Osamu Matsumura

Association between hemoglobin variability, serum ferritin levels, and adverse events/mortality in maintenance hemodialysis patients

In recent times, therapy for renal anemia has changed dramatically in that iron administration has increased and doses of erythropoiesis-stimulating agents (ESAs) have decreased. Here we used a prospective, observational, multicenter design and measured the serum ferritin and hemoglobin levels every 3 months for 2 years in 1086 patients on maintenance hemodialysis therapy. The associations of adverse events with fluctuations in ferritin and hemoglobin levels and ESA and iron doses were measured using a Cox proportional hazards model for time-dependent variables. The risks of cerebrovascular and cardiovascular disease (CCVD), infection, and hospitalization were higher among patients who failed to maintain a target-range hemoglobin level and who exhibited high-amplitude fluctuations in hemoglobin compared with patients who maintained a target-range hemoglobin level. Patients with a higher compared with a lower ferritin level had an elevated risk of CCVD and infectious disease. Moreover, the risk of death was significantly higher among patients with high-amplitude ferritin fluctuations compared with those with a low ferritin level. The risks of CCVD, infection, and hospitalization were significantly higher among patients who were treated with high weekly doses of intravenous iron compared with no intravenous iron. Thus, there is a high risk of death and/or adverse events in patients with hemoglobin levels outside the target range, in those with high-amplitude hemoglobin fluctuations, in those with consistently high serum ferritin levels, and in those with high-amplitude ferritin fluctuations.

Anemia and neutropenia due to copper deficiency in enteral nutrition.

Copper deficiency has been regarded a rare complication of total parenteral nutrition. This report describes the first known case of anemia and neutropenia caused by copper deficiency in a patient receiving long-term enteral nutrition. A 34-year-old man presented with bulbar palsy and tetraplegia after an operation for cerebellar hemorrhage on June 7, 1989. Nasopharyngeal tube feeding with a defined-formula diet (Besvion) was instituted on June 19, 1989. He developed normocytic anemia and neutropenia approximately 19 months after the initiation of the tube feeding. Serum copper and ceruloplasmin levels were markedly below normal. There were anisocytosis and erythrocyte deformities in the peripheral blood smear. Bone marrow aspirates revealed a hypocellular marrow with numerous myeloid and erythroid cells with cytoplasmic vacuoles. Because the amount of copper administered was estimated to be 2.6 to 5.1 mumol/d during the tube feeding, copper deficiency was suspected to be the cause of the hematologic disorders. The patients daily oral copper intake was increased to 34 mumol/d. His serum copper and ceruloplasmin concentrations reached a normal level after 16 days and 23 days of copper supplementation, respectively. A marked reticulocytosis occurred after 10 days of copper supplementation, and his anemia gradually improved over the next 3 months. His blood neutrophil count also returned to normal within 2 weeks.

A family with two sisters with collagenofibrotic glomerulonephropathy

Collagenofibrotic glomerulonephropathy is a recently recognized disease entity. Although an autosomal recessive inheritance pattern has been suggested for this condition, there are few reports of familial cases. Only four pairs of child siblings, with histological confirmation of the glomerular lesions, have been reported. The current report describes a family including two sisters with histological evidence of collagenofibrotic glomerulonephropathy. Serum concentrations of the procollagen III peptide were elevated in the affected sisters, whereas their parents and other siblings demonstrated neither proteinuria nor increased blood levels of the procollagen III peptide. Our findings support an autosomal recessive pattern of inheritance for this type of glomerulonephropathy. They also suggest that the serum concentration of the procollagen III peptide is a useful marker for collagenofibrotic glomerulonephropathy.

Eradication of Helicobacter pylori in patients with end-stage renal disease under dialysis treatment

The efficacy and safety of combination therapy with amoxicillin, lansoprazole, and plaunotol for the eradication of Helicobacter pylori in patients on dialysis were evaluated. The study subjects comprised 15 dialysis patients in whom H pylori had been found in the gastric mucosa. The patients were given 500 mg amoxicillin once a day for 3 weeks, 30 mg lansoprazole once a day for 8 weeks, and 80 mg plaunotol three times a day for 24 weeks. Endoscopy was performed on entry and at 4 and 24 weeks after cessation of amoxicillin. The concentrations of serum gastrin and gastric juice ammonia also were measured. Fourteen patients completed the treatment protocol, one having dropped out because of nausea and diarrhea. H pylori was eradicated in 11 of the 14 patients 4 weeks after the end of amoxicillin therapy (eradication rate, 78.6%). All but one patient was free of H pylori 24 weeks after the amoxicillin was discontinued. Patients who became negative for H pylori had significantly decreased serum gastrin and gastric juice ammonia concentrations. Our findings indicate that a combination of amoxicillin, lansoprazole, and plaunotol can be used to eradicate H pylori in patients on dialysis.

Improvement of Rice Biomass Yield through QTL-Based Selection.

Biomass yield of rice (Oryza sativa L.) is an important breeding target, yet it is not easy to improve because the trait is complex and phenotyping is laborious. Using progeny derived from a cross between two high-yielding Japanese cultivars, we evaluated whether quantitative trait locus (QTL)-based selection can improve biomass yield. As a measure of biomass yield, we used plant weight (aboveground parts only), which included grain weight and stem and leaf weight. We measured these and related traits in recombinant inbred lines. Phenotypic values for these traits showed a continuous distribution with transgressive segregation, suggesting that selection can affect plant weight in the progeny. Four significant QTLs were mapped for plant weight, three for grain weight, and five for stem and leaf weight (at α = 0.05); some of them overlapped. Multiple regression analysis showed that about 43% of the phenotypic variance of plant weight was significantly explained (P < 0.0001) by six of the QTLs. From F2 plants derived from the same parental cross as the recombinant inbred lines, we divergently selected lines that carried alleles with positive or negative additive effects at these QTLs, and performed successive selfing. In the resulting F6 lines and parents, plant weight significantly differed among the genotypes (at α = 0.05). These results demonstrate that QTL-based selection is effective in improving rice biomass yield.

Contribution of Residual Renal Function on Peritoneal Solute Transport in Dialysis Patients

Background: Increased peritoneal solute transport rate (PSTR) is primarily a consequence of continuous exposure to bioincompatible glucose-based peritoneal dialysis (PD) solutions. However, relationships between increasing PSTR and dialysate glucose load remain unclear. As some PD patients with preserved residual renal function do not show increased PSTR despite long-term PD, we examined whether loss of residual renal function is associated with increased PSTR on long-term PD. Methods: We evaluated 35 patients who started PD between 1997 and 2002 and received continuous PD treatment for >6 years. Data included baseline clinical data, residual renal function, urea and creatinine clearance, dialysate glucose load, ultrafiltration, and the use of icodextrin and renin-angiotensin system inhibitors. Peritoneal equilibration test results and data were collected annually for 6 years. Results: Both the glomerular filtration rate and urine volume at 6 years on PD showed significant negative correlations with the dialysate-to-plasma creatinine ratio (D/P Cr) at 6 years (r = –0.716 and r = –0.717, respectively). Multivariate analysis showed only urine volume at 6 years on PD as an independent covariate of the D/P Cr at 6 years on PD. Conclusions: Loss of residual renal function is directly associated with increased PSTR in patients on long-term PD.

ESA Hyporesponsiveness Is Associated with Adverse Events in Maintenance Hemodialysis (MHD) Patients, But Not with Iron Storage

Objective It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA) is associated with adverse events in patients on maintenance hemodialysis (MHD). However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA. Design and Method We measured serum ferritin, hemoglobin (Hb), and transferrin saturation (TSAT) levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI). Results A significant correlation (p<0.001, R = 0.89) between ferritin and Hb was only observed in the patients with ferritin levels <50 ng/mL. High-dose (≥50 mg/week) intravenous iron administration, female sex, low serum albumin, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were significant predictors of a high ERI value (>280); however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280) and a high ferritin level (≥100 ng/mL) was significantly greater (hazard ratio [HR], 2.09, P = 0.033) than that for patients with a high ERI and a low ferritin (<100 ng/mL) level. Conclusion Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.

Dialysate purification after introduction of automated hot water disinfection system to central dialysis fluid delivery system.

Most dialysis clinics in Japan have mainly adopted the central dialysis fluid delivery system (CDDS) to provide constant treatment to many patients. Chemical disinfection is the major maintenance method of the CDDS. Our clinic introduced an automated hot water disinfection system that used the heat conduction effect to disinfect a reverse osmosis (RO) device and dialysis fluid supply equipment. Endotoxin level and the amount of viable bacteria often showed abnormal values before introduction of this system. After its introduction, weekly disinfection resulted in endotoxin levels and the amount of viable bacteria lower than measurement sensitivity. In hot water disinfection, water heated to 90°C in the RO tank flows into the dialysis fluid supply equipment. The maximum temperature inside the tank of the supply equipment is 86.3°C. (We confirmed that the temperature was maintained at 80°C or more for 10 minutes or more during the monitoring.) Dialysate purification was maintained even after introduction of the automated hot water disinfection system and the dialysate could be supplied stably by the CDDS. Therefore, this disinfection system might be very useful in terms of both cost and safety, and can be used for dialysis treatment of multiple patients.

A Case of Water Intoxication with Prolonged Hyponatremia Caused by Excessive Water Drinking and Secondary SIADH

Water intoxication is a life-threatening disorder accompanied by brain function impairment due to severe dilutional hyponatremia. We treated a 22-year-old man without psychotic illness who had been put in a detention facility. He drank 6 liters of water over a 3-hour period at the facility as a games penalty, and he showed progressive psychiatric and neurological signs including restlessness, peculiar behavior and convulsions. On his admission, 15 h after the discontinuation of the water drinking, he was in a coma, showing intermittent convulsions and remarkable hyponatremia (120 mmol/l). Because his laboratory tests showed hypertonic urine and normal sodium excretion, the diagnosis of secondary development of syndrome of inappropriate secretion of antidiuretic hormone (SIADH) was strongly suggested and later confirmed by the suppression of the renin-aldosterone system and the inappropriately elevated secretion of ADH. Saline infusion and an initial administration of furosemide in addition to dexamethasone as treatments for the patients brain edema successfully improved his laboratory data and clinical signs by the 3rd hospital day, and he was returned to the facility without physical or psychiatric abnormalities on the 6th day. The secondary SIADH might have been due to the prolonged emesis, recurrent convulsions and rapid elevation of intracranial pressure.