Deep learning analysis of clinical course of primary nephrotic syndrome: Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Prognosis of nephrotic syndrome has been evaluated based on pathological diagnosis, whereas its clinical course is monitored using objective items and the treatment strategy is largely the same. We examined whether the entire natural history of nephrotic syndrome could be evaluated using objective common clinical items. METHODS: Machine learning clustering was performed on 205 cases from the Japan Nephrotic Syndrome Cohort Study, whose clinical parameters, serum creatinine, serum albumin, dipstick hematuria, and proteinuria were traceable after kidney biopsy at 5 measured points up to 2 years. The clinical patterns of time-series data were learned using long short-term memory (LSTM)-encoder-decoder architecture, an unsupervised machine learning classifier. Clinical clusters were defined as Gaussian mixture distributions in a two-dimensional scatter plot based on the highest log-likelihood. RESULTS: Time-series data of nephrotic syndrome were classified into four clusters. Patients in the fourth cluster showed the increase in serum creatinine in the later part of the follow-up period. Patients in both the third and fourth clusters were initially high in both hematuria and proteinuria, whereas a lack of decline in the urinary protein level preceded the worsening of kidney function in fourth cluster. The original diseases of fourth cluster included all the disease studied in this cohort. CONCLUSIONS: Four kinds of clinical courses were identified in nephrotic syndrome. This classified clinical course may help objectively grasp the actual condition or treatment resistance of individual patients with nephrotic syndrome.

Fluorescence Colour Control in Perylene-Labeled Polymer Chains Trapped by Nanotextured Silicon.

The ability to modulate, tune, and control fluorescence colour has attracted much attention in photonics-related research fields. Thus far, it has been impossible to achieve fluorescence colour control (FCC) for material with a fixed structure, size, surrounding medium, and concentration. Here, we propose a novel approach to FCC using optical tweezers. We demonstrate an optical trapping technique using nanotextured Si (black-Si) that can efficiently trap polymer chains. By increasing the laser intensity, the local concentration of perylene-labelled water-soluble polymer chains increased inside the trapping potential. Accordingly, the excimer fluorescence of perylene increased while the monomer fluorescence decreased, evidenced by a fluorescence colour change from blue to orange. Using nanostructure-assisted optical tweezing, we demonstrate control of the relative intensity ratio of fluorescence of the two fluorophores, thus showing remote and reversible FCC of the polymer assembly.

Formation of Single Double-Layered Coacervate of Poly(N,N-diethylacrylamide) in Water by a Laser Tweezer.

We demonstrate liquid-liquid phase separation involving both coacervation and coil-to-globule phase transition of a thermoresponsive polymer. By focusing a near-infrared laser beam into an aqueous solution of poly(N-isopropylacrylamide) (PNIPAM), a single phase-separated polymer microdroplet can be formed and stably trapped at the focal point. Such droplet formation is induced by a local elevation in temperature (induced by a photothermal effect) and an optical force. The technique allows us to selectively analyze a single polymer droplet trapped at the focal point. In this study, we applied this technique to poly(N,N-diethylacrylamide) (PDEA) in water and generated a double-layered PDEA droplet. Such an inhomogeneous and complex microstructure has not been previously observed both in steady-state heating of a PDEA solution and in the PNIPAM system. Moreover, we used micro-Raman spectroscopy to clarify that PDEA underwent dehydration due to a coil-to-globule phase transition. Despite this, the polymer concentration (Cpoly) of the trapped PDEA droplet was very low and was around 30 wt %. Cpoly depended on the molecular weight of PDEA and the laser power that regulates the temperature elevation. These results strongly indicate that PDEA undergoes coacervation in addition to a coil-to-globule phase transition. This study will help provide us with a fundamental understanding of the phase separation mechanisms of thermoresponsive polymers.

Electrophoretic Adhesion of Conductive Hydrogels.

For the development of next-generation wearable and implantable devices that connect the human body and machines, the adhesion of a conductive hydrogel is required. In this study, a conductive hydrogel is adhered using an electrophoretic approach through polyion complex formation at the interface of the hydrogels. Cationic and anionic conductive hydrogels adhere to anionic and cationic hydrogels, respectively. Moreover, the cationic and anionic conductive hydrogels adhere strongly to each other and the adhered conductive hydrogels exhibit conductivity. De-adhesion is possible by adding a salt and re-adhesion is demonstrated under aqueous conditions. It is believed that this innovative adhesion strategy for conductive hydrogels will be a fundamental technology for the connecting "soft" people and "hard" machines.

Duration of predialysis nephrological care and mortality after dialysis initiation.

BACKGROUND: The duration of predialysis nephrological care that can reduce all-cause and cardiovascular mortality after dialysis initiation has not been clarified. METHODS: A total of 1117 patients who started chronic dialysis treatment from 2006 to 2015 at Osaka General Medical Center were analyzed. Independent risk factors associated with all-cause and cardiovascular mortality after dialysis initiation and early death (death within 12 months after dialysis initiation) were identified using Cox proportional hazards analysis. Moreover, the duration of predialysis nephrology care that could reduce mortality was explored using several different definitions of early referral as well as "6 months" commonly used in previous studies. RESULTS: Of 1117 patients, 834 were referred 6 months before dialysis initiation. During the follow-up period (median, 34 months), 324 patients died after dialysis initiation. Although multivariate Cox analysis did not show a favorable association between early referral of "6 months before dialysis initiation" and all-cause and cardiovascular mortality, 20-month predialysis nephrological care was associated with better first-year overall survival after dialysis initiation (hazard ratio 0.58; 95% confidence interval 0.35-0.98; P = 0.040). CONCLUSION: More than 6 months nephrological care before dialysis initiation was not early enough to reduce all-cause and cardiovascular mortality after dialysis initiation. Our results suggest that nephrology referral 20 months before dialysis initiation would be necessary to reduce first-year overall survival after dialysis initiation.

Efficacy of corticosteroid therapy for IgA nephropathy patients stratified by kidney function and proteinuria.

BACKGROUND: Steroid therapy is one of the important therapies for IgA nephropathy (IgAN), but the features of the IgAN patients who have the benefit from this therapy remained unclear. METHODS: This retrospective observational study, using data of 874 patients with IgAN analyzed the proteinuria and kidney function of IgAN patients who had beneficial effect by steroid therapy. Two advantages of the present study were a large cohort and a long observational period. RESULTS: Corticosteroid therapy had ameliorated the kidney prognosis [incident rate ratio (IRR) 0.57 (95%CI 0.34-0.92), P = 0.029]. Because of interaction between kidney function and use of corticosteroid (P = 0.047), stratification analysis by kidney function revealed that prognosis of kidney function in IgAN patients whose eGFR was less than 60 ml/min/1.73m2 was ameliorated by corticosteroid therapy [IRR 0.50 (95%CI 0.26-0.97), P = 0.015); while, there was no change of kidney prognosis in IgAN patients whose eGFR was above 60 ml/min/1.73 m2. To make the target of corticosteroid therapy for IgAN patients more clear, IgAN patients, whose eGFR were less than 60 ml/min/1.73 m2, were stratified by proteinuria (1 g/day). In IgAN patients whose eGFR were under 60 ml/min/1.73 m2 and whose proteinuria were over 1.0 g/day, corticosteroid therapy seemed to ameliorate kidney function [IRR 0.39 (95%CI 0.19-0.86), P < 0.05]; while, there was obviously no change by corticosteroid therapy in IgAN patients whose eGFR were less than 60 ml/min/1.73 m2 and whose proteinuria were less than 1.0 g/day. CONCLUSION: Our results suggested that steroid therapy was especially effective for IgAN patients whose eGFR was less than 60 ml/min/1.73 m2 and whose proteinuria was more than 1.0 g/day.

Incidence of remission and relapse of proteinuria, end-stage kidney disease, mortality, and major outcomes in primary nephrotic syndrome: the Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: Despite recent advances in immunosuppressive therapy for patients with primary nephrotic syndrome, its effectiveness and safety have not been fully studied in recent nationwide real-world clinical data in Japan. METHODS: A 5-year cohort study, the Japan Nephrotic Syndrome Cohort Study, enrolled 374 patients with primary nephrotic syndrome in 55 hospitals in Japan, including 155, 148, 38, and 33 patients with minimal change disease (MCD), membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS), and other glomerulonephritides, respectively. The incidence rates of remission and relapse of proteinuria, 50% and 100% increases in serum creatinine, end-stage kidney disease (ESKD), all-cause mortality, and other major adverse outcomes were compared among glomerulonephritides using the Log-rank test. Incidence of hospitalization for infection, the most common cause of mortality, was compared using a multivariable-adjusted Cox proportional hazard model. RESULTS: Immunosuppressive therapy was administered in 339 (90.6%) patients. The cumulative probabilities of complete remission within 3 years of the baseline visit was ≥ 0.75 in patients with MCD, MN, and FSGS (0.95, 0.77, and 0.79, respectively). Diabetes was the most common adverse events associated with immunosuppressive therapy (incidence rate, 71.0 per 1000 person-years). All-cause mortality (15.6 per 1000 person-years), mainly infection-related mortality (47.8%), was more common than ESKD (8.9 per 1000 person-years), especially in patients with MCD and MN. MCD was significantly associated with hospitalization for infection than MN. CONCLUSIONS: Patients with MCD and MN had a higher mortality, especially infection-related mortality, than ESKD. Nephrologists should pay more attention to infections in patients with primary nephrotic syndrome.

Better remission rates in elderly Japanese patients with primary membranous nephropathy in nationwide real-world practice: The Japan Nephrotic Syndrome Cohort Study (JNSCS).

BACKGROUND: The aim of the present study was to clarify the prevalence of immunosuppressive drug use and outcomes in elderly and non-elderly patients with primary membranous nephropathy (MN) in nationwide real-world practice in Japan. PATIENTS AND METHODS: Between 2009 and 2010, 374 patients with primary nephrotic syndrome were enrolled in the cohort study (The Japan Nephrotic Syndrome Cohort Study, JNSCS), including 126 adult patients with MN. Their clinical characteristics were compared with those of nephrotic patients with primary MN registered in a large nationwide registry (The Japan Renal Biopsy Registry, J-RBR). Outcomes and predictors in the elderly (≥ 65 years) and non-elderly groups were identified. RESULTS: Similar clinical characteristics were observed in JNSCS patients and J-RBR patients (n = 1808). At the early stage of 1 month, 84.1% of patients were treated with immunosuppressive therapies. No significant differences were observed in therapies between age groups. However, elderly patients achieved complete remission (CR) more frequently than non-elderly patients, particularly those treated with therapies that included corticosteroids. No significant differences were noted in serum creatinine (sCr) elevations at 50 or 100%, end-stage kidney disease, or all-cause mortality between age groups. Corticosteroids were identified as an independent predictor of CR (HR 2.749, 95%CI 1.593-4.745, p = 0.000) in the multivariate Cox's model. sCr levels, hemoglobin levels, immunosuppressants, clinical remission, and relapse after CR were independent predictors of sCr × 1.5 or × 2.0. CONCLUSION: Early immunosuppressive therapy including corticosteroids for primary MN showed better remission rates in elderly patients in a nationwide cohort study.

Thrombotic thrombocytopenic purpura developed during the conservative treatment of anti-phospholipase A2 receptor antibody-positive idiopathic membranous nephropathy: a case report.

BACKGROUND: Idiopathic membranous nephropathy (MN) is one of the major glomerulonephritis that cause nephrotic syndrome. The phospholipase A2 receptor (PLA2R) has recently been identified as an endogenous antigen of idiopathic MN. Thrombotic thrombocytopenic purpura (TTP) is a disorder characterized by schistocytes, hemolytic anemia, thrombocytopenia, and organ dysfunction which occurs as a result of thrombi. Patients with acquired TTP have autoantibodies against a disintegrin and metalloprotease with thrombospondin type 1 motif 13 (ADAMTS13). These autoantibodies act as an inhibitor and cause ADAMTS13 deficiency. Idiopathic MN and acquired TTP are usually considered as independent autoimmune diseases. We experienced a patient who developed TTP during the conservative treatment of idiopathic MN, with the coexistence of ADAMTS13 inhibitor and anti-PLA2R antibody. CASE PRESENTATION: A 73-year-old man presented with thrombocytopenia, hemolytic anemia, disturbance of consciousness, and acute kidney injury after 4-year course of biopsy-proven idiopathic MN. ADAMTS13 activity was undetectable and the ADAMTS13 inhibitor was identified. Additionally, he was positive for anti-PLA2R antibody. The patient did not have any diseases that could cause secondary thrombotic microangiopathy, and he was diagnosed with acquired TTP. Steroid therapy and plasma exchange were initiated and the acquired TTP resolved. MN achieved remission 3 months after the anti-PLA2R antibody disappeared. CONCLUSIONS: This is the first reported case of acquired TTP developed during conservative treatment of idiopathic MN, with both ADAMTS13 inhibitor and anti-PLA2R antibody positive at the onset of the TTP. The present case suggests that idiopathic MN might be associated with the development of some cases of acquired TTP.

Benefits of incorporating urinary protein/creatinine ratio measurement in a school urine screening system: The experience of restructuring the school urinary screening system in Osaka Prefecture, Japan.

AIM: School urine screening has been established in several countries of Asia, including Japan, Korea and Taiwan. In Osaka prefectural schools, the urine screening system had some problematic issues including an unclear referral procedure for students with abnormal urinary findings. Therefore, the school urine screening system was reviewed and restructured in 2004. The aim of this study was to assess the improvement in school urine screening through evaluation of the restructured Osaka prefectural school urinary screening system. METHODS: The Osaka prefectural school urinary screening system was reviewed, mainly considering two points. One was the incorporation of standard urinary protein/creatinine ratio measurement instead of the traditional urine dipstick and urine sediment tests; the second point was that all students requiring further examination were referred to regional nephrologists. RESULTS: After restructuring, the number of students who were referred to a medical institute for detailed examinations decreased to 10%, although the number of students newly diagnosed with kidney disease and the types of diagnosis did not change. The positive predictive value of screening increased to about 8 times the value before the system restructuring. The reductions enabled students who required further examination to be referred to regional nephrologists and has contributed to a decreased cost for these examinations. CONCLUSION: Incorporating urinary protein/creatinine ratio measurement into the school urinary screening system, and updating the guiding principles, including referral to nephrology specialists, has enabled the school urinary screening system in Osaka Prefecture to become more efficient and have better cost performance.

Dynamics of the Phase Separation in a Thermoresponsive Polymer: Accelerated Phase Separation of Stereocontrolled Poly( N, N-diethylacrylamide) in Water.

We studied the dependence on tacticity of the dynamic phase separation behavior of thermoresponsive poly( N, N-diethylacrylamide) (PDEA) in an aqueous solution. Using a laser temperature-jump technique combined with transient photometry, we determined the time constants of the phase separation and found that both atactic and isotactic-rich PDEAs had fast and slow phase separation processes (τfast and τslow). The fast process (τfast) was independent of the tacticity, irrespective of the concentration. On the other hand, the slow process had a strong dependence on the tacticity. We found the slow phase separation process got considerably faster with increasing isotacticity in dilute solutions. This effect due to the tacticity of the PDEA is totally different from that of poly( N-isopropylacrylamide) and can be explained on the basis of the difference between the hydrophobicity of atactic PDEA and that of isotactic-rich PDEA.

Laser trapping/confocal Raman spectroscopic characterization of PLGA-PEG nanoparticles.

We have immobilized poly(ethylene glycol) (PEG) on the surfaces of poly(lactic-co-glycolic acid) (PLGA) nanoparticles by two different chemical methods, i.e., SOCl2 halogenate-alcoholysis and DCC dehydration. The immobilized PLGA nanoparticles were characterized by DLS, 1H NMR, FT-IR and laser trapping/confocal Raman spectroscopic techniques. As a result, especially the Raman spectra which were measured after optically trapping ca. 10 individual nanoparticles in solution indicated that the PLGA nanoparticles were successfully immobilized with the PEG by the chemical methods.

Regional variations in immunosuppressive therapy in patients with primary nephrotic syndrome: the Japan nephrotic syndrome cohort study.

BACKGROUND: The lack of high-quality clinical evidences hindered broad consensus on optimal therapies for primary nephrotic syndromes. The aim of the present study was to compare prevalence of immunosuppressive drug use in patients with primary nephrotic syndrome across 6 regions in Japan. METHODS: Between 2009 and 2010, 380 patients with primary nephrotic syndrome in 56 hospitals were enrolled in a prospective cohort study [Japan Nephrotic Syndrome Cohort Study (JNSCS)], including 141, 151, and 38 adult patients with minimal change disease (MCD), membranous nephropathy (MN), and focal segmental glomerulosclerosis (FSGS), respectively. Their clinical characteristics were compared with those of patients registered in a large nationwide registry of kidney biopsies [Japan Renal Biopsy Registry (J-RBR)]. The regional prevalence of use of each immunosuppressive drug was assessed among adult MCD, MN, and FSGS patients who underwent immunosuppressive therapy in the JNSCS (n = 139, 127, and 34, respectively). Predictors of its use were identified using multivariable-adjusted logistic regression models. RESULTS: The clinical characteristics of JNSCS patients were comparable to those of J-RBR patients, suggesting that the JNSCS included the representatives in the J-RBR. The secondary major immunosuppressive drugs were intravenous methylprednisolone [n = 33 (24.6%), 24 (19.7%), and 9 (28.1%) in MCD, MN, and FSGS, respectively] and cyclosporine [n = 25 (18.7%), 62 (50.8%), and 16 (50.0%), respectively]. The region was identified as a significant predictor of use of intravenous methylprednisolone in MCD and MN patients. CONCLUSION: Use of intravenous methylprednisolone for MCD and MN differed geographically in Japan. Its efficacy should be further evaluated in a well-designed trial.

Highly Sensitive Detection of Organic Molecules on the Basis of a Poly(N-isopropylacrylamide) Microassembly Formed by Plasmonic Optical Trapping.

We demonstrate that a poly(N-isopropylacrylamide) (PNIPAM) microassembly, formed by plasmonic optical trapping, can provide the platform for a highly sensitive detection technique for fluorescent and nonfluorescent organic molecules dissolved in aqueous solution. PNIPAM microassemblies can be easily formed by a combination with a photothermal effect and an enhanced optical force. These physical phenomena were obtained through resonant excitation of localized surface plasmon (LSP). Sparsely distributed fluorescent or nonfluorescent molecules dissolved in solution can be extracted into the PNIPAM assembly, resulting in an increase in fluorescence or Raman signals. In particular, we successfully detected quite small amounts of analytes (rhodamine B) at the 10-9 mol/L level. Using LSP is an alternative approach in analytical chemistry and can be used in addition to surface enhanced Raman scattering and surface enhanced fluorescence.

Plasmonic optical trapping of nanometer-sized J- /H- dye aggregates as explored by fluorescence microspectroscopy.

In the present study, we explored plasmonic optical trapping (POT) of nanometer-sized organic crystals, carbocyanine dye aggregates (JC-1). JC-1 dye forms both J- and H- aggregates in aqueous solution. POT behavior was analyzed using fluorescence microspectroscopy. POT of JC-1 aggregates was realized in an increase in their fluorescence intensity from the focus area upon plasmon excitation. Repeating on-and-off plasmonic excitation resulted in POT of JC-1 aggregates in a trap-and-release mode. Such POT of nanometer-sized dye aggregates lying in a Rayleigh scattering regime (< 100 nm) is important toward molecular manipulation. Furthermore, interestingly, we found that the J-aggregates were preferentially trapped than H-aggregates. It possibly indicates semi-selective optical trapping of nanoparticles on the basis of molecular alignments.

Hypomagnesemia is a significant predictor of cardiovascular and non-cardiovascular mortality in patients undergoing hemodialysis.

Although previous studies in the general population showed that hypomagnesemia is a risk for cardiovascular diseases (CVD), the impact of magnesium on the prognosis of patients on hemodialysis has been poorly investigated. To gain information on this we conducted a nationwide registry-based cohort study of 142,555 hemodialysis patients to determine whether hypomagnesemia is an independent risk for increased mortality in this population. Study outcomes were 1-year all-cause and cause-specific mortality with baseline serum magnesium levels categorized into sextiles. During follow-up, a total of 11,454 deaths occurred, of which 4774 had a CVD cause. In a fully adjusted model, there was a J-shaped association between serum magnesium and the odds ratio of all-cause mortality from the lowest to highest sextile, with significantly higher mortality in sextiles 1-3 and 6. Similar associations were found between magnesium and both CVD and non-CVD mortality. The proportion of patients with a baseline intact parathyroid hormone level under 50 pg/ml was significantly higher in the highest sextile; however, after excluding these patients, the CVD mortality risk in the highest sextile was attenuated. Thus, hypomagnesemia was significantly associated with an increased risk of mortality in hemodialysis patients. Interventional studies are needed to clarify whether magnesium supplementation is beneficial for improving patient prognosis.

Permanent fixing or reversible trapping and release of DNA micropatterns on a gold nanostructure using continuous-wave or femtosecond-pulsed near-infrared laser light.

The use of localized surface plasmons (LSPs) for highly sensitive biosensors has already been investigated, and they are currently being applied for the optical manipulation of small nanoparticles. The objective of this work was the optical trapping of λ-DNA on a metallic nanostructure with femtosecond-pulsed (fs) laser irradiation. Continuous-wave laser irradiation, which is generally used for plasmon excitation, not only increased the electromagnetic field intensity but also generated heat around the nanostructure, causing the DNA to become permanently fixed on the plasmonic substrate. Using fs laser irradiation, on the other hand, the reversible trapping and release of the DNA was achieved by switching the fs laser irradiation on and off. This trap-and-release behavior was clearly observed using a fluorescence microscope. This technique can also be used to manipulate other biomolecules such as nucleic acids, proteins, and polysaccharides and will prove to be a useful tool in the fabrication of biosensors.

Referral pattern to nephrologist and prognosis in diabetic kidney disease patients: Single center retrospective cohort study.

BACKGROUND: Management of diabetic kidney disease (DKD) to prevent end-stage kidney disease (ESKD) has become a major challenge for health care professionals. This study aims to investigate the characteristics of patients with DKD when they are first referred to a nephrologist and the subsequent prognoses. METHODS: A total of 307 patients who were referred to our department from October 2010 to September 2014 at Osaka General Medical Center were analyzed. Independent risk factors associated with renal replacement therapy (RRT) and cardiovascular composite events (CVE) following their nephrology referral were later identified using Cox proportional hazards analysis. RESULTS: Of 307 patients, 26 (8.5%), 67 (21.8%), 134 (43.6%), and 80 (26.1%) patients were categorized as having chronic kidney disease (CKD) stages 3a, 3b, 4, and 5, respectively. The median estimated glomerular filtration rate (eGFR) and urinary protein levels were 22.3 mL/min/1.73 m2 and 2.83 g/gCr, respectively, at the time of the nephrology referral. During the follow-up period (median, 30 months), 121 patients required RRT, and more than half of the patients with CKD stages 5 and 4 reached ESKD within 60 months following their nephrology referral; 30% and <10% of the patients with CKD stages 3b and 3a, respectively, required RRT within 60 months following their nephrology referral. CONCLUSION: Patients with DKD were referred to nephrologist at CKD stage 4. Although almost half of the patients with CKD stage 5 at the time of nephrology referral required RRT within one-and-a-half years after the referral, kidney function of patients who were referred to nephrologist at CKD stage 3 and 4 were well preserved.

A candidate gene approach to genetic contributors to the development of IgA nephropathy.

BACKGROUND: Genetic factors contributing to the development of IgA nephropathy remain to be elucidated. METHODS: The present multicenter cross-sectional case-control study measured genotype frequencies of 65 atherosclerotic disease-related gene polymorphisms in 230 Japanese patients with IgA nephropathy and 262 apparently healthy volunteers with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m(2) and negative or trace proteinuria and hematuria by dipstick test [non-chronic kidney disease (CKD) participants]. Clinical characteristics at kidney biopsy of patients with IgA nephropathy and those at the study recruitment of non-CKD participants were included as covariates in multivariate logistic regression models. RESULTS: Among 31 gene polymorphisms with ≥5% of minor genotype in non-CKD participants, methionine synthase MTR A2756G (D919G) was significantly associated with IgA nephropathy using χ(2) test even after controlling for family-wise error rate by the method of Bonferroni (P = 0.044). A multivariate nonconditional logistic regression model identified MTR A2756G as a significant contributor of IgA nephropathy [2756AG and GG versus AA, odds ratio 0.42 (95% confidence interval 0.25-0.69) and 0.21 (95% confidence interval 0.06-0.68), P(trend) < 0.001]. After each patient with IgA nephropathy was randomly matched to a non-CKD participant on age (±5 years), gender, mean arterial pressure (±5 mmHg) and eGFR (±5 mL/min/1.73 m(2)), a multivariate conditional logistic regression model also verified their significant association [odds ratio 0.42 (95% confidence interval 0.18-1.00) and odds ratio 0.09 (95% confidence interval 0.01-0.73), P(trend) = 0.004]. MTR A2756G was not associated with slope of eGFR (mL/min/1.73 m(2)/year) in 230 patients with IgA nephropathy. CONCLUSION: MTR A2756G was associated with the development, but not progression, of IgA nephropathy.

Serum hepcidin-25 levels predict the progression of renal anemia in patients with non-dialysis chronic kidney disease.

BACKGROUND: Hepcidin is associated with iron-restricted erythropoiesis. A previous cross-sectional study showed that serum hepcidin-25 levels are negatively associated with the hemoglobin concentration in non-dialysis chronic kidney disease (CKD) patients with sufficient iron stores. This longitudinal study aimed at ascertaining the association between hepcidin-25 levels and the progression of renal anemia. METHODS: We selected 335 non-dialysis CKD patients who showed hemoglobin concentrations >10 g/dL and who were not receiving erythropoiesis-stimulating agent (ESA) therapy, from among the subjects of our previous study, who had been recruited between February and June 2007 in a previous study. The primary outcome was the start of the ESA therapy or hemoglobin concentrations remaining below 10 g/dL for >3 months, by 31 December 2010. The patients were classified into high- and low-ferritin groups depending on their median ferritin levels. The Cox proportional hazard model with restricted cubic spline curve analysis was used to determine the association between hepcidin-25 levels and the outcome for each group. RESULTS: The hepcidin-25 level was a significant predictor both for the high-ferritin group (P = 0.04, linearity = 0.02) and for the low-ferritin group (P = 0.04, linearity P = 0.02). The spline curve for the high-ferritin group showed that higher hepcidin-25 levels had a high log-relative hazard. CONCLUSIONS: Higher hepcidin-25 levels predict the progression of anemia in non-dialysis CKD patients with sufficient iron stores, indicating the involvement of hepcidin in the progression of anemia in non-dialysis CKD patients.