Takao Suga

Acute Hydrothorax in Continuous Ambulatory Peritoneal Dialysis – A Collaborative Study of 161 Centers

Follow-up studies on 3,195 patients from 161 centers in Japan undergoing continuous ambulatory peritoneal dialysis (CAPD) were performed for 1-104 months to clarify the incidence as well as the clinical features of acute hydrothorax. In these studies, 50 patients (1.6%) developed this complication. Twenty-seven (54%) were men, and 23 (46%) were women, ranging in age from 6 to 79 (average 49) years. The interval between onset of CAPD and hydrothorax ranged from 1 day to 8 years. Four had left-sided, and 2 had bilateral hydrothorax, but the majority (88%) were right-sided. Dyspnea was experienced by 37 of these 50 patients, but the remaining 13 (26%) patients were asymptomatic. Hydrothorax was fully resolved in 27 of them following a brief interruption of CAPD or the combined use of small exchange volumes in a semi-sitting position and pleurodesis with tetracycline or other agents. The remaining 23 patients (46%) were switched to hemodialysis permanently. Despite recurrence, 1 patient continued successfully on CAPD. It was concluded that acute hydrothorax is one important possible complication, although the risk may be low. Constant surveillance is necessary to detect pleural effusions in patients during CAPD.

Survival advantage of lanthanum carbonate for hemodialysis patients with uncontrolled hyperphosphatemia

BACKGROUND Lanthanum carbonate is a non-calcium phosphate binder that is effective for the treatment of hyperphosphatemia. However, it is unknown whether treatment with lanthanum affects survival. METHODS We retrospectively collected data on maintenance hemodialysis patients at 22 facilities (n = 2292) beginning in December 2008, a time point immediately prior to the commercial availability of lanthanum in Japan. We compared 3-year all-cause mortality among patients who initiated lanthanum (n = 560) and those who were not treated with lanthanum during the study period (n = 560) matched by the propensity score of receiving lanthanum. Several sensitivity analyses were performed to test the robustness of the primary analysis. RESULTS After the market introduction of lanthanum, the percentage of patients receiving the binder increased gradually to 27%. In the propensity score-matched analysis, the mortality rate for the lanthanum group was not significantly lower than the non-lanthanum group [hazard ratio (HR), 0.71; 95% confidence interval (CI), 0.47-1.09). However, stratification by serum phosphorus disclosed significant survival benefit of lanthanum for patients with serum phosphorus >6.0 mg/dL (HR, 0.52; 95% CI, 0.28-0.95), but not in patients with serum phosphorus ≤6.0 mg/dL (HR, 1.00; 95% CI, 0.55-1.84). The survival benefit of lanthanum in patients with serum phosphorus >6.0 mg/dL was consistent across subgroups and robust in different analytical approaches. CONCLUSIONS Treatment with lanthanum was independently associated with a significant survival benefit in hemodialysis patients with inadequately controlled hyperphosphatemia. Further studies are required to confirm these findings.

Impaired Solubilization of Glomerular Immune Deposits by Sera From Patients With IgA Nephropathy

A study of the solubilization of glomerular immune deposits by sera from patients with IgA nephropathy is described. Renal biopsy specimens were obtained from patients with IgA nephropathy and other glomerular diseases. These specimens were incubated with fresh and heated sera from the same patients and healthy adults at 37 degrees C for one hour in plastic tubes. The sections were stained with fluorescein isothiocyanate (FITC)-labeled heavy chain specific anti-human IgA antiserum and then examined with a fluorescent microscope. It was shown that the solubilization of glomerular immune deposits by sera from patients with IgA nephropathy was significantly less than that by sera from healthy adults. It is possible that impaired solubilization of immune complexes in vivo could lead to the accumulation of glomerular immune deposits in patients with IgA nephropathy.

Carpal Tunnel Syndrome in Patients Undergoing CAPD: A Collaborative Study in 143 Centers

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed carpal tunnel syndrome (CTS) were retrospectively studied in 143 centers in Japan. Among the total 5,050 patients undergoing CAPD between 1980 and 1993 only 7 patients (0.14%) given CAPD developed CTS. Five of these 7 patients treated solely with CAPD developed CTS 12-108 months after starting CAPD. The remaining 2 patients who were initially treated with HD for 7-9 years and then switched to CAPD developed this complication 9 years after starting CAPD. All 7 patients were women, ranging in age from 32 to 70 (average 52) years. We detected the presence of amyloid deposits in 2 of 5 specimens and beta 2-microglobulin in 2 of 4 specimens from these patients. It was concluded that CAPD minimizes the emergence of CTS although constant surveillance is necessary to detect CTS in patients during CAPD.

IgA Nephropathy Associated with HLA-DR4 Antigen

This report describes 2 siblings with IgA nephropathy. Patient No. 1 was a 38-year-old woman with hematuria and proteinuria of 19 years duration. Her blood ABO type was A and Rh positive. She was found to have HLA-A2,Aw24; Bw54 , Bw48 ;Cwl,C-;DR1,DR4. Her renal specimen was diagnosed as the advanced stage of IgA nephropathy histologically. Patient No. 2 was a 41-year-old man who was a brother of patient No. 1. His blood ABO type was O and Rh positive. His serotype for the HLA was found to be HLA-Aw24,A-;Bw35, Bw54 ;Cw1,Cw3;DR4, DRw9 . His renal histology showed the advanced stage of IgA nephropathy. It is suggested that an abnormal immune response linked to gene coding for HLA-DR4 antigen might be involved in the development of IgA nephropathy.

Detection of IgA1-dominant immune complexes in peripheral blood polymorphonuclear leukocytes by double immunofluorescence in patients with IgA nephropathy

The amounts of IgA1- and/or IgA2-dominant immune complexes included in peripheral blood polymorphonuclear cells (PMN) were determined by the double immunofluorescence technique in patients with IgA nephropathy. The aim of the present study was to determine the prevalence of IgA1-and/or IgA2-dominant immune complexes phagocytized by PMN in patients with IgA nephropathy. 5 patients with IgA nephropathy and 10 healthy adults were examined. It was demonstrated that the percentages of IgA1 with C3 cytoplasmic inclusion bodies were significantly increased compared with those of IgA2 with C3 cytoplasmic inclusion bodies in patients with IgA nephropathy. It was suggested that IgA1-dominant immune complexes are phagocytized by peripheral blood PMN in patients with IgA nephropathy.

Glomerular expression of connective tissue growth factor mRNA in various renal diseases.

SUMMARY:  Connective tissue growth factor (CTGF) is a cysteine‐rich member of a new family of growth regulators. It is an important factor in the pathogenesis of mesangial matrix accumulation and progressive glomerulosclerosis. The present study was designed to elucidate the role of CTGF in diabetic nephropathy (DN), immunoglobulin A nephropathy (IgA‐N), membranous nephropathy (MN), and minimal change nephrotic syndrome (MCNS). We evaluated the expression and localization of CTGF mRNA in surgically excised renal tissue samples from 10 patients with DN, 10 with IgA‐N, 10 with MN, 10 with MCNS, and 10 normal human kidney (NHK) tissue samples, by using high‐resolution in situ hybridization with digoxigenin‐labelled oligonucleotide. To quantify CTGF mRNA expression, we counted all nuclei, and nuclei surrounded by CTGF‐positive cytoplasm, in at least 10 randomly selected cross‐sections of non‐sclerotic glomeruli, and expressed the results as a percentage of total glomerular cells. In all glomeruli, CTGF mRNA was expressed mainly in glomerular intrinsic cells, including glomerular mesangial and epithelial cells and some cells of Bowmans capsule. The percentage of cells positive for CTGF mRNA was significantly higher in DN and IgA‐N than in MN, MCNS and NHK. However, there was no significant difference in the percentage of CTGF mRNA‐positive cells between DN and IgA‐N. Our study indicates that CTGF may play an important role in the development and progression of glomerulosclerosis in DN and IgA‐N, which are both accompanied by mesangial matrix expansion and comprise two major causes of end‐stage renal failure.

Levels of Circulating IgA Immune Complexes after Gluten-Rich Diet in Patients with IgA Nephropathy

Measurement of IgA circulating immune complexes (IgA-CIC) in sera from patients with IgA nephropathy after a gluten-poor diet, an unrestricted diet and a gluten-rich diet is described. High levels of IgA-CIC in sera were detected in patients after these diets. However, the levels of IgA-CIC in sera 2 weeks after the gluten-rich diet were not significantly increased compared with those after the other diets. It is suggested that, for a short duration, the gluten-rich diet might not increase the levels of IgA-CIC in sera from Japanese patients with IgA nephropathy.

Specific Binding of Circulating IgA Antibodies in Patients With IgA Nephropathy

Detection of circulating IgA antibodies which are specific in patients with IgA nephropathy is described. Freeze and thawed extracts of pharyngeal cells obtained from patients with IgA nephropathy, other glomerular diseases, and healthy adults were cultured with fibroblasts such as Vero or Hel cells at 37 degrees C for 2 weeks. Serum samples were obtained from these patients and healthy adults. The cultured fibroblasts were fixed on slide glasses, and then incubated with the serum samples from the same or other patients with IgA nephropathy. The cells were stained with FITC-labeled heavy-chain specific anti-human IgA antiserum and then examined with a fluorescent microscope. It was demonstrated that the IgA antibodies in sera obtained from patients with IgA nephropathy or HSP nephritis were bound with the nuclear regions of such fibroblasts. It was suggested that IgA antibodies in sera could be bound with some antigenic substances which were transferred from pharyngeal cells of patients with IgA nephropathy to fibroblasts in vitro.

Rheumatoid factors and glomerulonephritis

It is presently unknown whether rheumatoid factors have a pathogenic role in the development of various types of glomerulonephritis with immune deposits. Three isotypes of rheumatoid factors (RFs), which are autoantibodies to IgG, were measured using the solid‐phase fluorescence immunoassay in sera from patients with diffuse proliferative lupus nephritis (DPLN), membranous lupus nephritis (MLN), IgA nephropathy (IgAN) and idiopathic membranous nephropathy (MN). RF activity of immunoglobulins deposited in the glomeruli from these patients was also studied by examining the binding of the FITC‐conjugated human IgG and Fc portion of IgG to the glomeruli of renal biopsy specimens. IgG, IgA and IgM RFs were significantly increased in sera from patients with DPLN. and the increase was significantly lower in patients with MLN. IgAN and MN. Human IgG bound to immunoglobulin on the glomeruli only in DPLN, but not in MLN, IgAN or MN. The Fc portion of IgG was demonstrated to be involved in this reaction. It was suggested that RFs and IgG may play a major role in immune deposits on the glomeruli in DPLN and may be involved in the development of DPLN; however, this is not likely in MLN, IgAN or MN.