correlated with serum HDL cholesterol (p<0.001). Multiple regression analysis identified that the serum C3 (p=0.043) as well as age (p<0.001), serum uric acid (p=0.009) and eGFR (p= 0.025) were independently associated with the severity of renal arteriolosclerosis. CONCLUSION: Our results suggest that the serum C3 level is a reliable marker of renal arteriolosclerosis. Components of metabolic syndrome were also correlated with the serum C3 level. Inflammation or metabolic syndrome may contribute to CKD through influencing the rate of progression of renal arteriolosclerosis.

Beneficial effect of aliskiren combined with olmesartan in reducing urinary protein excretion in patients with chronic kidney disease.

BACKGROUND: Blockade of the renin-angiotensin-aldosterone system is a therapeutic mainstay in patients with chronic kidney disease (CKD). However, the renoprotective effect of the novel direct renin inhibitor aliskiren is unknown. MATERIALS AND METHODS: We performed a prospective study in 10 CKD patients. All 10 patients with persistent proteinuria (urinary protein-to-creatinin ratio 0.3-3.5 g/g), despite good blood pressure control (<130/80 mmHg) with olmesartan, were started on 150 mg/day aliskiren. Clinical parameters were examined before and after 4, 8, 12, and 16 weeks of treatment. RESULTS: Urinary protein-to-creatinine ratio significantly decreased by about 40% at 16 weeks from baseline (P = 0.0002), although estimated glomerular filtration rate and blood pressure did not change throughout the study period. Plasma renin activity also decreased significantly from baseline (P = 0.019), although plasma aldosterone concentration did not change. CONCLUSIONS: Aliskiren combined with olmesartan reduces proteinuria in CKD patients.

A case of acute renal failure after exercise with renal hypouricemia demonstrated compound heterozygous mutations of uric acid transporter 1.

Familial renal hypouricemia is a hereditary disease characterized by extraordinary high renal uric acid (UA) clearance and is associated with acute renal failure (ARF). A 17-year-old Japanese male developed ARF after anerobic exercise. Renal function improved completely after approximately 2 weeks of hydration treatment. After remission, hypouricemia became evident (1.0 mg/dL) from the initial level of UA (4.8 mg/dL) and fractional excretion of uric acid (FEUA) was >50%. His parents showed normal levels of UA and FEUA. Polymerase chain reaction of a urate anion exchanger known to regulate UA level [SLC22A12 gene: UA transporter 1 (URAT1)] demonstrated compound heterozygous mutations (Q297X and R90H). Thus, we describe a Japanese male with hypouricemia complicated by anerobic exercise-induced ARF, with definite demonstration of a genetic abnormality in the responsible gene, URAT1.

Comparison of inhibitors of renin-angiotensin-aldosterone system (RAS) and combination therapy of steroids plus RAS inhibitors for patients with advanced immunoglobulin A nephropathy and impaired renal function.

BACKGROUND: The adaptation of steroid therapy and the effect of renin-angiotensin-aldosterone system inhibitors (RASIs) for advanced immunoglobulin A nephropathy (IgAN) patients with impaired renal function are still controversial. METHODS: We divided 63 IgAN patients with an estimated glomerular filtration rate (eGFR) of <60 ml/min/1.73 m(2) and proteinuria ≥ 0.5 g/day into two groups: the RASI group (RASI, n = 33), treated with RASIs alone; and the combination group (COMBI, n = 30), treated with corticosteroids and RASIs. We analyzed the clinical and histological background, renal survival rate, and the risk factors for progression. RESULTS: Renal function (mean eGFR: COMBI 46.4 vs. RASI 47.0 ml/min/1.73 m(2)), the amount of proteinuria (median: COMBI 1.39 vs. RASI 1.17 g/g creatinine) and histological backgrounds were not significantly different between the groups, but urinary red blood cells (U-RBCs) were significantly higher in the COMBI group than in the RASI group (median: COMBI 30.0 vs. RASI 10.0 counts/high-power field, P = 0.0171). The serial change in proteinuria did not differ until 5 years after treatment, but U-RBCs were significantly decreased in both groups (P < 0.0001), and eGFR was significantly decreased in the RASI group (P < 0.001) but not in the COMBI group. The results for each year after treatment did not differ significantly between both groups. The renal survival rate was not significantly different between the groups. There was no independent risk factor for progression by Cox regression analysis. CONCLUSION: Combination therapy with steroids and RASIs was not superior to monotherapy with RASIs for advanced IgAN with impaired renal function.

Induction of remission following a single dose of rituximab alone in a patient with minimal change nephrotic syndrome.

Treatment with a single dose of rituximab alone induced remission in a patient with relapsed minimal change nephrotic syndrome (MCNS). A 27-year-old man was given corticosteroid (prednisolone; PSL) and cyclosporine (CyA) therapy combined with rituximab for his fifth relapse in 2008. Thereafter, complete remission was achieved and maintained despite eventual discontinuation of the PSL and CyA. In 2010, we treated his sixth relapse with a single dose of rituximab. Complete remission was obtained 32 days later. This is the first report of rituximab monotherapy in the treatment of MCNS.

Long-term beneficial effects of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker therapy for patients with advanced immunoglobulin A nephropathy and impaired renal function.

BACKGROUND: There are few reports analyzing the effects of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs) on the long-term renal survival of advanced immunoglobulin A nephropathy (IgAN) patients. PATIENTS AND METHODS: In this retrospective cohort analysis, we divided 66 IgAN patients with an estimated glomerular filtration rate (eGFR) <60 ml/min into three groups: ACEI group (n = 20, treated with ACEIs), ARB group (n = 23, treated with ARBs), and control group (n = 23, treated with antiplatelet agents), and analyzed the clinical and histological background, renal survival rate until the primary endpoint of 50% decrease of eGFR from baseline, and the secondary endpoint of progression to end-stage renal disease, and the risk factors for progression. RESULTS: The clinical and histological background without serum IgA and C3 were not significantly different among the three groups. The renal survival rate until the primary and secondary endpoints was significantly higher in the ACEI and ARB groups than in the control group. The independent risk factors for progression were higher mean blood pressure (hazard ratio [HR] 1.76, P = 0.04), higher histological grade (HR 2.54, P = 0.0184) at baseline, and without ACEIs or ARBs (HR 7.09, P = 0.001), but decreased proteinuria and blood pressure. The risk factors with resistance to ACEIs or ARBs were higher blood pressure and lower eGFR at baseline. There was no difference regarding the survival rate and the risk for progression between ACEI s and ARBs. CONCLUSION: ACEIs or ARBs were effective for long-term renal survival of advanced IgAN, although proteinuria and blood pressure did not decrease.

Effect of single-dose rituximab on primary glomerular diseases.

BACKGROUND: A paradigm shift from such toxic 'nonspecific' therapies to selective immunomodulating regimens is necessary for glomerular diseases. Rituximab, which acts by inhibiting CD20-mediated B cell proliferation and differentiation, could be effective in the treatment of nephrotic syndrome as shown in recent reports. DESIGN: To assess the effects of rituximab in patients with primary glomerular diseases, including minimal-change disease, immunoglobulin A (IgA) nephropathy, focal segmental glomerulonephritis, membranous nephropathy and membranoproliferative glomerulonephritis, we performed a prospective trial of the effects of single-dose rituximab therapy in 24 patients. We prospectively evaluated the serum and urinary biochemical parameters before and after 6 months of therapy. RESULTS: In all of the patients studied, depletion of CD19 and CD20 cells was noted, with significant reduction in the degree of proteinuria from 3.7 ± 3.4 g/day at baseline to 1.3 ± 2.0 g/day at 6 months after the drug administration (p = 0.002). However, no significant changes of the serum creatinine, urinary RBC sediment, serum CD4/8 or serum IL-4 levels were observed at 6 months after the drug administration. In subjects with IgA nephropathy, while depletion of CD19 and CD20 cells was noted, no significant change in the severity of proteinuria was observed at 6 months after the drug administration as compared with the level at the baseline. CONCLUSION: For the treatment of primary glomerular diseases, the use of a single dose of rituximab is demonstrated with no serious adverse events. Further study of the mechanism of action of rituximab in successfully treated patients could encourage new perspectives in the treatment of primary glomerular diseases.

Three cases of late-onset oligomeganephronia.

Oligomeganephronia is classified as a subgroup of renal hypoplasia, characterized by histopathologic abnormalities which progress to end-stage renal disease (ESRD) by school age. We describe three adult cases of oligomeganephronia who have not yet developed ESRD. We performed a renal biopsy in all of them. The pathological features, consisting of a reduced number of enlarged glomeruli, were diagnostic of oligomeganephronia. It was assumed that the condition had not progressed to ESRD in the patients because the degree of loss of glomeruli may have been milder than that in typical cases of oligomeganephronia.

Risedronate therapy for the prevention of steroid-induced osteoporosis in patients with minimal-change nephrotic syndrome.

BACKGROUND: Minimal-change nephrotic syndrome (MCNS) is treated by the administration of prednisolone (PSL) at high doses. Steroid-induced osteoporosis is a serious adverse effect of this drug. METHODS: Patients with MCNS were randomly assigned to two groups, the risedronate (2.5 mg/day) + alfacalcidol (0.25 µg/day) group (n=20) and the alfacalcidol (0.25 µg/day)-alone group (n=20). All the patients had received PSL and the clinical characteristics were compared between the two groups at baseline and at 12 months. RESULTS: A significant decrease of the mean bone mineral density (BMD) of the lumbar spine from 0.710±0.162 (g/cm(2)) to 0.588±0.125 was observed in the alfacalcidol-alone group (p=0.02), while no such decrease of the bone mineral density was found in the risedronate + alfacalcidol group (0.663±0.169 at baseline and 0.626±0.129 at 12 months). No significant differences in the results of other biochemical tests performed at the baseline and at 12 months were observed between the two groups. The likelihood of development of steroid-induced osteoporosis was influenced by the cumulative dose of PSL, the mean BMD at the baseline, occurrence of disease relapse, and risedronate therapy. CONCLUSION: Risedronate appears to be effective in preventing steroid-induced osteoporosis. It is necessary to use bisphosphonates to maintain the BMD in patients with MCNS receiving prolonged steroid therapy.

A case of AL amyloidosis with renal rupture.

We report a 59-year-old woman with AL amyloidosis who presented with massive bleeding from the right kidney, in whom emergency surgery proved to be life saving. The patient had been diagnosed as having AL amyloidosis 16 years previously. After 5 years, hemodialysis had been initiated. In 2007, a large right-sided perinephric, intracapsular hematoma was detected. Right nephrectomy was performed and the patient recovered with no sequelae. Histopathological examination revealed a greater degree of amyloid deposition in the resected kidney than that at the time of diagnosis. Amyloid angiopathy may promote bleeding.

[Case of MMF monotherapy for membranous nephropathy].

We report the case of a 58-year-old male patient who visited our hospital for the management of edema and proteinuria. He was diagnosed as having nephrotic syndrome, with serum total protein and albumin levels of 4.6 g/dL and 2.1 g/dL, respectively, and a urinary protein excretion level of 6.0 g/day. A percutaneous renal biopsy showed features of membranous glomerulonephritis, with capillary-wall granular deposits of IgG and C3 on immunofluorescence and subepithelial immune complex deposits on electron microscopy. No other secondary cause of membranous glomerulopathy was found even after extensive investigations. The patient was started on mycophenolate mofetil (MMF) monotherapy (1,500 mg/day), and 18 months after the start of this therapy, the proteinuria decreased to 0.5 g/day, with return to a normal serum albumin level. No digestive symptoms, kidney function worsening or increase in blood pressure were noted during treatment. These findings suggest that MMF monotherapy is effective and safe for the treatment of membranous nephropathy.

[Clinico-pathological features and outcome in adult patients with Henoch-Schönlein purpura nephritis].

We examined the data of 24 patients with Henoch-Schönlein purpura nephritis (HSPN) over a 5-year follow-up period. Proteinuria, sediment RBC and CRP significantly decreased between the time of diagnosis and the end of the 5-year period. In the steroid usage group (n = 16), proteinuria was significantly higher, and crescent formation was significant higher at the time of diagnosis than in the non-steroid usage group (n = 8). However, there was no significant difference in the decrease in eGFR from the baseline at the end of the 5-year period between the two groups. Furthermore, to clarify the factors influencing the risk of renal function deterioration, we divided the patients into two groups, the (delta eGFR/pre eGFR) <0.25 group (n = 13) and (delta eGFR/pre eGFR) >0.25 group (n = 11), and compared the clinico-pathophysiological characteristics between the two groups. In the (delta eGFR/pre eGFR) >0.25 group, the ratio of glomerular obsolescence at the time of diagnosis was significantly higher than in the (delta eGFR/pre eGFR) <0.25 group. Glomerular obsolescence was identified as an independent risk factor for renal function deterioration. In this study, the prognosis of HSPN was related to glomerular obsolescence rather than to the disease activity. It may be necessary to consider the decrease in nephrons, in accordance with non-immunological glomerular obsolescence, in addition to immunological treatment to clarify the prognosis.

MMP-9 inhibition by ACE inhibitor reduces oxidized LDL-mediated foam-cell formation.

AIM: Angiotensin-converting enzyme inhibitors (ACEIs) have been shown to block matrix metalloproteinase (MMP)-9 activity, which plays a role in atherogenesis. MMP-9 activity of macrophages is increased during foam cell formation. To investigate the contribution of ACEIs to foam cell formation, we studied the effects of an ACEI, imidaprilat, on THP-1 macrophages and the underlying molecular mechanisms in vitro. METHODS AND RESULTS: Pre-treatment of THP-1 macrophages with imidaprilat (100 nmol/L, 4 hours) significantly decreased foam cell formation induced by oxidized LDL (OxLDL). Imidaprilat reduced the protein level of MMP-9 in THP-1 macrophages and attenuated OxLDL-induced MMP-9 activity in the culture supernatants. Indeed, pretreatment of THP-1 macrophages with an MMP-2/9 inhibitor (20 micromol/L, 4 hours) attenuated OxLDL-induced foam-cell formation. Imidaprilat or the MMP-2/9 inhibitor blocked OxLDL-induced expressions of LOX-1 and scavenger receptor-A (SR-A), but not that of CD36, in THP-1 macrophages. In addition, OxLDL-induced activation of p38 mitogen-activated protein kinase (MAPK) and ERK, but not JNK, was blunted by imidaprilat or the MMP-2/9 inhibitor. Finally, siRNA against MMP-9 inhibited foam cell formation as well as lipid accumulation in THP-1 macrophages. CONCLUSION: These findings suggest that imidaprilat reduces OxLDL-triggered foam-cell formation in THP-1 macrophages via modulation of MMP-9 activity and may indicate a novel antiinflamma-tory mechanism of imidaprilat in atherogenesis.