Prediction of presepsin concentrations through commensurate decline in kidney function in the elderly.

BACKGROUND: Presepsin is a useful biomarker to diagnose sepsis. However, the correlation between plasma presepsin concentrations and kidney function in the elderly with chronic kidney disease (CKD) remains to be elucidated. We determined whether plasma presepsin concentrations were influenced by kidney function decline in the elderly. METHODS: One hundred seventy outpatients with CKD aged ≥65 y were enrolled. Plasma presepsin concentrations were measured using immunoassay analysis. The relationship between plasma presepsin concentration and kidney function was assessed. RESULTS: The median age of patients of this cohort was 778 (72-85) y and the mean estimated glomerular filtration rate was 51.8 ±â€¯28.1 ml/min/1.73 m2. Plasma presepsin concentrations in those with CKD G4-G5 (362 pg/ml [273-553]) were significantly higher than in those with CKD G1-G2 (111 pg/ml [91-113]) and CKD G3 (145 pg/ml [124-205]) (p < 0.001, p < 0.001, respectively). A high correlation between plasma presepsin concentrations and kidney function was observed (R2 = 0.733, p < 0.001). Even after adjusting for confounders, plasma presepsin concentrations were independently associated with kidney function. CONCLUSIONS: Increases in plasma presepsin concentrations were exponentially correlated to kidney function decline in the elderly with CKD.

Spot urine protein/creatinine ratio as a reliable estimate of 24-hour proteinuria in patients with immunoglobulin A nephropathy, but not membranous nephropathy.

BACKGROUND: Proteinuria is known to be associated with both kidney function deterioration and cardiovascular diseases. While proteinuria estimation from 24-h urine samples has traditionally been considered as the standard method for assessment of the degree of urinary protein excretion, sample collection is associated with several technical problems such as inaccurate collection and the potential spread of drug-resistant pathogens. Therefore, the spot urine protein/creatinine ratio (PCR) assessment is currently recommended as an alternative. While the utility of PCR has been validated, studies on the association between spot urine PCR and 24-h proteinuria (24HP) in patients with chronic glomerular nephritis (CGN) and nephrotic syndrome (NS) are limited. This study aimed to evaluate whether an estimated result from a spot urine PCR could sufficiently approximate the daily urine protein excretion amount from a 24-h urine sample in patients with immunoglobulin A nephropathy (IgAN), minimal change disease (MCD), and membranous nephropathy- nephrotic syndrome (MN-NS). METHODS: The study participants included 161 patients with IgAN, MCD, or MGN-NS at the Jikei University Kashiwa Hospital and Kanagawa Prefecture Shiomidai Hospital. The correlation between spot urine PCR and a 24-h urine protein was investigated using linear regression analysis with Spearman's correlation (r) coefficient and intraclass correlation coefficient (ICC). RESULTS: While high correlation coefficients (r = 0.86, P < 0.001) and substantial agreement (ICC: 0.806, P < 0.001) were observed in patients with IgAN, similar correlations were not observed in patients with MCD or MN-NS. In the patients with MCD, r was 0.53 (P < 0.001), which signified a slight correlation, and in the patients with MN-NS, r was 0.289 (P = 0.17), which was not statistically significant. CONCLUSIONS: This study revealed that spot urine PCR is a reliable estimate of 24HP value in patients with IgAN. In contrast, there is a considerable difference between the daily urine protein excretion amount based on a 24-h urine sample and that which is calculated from spot urine PCR in patients with NS.

A novel treatment of hyperinsulinemic hypoglycemia induced by insulin antibodies with alkali administration: a case report.

BACKGROUND: Insulin autoimmune syndrome is a rare cause of hyperinsulinemic hypoglycemia characterized by autoantibodies to human insulin without previous insulin use. We report a case of a patient with hyperinsulinemic hypoglycemia possibly caused by insulin antibodies induced by insulin analogs and a novel therapeutic measure for this condition. CASE PRESENTATION: An 84-year-old Japanese man with a 28-year history of type 2 diabetes and chronic kidney disease, treated with biphasic insulin aspart 30, experienced persistent early morning hypoglycemia with daytime hyperglycemia. Despite discontinuation of biphasic insulin aspart 30, the condition persisted even after the patient ate small, frequent meals. Sodium bicarbonate was administered to correct the chronic metabolic acidosis, which then rectified the early morning glucose level. CONCLUSIONS: We believe this to be the first published case of a therapeutic approach to the treatment of hyperinsulinemic hypoglycemia associated with insulin antibodies that factors in blood pH and the correction of acidosis using sodium bicarbonate, which physicians could consider.

Measurement of daily sodium excretion in patients with chronic kidney disease; special reference to the difference between the amount measured from 24 h collected urine sample and the estimated amount from a spot urine.

It is important to grasp a patient's daily sodium intake in the management of chronic kidney disease, as sodium intake is widely recommended at 6 g/day or less. There are multiple equations widely known for estimating the daily sodium excretion from a spot urine sample, but these are aimed at healthy people. There are few reports that validate equations in patients with chronic kidney disease. The purpose of this study is to evaluate whether the amount of measured daily sodium excretion from a sample collected for 24-h urine (24HU) is equal to that of using an equation from a spot urine sample (SU) in patients with chronic kidney disease. One hundred sixty-two patients with chronic kidney disease from Kanagawa Prefecture Shiomidai Hospital, Japan and the Jikei University Kashiwa Hospital, Japan participated in the study. Daily sodium excretion was measured from 24HU and compared with it from SU by using the formula according to Tanaka et al. Sodium excretion by 24HU was 2744 mg/day and estimating daily sodium excretion from SU was 3315 mg/day. The coefficient of determination was 0.17 (p < .001) in multivariate regression analysis. The coefficient of determination was extremely low. Thus, there is a considerable difference between the amount of sodium excretion calculated from a 24HU and that from a SU in patients with chronic kidney disease.

A new peritoneal dialysis fluid for Japanese patients: a randomized non-inferiority clinical trial of safety and efficacy.

BACKGROUND: We report here two new peritoneal dialysis fluids (PDFs) for Japan [BLR 250, BLR 350 (Baxter Limited, Japan)]. The PDFs use two-chamber systems, and have bicarbonate and lactate buffer to a total of 35 mmol/L. In separate trials, the new PDFs were compared to two "standard" systems [PD-4, PD-2 (Baxter Limited, Japan)]. The trials aimed to demonstrate non-inferiority of peritoneal creatinine clearance (pCcr), peritoneal urea clearance (pCurea) and ultrafiltration volume (UF), and compare acid-base and electrolyte balance. METHODS: We performed randomized, multicenter, parallel group, controlled, open-label clinical trials in stable continuous ambulatory peritoneal dialysis (CAPD) patients. The primary endpoints were pCcr and UF. The secondary endpoints were serum bicarbonate and peritoneal urea clearance. The active phase was 8 weeks. These trials were performed as non-inferiority studies, with the lower limit of non-inferiority for pCcr and UF set at 3.2 L/week/1.73 m2 and 0.12 L/day, respectively. RESULTS: 108 patients (28 centers) and 103 patients (29 centers) took part in the two trials. Groups were well balanced at baseline. The investigative PDFs were non-inferior to the "standard" ones in terms of primary endpoints, comparable in terms of pCurea, and superior in terms acid-base balance, especially correcting those with over-alkalinization at baseline. CONCLUSIONS: We demonstrated fundamental functionality of two new PDFs and showed superior acid-base balance. Given the propensity of Japanese CAPD patients for alkalosis, it is important to avoid metabolic alkalosis which is associated with increased cardiovascular mortality risk and accelerated vascular calcification. The new PDFs are important progress of CAPD treatment for Japanese patients.

Frequencies of hepatitis B and C infections among haemodialysis and peritoneal dialysis patients in Asia-Pacific countries: analysis of registry data.

BACKGROUND: The impact of dialysis modality on the rates and types of infectious complications has not been well studied. The aim of the present investigation was to evaluate the rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in peritoneal dialysis (PD) and haemodialysis (HD) patients in the Asia-Pacific region. METHODS: The study included the most recent period-prevalent data recorded in the national or regional dialysis registries of the 10 Asia-Pacific countries/areas (Australia, New Zealand, Japan, China, Taiwan, Korea, Thailand, Hong Kong, Malaysia and India), where such data were available. Longitudinal data were also available for all incident Australian and New Zealand patients commencing dialysis between 1 April 1995 and 31 December 2005. Rates of HCV and HBV infections were compared by chi-square, Poisson regression and Kaplan-Meier survival analyses, as appropriate. RESULTS: Data were obtained on 201,590 patients (HD 173,788; PD 27,802). HCV seroprevalences ranged between 0.7% and 18.1% across different countries and were generally higher in HD versus PD populations (7.9% +/- 5.5% versus 3.0% +/- 2.0%, P = 0.01). Seroconversion rates on dialysis were also significantly higher in HD patients (incidence rate ratio PD versus HD 0.33, 95% CI 0.13-0.75). HCV infection was highly predictive of mortality in Japan (relative risk 1.37, 95% CI 1.15-1.62, P = 0.003) and in Australia and New Zealand (adjusted hazards ratio 1.29, 95% CI 1.05-1.58). HBV infection data were limited, but less clearly influenced by dialysis modality. CONCLUSIONS: Dialysis modality selection significantly influences the risk of HCV infection experienced by end-stage renal failure patients in the Asia-Pacific region. No such association could be identified for HBV infection.

Differences in corrective mode for divalent ions and parathyroid hormone between standard- and low-calcium dialysate in patients on continuous ambulatory peritoneal dialysis--result of a nationwide survey in Japan.

BACKGROUND: In patients on continuous ambulatory peritoneal dialysis (CAPD), dialysate calcium concentration has a strong influence on correction of serum calcium, phosphorus, and parathyroid hormone (PTH); however, the optimal concentration of Ca in PD solution is still uncertain. The aim of the survey reported here was to evaluate the prevalence of patients treated with standard- [SCD (approximately 3.25 - 4.0 mEq/L)] or low-calcium [LCD (approximately 1.8 - 2.5 mEq/L)] dialysate and differences in the clinical effects for correction of abnormalities in divalent ions and PTH. MATERIALS AND METHODS: We used a questionnaire to survey 333 peritoneal dialysis facilities nationwide in Japan. Then, we analyzed serum Ca, P, and PTH levels and the prescription rates for CaCO(3) as a P binder and for vitamin D (VitD) analogs. RESULTS: The 2384 CAPD patients enrolled in this analysis had a mean age of 60.5 +/- 14.2 years and a mean duration of CAPD of 44.1 +/- 39.2 months. The prevalences of SCD, LCD, and combination of SCD and LCD were, respectively, 49%, 50%, and 1% at initiation, and 40%, 38%, and 22% at the time of the survey. In 735 and 876 patients respectively, LCD and SCD had been prescribed from initiation to the time of the survey. In these two groups, we observed no difference in initiation and current serum levels of Ca and P. But prescription rates for CaCO(3) and VitD analogs were higher in the LCD group than in the SCD group, and PTH levels were higher in the LCD group than in the SCD group. CONCLUSIONS: A beneficial effect of LCD was revealed in the increased doses of CaCO(3) and VitD analogs seen in that group without the occurrence of hypercalcemia; however, PTH levels in that group were not maintained within an acceptable range. The survey suggests that more serious attention should be paid to the Ca concentration in peritoneal dialysate so as to lessen mineral and PTH disorders in CAPD.

A role for the Asian peritoneal dialysis community in renal replacement therapy worldwide.

Prevalence and incidence of peritoneal dialysis (PD) in Asia are both increasing, but the increase is not homogenous. In some countries and regions, PD is not used as one of the standard therapeutic modalities, because of either insufficient medico-economic infrastructure or a lack of clinical experience and knowledge-or sometime both. In the present article, we would like to introduce a little "Asian heat" with regard to PD utilization and academic and scientific contributions to the PD community in the world.

Various obstacles to peritoneal dialysis development in Japan: too much money? Too much fear?

At 31 December 2005, the number of patients on maintenance dialysis in Japan was 257,765, with 9599 patients having started dialysis that year. Kidney transplant cases in Japan number about 1000 annually. Thus, almost all endstage renal disease patients in Japan are likely to live on dialysis for the remainder of their lives. For various reasons, peritoneal dialysis has a lower penetration rate among Japanese dialysis patients, and work to educate patients and nephrologists about PD needs to be done.

Increased utilization of peritoneal dialysis to cope with mounting demand for renal replacement therapy--perspectives from Asian countries.

With the number of end-stage renal disease (ESRD) patients growing, one of the crucial questions facing health care professionals and funding agencies in Asia is whether funding for dialysis will be sufficient to keep up with demand. During the ISPD's 2006 Congress, academic nephrologists and government officials from China, Hong Kong, India, Indonesia, Japan, Macau, Malaysia, Philippines, Singapore, Taiwan, Thailand, and Vietnam participated in a roundtable discussion on dialysis economics in Asia. The focus was policy and health care financing. The roundtable addressed ESRD growth in Asia and how to obtain enough funding to keep up with the growth in patient numbers. Various models were presented: the "peritoneal dialysis (PD) first" policy model, incentive programs, nongovernmental organizations providing PD, and PD reimbursement in a developing economy. This article summarizes the views of the participant nephrologists on how to increase the utilization of PD to improve on clinical and financial management of patients with ESRD.

Effects of icodextrin on glycemic and lipid profiles in diabetic patients undergoing peritoneal dialysis.

AIM: Icodextrin reduces glucose absorption from the peritoneal dialysate. We conducted this prospective, open-labeled, multicenter study to determine the effects of icodextrin on glycemic and lipid parameters in diabetic patients undergoing continuous ambulatory peritoneal dialysis (PD) or automated PD. METHODS: Patients were recruited from 15 institutions in Japan, and a total of 51 patients (15 women and 36 men, mean age: 59 +/- 10 years, median duration of PD: 13 months) were enrolled. The patients were administered an overnight or daytime dwell of 1.5 or 2.0 l of 7.5% icodextrin-containing solution. At baseline and 3, 6, 9 and 12 months after the start of icodextrin, nonfasting blood was drawn for measurement of glycated hemoglobin (HbA1C) and serum lipids. RESULTS: During icodextrin treatment, there was no change in overall HbA1C levels compared to baseline values; however, for those with baseline HbA1C > or =6.5% (n = 22), significant decreases in HbA1C were observed. Mean total/LDL cholesterol and triglycerides were decreased significantly during icodextrin treatment, with greater decreases for patients with baseline total cholesterol > or =220 mg/dl, LDL cholesterol > or =120 mg/dl or triglycerides > or =150 mg/dl. HDL cholesterol did not differ at any time point; however, values for patients with baseline HDL cholesterol <40 mg/dl tended to increase with marginal significance. CONCLUSIONS: In the current study, switching from glucose-containing dialysis solution to icodextrin resulted in improved lipid profiles and possibly a favorable metabolic profile, particularly in patients with poor glycemic control. These hypotheses remain to be proven in controlled clinical trials.

Association of mineral metabolism factors with all-cause and cardiovascular mortality in hemodialysis patients: the Japan dialysis outcomes and practice patterns study.

Abnormalities in mineral metabolism have been linked to mortality in hemodialysis (HD) patients. We postulated that these abnormalities would have a particularly large deleterious impact on deaths due to cardiovascular causes in Japan. This study describes the recent status of abnormal mineral metabolism, significant predictors, and potential consequences in the Dialysis Outcomes and Practice Patterns Study (DOPPS), Phases 1 and 2, in Japan. Major predictor variables were patient demographics, comorbidities, and laboratory markers of mineral metabolism such as albumin-adjusted serum calcium (calciumAlb), phosphorus, and intact PTH (iPTH). In a cross section of 3973 Japanese HD patients in DOPPS I and II, a large faction had laboratory values outside of the recommended Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline range for serum concentrations of phosphorus (51% of patients above upper target range), calciumAlb (43.7% above), calcium-phosphorus (Ca x P) product (41.1% above), and iPTH (18.6% above). All-cause mortality was significantly and independently associated with calciumAlb (relative risk [RR]=1.22 per 1 mg/dL, p=0.0005) and iPTH (RR=1.04 per 100 pg/mL, p=0.04). Cardiovascular mortality was significantly associated with calciumAlb (RR=1.28, p=0.02), phosphorus (RR=1.13 per 1 mg/dL, p=0.008), Ca x P product (RR=1.07 per 2 mg(2)/dL(2), p=0.002), and PTH (RR=1.08, p=0.0001). This study expands our understanding of the relationship between altered mineral metabolism and mortality outcomes, showing slightly stronger associations with cardiovascular causes than observed for all-cause mortality. These findings have important therapeutic implications for Japanese HD patients.

Health-related quality of life of predialysis patients with chronic renal failure.

BACKGROUND: Health-related quality of life (HQOL) of predialysis patients with chronic renal failure (CRF) has received less attention than that of dialysis patients. We investigated changes in SF-36 over 1 year and examined associations between clinical parameters and SF-36 in predialysis CRF patients. METHODS: Subjects were 471 predialysis CRF patients. SF-36 and clinical parameters were measured every 8 weeks for 48 weeks. Of the 471 subjects, 294 underwent one or more follow-ups. We analyzed the pooled dataset of the 294 CRF patients and 2002 subjects from Japanese general population using analysis of covariance. RESULTS: After adjustment for age and sex, the 1-year declines in SF-36 domains were significantly greater in the predialysis patients than in the general population. For a 10% decline in hematocrit from the baseline survey value, the decline in vitality of SF-36 was 4.5 points (p = 0.003), while for a 10% increase in serum creatinine from the baseline survey value, respective declines in physical functioning, role-physical and mental health were 1.2 (p = 0.004), 1.9 (p = 0.035), and 1.0 points (p = 0.008). CONCLUSION: Among these predialysis CRF patients, the decline in HQOL was faster than that in the general population, and was associated with an increase in serum creatinine and decline in hematocrit.