Search

Background Because of the potential anti-inflammatory effects, linagliptin, a therapeutic dipeptidyl peptidase-4 inhibitor, is used as an effective drug for diabetic patients for whom inflammation is a prognosis-related factor. We investigated the anti-inflammatory mechanism of linagliptin using seven markers. Methods We pretreated human umbilical vein endothelial cells (HUVECs), with linagliptin and lipopolysaccharide (LPS). The cytosolic fractions were evaluated for protein kinase A (PKA), protein kinase B (PKB), protein kinase C (PKC), ratio of reactive oxygen species (ROS) and Cu/Zn superoxide dismutase (SOD), activator protein 1 (AP-1), and adenosine 3′,5′-cyclic monophosphate (cAMP). Results Linagliptin increased the PKA and PKC activities and the cAMP levels in LPS-treated cells. However, it inhibited LPS-induced PKB phosphorylation, ratio of ROS and Cu/Zn SOD, and LPS-stimulated AP-1 nuclear translocation. Conclusion We reaffirmed the anti-inflammatory and antioxidant effects of linagliptin. These effects might be related to the three protein kinases. Our findings suggest that linagliptin has a wide range of anti-inflammatory effects.

Purpose Dipeptidyl peptidase-4 inhibitors, including linagliptin, prevent inflammation. However, the in vitro effects of linagliptin are unclear. Moreover, although linagliptin inhibits lipopolysaccharide (LPS)-induced inflammation, the anti-inflammatory effects of linagliptin in this context are not concentration-dependent. In the absence of LPS-binding protein (LBP), the pro-inflammatory effects of LPS involve pathways other than the Toll-like receptor (TLR) 4 pathway. Here, we aimed to determine the anti-inflammatory mechanisms of linagliptin in an experimental model in which LBP was added to the medium. Methods Human U937 monocytes were cultured at 1 × 106 cells/mL in Roswell Park Memorial Institute medium and differentiated into macrophages using phorbol myristate acetate. All processes were carried out in medium containing 10% fetal bovine serum (FBS). After 48 hrs of culture, we replaced the medium and pretreated the cells with 100, 250, 500, or 2500 nM linagliptin for 1 hr. We exchanged the medium again, and the cells were treated with 1 ng/mL LPS with or without 100, 250, 500, or 2500 nM linagliptin. Interleukin (IL)-6 and LBP in the supernatant, nuclear factor (NF)-κB/p65 in the nucleus, and reactive oxygen species (ROS) in the cells, as important markers of the mechanism of inflammation induction by LPS, were measured using enzyme-linked immunosorbent assay kits. Results Linagliptin significantly prevented LPS-stimulated IL-6 production and intranuclear NF-κB/p65 levels in a concentration-dependent manner. LPS-induced intracellular ROS levels were significantly decreased by linagliptin at all concentrations. LBP levels were markedly higher in FBS-containing medium than in medium without FBS. However, LBP levels did not change following administration of linagliptin and/or LPS. Conclusion Concentration-dependent and -independent inflammatory suppression was observed following linagliptin treatment in the context of LPS-induced pro-inflammatory responses. Thus, our findings suggested that linagliptin induced two different mechanisms to repress inflammation, i.e., TLR4-dependent and -independent mechanisms.

Background: A patient’s motivation for consulting a physician is paramount to the first steps of achieving an early diagnosis of hereditary angioedema (HAE). Understanding what triggers this motivation can help in the design of strategies to increase the number of visits to a specialist physician following early symptoms of HAE. The aim of the present study was to identify the reasons that led patients to seek the opinion of an HAE expert physician.

BACKGROUND/AIMS Hepcidin-25 (HEP-25) and erythroferrone (ERFE) are key regulators of iron homeostasis. Correlations among serum ferritin, ERFE and HEP-25 levels and improvements in anaemia have not been evaluated after administration of ferric citrate hydrate (FCH). METHODS This retrospective observational study investigated 24 patients on haemodialysis with both anaemia (haemoglobin (Hb)

Background Atherosclerosis and inflammation are more common in patients with diabetes than in patients without diabetes, and atherosclerosis progression contributes to inflammation. Therefore, anti-inflammatory therapy is important for the prognosis of patients with diabetes. Linagliptin is the only bile-excreted, anti-diabetic oral dipeptidyl peptidase-4 (DPP-4) inhibitor. Although the anti-inflammatory effects of DPP-4 inhibitors in vivo and in vitro have been reported, few in vitro studies have examined the effects of linagliptin using monocytes, which play a central role in arteriosclerosis-related inflammation. Herein, we assessed the anti-inflammatory effects of linagliptin in human U937 monocytes. Methods U937 cells at densities of 1 × 106 cells/mL were cultured in Roswell Park Memorial Institute medium supplied with 10% fetal bovine serum and treated with 100 nM phorbol myristate acetate for 48 h for differentiation into macrophages. The media were replaced, and the cells were pretreated with 1, 5, 10, 50, and 100 nM linagliptin for 1 h or were left untreated. The media were then replaced again, and the cells were treated with 1 μg/mL lipopolysaccharide (LPS) or 10 nM interleukin (IL)-1β only, in combination with 1, 5, 10, 50, and 100 nM linagliptin or were left untreated. The extracted media were used to measure IL-6 and tumor necrosis factor (TNF)-α levels using enzyme-linked immunosorbent assay kits. Results LPS alone significantly increased IL-6 and TNF-α production compared with the control treatment. The treatment of cells with linagliptin at all concentrations significantly inhibited the LPS-stimulated IL-6 and TNF-α production. Meanwhile, IL-1β alone significantly increased IL-6 production compared with the control treatment. No significant difference in IL-6 production was noted between the cells treated with IL-1β and simultaneous treatment with IL-1β and linagliptin. Conclusions Linagliptin inhibited LPS-induced inflammation in human monocytic U937 cells.

A 35-year-old woman with fever, edema and rash was admitted. Pleural effusion and cardiomegaly were observed. A laboratory analysis revealed anemia with iron deficiency and elevated human parvovirus B19 (B19V) immunoglobulin M. The patient's hepcidin-25 and erythroferrone levels were not elevated compared to those observed later in her clinical course. On the other hand, her growth differentiation factor-15 (GDF-15) levels were elevated. She was diagnosed to have heart failure symptoms and anemia with specific iron metabolism abnormalities due to a B19V infection. After providing supportive treatment, the heart failure symptoms disappeared and her anemia had improved. This case emphasizes the need to include a B19V infection in the differential diagnosis when we encounter cases demonstrating reversible heart failure with anemia.

Background: Mesangioproliferative glomerulonephritis is the most common type of chronic glomerulonephritis (CGN). However, the clinical characteristics and prognosis are not fully understood in patients without Immunoglobulin A (IgA) deposition. To explore the clinical and pathological characteristics of patients with mesangioproliferative glomerulonephritis without IgA deposition (N-IgAN), we performed dual retrospective analyses. Methods: A single-center study was performed in 60 patients with biopsy-proven N-IgAN. 98 ageand sex-matched IgA nephropathy (IgAN) patients were randomly selected as a control group. The clinical and histopathological data at the time of renal biopsy were compared between N-IgAN and IgAN. In a second study, the data for 477 patients who had undergone maintenance renal replacement therapy (RRT) was collected and examined for the causal primary diseases. Results: Duration from onset of renal symptoms to renal biopsy in patients with N-IgAN (71.2 ± 123.3 months) was significantly longer than that in patients with IgAN (65.9±74.9 months) (p=0.0328). Urinary protein excretion in N-IgAN patients (0.6±1.1 g/gCr) was significantly lower than that in IgAN (1.0 ± 1.3 g/gCr) (p < 0.0001). Ratio of global sclerosis, segmental sclerosis, crescents, interstitial mononuclear cell infiltration, interstitial fibrosis, and tubular atrophy were significantly lower in N-IgAN patients. Of the 477 patients who had undergone maintenance RRT, 95 patients had CGN (19.9%). Among them, 37 patients had received a renal biopsy, only one patient was N-IgAN (1%). Conclusion: It appears that N-IgAN can be recognized as a benign disease entity in comparison with IgAN.

Key Clinical Message Gastrorenal shunts may induce hyperammonemia. Portosystemic shunts should be suspected when hyperammonemia occurs in patients with chronic kidney disease.

Background The impact of being overweight remains unclear in Asian populations that tend to be lean. The objective of this study is to clarify the impact of body mass index (BMI) and metabolic factors on the prognosis of Japanese patients with IgA nephropathy (IgAN). Methods A total of 193 patients with IgAN were divided into three groups equally according to BMI: Group L (lean group, BMI: 15.6–20.1 kg/m2), Group M (middle group, BMI: 20.2–23.0 kg/m2), and Group O (obesity group, BMI: 23.1–31.9 kg/m2). Clinical data at the time of renal biopsy and the progression of the patients after renal biopsy were analyzed. Results At the time of renal biopsy, hypertension, dyslipidemia, hyperuricemia, and hypercomplementemia in Group O were more significant compared with those in Group L and/or Group M. Uric acid, triglyceride, C3, C4, high-density lipoprotein cholesterol, serum creatinine, systolic blood pressure (BP), and diastolic BP were significantly correlated with BMI. In Group O, the remission of urinary protein over 5 years was significantly delayed using a log-rank test. At the final observation, the BMI of each group was as similar as that at renal biopsy. The patients with aggressive therapy, such as steroid therapy and/or tonsillectomy in Group O did not have major side effects, except for a slight elevation of total cholesterol and low-density lipoprotein cholesterol. Conclusion Even slightly high BMI seems to be a risk factor for progress in Japanese patients with IgAN.

Purpose This study was performed to investigate important factors of exercise therapies for diabetes patients in Japan.

Otitis media (OM) is well known as a common feature of proteinase 3 antineutrophil cytoplasmic antibody (PR3-ANCA)-related Wegener granulomatosis, but is a very rare condition in myeloperoxidase ANCA (MPO-ANCA)-related vasculitis. In addition, there have been a few reports showing an association of MPO-ANCA-positive OM with cranial polyneuropathy. In this report, we describe 2 patients with bilateral facial nerve palsy due to MPO-ANCA-related OM. One patient also had bilateral trigeminal neuropathy, pachymeningitis and MPO-ANCA-related glomerulonephritis, whereas the other showed isolated bilateral facial nerve palsy with OM. In both the patients, treatment with prednisolone and immune-suppressant drugs resulted in an improvement of OM and cranial polyneuropathy. Physicians should be aware that MPO-ANCA-positive OM can cause bilateral facial nerve palsy.

Background Since the degree and increase of albuminuria predict cardiovascular and renal diseases even within the range of normoalbuminuria. The high-performance liquid chromatography (HPLC) assay has been reported as a useful tool for earlier detection of microalbuminuria than turbidimetric immunoassay (TIA) in diabetes but has not been evaluated for other common diseases that caused chronic kidney disease (CKD). Methods We measured albumin in spot urine by TIA and HPLC assay in 119 patients with diabetes, hypertension, IgA nephropathy in complete remission, or autosomal-dominant polycystic kidney disease whose dipstick screening tests were negative. Results There were significant correlations (r = 0.946) between TIA and HPLC assay, and the ratios of urine albumin/creatinine (ACR) measured by HPLC assay were always higher than those measured by TIA. The value of microalbuminuria was highest in IgA nephropathy patients, and higher in diabetic patients with hypertension than in those without hypertension. Fifty-one patients were classified as having normoalbuminuria and 42 as having microalbuminuria by both TIA and HPLC assay. However, 26 patients (21.8%) were classified having as normoalbuminuria by TIA but microalbumnuria by HPLC assay. Three of these patients were reclassified as microalbuminuria by both assays within 1 year. Conclusion These results suggest that ACR measurements by HPLC assay are better than TIA for early detection and monitoring of microalbuminuria in patients with diabetes and hypertension.

Macroscopic hematuria is a common symptom in IgA nephropathy and is also one of the most frequent complications after a percutaneous renal biopsy. Here, we describe a patient with IgA nephropathy and recurrent macroscopic hematuria who developed an arteriovenous fistula after renal biopsy.

The pathogenic roles of glomerular deposition of components of the complement cascade in IgA nephropathy (IgAN) are not completely clarified. To investigate the pathologic role of complement pathways in IgAN, two IgAN-prone mouse models were examined. Grouped ddY (gddY) mice showed significant high proteinuria, severe glomerular lesions, and extracellular matrix expansion compared with high serum IgA (HIGA) mice but with similar intensity of glomerular IgA deposition. Glomerular activation of the classical, lectin, and alternative pathways was demonstrated by significantly stronger staining for complement (C)3, C5b-9, C1q, C4, mannose-binding lectin (MBL)-A/C, MBL-associated serine protease-2, and factor B and properdin in gddY mice than in HIGA mice. Similarly, the serum levels of IgA-IgG2a/IgM and IgA–MBL-A/C immune complexes and polymeric IgA were significantly higher in gddY mice than in HIGA mice. Moreover, the serum levels of aberrantly glycosylated IgA characterized by the binding of Sambucus nigra bark lectin and Ricinus communis agglutinin I were significantly higher in gddY mice than in HIGA mice. This aberrancy in glycosylation was confirmed by monosaccharide compositional analysis of purified IgA using gas-liquid chromatography. This study is the first to demonstrate that aberrantly glycosylated IgA may influence the formation of macromolecular IgA including IgA-IgG immune complexes and subsequent complement activation, leading to full progression of IgAN.

Relatively high circulating levels of soluble tumor necrosis factor (TNF) receptors (TNFRs: TNFR1, TNFR2) have been associated with not only progression to end-stage renal disease but also mortality in patients with diabetes. It remains unknown whether elevated TNFR levels in haemodialysis patients are associated with mortality. We studied 319 patients receiving maintenance haemodialysis who were followed for a median of 53 months. Circulating markers of TNF pathway (TNFα and TNFRs) were measured with immunoassay. Strong positive correlations between TNFR1 and TNFR2 were observed (r = 0.81, P

Sitagliptin Inhibits the Lipopolysaccharide-Induced Inflammation Abstract Objective: Sitagliptin is an anti-diabetic Dipeptidyl peptidase-4 (DPP-4) inhibitor; used worldwide with a well-established evidence base as an effective anti-diabetic therapy and the lowest cost of all DPP-4 inhibitors. Atherosclerosis and inflammation are more common in diabetic patients than in nondiabetic patients, and progression of atherosclerosis contributes to this inflammation. Therefore, anti-inflammatory therapy is important for the prognosis of diabetic patients. Although several reports have investigated the anti-inflammatory mechanisms of sitagliptin in vitro, none of these studies has described its effects on mitogenactivated protein kinase (MAPK) in human umbilical vein endothelial cells (HUVECs) stimulated with lipopolysaccharide (LPS). We assessed the MAPK-dependent anti-inflammatory effects of sitagliptin in HUVECs. Methods: HUVECs (1–2 × 105 cell/mL) were either pretreated with different doses of sitagliptin for 1 h or left untreated. Subsequently, HUVECs were either incubated with lipopolysaccharide (LPS) together with sitagliptin (after treatment) or left untreated. Five hours post incubation, the culture medium was sampled for interleukin (IL)-6. Additionally, intranuclear p65 levels were measured 5 h after simultaneous treatment with LPS and sitagliptin. p38 MAPK levels and PKC activity were measured in the cytosolic fractions 30 min after simultaneous treatment with LPS and sitagliptin. Results: Treatment with LPS alone induced significant IL-6 production compared with untreated control cells. Pretreatment of cells with sitagliptin at all concentrations tested significantly reduced LPS-stimulated IL-6 production. However, after treatment of cells with sitagliptin at any concentration did not inhibit LPS-stimulated IL-6 production. Compared to untreated cells, treatment with 5 nM sitagliptin significantly inhibited LPS-stimulated intranuclear p65 expression, and p38 MAPK phosphorylation. There was no significant difference in PKC activity with LPS or sitagliptin. Conclusion: In HUVECs, sitagliptin elicits its anti-inflammatory effects through MAPK-dependent mechanisms.

Background. The aim of the present study was to explore the significance of extraglomerular (Bowman’s capsule and/or arteriole) C3 (ex-C3) deposits in IgA nephropathy (IgAN). Methods. One hundred and seventy patients with IgAN were divided into two groups: Group A (n = 79), patients who did not have ex-C3 deposits, and Group B (n = 91), patients who had ex-C3 deposits. Results. At the time of renal biopsy, Group B was characterized by a marked increase in diastolic blood pressure, total cholesterol, triglyceride and low-density lipoprotein-cholesterol compared with those of Group A. After 4 years, the estimated glomerular filtration rate (eGFR) in Group B was significantly worse than that of Group A. Upon examination by electron microscopy, the arteriolar dense deposits in Group B were found to occur in significantly higher amounts than in Group A. One hundred and thirty-four patients underwent a 3-year follow-up study after intervention and were re-divided by therapeutic factors as follows: ‘conventional therapy’, treatment with anti-hypertensive drugs and/or anti-platelet drugs, and ‘aggressive therapy’, additional treatment with either tonsillectomy or corticosteroid. Patients treated with conventional therapy in Group B had significantly higher body mass index and levels of C3 and CH50 compared with other Groups. Aggressive therapy was significantly effective in urinary protein reduction in both Group A and Group B. Except for the patients who received aggressive therapy in Group A, the levels of the eGFR gradually declined. Conclusions. It appears that IgAN patients who have ex-C3 deposits have worse clinical outcomes.

Background Accurate estimation of the glomerular filtration rate (GFR) is very important in clinical practice. Although renal inulin clearance (Cin) is the gold standard for measuring GFR, the procedure for Cin measurement is complicated. Use of GFR-estimating equations has been increasing recently due to their simplicity. The objectives of the present study are to analyze the correlation between Cin and other GFR-estimating parameters and to investigate their clinical usefulness and limitation. Methods Seventy-two Japanese patients were enrolled in this study. Cin was measured by the continuous infusion method. Serum creatinine (s-Cr), cystatin C, uric acid (UA), and hemoglobin (Hb) were measured. The Japanese formula of estimated GFR (eGFR) was as follows: eGFR (ml/min/1.73m2) = 194 × s-Cr−1.094 × Age−0.287 × 0.739 (if female). The endogenous creatinine clearance test was also performed. Results Levels of Cin were highly correlated with those of endogenous creatinine clearance (Ccr) (R2 = 0.7585) and eGFR (R2 = 0.5659). However, patients with lower Cin showed unexpectedly elevated levels of endogenous Ccr and eGFR. Moreover, the levels of eGFR tended to be unexpectedly increased in patients with low body surface area. Conclusion Although GFR-estimating equations are useful for estimating GFR accurately, they pose a risk of overestimation of kidney function in patients with decreased GFRor a poor physique. J. Clin. Lab. Anal. 26:248-253, 2012. © 2012 Wiley Periodicals, Inc.

Thyroid function test values are generally at low levels in patients with end-stage kidney disease. Life-threatening thyrotoxicosis or thyroid storm is rare, especially in hemodialysis (HD) patients, and is characterized by multisystem involvement and a high mortality rate if not immediately recognized and treated. Here, we report a female patient with severe symptomatic thyroid storm, receiving long-term HD and glucocorticoid therapy. Methimazole at a dose of 15 mg per day, β-adrenergic blockade and HD succeeded in controlling the patient's condition by gradually adjusting the target dry weight for hyperthyroidism-induced weight loss. When she was discharged from the hospital, her dry weight was reduced from 47.2 to 39.2 kg. The management of patients with severe symptomatic thyroid storm on HD represents a rare scenario. It is essential to initiate the available treatments as early as possible to reduce its mortality.

A deeper understanding of the mechanism of complement activation may help to elucidate the pathogenesis of IgA nephropathy (IgAN). Traditionally, the activation of an alternative pathway (AP) has been recognized as an enhancer mechanism of glomerular damage. This paper documents contemporary information concerning the possible pathological mechanisms of the lectin pathway (LP) in the circulation and in the glomerulus. The circulating initiator of LP activation is not fully understood. However, ligands for mannose-binding lectin (MBL) which are among the starter molecules of the LP are aberrant glycosylated molecules-containing immune complex. Recent reports have focused onN-glycans on secretory IgA as a candidate ligand. Mesangial deposits of MBL are seen in 25% of patients with IgAN. Mesangial deposits of MBL and C4 and/or C4 breakdown products are implicated as markers for disease progression of IgAN. On the other hand, patients with MBL deficiency tend to show better clinical presentation and lower levels of urinary protein and serum creatinine than MBL-sufficient patients. It is now recognized that involvement of AP and LP constitutes an additional mechanism for explaining the progression of IgAN.

Background. We have recently demonstrated that hemodialysis (HD) patients have significantly higher levels of functional complement activity (FCA) in all three pathways, i.e. the classical pathway, alternative pathway and lectin pathway (LP), than in age-matched controls, though the role of FCA during HD still remains unknown. Methods. Serial plasma or serum samples were obtained from five patients during HD in order to investigate the kinetics of complement components. The levels of the C5b-9 complex, the FCA of the three pathways, a derivative of C3a (C3a desArg) and a derivative of C5a (C5a desArg) in the samples were analyzed. Results. The levels of the C5b-9 complex at 60 min were significantly increased when compared with those at 0 min. Functional activities for all three pathways showed different patterns so the same tendency between pathways was not observed. The levels of C3a desArg and C5a desArg at 60 min were markedly increased when compared with those at 0 min. A Spearman’s rho test showed a strong positive correlation between functional LP activity and C5a desArg. Conclusions. These findings lead to new insights into the FCA during HD and suggest that functional LP activity has an important role in C5 activation.

This guideline was provided by the Japanese Association for Complement Research targeting clinicians for making an accurate diagnosis of hereditary angioedema (HAE), and for prompt treatment of the HAE patient in Japan. This is a 2010 year version and will be updated according to any pertinent medical advancements.

To clarify the diversity in hypoglycemic actions of sulfonylureas, chronic effects of three sulfonylureas were compared on in vivo insulin-induced glucose uptake in peripheral tissues. After oral administration of glimepiride (CAS 93479-97-1), glibenclamide (CAS 10238-21-8), gliclazide (CAS 21187-98-4), or saline as control, two-step euglycemic clamp procedures were performed. During physiological hyperinsulinemia induced by 6 mU/kg/min insulin infusion, metabolic clearance rates (MCR) of glucose of the glimepiride-administered group (GP) significantly (p0.01) increased to 153% of the saline-administered group (SA). There was no significant statistical difference between the glibenclamide-administered group (GC), gliclazide-administered group (GZ) and SA. During 30 mU/kg/min clamps that lead to maximal insulin action, MCR of either GP or GC were significantly higher than those of SA (128% and 141%, p0.05 and p0.01, respectively). MCR of GZ were lower than those of GC (80%, p0.05), and showed no significant difference from those of SA. These data indicate that glimepiride activates insulin binding levels to a greater degree than the other two sulfonylureas, and that glibenclamide and glimepiride activate post-receptor binding mechanisms in peripheral tissues much more than gliclazide. These results suggest that hypoglycemic actions of sulfonylureas at the extra pancreatic levels vary with the nature of each reagent.

Subacute bacterial endocarditis (SBE) associated with antiproteinase-3 antineutrophil cytoplasmic antibodies (PR3-ANCA) has previously been reported in 10 cases of Streptococcus viridans and in 1 case of Escherichia faecalis infection. Most of these patients had hypocomplementemia and were positive for several autoantibodies. The infections in most of these patients showed good responses to antibiotic treatment. We report three patients with ANCA-positive SBE, which was induced by attenuated slow-growing intracellular pathogens; these patients had severe complications, such as acute kidney injury, cerebral embolism, and aortic valve destruction.

Mannose-binding lectin (MBL), L-ficolin and MBL associated serine protease-2 (MASP-2) are molecules involved in initiation of the lectin pathway (LP) in the complement system. Although MBL deficiency is observed in almost 10% of healthy people, studies of associations between MBL deficiency and end-stage renal disease (ESRD) remain rare. The objective of the present study is to clarify the significance of the LP in maintenance hemodialysis (HD) patients, especially in terms of MBL levels. Two hundred and forty-four HD patients who had been followed up for 74±84months and 199 healthy controls were included in this study. Measurements of serum concentrations of MBL, L-ficolin, and MASP-2 were performed. Low serum MBL levels (

A 59-year-old man was diagnosed with IgG4-related tubulointerstitial nephritis. His symptoms as well as laboratory and imaging findings were improved after initiation of steroid therapy. Serologically, he showed hypocomplementemia (C3 23 mg/dl, C4

BACKGROUND The long-term antiproteinuric effects of benidipine, a calcium channel blocker (CCB), have not been evaluated in detail in hypertensive patients with chronic kidney disease (CKD). METHODS Benidipine (4 mg/day) was administered to previously untreated hypertensive patients with CKD, or hypertensive patients with CKD not achieving target blood pressure (BP) despite taking an angiotensin II receptor blocker (ARB). The patients were followed up for 1 year. If target BP was not achieved by 2 weeks after the start of benidipine treatment, the dosage was increased to 8 mg/day. The urinary protein to creatinine (UP/cre) ratio was evaluated before and after benidipine treatment. RESULTS This study evaluated 65 hypertensive patients with CKD. BP (systolic/diastolic) decreased from 154 ± 19 / 91 ± 12 mm Hg before treatment to 134 ± 16 / 78 ± 10 mm Hg at 1 year after treatment (p

A 55-year-old woman presented with heavy proteinuria (6.2 g/day) in April 2007. Because monoclonal IgG-k was detected in serum and urine samples, bone marrow aspiration and renal biopsy were performed. She was diagnosed with plasma cell dyscrasia because a bone marrow aspiration specimen showed plasma cells at 6.1%. Renal tissues revealed the formation of nodular glomerulosclerosis which was negative for Congo-red staining. Renal immunohistochemistry showed positive staining for kappa light chains in the nodular lesions, proximal tubules and part of Bowman's capsules. Her renal involvement was diagnosed as light chain deposition disease. Proteinuria disappeared and renal function stabilized after high-dose chemotherapy and autologous stem cell transplantation. It appears that an early initiation of active therapy such as high-dose chemotherapy and autologous stem cell transplantation may be beneficial for patients with light chain deposition disease.

The aim of this study was to explore the association between the serum concentration of complement component 3 (C3) and a variety of metabolic parameters. The study involved 125 patients in our outpatient clinic. Anthropometric and clinical laboratory data were collected and statistical associations between the serum concentration of C3 and other parameters were evaluated in a cross‐sectional as well as a prospective manner. A group of male patients with metabolic syndrome (Mets, n=35) were characterized by marked increase in serum concentrations of C3, body mass index (BMI), waist circumference, hemoglobin (Hb) A1c, insulin resistance (HOMA‐IR), triglyceride, uric acid, urinary protein, and Hb. In a one‐way analysis of variance of all subjects, the serum concentration of C3 was significantly elevated as the number of items of complying with the Mets diagnostic criteria increased. In 60 of 125 patients who did not have diabetes and were given anti‐lipogenetic medication, the serum concentration of C3 showed significant positive associations with serum levels of CH50, insulin, HOMA‐IR, total cholesterol, hematocrit, LDL‐c, C4, Hb, triglyceride, BMI, and albumin. In a prospective follow‐up evaluation (n=35), there was a significant positive association between ΔC3 (the second concentration of serum C3 minus the first concentration of serum C3)and ΔHOMA‐IR (the second concentration of HOMA‐IR minus the first concentration of HOMA‐IR). In conclusion, in Japanese patients, there is evidence implicating C3 concentration as a marker of Mets coinciding with insulin resistance. J. Clin. Lab. Anal. 24:113–118, 2010. © 2010 Wiley‐Liss, Inc.

Type B insulin resistance syndrome is a rare disease. Auto-antibodies to the insulin receptor frequently appear in the case of systemic lupus erythematosus (SLE). We report herein a case of a 56-year-old man who had presented discoid skin lesions since 1990. He was admitted to the hospital because of unconsciousness and severe hypoglycemia in 2006, and was diagnosed as having Type B insulin resistance syndrome with the presence of insulin receptor antibody. He had frequently repeated hypoglycemic and hyperglycemic episodes in spite of treatment with prednisolone (5 - 10 mg/day), and mild proteinuria of 1.5 g/day was observed. His laboratory findings on admission revealed pancytopenia and positive titer for antinuclear antibody (ANA). From these findings and his past history of skin lesions, we diagnosed him as SLE. We performed renal biopsy and his histological diagnosis was lupus nephritis Class 5 with the findings of podocytic shedding. Prednisolone dosage was increased from 10 to 60 mg/day. Thereafter, his glucose metabolism improved and proteinuria disappeared. The dose of prednisolone was tapered to 30 mg/day without recurrence of hypoglycemia and proteinuria. Early treatment with prednisolone might ameliorate proteinuria and insulin resistance. We experienced a rare case of Type B insulin resistance syndrome with increased activity of SLE, complicated with lupus nephritis. It appears that Type B insulin resistance syndrome should be suspected in differential diagnosis of hypoglycemia in SLE patients.

A 49-year-old man with pulmonary sarcoidosis was admitted to our hospital because of nephrotic syndrome. Renal biopsy revealed membranous nephropathy and granulomatous interstitial nephritis. DNA and cell membrane constituents of Propionibacterium acnes were detected in the patient’s glomeruli and tubular epithelial cells. Treatment with corticosteroids and an antimicrobial agent resulted in remission of the nephrotic syndrome. This is the second case in which components of P. acnes were found in renal tissue, suggesting latent pathogenesis of P. acnes infection in renal sarcoidosis.

Aims: The aim of the present study was to determine whether or not the effect of parenting by the father and mother on outcomes for depression may be different between male and female subjects. Methods: A total of 115 patients were involved in this investigation: 74 had states of depression that continued for more than 2 years, and 41 had symptoms that remitted within 4 months. The Parental Bonding Instrument (PBI) was used to test for gender differences in the PBI score, the level of education, and the age at which the depression began, using an unpaired t-test. Results: It is suggested that female patients with low paternal care and low levels of education have a higher likelihood of showing symptoms of prolonged depression in a primary episode. No relationship was found among prolongation of depression, educational level, and parental care in male patients. Furthermore, comparing the PBI quadrants established by Parker showed that female patients who were exposed to paternal care as ‘Affectionless Control’, had a tendency towards a higher risk of prolonged depression than female patients who received ‘Optimal Parenting’. Conclusion: Especially in female patients, the prolongation of depression is likely a result of low levels of paternal care and low education.

Mannose-binding lectin (MBL), L-ficolin and H-ficolin are human serum lectins, all of which form complexes with MBL-associated serine proteases (MASP). The lectin-MASP complexes bind to the surface of microbes, leading to activation of the lectin pathway of complement. Enzyme-linked immunosorbent assays (ELISA) of the lectin pathway activity reported so far determined the activity via either MBL or L-ficolin, but an assay of activity via plural host defense lectins has not been established. To measure the lectin pathway activation mediated by plural lectins simultaneously, we developed an ELISA system in which N-acetylglucosamine-pentamer conjugated to dipalmitoylphosphatidylethanolamine (GN5-DPPE) was employed as a ligand for the lectins. In our ELISA system, both purified MBL and L-ficolin isolated from serum diluted in a buffer containing high ionic NaCl bound to GN5-DPPE and activated C4. Purified H-ficolin was not capable of binding to GN5-DPPE. MBL and L-ficolin in MBL-sufficient serum also bound to GN5-DPPE and activated C4. Mannose and N-acetylgalactosamine inhibited binding of MBL and L-ficolin to GN5-DPPE, respectively. MBL-deficient serum that had been depleted of L-ficolin did not exhibit C4 activation, but addition of both or either purified MBL and/or L-ficolin to the serum restored the activation in a dose-dependent manner. Thus, C4 cleaving activity could be evaluated with the co-existence of MBL and L-ficolin in vitro. In conclusion, we propose a novel method using GN5-DPPE for investigating the MBL- and L-ficolin-dependent lectin pathway and anticipate that this method will be useful in innate immunity and clinical research.

Background The binding of advanced glycation end-products (AGEs) to their receptor for AGEs (RAGE) may play an important role in the development of diabetic vascular complications. Recently, soluble RAGE (sRAGE) has been identified as an alternative splicing form of RAGE. Furthermore, administration of sRAGE improved atherosclerosis in type 2 diabetic mice. Objective The objective of the present study is to investigate the role of endogenous secretory RAGE (esRAGE) as a biological marker for type 2 diabetic nephropathy, and also to determine whether serum esRAGE levels are associated with serum AGEs [including Nɛ–(carboxymethyl) lysine–protein adducts (CML) and pentosidine] levels. Materials and methods Serum esRAGE levels were examined in 107 type 2 diabetic patients including those on hemodialysis (HD). Diabetic patients were divided into three groups as follows: Group A [patients without nephropathy, i.e. normoalbuminuric stage (AER 30 μg/mg creatinine) but excluding HD patients], and Group C (HD patients). Results Serum esRAGE and AGEs (including CML and pentosidine) levels in Group C were significantly higher than in Group A or B. In single linear univariate correlation, serum esRAGE levels were correlated using body mass index (BMI), duration of diabetes, and serum creatinine, high-density lipoprotein (HDL)-cholesterol and AGEs (including CML and pentosidine) levels. Furthermore, in stepwise multivariate regression analysis, the levels of serum creatinine and duration of diabetes were independently associated with serum esRAGE levels. Conclusion Serum esRAGE levels are associated with the severity of renal dysfunction and duration of diabetes in type 2 diabetic patients.

Several clinical markers correlate well with the diagnosis and prognosis of IgA nephropathy (IgAN). In the present study, we re‐evaluated the usefulness of these four clinical markers for prediction of the diagnosis of patients with IgAN through a comparison between many more patients with IgAN and those with other types of renal diseases. 364 patients with IgAN and 289 with other types of renal disease were examined. An analysis was performed prior to renal biopsy, using clinical markers including, serum IgA, serum IgA/C3 ratio, number of red blood cells in urinary sediments, and urinary protein. Patients with IgAN were divided into four groups according to histopathological findings. Presence of microscopic hematuria, persistent proteinuria, high serum IgA levels, and the serum IgA/C3 ratios are useful for prediction of diagnosis of IgAN and distinguishing it from other renal diseases. Blood pressure, urinary protein, serum uric acid, renal function, and urinary sediment findings may be useful for prediction of prognostic grading in patients with IgAN. J. Clin. Lab. Anal. 22:114–118, 2008. © 2008 Wiley‐Liss, Inc.

IgA nephropathy (IgAN) is the most common form of chronic glomerulonephritis. Although glomerular deposition of complement components is well known, the evidence of serological complement activation in IgAN is inconclusive. We hypothesized that serum levels of complement components and regulatory proteins in patients with IgAN are correlated with its pathogenesis. In the present study we measured complement components in 50 patients with IgAN and 50 healthy volunteers. C5, C1 inhibitor, factor B, C4 binding protein, factor H, and factor I were measured with the use of single radial immunodiffusion. Mannose‐binding lectin (MBL) and properdin (P) were measured by enzyme‐linked immunosorbent assay (ELISA). The correlations among complements in the sera of patients with clinical gradings for IgAN (i.e., the good prognosis group, relatively good prognosis group, relatively poor prognosis group, and poor prognosis group) were evaluated. CH50, C4, factor B, P, factor I, and factor H were significantly higher in IgAN patients than in healthy controls. There were significant correlations between C5 and C4 binding protein, between C3 and C5, or between C4 and factor B in patients with IgAN. In the poor prognosis group, C4 binding protein was significantly higher than in the other groups of IgAN patients. hypercomplementemia occurs in IgAN and is associated with an increase in complement regulatory protein (CRP). C4 binding protein analyses can be used to predict disease prognosis. J. Clin. Lab. Anal. 21:77–84, 2007. © 2007 Wiley‐Liss, Inc.