Circulating fibrocytes in ischemia-reperfusion injury and chronic renal allograft fibrosis.

BACKGROUND: Interstitial fibrosis in chronic allograft injury has been suggested as a major cause of the loss of allograft. METHODS: To clarify the involvement of circulating fibrocytes (CF) and α-smooth muscle actin (SMA)-positive cells in renal allograft injury, we investigated 36 renal transplanted cases at 0 h, 1 h, 2-4 weeks, 4-8 weeks, and 1 year, and 5 normal controls. Double immunofluorescence analysis for both COL1 and CD45 indicating CF (/mm(2)), and the positive area (%) of α-SMA and Masson trichrome (MT) stain were detected by an image analyzing system. RESULTS: The mean number of CF was 0 in controls and 4.0 in total transplanted specimens (p < 0.05). CF correlated with the α-SMA-positive area in the graft (R(2) = 0.39, p < 0.01), but not with Banff 2005 scores. The number of CF increased in 2-4 weeks; however, decreased 1 year after transplantation. α-SMA-positive area gradually increased at 1 year concomitant with the increase of MT-positive area. A similar phenomenon was observed in a case of primary nonfunction kidney from 0 h to 6 weeks after transplantation. The electron microscopy score of fibrosis around peritubular capillaries was correlated positively with COL1-positive area (R(2) = 0.72, p < 0.01), but negatively with infiltrated CF (R(2) = 0.25, p < 0.05). CONCLUSION: CF were transiently induced, probably due to ischemia-reperfusion injury, but fibrosis only slightly progressed in this process. The α-SMA-positive myofibroblasts may accelerate the expansion of fibrosis around peritubular capillaries in chronic allograft injury.

A case of second renal transplantation with acute antibody-mediated rejection complicated with BK virus nephropathy.

We reported a 40-year-old female case of second renal transplantation with antibody-mediated rejection (AMR) complicated by BK virus nephropathy. She started hemodialysis (HD) at the age of 17 because of IgA nephropathy. At the age of 18, she underwent living-donor kidney transplantation from her father, but two and a half years after transplantation, she developed chronic rejection. This time, she received cadaveric renal transplantation under the negative cross-match (AHG-LCT), and HLA-AB 1 mismatch and -DR 1 mismatch. Immunosuppressive therapy was initiated using the following four immunosuppressants: methylprednisolone, mycophenolate mofetil, cyclosporine, and basiliximab. However, renal graft showed delayed function, the biopsy showed glomerulitis (g2), endarteritis (v1), and cellular infiltration (ptc3) consisting mainly of mononuclear cells in the peritubular capillary with diffusely positive C4d and anti-SV 40 large T-antigen-positive renal tubular epithelial cells on post-operative day 19. The donor-specific antibody for HLA-B46 was proven by the LAB screen method. We performed plasma exchange three times and administered immunoglobulin (15 g in total). Then, methylprednisolone pulse therapy was added, and the serum creatinine (SCr) levels gradually decreased. On post-operative day 44, the patient was removed from HD and was discharged with SCr level of 3.3 mg/dL.

Effectiveness of weekly percutaneous maxacalcitol injection therapy in patients with secondary hyperparathyroidism.

Percutaneous injection therapy with vitamin D has been applied in the treatment of hyperparathyroidism (HPT); however, the application of percutaneous injection therapy with vitamin D lacks established guidelines regarding the volume of injected solution and the frequency of injection. We have developed an outpatient treatment regimen using percutaneous maxacalcitol injection therapy (PMIT) on a weekly basis for 4-6 weeks following dialysis without major complications. Intact parathyroid hormone decreased from 797 +/- 178 pg/mL to 253 +/- 25 pg/mL, and the parathyroid gland volume initially increased during the first week, but thereafter, it gradually decreased with weekly PMIT (wPMIT). Finally, the parathyroid gland volume decreased from 1.27 +/- 1.06 cm(3) to 0.24 +/- 0.15 cm(3) after wPMIT. The benefits of our method were confirmed on weekly ultrasonographic examinations, which detailed the gradual reduction in gland size following an initial increase after the first injection. Therefore, we conclude that our carefully implemented PMIT method would be an effective treatment against refractory secondary HPT.

[Relationship between initial diagnosis and long-term prognosis in lupus nephritis].

UNLABELLED: To clarify the outcomes of patients with lupus glomerulonephritis (LGN), we performed a retrospective study of 31 patients (27 females and 4 males) with LGN between January 1975 and June 2006. All these 31 patients fulfilled the SLE criteria of the American College of Rheumatology evaluated by pathohistological diagnosis using renal biopsies. According to 2003 ISN/RPS classification, we reclassified all initial renal biopsies as class II 16%, class III 16%, class IV 48%, and class V 19.5%. Activity and chronicity indices were also calculated according to the scores proposed by Austin et al. All patients were treated by oral corticosteroids in induction therapy, then subsequeatly 18 patients (61%) were treated with intravenous methylprednisolone pulse therapy, and 16 patients with immunosuppressive agents (58%). Clinical remission rate was 94% by induction therapy and 13% by recurrence rate. Patient survival rate was 85% at 10 years and 76% at 20 years. Renal survival rate was 96% at 10 years and 86% at 20 years, 100% at 10 years and 80% at 20 years in ClassIV-G. In the multivariate Cox hazard analysis of the clinicopathologic factors, serum creatinine was selected as the most significant risk factor for death and/or end-stage renal failure (p=0.036). In addition, the chronicity index was also a significant risk factor for renal survival of LGN. CONCLUSION: This retrospective analysis of LGN showed better outcomes than expected. Overall, early diagnosis and suitable initial therapy may improve the renal survival of LGN in both groups of patients.

A case report of an adult with severe hyperlipidemia during acute lymphocytic leukemia induction therapy successfully treated with plasmapheresis.

Plasmapheresis for the treatment of hypertriglyceridemia has previously been performed in patients with sudden onset severe hypertriglyceridemia and acute pancreatitis; however, only a few reports of this procedure have been published. We report here on a case showing severe hypertriglyceridemia during asparaginase (Asp) treatment for acute lymphocytic leukemia (ALL), and give an overview of a lipid-lowering apheresis therapy. To prevent the complication of pancreatitis due to hypertriglyceridemia, we performed plasma exchange (PE) three times using fresh frozen plasma. PE remarkably reduced both serum triglyceride and total cholesterol levels from 5430 mg/dL to 403 mg/dL and from 623 mg/dL to 204 mg/dL, respectively. The causes of severe hyperlipidemia in this patient were considered to include: the Asp treatment for ALL, and a genetic background with a heterozygote of familial lipoprotein lipase (LPL) defect syndrome, because the patient's plasma LPL level after intravenous heparin injection was low at 137 ng/mL. Hence, PE using fresh frozen plasma may be useful not only to remove lipoproteins, but also to supply defective factors, such as LPL, in similar cases.

Advances in apheresis therapy for glomerular diseases.

This article is an overview of the immunomodulatory effects of apheresis in renal diseases, especially primary and secondary glomerulonephritis, and the clinical evidence for the efficacy of apheresis therapy. Permeability factor(s) derived from circulating T cells are speculated to have a crucial role in the proteinuria of nephrotic syndrome (NS). Plasma exchange (PE); immunoadsorption plasmapheresis (IAPP), using protein A sepharose cartridges; low-density lipoprotein apheresis; and lymphocytapheresis (LCAP) have been used to remove such factors or pathogenic T cells. Other glomerular diseases induced by specific antibodies such as anti-glomerular basement membrane antibodies, anti-neutrophil cytoplasmic antibodies, and immune-complexes have also been treated with PE, double-filtration plasmapheresis, IAPP, and LCAP. Recommendations, based on the evidence from recent randomized controlled studies, have been established in apheresis therapy for various glomerular diseases.

Proteomic analysis of serum, outflow dialysate and adsorbed protein onto dialysis membranes (polysulfone and pmma) during hemodialysis treatment using SELDI-TOF-MS.

AIMS: Alterations in the profiling of peptides and proteins in the serum, outflow dialysate and adsorbed protein on the dialysis membrane were investigated. METHODS: Alterations in the protein profiling of routine hemodialysis using polysulfone (TS-UL) and PMMA (moderate flux membrane of polymethylmethacrylate: BK-U) in 8 patients and that of adsorption onto polysulfone and PMMA membranes in 4 patients were evaluated by SELDI-TOF-MS and ProteinChip array. Mass-to-charge ratios (m/z) between 2,000 and 120,000 were analyzed. RESULTS: The protein with a relative intensity of m/z 11,730 measured by SELDI-TOF-MS was present in a small amount in the outflow dialysate and in a large amount in adsorption (identified as beta2-microglobulin) onto PMMA membrane. Unexpectedly, 68 molecular masses of peptides that were adsorbed more onto polysulfone than onto PMMA membrane were observed. There were more peptides less than m/z 11,730 adsorbed onto polysulfone membrane than onto PMMA membrane. Dominant peaks, m/z 6,629 and 6,431 adsorbed onto polysulfone membrane were identified as apolipoprotein CI and truncated apolipoprotein CI, respectively. 37 proteins with molecular weights larger than m/z 11,730 showed greater filtration through PMMA membrane than through polysulfone membrane. 149 molecular masses that were adsorbed onto PMMA or more onto PMMA membrane than onto polysulfone membrane were observed. CONCLUSION: This experiment suggests that membrane adsorption is an important mechanism for the removal of middle-molecular-weight proteins by hemodialysis using not only PMMA membrane but also polysulfone membrane. Adsorption of peptide or protein onto a dialysis membrane may depend not only on the membrane material, but also on the peptide or protein.

Proteomic analysis of rat plasma by SELDI-TOF-MS under the condition of prevention of progressive adriamycin nephropathy using oral adsorbent AST-120.

AIMS: To determine changes in relative peak intensities of mass-to-charge ratio (m/z) between 2,000 and 15,000, which are difficult to evaluate by 2-dimensional gel electrophoresis, SELDI-TOF-MS (surface-enhanced laser desorption/ionization time of flight-mass spectrometry) proteomic changes in rat models of adriamycin nephropathy with or without AST-120 were investigated. METHODS: A normal group (n = 5), an adriamycin nephropathy group (n = 9), and an adriamycin nephropathy + AST-120 group (4 g/head/day) (n = 9) were established in SD rats. Anion exchange chips, Q10, washed by 50 mM Tris-HCl pH 8 as a ProteinChip and sinapinic acid were used. The mass range between 2,000 and 15,000 Da was measured. Twenty to 34 weeks after adriamycin 3 mg/kg injection, the adriamycin nephropathy + AST-120 group (plasma creatinine value: 2.1 +/- 0.8 mg/dl) clearly demonstrated slight renal dysfunction compared with that in the adriamycin nephropathy group (5.4 +/- 2.0 mg/dl). RESULTS: The relative intensities in the adriamycin nephropathy group were significantly higher in 7 peaks (such as 8,640, and 8,822 Da) and lower in 8 peaks (such as 4,188, and 8,358 Da) than those in the normal group. The relationship between the relative intensity of peaks and the plasma creatinine value demonstrated a positive correlation in 11 peaks (such as 8,640, and 8,822 Da), and a negative correlation in 6 peaks (such as 4,188 and 8,358 Da). Although the relative intensities of peaks in the adriamycin nephropathy + AST-120 group were between that of the adriamycin nephropathy group and that of the normal group, the relative intensities of 4 peaks (such as 3,664 and 5,179 Da) in the adriamycin nephropathy + AST-120 group demonstrated higher values than in the two other groups. The m/z 3,664 peak was purified and identified as a C-terminal fragment of apolipoprotein C-III. CONCLUSION: Low-molecular proteins and peptides in plasma in this chronic renal failure model showed not only increases but also decreases in some peaks. The relative intensities in some peaks increased in the adriamycin nephropathy + AST-120 group more than in the two other groups. One of these peaks was identified as the apolipoprotein C-III fragment. The relationship between these changes and the prevention of progression of chronic renal failure by AST-120 remains to be established.

Cystic renal cell carcinoma, suspected because of lack of regression of renal cysts after renal transplantation in a dialysis patient with acquired renal cystic disease.

A 34-year-old man who had been on dialysis for about 6 years, and had acquired renal cystic disease, received a renal transplantation. However, in spite of the success of the transplantation, one area without cyst regression was observed in the original kidney. Therefore, carcinoma was suspected and nephrectomy was performed. Histology revealed cystic renal cell carcinoma (RCC). No case of cystic RCC occurring in a dialysis patient has previously been reported. Cystic RCC should be suspected in a cystic mass in the original kidney which does not regress after successful renal transplantation.