Atsushi Kurusu

Detection of Serum IL-6 in Patients with Diabetic Nephropathy

Yasuhiko Tomino. MD, Division of Nephrology, Department of Medicine, Juntentto University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113 (Japan) Dear Sir, A study on the detection of serum IL-6 in patients with non-insulin-dependent diabetes mellitus (NIDDM) with or without nephropathy is described. IL-6 is generally regarded as a multifunctional cytokine which has a variety of biological activities, including the ability to stimulate bone marrow stem cell proliferation, B cell differentiation, immuno-globulin secretion, T cell activation, and acute phase protein synthesis [1, 2], IL-6 is also produced by the renal glomerular mesan-gial cells. Cytokines are known to play an important role in autoimmunity and appear to be involved in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). However, Cavallo et al. [3] reported that detectable levels of serum IL-6 were observed in only 10% of IDDM patients. Serum samples were obtained from 9 patients with NIDDM with nephropathy (diabetic nephropathy), 9 patients with NIDDM without nephropathy and 29 patients with chronic glomerulonephritis (CGN). NIDDM was diagnosed with a 75-gram glucose tolerance test. Patients with diabetic nephropathy continuously showed more than 200 mg/24 h. Serum IL-6 levels were measured with ELISA as described previously [4]. Mouse monoclonal anti-IL-6 antibody (HH61-10) and monoclonal horse radish peroxidase-conjugated anti-IL-6 antibody (HH61-2 Fab’) were used in a double-antibody sandwich ELISA [5]. Levels of serum IL-6 of healthy controls were less than 4.0 pg/ml [5]. The mean levels of serum IL-6 in all patients with NIDDM were significantly higher than those in patients with CGN (p < 0.05). The levels of serum IL-6 in patients with diabetic nephropathy were significantly higher than those in cases of CGN or NIDDM without nephropathy (p < O.Ol and p < 0.05, respectively; table 1). It appears that the presence of IL-6 in the patients’ sera may reflect increased localized production of this cytokine at the pancreatic and/or glomerular me-sangial levels. The measurement in serum IL-6 may add

Urinary levels of interleukin-8 (IL-8) and disease activity in patients with IgA nephropathy.

Using quantitative sandwich ELISA, we studied 27 patients with IgA nephropathy to determine whether the levels of urinary IL‐8 might reflect the disease activity. The levels of urinary IL‐8 in patients with advanced stage IgA nephropathy were significantly higher than those in the patients with the mild stage of this disease, or in the healthy controls. The results showed a positive significant correlation between the levels of IL‐8 and disease activity, i.e., between levels of urinary protein and urinary casts. A significant correlation between levels of urinary IL‐8 and tubular function damage was also found. It was thus suggested that measurement of urinary IL‐8 might be useful in evaluating the degree of renal injuries and/or prognosis in patients with IgA nephropathy. J. Clin. Lab. Anal. 15:30–34, 2001.

Effects of the new hydroxy-3-methylglutaryl coenzyme a reductase inhibitor fluvastatin on anti-oxidant enzyme activities and renal function in streptozotocin-induced diabetic rats.

1. The effects of 11 week treatments with the new hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitor fluvastatin on renal intrinsic anti‐oxidant enzyme (AOE) activities and renal function were evaluated in streptozotocin (STZ)‐induced diabetic rats.

Increase of Urinary Type IV Collagen in Normoalbuminuric Patients with Impaired Glucose Tolerance

Accessible online at: http://BioMedNet.com/karger Dear Sir, Microalbuminuria is the only early clinical sign of the subsequent diabetic nephropathy. However, it is also known that significant structural changes have already appeared even at the stage of microalbuminuria in non-insulin-dependent diabetes mellitus (NIDDM) patients. Thus, it is necessary to develop a more sensitive measurement for detecting the early stage of renal injury in patients with diabetic nephropathy. Since type IV collagen is the principal component of glomerular basement membrane and mesangial matrix, the levels of type IV collagen in sera and urinary samples may reflect the rate of its turnover, such as the balance of production by intrinsic renal cells and degradation by matrix proteinases in diseased kidneys. To investigate the alteration of renal turnover of type IV collagen in patients with impaired glucose tolerance (IGT), urinary type IV collagen (uIV) was measured by a highly sensitive one-step sandwich enzyme immunoassay (EIA) (Fuji Chemical Industries, Co. Ltd, Takaoka, Toyama, Japan) [1]. Diagnosis of NIDDM was made according to the criteria of the 75-gram oral glucose tol-

Fluctuation of serum C3 levels reflects disease activity and metabolic background in patients with IgA nephropathy.

BACKGROUND We focused on the fluctuations of serum C3 levels throughout the clinical course of patients and investigated the relationship between these fluctuations and clinical findings. METHODS IgA nephropathy patients (n = 122) were enrolled in the present study. Serum C3 and other clinical markers were compared at the time of renal biopsy and at last follow-up (6.67 ± 2.07 years). Patients were divided into 3 groups based on serum C3 levels: Group I with first C3 levels below the mean -1 SD, which turned into an increase at last observation; group II with first C3 levels more than the mean +1 SD, which turned into a decrease at last observation; and group III, with first C3 levels more than the mean +1 SD, which turned into an increase at last observation. First and last levels of clinical markers were compared among the 3 groups. RESULTS Serum C3 levels of the patients whose renal symptoms, including hematuria, proteinuria and estimated glomerular filtration rate (eGFR), were improved, were significantly increased at last observation (p<0.05, p<0.01, p<0.01, respectively). Age, total cholesterol and triglyceride levels in group III were significantly higher than those in group I. Group II showed a significant reduction of urinary protein. Groups I and II maintained renal function, but group III showed a significant deterioration of renal function. CONCLUSIONS The levels and fluctuations of serum C3 might reflect the disease activity and metabolic alteration in patients with IgA nephropathy.

USEFULNESS OF A BODY COMPOSITION ANALYZER, INBODY 2.0, IN CHRONIC HEMODIALYSIS PATIENTS

The objective of the present study was to investigate whether InBody 2.0 might be useful in measuring the dry weight of chronic hemodialysis (HD) patients. Thirty‐five HD patients (22 males and 13 females; mean age 62.6 ± 14.0 years; mean HD duration 101.0 ± 118.06 months) were examined. Multifrequency bioelectric impedance analysis was used to estimate the ratio of extracellular water (ECW) to total body water (TBW). The body resistance was measured at frequencies ranging from 1 kHz to 1 MHz. The impedance index was determined at a low frequency (5 kHz) and correlated closely with ECW, using sodium bromide dilution as standard comparison. The levels of serum albumin, prealbumin, total cholesterol (TC), triglycerides (TG), transferrin, and human atrial natriuretic peptide (hANP) were measured by routine methods in our hospital. The ECW/TBW ratio was significantly associated with the levels of hANP (p < 0.05). However, no associations between the levels of serum albumin, TC, TG, or transferrin and the ECW/TBW were observed. It appears that the body composition analyzer, InBody 2.0, may be useful for estimating the dry weight in chronic HD patients.

Campylobacter Bacteremia in Hemodialysis Patients by Eating Raw Meat – The Importance of Sanitary Education

In 2011, simultaneous, widespread outbreaks of food poisoning by contaminated enterohemorrhagic Escherichia coli in beef, which killed four and hospitalized more than 30 people, occurred in Japan. While the press was widely reporting this disaster, two maintenance hemodialysis patients were suffering from Campylobacter bacteremia by eating undercooked meat. One patient was infected with C. upsaliensis and the other with C. fetus. Although these patients could be successfully treated, they led us to consider the characteristics of C. upsaliensis and C. fetus as opportunistic pathogens, as well as changes in dietary behaviors and food markets. Moreover, they emphasized the need for hemodialysis patients to be not only educated in that they should restrict potassium, phosphate and water intake, but also that they should take care of food sanitation.

Effects of Acetate-Free Citrate Dialysate on Glycoxidation and Lipid Peroxidation Products in Hemodialysis Patients

Background/Aims: Previous studies have shown the presence of high levels of glycoxidation and lipid peroxidation products in association with atherosclerosis in patients with end-stage kidney disease. Acetates are commonly used buffer for correcting metabolic acidosis in hemodialysis (HD) patients. Since the toxic effects of acetates are well established, acetate-free citrate dialysate (AFD) has become available in Japan. The objective of the present study was to evaluate the suppressive effects of AFD on oxidative stress in maintenance HD patients by measuring plasma pentosidine and malondialdehyde-modified low-density lipoprotein (MDA-LDL) levels as markers for glycoxidation and lipid peroxidation products. Methods: Plasma pentosidine, MDA-LDL and other laboratory parameters were examined on maintenance HD at the Juntendo University Hospital before and after switching to AFD. Results: MDA-LDL levels divided by LDL cholesterol were significantly lower than those before switching to AFD. Furthermore, levels of plasma pentosidine were lower than those before switching to AFD. Stepwise multiple regression analysis revealed that the percent change of the calcium-phosphorus product in the nondiabetic group and that of phosphorus in the diabetic group were predictive variables for the percent change of MDA-LDL/LDL, whereas the percent change of log high-sensitive C-reactive protein and that of systolic blood pressure in the nondiabetic group and that of diastolic blood pressure in the diabetic group were predictive variables for the percent change of plasma pentosidine. Conclusions: It appears that AFD decreases glycoxidation and lipid peroxidation products when compared with acid citrate dextrose in HD patients. The reduction of oxidative stress by AFD during HD may have possible beneficial effects on atherosclerosis through calcium-phosphorus metabolism and blood pressure.

One-year results of an open-label study on antiproteinuric effect of benidipine in elderly patients with chronic kidney disease.

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<0.001). The UP/cre ratio decreased significantly from 2.21 ± 2.47 g/g creatinine (g/g cre) before treatment to 1.43 ± 2.21 g/g cre after treatment (p<0.001). In both the untreated and ARB-treated groups, the BP and UP/cre ratio decreased significantly at 1 year after treatment. The percentage change in the UP/cre ratio was significantly greater in patients aged 65 years or older than in those less than 65 years (79.1% vs. 48.7%, p=0.038). CONCLUSIONS Benidipine treatment reduced the UP/cre ratio in hypertensive patients with CKD, and the percentage decrease of the UP/cre ratio was greater in elderly patients, suggesting that benidipine may have more potent antiproteinuric effects in elderly hypertensive patients with CKD.

A case of primary immunoglobulin light chain amyloidosis with a delayed appearance of Bence Jones protein in urine.

SUMMARY:  We report here a case of a 58‐year‐old man who had nephrotic syndrome and immunoglobulin light chain (AL) amyloidosis. This patient underwent a renal biopsy to confirm the diagnosis. Treatment with permanganate before Congo red staining showed systemic secondary amyloidosis (AA) fibrils, which were sensitive to permanganate oxidation. Although this patient was initially diagnosed as having AA amyloidosis, he did not have any chronic inflammatory disease and/or malignancy. The level of amyloid A protein (7.9 µg/mL) in sera was within the normal range (0–8.0 µg/mL). Therefore, we performed an immunostaining of the precursor protein (amino terminus of constant region: κ and λ light chains, and AA protein) using duodenal biopsy specimens for a precise diagnosis. Immunostaining was positive for the amino terminus of constant region of the λ light chain, and negative for the amino terminus of constant region of the κ light chain and AA protein. No plasma cell proliferation in the bone marrow was observed. We finally diagnosed this patient as having primary AL amyloidosis. It appears that a pathological diagnosis must be performed by immunostaining the precursor proteins with the permanganate digestion technique in tissue of patients with amyloidosis. There were no abnormalities in serum and urine immunoelectrophoresis at the time of renal biopsy in this patient. During the follow‐up period, after discharge, Bence Jones protein appeared in the urine, but not in the serum. It is necessary to observe patients with primary AL amyloidosis carefully to determine if they their condition will progress to multiple myeloma.