Suplatast Tosilate and Eicosapentaenoic Acid as a Possible Strategy for Maintaining Remission in Minimal Change Nephrotic Syndrome: A Case Report.

We report a case of a sudden onset of minimal change nephrotic syndrome (MCNS) in a 33-year-old woman with type 1 diabetes mellitus (T1DM), stable microalbuminuria, and chronic thyroiditis. She was successfully treated with intravenous corticosteroids to finally attain a complete remission. Four years later, she also experienced a relapse of MCNS in the same season as the first onset. The chronological levels of serum immunoglobulin E (IgE) showed that extremely high serum IgE levels preceded the onset or the relapse of MCNS, which may suggest an allergic mechanism of MCNS. Eicosapentaenoic acid (EPA) was reported to be beneficial in treating allergic diseases. Suplatast tosilate is an anti-allergic medication that suppresses serum IgE and was reported to be beneficial in reducing corticosteroid dose in nephrotic syndrome in a pilot study. Therefore, during the tapering of corticosteroids to the relapse of MCNS, suplatast tosilate and EPA were administered, and the IgE levels were considerably controlled. The patient was able to maintain remission even after the cessation of corticosteroids. In conclusion, suppressing IgE levels using suplatast tosilate and EPA may be beneficial in maintaining complete remission without corticosteroids in T1DM.

Efficacy of comprehensive group-based education in lowering body weight, uric acid levels, and diuretic use in patients with chronic kidney disease: a retrospective study.

BACKGROUND: Patient education for the management of chronic kidney disease (CKD) is attracting attention. Therefore, this study aimed to analyze changes in body weight, uric acid, and estimated-glomerular filtration rate (eGFR) in patients with CKD after a group-based education during admission. METHODS: Overall, 157 patients with CKD, who were discharged from the nephrology department of our hospital between January 2015 and October 2019, received group-based education or individual-based education by nurses at admission. Deltas of body weight, uric acid, and eGFR, 6 months from baseline, were compared between group- and individual-based education using the Wilcoxon rank sum test. RESULTS: In total, 60 patients receiving group-based education (G group, n =35) or individual-based education (I group, n =25) during admission were included in this retrospective study. The patient characteristics at baseline were as follows: age mean, 72 ± SD 9; 16 females and 44 males; body weight, 62 ± 17 kg; eGFR median, 21 (IQR: 14, 29) mL/min/1.73 m2; UA, 7 (6.1, 7.5) mg/dL; and estimated intake of salt 6.9 (6.2, 8.4) g/day. Delta eGFR (mL/min/1.73 m2) was -1 (-3, 3) for G group and -1 (-2.5, 2) for I group (p = 0.8039). Delta body weight (kg) was -0.4 (-1.6, 0) for G group and 0 (-0.45, 0.95) for I group (p = 0.0597). Delta uric acid (mg/dL) was -1.1 (-1.6, 0.1) for G group and -0.2 (-1.1, 0.5) for I group (p = 0.0567). In patients with higher sodium intake (≥ 117.4 mEq/day), delta body weight was significantly lower in the group-based education group than in the individual-based education group (p = 0.0398). CONCLUSIONS: A comprehensive group-based education in patients with CKD may effectively suppress body weight and uric acid in 6 months along with less frequent diuretic use.

Alcohol Consumption and a Decline in Glomerular Filtration Rate: The Japan Specific Health Checkups Study.

Previous studies have reported conflicting results on the clinical impact of alcohol consumption on the glomerular filtration rate (GFR). This retrospective cohort study aimed to assess the dose-dependent association between alcohol consumption and the slope of the estimated GFR (eGFR) in 304,929 participants aged 40-74 years who underwent annual health checkups in Japan between April 2008 and March 2011. The association between the baseline alcohol consumption and eGFR slope during the median observational period of 1.9 years was assessed using linear mixed-effects models with the random intercept and random slope of time adjusting for clinically relevant factors. In men, rare drinkers and daily drinkers with alcohol consumptions of ≥60 g/day had a significantly larger decline in eGFR than occasional drinkers (difference in multivariable-adjusted eGFR slope with 95% confidence interval (mL/min/1.73 m2/year) of rare, occasional, and daily drinkers with ≤19, 20-39, 40-59, and ≥60 g/day: -0.33 [-0.57, -0.09], 0.00 [reference], -0.06 [-0.39, 0.26], -0.16 [-0.43, 0.12], -0.08 [-0.47, 0.30], and -0.79 [-1.40, -0.17], respectively). In women, only rare drinkers were associated with lower eGFR slopes than occasional drinkers. In conclusion, alcohol consumption was associated with the eGFR slope in an inverse U-shaped fashion in men but not in women.

Severe leukocytopenia due to copper deficiency induced by zinc supplementation in a patient on peritoneal dialysis: a case report.

Zinc deficiency is one cause of anemia. However, it has been reported that some patients who were treated with zinc supplementation to resolve this anemia subsequently experienced copper deficiency, which lead to continued anemia, as well as leukocytopenia and other symptoms. However, only two patients with copper deficiency induced by zinc supplementation undergoing peritoneal dialysis have been reported. Here, we report the case of a 59 year-old man with copper deficiency after zinc supplementation undergoing peritoneal dialysis (PD). He took meals only once a day and drank about 750 mL/day of wine every day. He had been receiving zinc supplementation for 4 months. He was diagnosed with severe leukocytopenia and worsening anemia at a planned outpatient visit; in addition, his copper levels had markedly decreased. Thus, zinc supplementation was discontinued, and the patient was instructed to take cocoa for copper supplementation. Because of severe leukocytopenia, he was admitted to our hospital, and granulocyte colony-stimulating factor was administered. Red blood cell transfusions were performed for anemia. After discontinuing zinc supplementation, his white blood cell count and hemoglobin levels improved.To avoid Cu deficiency, patients' dietary history should be checked in detail and Cu should be monitored carefully when Zn is supplemented in patients undergoing PD.

Tolvaptan Reduces Extracellular Fluid per Amount of Body Fluid Reduction Less Markedly than Conventional Diuretics.

Objective Tolvaptan, a vasopressin V2 receptor antagonist, is a water diuretic, removing electrolyte-free water from the kidneys and affecting the water balance between the intracellular and extracellular fluid. We previously reported that tolvaptan efficiently reduced the intracellular fluid volume, suggesting its utility for treating cellular edema. Furthermore, tolvaptan is known for its low incidence of worsening the renal function, with conventional diuretics use associated with worsening of the renal function Methods In this retrospective observational study, five chronic kidney disease (CKD) patients with fluid retention were assessed by the bioelectrical impedance (BIA) method twice (before and after tolvaptan therapy). Tolvaptan was used with conventional diuretics. The post/pre ratio of extracellular water (ECW)/total body water (TBW) in the tolvaptan group was compared with that in 18 CKD patients undergoing body fluid reduction with conventional diuretics alone (conventional diuretics groups), taking the reduced amount of body fluid into consideration. Results Removing body fluid, either by tolvaptan or by conventional diuretics alone, decreased the ECW/TBW ratio. Of note, the reduction in extracellular fluid was milder in the tolvaptan group than in the conventional diuretics group. Conclusion Tolvaptan reduces the extracellular fluid per amount of body fluid reduction less markedly than conventional diuretics.

A Formula for the Estimation of 24-Hour Urinary Creatinine Excretion: A Derivation and Validation Study.

OBJECTIVE: Twenty-four-hour urinary creatinine (Cr) excretion (24h-uCr) is the basis of Cr clearance and urinary protein-Cr ratio, and it is related to frailty, worsening kidney function, and mortality in patients with chronic kidney disease. Although subjects with lower estimated glomerular filtration rate (eGFR) tend to have lower 24h-uCr, previous formulae for the estimation of 24h-uCr did not include Cr as a predictor. METHODS: This retrospective study included patients admitted to the Department of Nephrology at our hospital (derivation cohort and validation cohort: patients admitted between April 2016 and March 2020). The prediction formula of 24h-uCr was calculated using a multivariate linear regression model with the bootstrap method. Age, height, weight, sex, Cr, and cystatin C were used as predictors. RESULTS: The derivation and validation cohorts included 187 and 63 patients, respectively. The characteristics of the derivation and validation cohorts were as follows: age 73 (61-79.5) years and 70 (58.5-79) years; males, 61.5% and 60.3%; eGFRCr 27.0 (13.7-48.6) mL/min/1.73 m2 and 26.3 (14.0-51.5) mL/min/1.73 m2; and 24-hour urinary protein excretion 0.79 (0.17-2.12) g/day and 1.08 (0.26-2.55) g/day, respectively. Seven prediction formulae were derived. In all models, the Pearson's correlation coefficient was relatively high and statistically significant. However, previous models tended to overestimate the 24h-uCr. Furthermore, the predicted 24h-uCr calculated by the models that do not include Cr as a predictor fluctuates depending on the eGFRCr. CONCLUSION: The best formula for predicting 24h-uCr (mg/day) in a wide range of eGFR populations is a Cr-containing formula: [-9.04 × age (years) + 8.03 × weight (kg) + 0.66 × height (cm) + 188.59 (if male) - 32.11 × Cr (mg/dL) + 779.14].

User of angiotensin-converting-enzyme inhibitor and/or angiotensin II receptor blocker might be associated with vascular calcification in predialysis chronic kidney disease patients: a retrospective single-center observational study : ACEI/ARB and vascular calcification.

BACKGROUND: Vascular calcification is a prominent feature in chronic kidney disease (CKD) and diabetes mellitus. A recent report suggests that angiotensin II is protective to vascular calcification. Therefore, we investigated the relationship between vascular calcification and use of angiotensin-converting-enzyme inhibitor (ACEI) and/or angiotensin II receptor blocker (ARB) from a cross-sectional view. METHODS: A total of 121 predialysis CKD patients (age 71 ± 12 y; male 72; estimated glomerular filtration rate (eGFR) 20.2 (11.8 - 40.3) mL/min/1.73 m2) who underwent thoracoabdominal plain computed tomography scan were included in this study. The total vascular calcification volume (Calc) was calculated with a three-dimensional imaging software and standardized by body surface area (BSA). The relevance between log [Calc/BSA] and ACEI/ARB use was investigated by multivariate linear regression analyses with or without a time-duration factor of ACEI/ARB use. RESULTS: The Calc/BSA was 5.62 (2.01 - 12.7) mL/m2 in 121 patients. In multivariate analyses adjusted with age, sex, ACEI/ARB and log [eGFR], ACEI/ARB use is significantly and positively associated with log [Calc/BSA] (ß = 0.2781, p = 0.0007). Even after the adjustment by age, sex, log [eGFR], phosphate, diabetes mellitus, systolic blood pressure, warfarin, hypertension, dyslipidemia, low-density lipoprotein cholesterol, diuretics and ACEI/ARB, ACEI/ARB use is significantly and positively associated with log [Calc/BSA] (ß = 0.1677, p = 0.0487). When 90 patients whose time-duration of ACEI/ARB use was clear in medical records were studied, a multivariate analysis adjusted with age, sex, log [eGFR], and ACEI/ARB duration factors showed that the longer use of ACEI/ARB more than 2 years was significantly, independently and positively associated with log [Calc/BSA] (ß = 0.2864, p = 0.0060). CONCLUSIONS: ACEI/ARB user was associated with vascular calcification in predialysis patients with low eGFR. Prospective studies with larger numbers of patients or more in vitro studies are needed to confirm whether this phenomenon is due to the use of ACEI/ARB itself, the underlying disease condition or the prescription bias.

Lactate predicts the 28-day survival rate in patients with septic shock treated with the combination of PMX-DHP and rTM.

We have previously reported that combination therapy with polymyxin-B direct hemoperfusion (PMX-DHP) and recombinant thrombomodulin (rTM) is effective in patients with septic shock accompanied by disseminated intravascular coagulation (DIC). Two previous studies reporting the favorable effect of early initiation of PMX-DHP for septic shock did not focus on the combination therapy of PMX-DHP and rTM. This retrospective study included 47 consecutive patients who underwent the combination therapy of PMX-DHP and rTM for septic shock with DIC from August 2011 to August 2016. Main exposure was early or late initiation of PMX-DHP. PMX-DHP initiated within 12 hours after catecholamine administration was designated as early group (N = 25) and later than 12 hours as late group (N = 22). Main outcome was 28-day survival rate. The patient characteristics were age median 73 (IQR 68-78) years, 26 men (55%), APACHE II score 32.7 ± 7.7 and lactate 26.0 (18.0-41.0) mg/dL. The 28-day survival rate after PMX-DHP initiation was 76.6% and was not significantly different in the two groups. In the early group, APACHE II score was lower (P = .02), and lactate was higher (P = .005) than in the late group. Lactate was the only predictor of 28-day mortality [odds ratio (95%CI) per 1 mg/dL, 1.08 (1.03-1.19); P = .037] in multivariate logistic regression analysis adjusted with age, sex, APACHE II score, lactate and timing of PMX-DHP initiation. Late PMX-DHP initiation did not lead to statistically worse 28-day survival rate in this combination therapy. The combination therapy of PMX-DHP and rTM may improve the therapeutic effect of PMX-DHP and modify the effect of early PMX-DHP on the prognosis. Lactate may be an appropriate indicator rather than time after catecholamine administration if we discuss when to start PMX-DHP in this combination therapy.

Evaluation of IgA1 O-glycosylation in Henoch-Schönlein Purpura Nephritis Using Mass Spectrometry.

BACKGROUND: Glomerular deposition of IgA1 is a common feature of Henoch-Schönlein purpura nephritis (HSPN) and is indistinguishable from that seen in IgA nephropathy (IgAN). Serum IgA1 is abnormally O-glycosylated in IgA nephropathy, which may contribute to the development of glomerular injury. Abnormal O-glycosylated IgA1 was also detected in HSPN using lectin enzyme-linked immunosorbent assay; however, this method cannot provide the exact structural information of O-glycans. Mass spectrometry is an effective means of quantification of O-glycans, and there is no report to evaluate IgA1 O-glycans in HSPN using mass spectrometry. MATERIALS AND METHODS: We investigated O-glycosylation profile in serum IgA1 from 7 HSPN recipients, 26 IgAN recipients, 25 recipients with other kidney diseases (OKDs), and 26 normal healthy donors using mass spectrometry. RESULTS: Of the 14 GalNac-Gal combinations detected using mass spectrometry, the percentage of the only 6GalNAc-2Gal combination was significantly different between HSPN and IgAN. The percentage of GalNAc 3 in HSPN recipients was significantly higher than that in OKDs recipients and healthy donors (P = .0027 and P < .0001, respectively). Inversely, the percentage of GalNAc 5 in HSPN recipients was significantly lower than that in OKDs recipients and healthy donors (P = .0008, P < .0001, respectively). Moreover, the Gal content and the Gal/GalNAc ratio of HSPN recipients were significantly lower than OKDs recipients and healthy donors. CONCLUSIONS: Examination of Henoch-Schönlein purpura recipients revealed that the number of GalNAc fell and the Gal attachment to GalNAc was reduced compared to other kidney diseases and healthy donors. The IgA1 O-glycosylation profile of HSPN was very similar to that of IgAN.

Difference in IgA1 O-glycosylation between IgA deposition donors and IgA nephropathy recipients.

IgA nephropathy (IgAN) is the most common form of primary glomerulonephritis, and disease recurrence often occurs after transplantation. On the other hands, Asymptomatic IgA deposition (IgAD) is occasionally observed in donated kidney. It is recognized that IgAD does not progress to IgAN, but the mechanism has not demonstrated yet. In IgAN, aberrant IgA1 O-glycan structure in the hinge region (HR) of serum IgA is suggested as one of the most convincing key mediators. However, little is known about IgA1 O-glycan structure in IgAD patients. Herein, we investigated the prevalence of IgAD in living renal transplant donors in our cohort. IgAD was observed in 21(13.0%) among 161 renal transplant donors and have statistically significant blood relationship with IgAN recipients (28.6% in relatives vs. 9.8% in non-relatives, respectively; p = 0.0073). Next, we evaluated the IgA1 O-glycan structure of serum IgA from IgAN recipients (n = 26), IgAD donors (n = 17), and non-IgAD helthy donors (n = 27) using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). The numbers of GalNAc and Gal and the Gal/GalNAc ratio in the HR of the IgAN recipients had significantly lower comparing to the IgAD and non-IgAD healthy donors. The decreased Gal/GalNAc ratio in IgAN recipients means the increased ratio of galactose-deficient IgA1. To the best of our knowledge, this is the first report to compare the O-glycan structures in IgAN recipients and IgAD donors using MALDI-TOF MS. We concluded that IgAD was more common in IgAN related donors. Overall, decreased GalNAc and Gal contents in HR could play a material pathogenic role in IgAN.

Tolvaptan Efficiently Reduces Intracellular Fluid: Working Toward a Potential Treatment Option for Cellular Edema.

Objective Tolvaptan is a class of diuretics that reduce body water through aquaresis. One of the most prominent characteristics of these agents is that worsening of the renal function is less likely to occur. We investigated the underlying mechanism concerning the change in the intracellular fluid (ICF) when the body fluid is reduced. Methods In this retrospective observational study, five overhydrated chronic kidney disease (CKD) patients with edema or pleural effusion treated with tolvaptan were assessed by the bioelectrical impedance method twice: once before and once after tolvaptan therapy. The changes in the ICF rate were compared with those in 11 hemodialysis patients undergoing body fluid reduction by hemodialysis. Results Removal of the body fluid either by tolvaptan or by hemodialysis increased the post/pre-ratio of ICW/total body water (TBW). Tolvaptan reduced the ICF more efficiently than hemodialysis. Conclusion Tolvaptan treatment lessens body fluid by the efficient reduction of the ICF.

Tolvaptan promotes urinary excretion of sodium and urea: a retrospective cohort study.

BACKGROUND: Tolvaptan (TLV) promotes aquaresis; however, little is known about its effect on solute excretion in chronic kidney disease (CKD). METHODS: We retrospectively studied CKD patients with decompensated heart failure (HF) or those with autosomal dominant polycystic kidney disease (ADPKD) receiving TLV. Patients with an increased urine volume of more than twice of daily variance were defined as "responders" in HF. We compared the ability of the urinary osmolality (U-OSM) change and urinary creatinine concentration ([U-Cr]) change to discriminate "responders". The fractional excretion of sodium (FeNa) and urea nitrogen (FeUN), and blood urea nitrogen (BUN) were monitored. RESULTS: In 30 responders among 53 HF patients, TLV increased FeUN significantly from 36.1 to 44.2% after starting TLV, but not FeNa. Since U-OSM is determined partially by urinary UN concentration, the decrease of [U-Cr] after treatment outperformed the U-OSM decrement to discriminate responders, as shown in receiver operating characteristic curve analysis and significantly higher net reclassification index. In 13 ADPKD patients, TLV increased FeUN (34.8, 47.3%, p = 0.02), and significant decrease of BUN by 2.3 (95% confidence interval 0.4-4.2) mg/dL was observed even 3 months after the intervention. Systolic blood pressure decreased significantly by 14.2 (95% confidence interval 4.0-24.4) mmHg along with the increase in FeNa, leading to reduced dosage of antihypertensives in 6 patients. CONCLUSION: TLV promotes the excretion of sodium and urea. The change in [U-Cr] is useful for early discrimination of responders. Hypotension should be carefully monitored during high-dose TLV therapy.

Myeloperoxidase/HLA Class II Complexes Recognized by Autoantibodies in Microscopic Polyangiitis.

OBJECTIVE: Autoantibodies against myeloperoxidase (MPO) that are expressed in neutrophils play an important role in the pathogenesis of microscopic polyangiitis (MPA). We recently observed that misfolded cellular proteins are transported to the cell surface by HLA class II molecules and are targeted by autoantibodies in patients with rheumatoid arthritis or antiphospholipid syndrome, suggesting that HLA class II molecules play an important role in autoantibody recognition. The aim of this study was to address the role of HLA class II molecules in the cell surface expression of MPO in patients with MPA. METHODS: The association of MPO with HLA-DR was analyzed using MPO and HLA-DR transfectants as well as neutrophils from healthy donors and patients with MPA. Autoantibody binding to the MPO/HLA-DR complex was analyzed by flow cytometry. The association of MPO with HLA-DR was assessed using the immunoprecipitation technique. The function of MPO-antineutrophil cytoplasmic antibody (ANCA) was assessed using a neutrophil-like cell line expressing HLA-DR and MPO. RESULTS: MPO protein was detected on the cell surface in the presence of HLA-DR, and the MPO/HLA-DR complex was recognized by MPO-ANCA. A competitive inhibition assay suggested that MPO associated with HLA-DR expresses cryptic autoantibody epitopes for MPO-ANCA. Autoantibody binding to the MPO/HLA-DR complex was correlated with disease susceptibility conferred by each HLA-DR allele, suggesting that the MPO/HLA-DR complex is involved in the pathogenicity of MPA. Indeed, MPO-HLA class II complexes were detected in neutrophils from a patient with MPA as well as in cytokine-stimulated neutrophils from healthy donors. Moreover, MPO-ANCA stimulated MPO/HLA-DR complex-expressing HL-60 cells. CONCLUSION: Our findings suggest that MPO complexed with HLA class II molecules is involved in the pathogenesis of MPA as a target for MPO-ANCA.

IFI27 Is a Useful Genetic Marker for Diagnosis of Immunoglobulin A Nephropathy and Membranous Nephropathy Using Peripheral Blood.

Diagnosis of chronic glomerulonephritis (CGN) depends primarily on renal biopsy, which is expensive and requires hospitalization, creating a demand for noninvasive diagnostic method for this disease. We used DNA microarray analysis to search for genes whose expression levels in peripheral blood mononuclear cells (PBMCs) could distinguish between patients with CGN and healthy volunteers (HVs). We selected immunoglobulin A nephropathy (IgAN) and membranous nephropathy (MN) as typical forms of CGN. The mRNA level of the gene encoding interferon (IFN)-alpha-inducible protein 27, IFI27, which is preferentially expressed in podocytes of glomeruli, was lower in PBMCs of IgAN and MN patients than in those of HVs. This result was confirmed by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Moreover, qRT-PCR analysis revealed that the IFI27 mRNA level was reduced in PBMCs of patients with other types of chronic glomerulonephritis. IFI27 immunohistochemical staining of biopsied specimens also confirmed reduced expression of IFI27 protein in IgAN and MN patients. Based on these results, we propose that IFI27 could serve as a noninvasive diagnostic marker for CGNs using peripheral blood.

Continuous Hemodiafiltration with an AN69ST Hemofilter (AN69ST-CHDF) as FGF-23-Lowering Therapy.

BACKGROUND: Recent studies have shown that fibroblast growth factor-23 (FGF-23) is elevated not only in chronic kidney disease (CKD), but also in acute illnesses such as acute kidney injury, septic shock, and acute heart failure. FGF-23 would be not only a simple biomarker but also a direct toxic factor in acute illness. Therefore, lowering circulating FGF-23 levels in clinical practice would be an exciting and valuable interventional strategy. Continuous hemodiafiltration (CHDF) is often performed for the treatment of the aforementioned acute illnesses. We have previously reported that an acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has a greater capacity for in vitro FGF-23 adsorption than polysulfone and polymethyl methacrylate membranes. However, reports related to the influence of AN69ST-CHDF on serum FGF-23 levels in acute illness are lacking. In this study, we investigated the effect of AN69ST-CHDF on circulating FGF-23 concentrations in clinical practice. METHODS: Subjects comprised six inpatients who underwent AN69ST-CHDF for an acute illness. Blood samples for the measurement of serum FGF-23 were collected at 0, 3, and 12 hours post-treatment. Blood samples were also drawn from the extracorporeal circuit at the inlet and outlet of the hemofilter 3 hours after CHDF initiation, in order to calculate the clearance of serum FGF-23. RESULTS: Three and 12 hours after the start of AN69ST-CHDF, circulating FGF-23 levels decreased from baseline values with a marginal statistical significance (p = 0.0625 and 0.0938, respectively). An FGF-23 clearance of 27.5 [interquartile range: 19.4 - 29.2] mL/minute 3 hours after the initiation of AN69ST-CHDF was achieved. CONCLUSIONS: Our results suggest that AN69ST-CHDF can be a novel FGF-23 lowering therapy for acute illnesses requiring acute blood purification.

Minimal Change Nephrotic Syndrome Which Was Most Likely Caused by Chronic Sinusitis.

A 33-year-old Japanese man was admitted with severe edema, and a renal biopsy confirmed minimal change nephrotic syndrome (MCNS). CT revealed his severe chronic sinusitis, and he first received antimicrobial therapy, which resulted in decreased proteinuria. The surgical operation for sinusitis resulted in the complete disappearance of proteinuria without corticosteroid or immunosuppressant therapy within one week. MCNS may be triggered by infection, but there are no previously reported cases of MCNS that is completely remitted by infection control alone. Therefore, we herein report the first case of MCNS that attained complete remission following therapy for chronic sinusitis alone, which suggests a strong etiology of chronic sinusitis for MCNS.

Magnesium modifies the association between serum phosphate and the risk of progression to end-stage kidney disease in patients with non-diabetic chronic kidney disease.

It is known that magnesium antagonizes phosphate-induced apoptosis of vascular smooth muscle cells and prevents vascular calcification. Here we tested whether magnesium can also counteract other pathological conditions where phosphate toxicity is involved, such as progression of chronic kidney disease (CKD). We explored how the link between the risk of CKD progression and hyperphosphatemia is modified by magnesium status. A post hoc analysis was run in 311 non-diabetic CKD patients who were divided into four groups according to the median values of serum magnesium and phosphate. During a median follow-up of 44 months, 135 patients developed end-stage kidney disease (ESKD). After adjustment for relevant clinical factors, patients in the lower magnesium-higher phosphate group were at a 2.07-fold (95% CI: 1.23-3.48) risk for incident ESKD and had a significantly faster decline in estimated glomerular filtration rate compared with those in the higher magnesium-higher phosphate group. There were no significant differences in the risk of these renal outcomes among the higher magnesium-higher phosphate group and both lower phosphate groups. Incubation of tubular epithelial cells in high phosphate and low magnesium medium in vitro increased apoptosis and the expression levels of profibrotic and proinflammatory cytokine; these changes were significantly suppressed by increasing magnesium concentration. Thus, magnesium may act protectively against phosphate-induced kidney injury.

Urine osmolarity predicts the body weight-reduction response to tolvaptan in chronic kidney disease patients: a retrospective, observational study.

BACKGROUND/AIMS: Tolvaptan, a vasopressin V2 receptor antagonist, promotes the excretion of electrolyte-free water. Patients with heart failure or liver cirrhosis, whose urine osmolarity is high due to increased vasopressin, show a good response to tolvaptan; however, it remains dubious whether tolvaptan is also effective in patients with low urine osmolarity due to decreased renal function. The aim of this study was to investigate whether urine osmolarity predicts the effect of tolvaptan in patients with decreased renal function. METHODS: In this retrospective, observational study, 17 overhydrated chronic kidney disease patients with heart failure or liver cirrhosis who were admitted to Osaka University Hospital were included. They were treated with sodium-excreting diuretics first, and then tolvaptan was added. The clinically relevant parameters were evaluated before and after the use of tolvaptan, and they, including urine osmolarity before use of tolvaptan, were compared between the responder group and the non-responder group. The definition of responder was based on the decrease of body weight by ≥5% in one week, which is a more rigorous indicator of the effectiveness of tolvaptan than the increase in urine output. RESULTS: The parameter that showed a significant difference between the responder and non-responder groups was urine osmolarity before the use of tolvaptan. The cut-off point derived from the receiver operating characteristic (ROC) curve analysis was 279 mOsm/kg H2O, with sensitivity of 0.86 and specificity of 0.80. CONCLUSIONS: In patients with decreased renal function, urine osmolarity before the use of tolvaptan predicted the effectiveness of diuretics in terms of body weight reduction.

ACE insertion/deletion polymorphism (rs1799752) modifies the renoprotective effect of renin-angiotensin system blockade in patients with IgA nephropathy.

INTRODUCTION: Little is known about genetic predictors that modify the renoprotective effect of renin-angiotensin system (RAS) blockade in IgA nephropathy (IgAN). MATERIALS AND METHODS: The present multicenter retrospective observational study examined effect modification between RAS blockade and three RAS-related gene polymorphisms in 237 IgAN patients, including ACE I/D (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699). RESULTS: During 9.9 ± 4.2 years of observation, 63 patients progressed to a 50% increase in serum creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective effect of RAS blockade (p for interaction between ACE DD and RAS blockade = 0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade 1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of slope of estimated glomerular filtration rate (p = 0.045 for interaction). CONCLUSION: ACE I/D predicted the IgAN progression and the renoprotective effect of RAS blockade in IgAN patients whereas neither AT1R A1166C nor AGT T704C did.