Nephrology referral slows the progression of chronic kidney disease, especially among patients with anaemia, diabetes mellitus, or hypoalbuminemia: A single-centre, retrospective cohort study.

BACKGROUND: The Kidney Disease Improving Global Outcomes guidelines recommend nephrology referral for patients with chronic kidney disease (CKD) stages 4 to 5, significant proteinuria and persistent microscopic haematuria. However, the recommendations are opinion-based and which patients with CKD benefit more from nephrology referral has not been elucidated. METHODS: In this retrospective cohort study, patients referred to our nephrology outpatient clinic from April 2017 to March 2019 were included. We excluded patients considered to have an acute decline in kidney function (annual decline in estimated glomerular filtration rate [eGFR] >10 mL/min/1.73 m2). The slopes of eGFR before and after nephrology referral were estimated and compared by linear mixed effects models. Interaction between time and referral status (before or after referral) was assessed and effect modifications by the presence of diabetes, proteinuria (defined by urine dipstick protein 2+ or more), urine occult blood, hypoalbuminemia (defined by albumin levels less than 3.5 g/dL) and anaemia (defined by haemoglobin levels less than 11.0 g/dL) were evaluated. RESULTS: The eGFR slope significantly improved from -2.05 (-2.39 to -1.72) to -0.96 (-1.36 to -0.56) mL/min/1.73 m2/year after nephrology referral (p < .001). The improvement in eGFR slope was more prominent among those with diabetes mellitus, anaemia, and hypoalbuminemia (all p-values for three-way interaction <.001 after adjustment for covariates). Further adjustments for time-dependent haemoglobin levels, the use of erythropoiesis-stimulating agents, iron supplementation, anti-hypertensives and anti-diabetic medications did not change the significance of the interactions. CONCLUSIONS: Nephrology referral slows CKD progression, especially among those with hypoalbuminemia, diabetes or anaemia. Patients with hypoalbuminemia, diabetes or anaemia might benefit more from specialized care and lifestyle modifications by nephrologists. The inclusion of anaemia and hypoalbuminemia in nephrology referral criteria should be considered.

High-resolution prediction of leaf onset date in Japan in the 21st century under the IPCC A1B scenario.

Reports indicate that leaf onset (leaf flush) of deciduous trees in cool-temperate ecosystems is occurring earlier in the spring in response to global warming. In this study, we created two types of phenology models, one driven only by warmth (spring warming [SW] model) and another driven by both warmth and winter chilling (parallel chill [PC] model), to predict such phenomena in the Japanese Islands at high spatial resolution (500 m). We calibrated these models using leaf onset dates derived from satellite data (Terra/MODIS) and in situ temperature data derived from a dense network of ground stations Automated Meteorological Data Acquisition System. We ran the model using future climate predictions created by the Japanese Meteorological Agency's MRI-AGCM3.1S model. In comparison to the first decade of the 2000s, our results predict that the date of leaf onset in the 2030s will advance by an average of 12 days under the SW model and 7 days under the PC model throughout the study area. The date of onset in the 2090s will advance by 26 days under the SW model and by 15 days under the PC model. The greatest impact will occur on Hokkaido (the northernmost island) and in the central mountains.

Accurate measurement of optical properties of narrow leaves and conifer needles with a typical integrating sphere and spectroradiometer.

Accurate information on the optical properties (reflectance and transmittance spectra) of single leaves is important for an ecophysiological understanding of light use by leaves, radiative transfer models and remote sensing of terrestrial ecosystems. In general, leaf optical properties are measured with an integrating sphere and a spectroradiometer. However, this method is usually difficult to use with grass leaves and conifer needles because they are too narrow to cover the sample port of a typical integrating sphere. Although ways to measure the optical properties of narrow leaves have been suggested, they have problems. We propose a new measurement protocol and calculation algorithms. The protocol does not damage sample leaves and is valid for various types of leaves, including green and senescent. We tested our technique with leaves of Aucuba japonica, an evergreen broadleaved shrub, and compared the spectral data of whole leaves and narrow strips of the leaves. The reflectance and transmittance of the strips matched those of the whole leaves, indicating that our technique can accurately estimate the optical properties of narrow leaves. Tests of conifer needles confirmed the applicability.

Comparison of effective impact among tonsillectomy alone, tonsillectomy combined with oral steroid and with steroid pulse therapy on long-term outcome of immunoglobulin A nephropathy.

BACKGROUND: To clarify the therapeutic impact of tonsillectomy and combined therapies of tonsillectomy plus steroid on the long-term prognosis of immunoglobulin A nephropathy (IgAN). METHODS: A retrospective study was conducted on 208 patients with IgAN between 1986 and 2009. According to the strategies for treatments, patients were divided into four groups: tonsillectomy and steroid pulse (TSP, n = 47), tonsillectomy and oral steroid (TOS, n = 33), tonsillectomy alone (T, n = 56), and N group (no particular therapy, n = 72). Multivariate analysis based on the Cox's regression model was used to assess the relative risk of reaching the outcome of doubling creatinine based on the influence of baseline prognostic factors. RESULTS: The mean observation periods were 53.8 months in the TSP group, 122.0 months in the TOS group, 102.9 months in the T group, and 84.6 months in the N group. During an observation period, serum creatinine levels doubled as follows: one in the TSP group (2.1 %), two in the TOS group (6.1 %), five in the T group (8.9 %), histological severity, and 22 in the N group (30.6 %). The Cox's regression proportional hazard model showed that gender, age, histological activity, dialysis induction risk and therapy were associated with doubling creatinine levels. Hazard ratios (95 % CI) and (P value) in T, TOS, and TSP groups versus N were 0.314 (0.11-0.93, P = 0.037), 0.213 (0.04-1.10, P = 0.065), and 0.032 (0.00-0.28, P = 0.002), respectively. CONCLUSION: A combination therapy of tonsillectomy and steroid pulse had the most significant therapeutic impact compared to other therapies.

A potential therapeutic system for Alzheimer's disease using adsorbents with alkyl ligands for removal of blood amyloid ß.

Amyloid beta proteins (Aß) in the brain are the main cause of Alzheimer's disease. Peripheral administration of Aß-binding substances, which may act as a sink for Aß from the brain, has been reported to reduce brain Aß. We previously found C16-cellulose beads had high Aß-removal activity in vitro. In this study, we investigated the optimum surface properties of adsorbents for removal of Aß in vitro and in humans. Batch analysis was performed with porous cellulose beads or silica beads with or without 2-22 methylene groups. Aß-removal activity of C16-cellulose beads increased with increasing alkyl chain length. In contrast, with cellulose the amount of Aß removed by the silica beads decreased with increasing alkyl chain length. Cellulose beads with 16 or 22 methylene groups were best (over 99 % removal) among all the beads tested (p ≤ 0.01). The adsorbent surfaces were analyzed by near-infrared spectroscopy, which revealed that the optimum beads had a sufficiently hydrophobic surface with an appropriate amount of adsorbed water accessible on the surface. Aß removal efficiency by C16-cellulose beads was investigated for 5 renal failure patients on hemodialysis, resulting in 51.1 ± 6.6 % for Aß1-40 and 43.8 ± 4.5 % for Aß1-42 (p ≤ 0.01). In conclusion, cellulose beads with 16 or 22 methylene groups and an appropriate amount of adsorbed water were the optimum Aß adsorbents. The device with C16-cellulose beads had high Aß removal activity in humans. These adsorbents might be useful for Alzheimer's disease therapy.

Potential therapeutic system for Alzheimer's disease: removal of blood Aßs by hemodialzyers and its effect on the cognitive functions of renal-failure patients.

The pathological changes of Alzheimer's disease include the deposition of amyloid ß protein (Aß) as senile plaques in the brain. We hypothesized that the rapid removal of Aßs from the blood may act as a peripheral Aß drainage sink from the brain. In this study, the plasma Aß concentrations and the cognitive functions were investigated for in 57 patients on hemodailysis (69.4 ± 3.8 years), 26 renal-failure patients without hemodialysis (66.6 ± 14.7 years), and 17 age-matched healthy controls (66.6 ± 4.1 years). The concentrations of plasma Aßs increased along with the decline of renal functions. Moreover, the renal-failure patients without hemodialysis and with poorer renal functions showed lower cognitive functions. The plasma concentrations of Aß(1-42) correlated with serum creatinine (P < 0.001) and Mini-Mental-State Examination scores (P = 0.017). The dialyzers effectively removed Aßs in the blood during hemodialysis sessions. The plasma Aß concentrations showed steady or slightly decreasing along with duration of hemodialysis. The total amount of Aßs removed during a hemodialysis session was calculated to be comparable to the Aßs dissolved in the blood and the cerebrospinal fluid. The MMSE scores of the hemodialysis patients showed no clear decrease in longer hemodialysis duration. Therefore, the therapeutic approach for Alzheimer's disease by removing Aßs from the blood is worthy of further investigation, including whether or not Aßs in the brain decrease.

Evaluation of blood purification and bortezomib plus dexamethasone therapy for the treatment of acute renal failure due to myeloma cast nephropathy.

Aggressive removal of circulating free light chains (FLC) by blood purification accompanied by chemotherapy is a promising approach for the treatment of acute renal failure due to myeloma cast nephropathy. Plasma exchange has been performed to remove serum FLC; in order to examine an alternative strategy we performed hemodiafiltration using protein-leaking dialyzers for the treatment of dialysis-dependent acute renal failure due to myeloma cast nephropathy. In the first case with κ-light chain cast nephropathy, the pre-treatment serum creatinine was 9.65 mg/dL, and the serum κ-FLC was 27100 mg/L. Plasma exchange or hemodiafiltration was performed from Monday to Friday during the first several weeks. Chemotherapy was started with high-dose dexamethasone and then switched to bortezomib plus dexamethasone. The mean removal rates of κ-FLC were 45.8% (one plasma volume) and 66.9% (one-and-a-half plasma volumes) by plasma exchange. The removal rates of κ-FLC by hemodiafiltration (66.9%, FB210UHß; 71.6%, PES210Dα; 75.2%, FXS220) were comparable to those by plasma exchange. In the second case with λ-light chain cast nephropathy, the pre-treatment serum creatinine was 4.14 mg/dL, and the serum λ-FLC was 4140 mg/L. The mean removal rates of λ-FLC were 60.2% (FXS140) and 64.2% (FB210UHß) by hemodiafiltration. Both cases became dialysis-independent. The combination of an intense blood purification regimen and bortezomib plus dexamethasone therapy appears to be an efficient approach to renal recovery. Hemodiafiltration using protein-leaking dialyzers could become an alternative to plasma exchange as a method of removing FLC.

Acute kidney injury caused by zonisamide-induced hypersensitivity syndrome.

Drug rash with eosinophilia and systemic symptoms (DRESS), also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction affecting multiple organs caused by drug treatment. The current report describes a man who was prescribed zonisamide for epilepsy and subsequently developed widespread skin rash, acute kidney injury, high-grade fever, eosinophilia, liver dysfunction, lymphadenopathy and an increase in antihuman herpesvirus-6 immunoglobulin G titer. Hypersensitivity to zonisamide was confirmed by the skin patch test. Based on these findings, the patient was diagnosed with DRESS/DIHS caused by zonisamide. This is the first report of acute kidney injury due to zonisamide-induced DRESS/DIHS.

Novel therapeutic approach for Alzheimer's disease by removing amyloid beta protein from the brain with an extracorporeal removal system.

The accumulation of amyloid beta (Abeta) protein in the brain reflects the cognitive impairment noted in Alzheimer's disease. Recent studies have shown that brain Abeta disappeared and cognitive improvement occurred as a result of passive or active Abeta immunization. Peripheral administration of nonimmunization substances, such as GM1 ganglioside, also reduced brain Abeta. Therefore, we hypothesized that the rapid removal of Abeta from the blood by an extracorporeal system may act as a peripheral Abeta sink from the brain. In the present study, we investigated the Abeta removal activity of medical materials as a first step toward the design of an Abeta removal system. First, the removal activities of six materials were studied for Abeta(1-40) and Abeta(1-42) by batch analysis in albumin solution or in human plasma for 1-16 h. Two of the six materials reduced the Abeta concentrations by 90-99% within 1 h. Next, the two effective materials, hexadecyl-alkylated cellulose particles (HDC) and charcoal, were analyzed in a continuous single-pass system with minicolumns. Both materials showed around 81-90% removal activity for more than 2 h, which corresponded to over 4 l of plasma treatment in humans. In a human extracorporeal system, HDC also removed both Abeta(1-40) and Abeta(1-42) from whole blood circulation. In conclusion, biomedical materials were found that could remove Abeta(1-40) and Abeta(1-42) effectively in an extracorporeal system. It is now conceivable that further studies can be undertaken to reduce Abeta concentrations in the brain to improve cognitive function.

Expression of tumor necrosis factor receptors on granulocytes in patients with myeloperoxidase anti-neutrophil cytoplasmic autoantibody-associated vasculitis.

BACKGROUND/AIMS: To clarify the clinical significance of tumor necrosis factor (TNF) receptors in patients with myeloperoxidase (MPO)-anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, we evaluated the cell surface expression of TNF receptor 1 (TNFR1) and TNF receptor 2 (TNFR2). PATIENTS AND METHODS: 43 patients with MPO-ANCA-associated vasculitis, 16 patients with chronic renal failure, 10 patients with sepsis, 15 patients with systemic lupus erythematosus, and 18 healthy controls were enrolled in this study, and the surface expression levels of TNFR1, TNFR2, CD63, and CD64 on granulocytes were assessed. In 21 patients with MPO-ANCA-associated vasculitis, soluble TNFR1 (sTNFR1), soluble TNFR2(sTNFR2), and TNF-alpha in the serum were also measured. RESULTS: The surface expression levels of TNFR1 and TNFR2 on granulocytes were significantly higher in patients with MPO-ANCA-associated vasculitis than in the healthy controls, and positively correlated with the Birmingham Vasculitis Activity Score (BVAS). The levels of sTNFR1, sTNFR2, and TNF-alpha in the serum were also significantly higher in patients with MPO-ANCA-associated vasculitis than in the healthy controls. Serum levels of sTNFR1 and sTNFR2 correlated with serum creatinine, while the surface expression of TNFR1 and TNFR2 on the granulocytes did not. There was no significant correlation between the BVAS and CD63 or BVAS and CD64. CONCLUSION: The surface expression levels of TNFR1 and TNFR2 on granulocytes were upregulated in patients with MPO-ANCA-associated vasculitis and reflected disease activity.

Serum levels of 5-s-cysteinyldopa are correlated with skin colors in hemodialysis patients but not in peritoneal dialysis patients.

BACKGROUND: Diffuse hyperpigmentation is common in patients with chronic renal failure undergoing hemodialysis (HD) or peritoneal dialysis (PD). We previously reported that serum levels of 5-S-cysteinyldopa (5SCD, a pheomelanin precursor) and pheomelanin were significantly elevated in HD patients. METHODS: Skin color was assessed using a Mexameter that measures the melanin index (MI) and the erythema index (EI). The upper inner arms (non-sun-exposed site) and the foreheads (sun-exposed site) of HD and PD patients and control subjects were analyzed. RESULTS: MI values on the upper inner arms and on the foreheads of HD and PD patients were significantly higher than in controls. In HD patients, significant correlations were found for serum 5SCD levels with MI and EI on the upper inner arm, and for EI on the forehead. In PD patients, no such correlations were found. CONCLUSIONS: Hyperpigmentation in HD patients results partly from accumulation of pheomelanin in the skin.

Protective role of anti-synthetic hinge peptide antibody for glomerular deposition of hypoglycosylated IgA1.

BACKGROUND: The KM mouse lacks endogenous genes for immunoglobulins and carries the entire human IgH locus and the IgLk transgene. Therefore, human IgA1 does not provoke a hetero-immune response. We had observed mesangial IgA deposits in KM mice given desialo-degalacto (DeS/DeGal) IgA1. METHODS: In this study, the mice were immunized with synthetic IgA1 hinge (glyco-)peptide before administration of DeS/DeGal IgA1, and the effects of the pre-immunization were evaluated. Mice were divided into sHP, 5GalNAc-sHP and non-immunization groups. In two pre-immunization groups, KLH-conjugated sHP or KLH-5GalNAc-sHP, which has five GalNAc residues, was subcutaneously given three times every 2 weeks. Two weeks after the final pre-immunization, DeS/DeGal IgA1 was administered daily for 5 weeks. Serial serum levels of anti-sHP and anti-IgA1 antibodies were evaluated by ELISA. On the day of the last administration of IgA1, renal biopsy was performed. RESULTS: Mesangial IgA deposits were observed in all non-immunized mice. In pre-immunized mice, IgA deposition was not detected in 6 of 13 sHP mice and 1 of 4 5GalNAc-sHP mice. The intensities of IgA deposits were significantly different between sHP groups and non-immunized (P = 0.003) groups. There was a significant inverse correlation between the intensities of IgA deposits and the anti-sHP antibody titers (P = 0.016). CONCLUSIONS: These results suggest that the anti-IgA1 hinge peptide antibody plays a role in the inhibition of glomerular IgA deposition.

Serum levels of pigmentation markers are elevated in patients undergoing hemodialysis.

BACKGROUND: Diffuse hyperpigmentation is common among patients with chronic renal failure undergoing hemodialysis (HD). We have examined serum levels of 5-S-cysteinyldopa (5SCD, a pheomelanin precursor), pheomelanin, eumelanin, and protein-bound (PB-) 3,4-dihydroxyphenylalanine (DOPA) and PB-5SCD in HD patients. METHODS: Pheomelanin and eumelanin were assayed by chemical degradation methods. RESULTS: Serum levels of free 5SCD in HD patients (n = 16) were 9-fold higher than in healthy controls (n = 16). Levels of pheomelanin in HD patients were 2.6-fold higher than in controls, while levels of eumelanin did not differ between HD patients and controls. Levels of PB-DOPA and PB-5SCD in HD patients were approximately 1.5-fold higher than in controls. Serum levels of free 5SCD were positively correlated to the duration of HD therapy. CONCLUSIONS: The high constitutive levels of free 5SCD, pheomelanin, and PB-DOPA in the blood may be deteriorating in HD patients through the production of reactive oxygen species.

Effects of cytapheresis on tumor necrosis factor receptor and on expression of CD63 in myeloperoxidase--antineutrophil cytoplasmic autoantibody-associated vasculitis.

To evaluate the therapeutic potential of cytapheresis in myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis, plasma levels of soluble tumor necrosis factor receptors (sTNFR1, sTNFR2) and the expression of TNFR1, TNFR2, and CD63 on granulocytes were measured. The levels of sTNFR1 and sTNFR2, and the expression of TNFR1 and TNFR2 were significantly higher in MPO-ANCA-associated vasculitis patients than in normal controls. The levels of sTNFR1 and sTNFR2 increased significantly after cytapheresis (P < 0.001). The expression of TNFR1 showed a tendency to decrease after cytapheresis (P = 0.0535). The expression of CD63 decreased significantly after cytapheresis (P < 0.05). Because sTNFR1 and sTNFR2 act as TNF-antagonists, the increases of sTNFR1 and sTNFR2 after cytapheresis might contribute to inhibit the action of TNF-alpha. The decreased expression of TNFR1, which mediates the signal for polymorphonuclear cell respiratory burst, might also contribute to the reduction of inflammation. From these results, the inhibition of TNF action and removal of degranulated granulocytes appear to be related to the mechanism whereby cytapheresis can exert a beneficial and therapeutic function in the treatment of MPO-ANCA-associated vasculitis.

Severe metabolic acidosis and hypokalemia in a patient with enterovesical fistula.

We report a case of a 59-year-old woman who had severe metabolic acidosis and hypokalemia due to an enterovesical fistula. The patient came to our hospital complaining of systemic weakness and numbness of the fingers. She was found to have hyperchloremic metabolic acidosis (arterial bicarbonate, 2.8 mEq/l) and hypokalemia (serum potassium, 1.9 mEq/l) and was admitted for treatment. Following the correction of metabolic acidosis and hypokalemia, the patient was examined for the underlying cause of these electrolyte and acid-base disorders. She had a history of total hysterectomy followed by radiotherapy due to uterine cancer 30 years previously. After the surgery, she had suffered postoperative neurogenic bladder dysfunction, necessitating intermittent self-catheterization. Two years before admission, she had begun to experience watery diarrhea. A radiographic study after recovery from the acid-base and electrolyte disorders revealed the presence of an enterovesical fistula. The fistula was surgically resected and the metabolic acidosis completely cleared. Unexplained hyperchloremic metabolic acidosis with hypokalemia may suggest the presence of an enterovesical fistula in patients with a surgical history of malignant pelvic tumor and neurogenic bladder dysfunction.

Accumulation of bisphenol A in hemodialysis patients.

Bisphenol A [BPA, 2,2-bis(4-hydoxyphenyl)propane], an industrial chemical used in the production of polycarbonate, epoxide resin, and polyarylate, is considered to be an endocrine-disrupting chemical. BPA may be present in some hollow-fiber dialyzers used in hemodialysis. In this study, we tested the amounts of BPA eluted from various hollow fibers. Furthermore, we measured the BPA concentration in the sera of 22 renal disease predialysis patients, as well as 15 patients who were receiving hemodialysis, to see if there is BPA accumulation in these patients. The elution test of BPA showed that a much larger amount of BPA was eluted from polysulfone (PS), and polyester-polymeralloy hollow fibers. Among renal disease patients who had not undergone hemodialysis, the serum BPA concentration increased as the renal function deteriorated, showing a significant negative association. In a crossover test between PS and cellulose (Ce) dialyzers, the predialysis serum BPA concentration of PS dialyzer users decreased after changing to a Ce dialyzer, and the serum BPA increased again after switching back to PS dialyzers. In patients who were using PS dialyzers, the BPA level significantly increased after a dialysis session. However, in the Ce dialyzer users, the BPA level decreased. Since accumulation of BPA could affect the endocrine or metabolic system of the human body, it is important to perform further investigations on dialysis patients.

Cytapheresis for the treatment of myeloperoxidase antineutrophil cytoplasmic autoantibody-associated vasculitis: a pilot study of 21 patients.

Twenty-one patients with myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis were treated using cytapheresis. Of these, 17 were treated for glomerulonephritis and four were treated for pulmonary hemorrhage. The overall survival rate was 85.7% with a follow-up duration of 24.0 +/- 13.8 months. In the 17 patients with MPO-ANCA-associated glomerulonephritis, pretreatment creatinine was 3.2 +/- 1.6 mg/dL, and renal function recovered in 76.5%. Pulmonary hemorrhage was ameliorated in all four patients. Abdominal pain occurred in three of the 21 patients but symptoms resolved soon after the cytapheresis procedure was completed. No other adverse effects occurred during cytapheresis. From these results, cytapheresis can be considered a safe and effective treatment for MPO-ANCA-associated vasculitis. As for the mechanism of its action, soluble tumor necrosis factor receptor 1 (sTNFR), sTNFR2 and interleukin 1 receptor antagonist were elevated soon after cytapheresis and those levels 2 h after the cytapheresis procedure were higher than before the procedure in some cases. These elevations might be related to the efficacy of cytapheresis.

Evaluation of endocrine disrupting activity of plasticizers in polyvinyl chloride tubes by estrogen receptor alpha binding assay.

Polyvinyl chloride (PVC) tubing is an indispensable medical material for extracorporeal circulation therapy. However, di(2-ethylhexyl)phthalate (DEHP), a suspected endocrine disruptor, can be eluted from PVC, suggesting that an alternative material that does not contain DEHP is needed for clinical applications. First, we evaluated the endocrine disrupting risks of the plasticizers contained in PVC tubes by investigating their binding affinities for the human estrogen receptor alpha (ERalpha). Our results revealed that, while DEHP has some binding affinity for ERalpha, neither epoxidized soybean oil nor tris(2-ethylhexyl)trimellitate (an alternative to DEHP) has any affinity for ERalpha. Second, we evaluated the endocrine disrupting risks of a tube made of newly developed plasticizer-free (PF) materials. We confirmed the presence of DEHP and detected several unidentified substances in plasma stored within the PVC tube. This plasma's competitive binding affinity for ERalpha was significantly higher than that of control plasma (P < 0.01). In contrast, the profile of plasma stored in the PF tube was similar to that of the control, both in terms of high-performance liquid chromatography chromatograms and competitive binding capacity for ERalpha, suggesting that the PF tube is biocompatible and is useful for reducing the elution of substances capable of binding to ERalpha.

Treatment with cytapheresis for antineutrophil cytoplasmic antibody-associated renal vasculitis and its effect on anti-inflammatory factors.

To evaluate the efficacy of cytapheresis for the treatment of rapidly progressive glomerulonephritis (RPGN) caused by myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis, the renal prognosis and the mortality rate at 1 year after treatment were compared between a Cytapheresis Group and a Steroid Pulse Group. The Cytapheresis Group included 10 patients who were treated with cytapheresis and oral corticosteroids. Five had granulocytapheresis with the Adacolumn (Japan Immuno Research Laboratories Co. Ltd, Takasaki, Japan) and the remaining five had leukocytapheresis with the leukocyte removal filter, Cellsorba (Asahi Medical Co. Ltd, Tokyo, Japan). The Steroid Pulse Group was comprised of 12 patients who were treated with methylprednisolone pulse therapy and oral corticosteroids. In the Cytapheresis Group, renal function recovered in 70% of the patients and the mortality rate was 10%. In the Steroid Pulse Group, renal function recovered in 66.7% and the mortality rate was 33.3%, with infection as the cause of death. Total doses of corticosteroids converted to prednisolone dose during a 1 month period, ranged from 280 mg to 1226 mg in the Cytapheresis Group. On the other hand, these dosages ranged from 2375 mg to 8380 mg in the Steroid Pulse Group. These results indicated that the mortality rate by infection could be reduced by adding cytapheresis therapy. Concerning the mechanism of cytapheresis, anti-inflammatory factors such as soluble tumor necrosis factor receptor, and interleukin-10 reduced after cytapheresis. These changes might be responsible for the efficacy of cytapheresis. In conclusion, cytapheresis is thought to be one of the effective treatments for RPGN caused by MPO-ANCA-associated vasculitis, reducing the levels of anti-inflammatory factors.

Complement C4d deposition in transplanted kidneys: preliminary report on long-term graft survival.

The effects of antibody-mediated rejection on long-term graft survival have not been fully investigated. The aim of this study is to clarify the influence on long-term survival of deposition of the complement split product C4d in allografts using polyclonal anti-C4d antibody. Inclusion criteria were recipients who underwent graft biopsy during acute deterioration of graft function within the first 2 yr after transplantation. Patients whose graft did not survive more than 1 yr and who received graft from an human leucocyte antigen (HLA)-identical sibling or an ABO-incompatible donor were excluded. Among the 92 recipients investigated, 22 (23.9%) had peritubular capillary C4d deposition, 15 (16.3%) had glomerular capillary C4d deposition and seven (7.6%) had both peritubular and glomerular capillary C4d deposition. Twenty of these 22 patients revealed acute cellular rejection, including borderline changes. There was no significant relationship between pathological severity of acute rejection and presence or absence of peritubular capillary C4d deposition. Graft survival was inferior in patients with peritubular capillary C4d deposition to that in patients without C4d deposition (p = 0.0419). Graft survival in patients with glomerular C4d deposition did not differ from that in patients without C4d deposition. In conclusion, C4d deposition in peritubular capillaries has a substantial impact on long-term graft survival.