Daijo Inaguma

Prevalence of chronic kidney disease (CKD) in the Japanese general population predicted by the MDRD equation modified by a Japanese coefficient

BackgroundThe number of patients with end-stage renal disease (ESRD) in Japan has continuously increased in the past three decades. In 2005, 36 063 patients whose average age was 66 years entered a new dialysis program. This large number of ESRD patients could be just the tip of the iceberg of an increasing number of patients with chronic kidney disease (CKD). However, to date, a nationwide epidemiological study has not been conducted yet to survey the CKD population.MethodsData for 527 594 (male, 211 034; female, 316 560) participants were obtained from the general adult population aged over 20 years who received annual health check programs in 2000–2004, from seven different prefectures in Japan: Hokkaido, Fukushima, Ibaraki, Tokyo, Osaka, Fukuoka, and Okinawa prefectures. The glomerular filtration rate (GFR) for each participant was estimated from the serum creatinine values, using the abbreviated Modification of Diet in Renal Disease (MDRD) study equation modified by the Japanese coefficient.ResultsThe prevalences of CKD stage 3 in the study population, stratified by age groups of 20–29, 30–39, 40–49, 50–59, 60–69, 70–79, and 80–89 years, were 1.4%, 3.6%, 10.8%, 15.9%, 31.8%, 44.0%, and 59.1%, respectively, predicting 19.1 million patients with stage 3 CKD in the Japanese general adult population of 103.2 million in 2004. CKD stage 4 + 5 was predicted in 200 000 patients in the Japanese general adult population. Comorbidity of hypertension, diabetes, and proteinuria increased as the estimated GFR (eGFR) decreased. The prevalence of concurrent CKD was significantly higher in hypertensive and diabetic populations than in the study population overall when CKD was defined as being present with an eGFR of less than 40 ml/min per 1.73 m2 instead of less than 60 ml/min per 1.73 m2.ConclusionsAbout 20% of the Japanese adult population (i.e., approximately 19 million people) are predicted to have stage 3 to 5 CKD, as defined by a GFR of less than 60 ml/min per 1.73 m2.

Peritonitis is still an important factor for withdrawal from peritoneal dialysis therapy in the Tokai area of Japan

BackgroundIn Japan, the population of patients on peritoneal dialysis (PD) is <4% of the total number of patients with end-stage renal disease. Few systemic analyses have examined why the number of PD patients has not increased in Japan. We organized a registry to analyze PD patients and retrospectively investigated 561 PD patients (about 5% of all Japanese PD patients) from 13 hospitals in the Tokai area for 3 years from 2005.MethodsWe investigated background, physical status, laboratory data, status of PD therapy, and the occurrence of PD-related complications, and analyzed reasons for withdrawal from PD.ResultsNutrition did not change significantly during our observation. Urinary volume showed continued decreases after the introduction period. In contrast, PD fluid demand and ultrafiltration volume were significantly increased. For calcium metabolism, multiple phosphate binders were required after the second year of PD therapy. Early drop-out within 3 years after starting PD therapy comprised 50.9% of total withdrawals, with PD-related peritonitis as the most common reason, mainly caused by Gram-positive organisms. Incidence of peritonitis was 42.8 months/patient. Culture-negative results were obtained for 32% of peritonitis cultures. Diabetes affects the prognosis of PD therapy, but not the incidence of peritonitis.ConclusionWe examined clinical status over 3 years in the Tokai area. The results suggest that the incidence of peritonitis needs to be decreased to prevent early withdrawal of PD patients. Education systems to decrease the incidence of peritonitis and techniques to decrease culture-negative results might be important for improving the prognosis of peritonitis.

Effect of an educational program on the predialysis period for patients with chronic renal failure

BackgroundThe purpose of the treatment and management of chronic renal failure during the predialysis period is mainly to retard the progression of the deterioration of renal function. Optimal dialysis initiation is important to improve the patients outcome after therapy. We investigated whether providing information through an original educational program could facilitate dialysis initiation, with the patient in a better condition, and therefore greater cost-effectiveness.MethodsOne hundred and seventy-six patients who underwent dialysis initiation for chronic renal failure in our hospital between April 2002 and March 2005 were divided into two groups according to their participation or nonparticipation in an educational program. Participation in the education program was of their own free will. The instructors consisted of nephrologists, nursing staff, clinical engineering technologists, national registered dietitians, and medical social workers. We investigated whether the education program facilitated trouble-free dialysis initiation by comparing findings of blood tests at the start, the existence of heart-failure symptoms, type of blood access, percentage of scheduled initiation, and the number of days and cost of hospitalization as indices between participating and nonparticipating groups.ResultsThe number of patients using a double-lumen dialysis catheter, and the duration and cost of hospitalization in training the participating group, were significantly less than those in the nonparticipating group. Although there was no significant difference in renal function at the initiation of renal replacement therapy (RRT) between the two groups, serum albumin, hemoglobin, and hematocrit in the participating group were significantly higher than those of the nonparticipating group.ConclusionsThis study suggests that providing sufficient information before dialysis initiation may be effective in both physical condition at dialysis initiation, and medical economic benefits through the understanding of the dialysis.

Japanese Society for Dialysis Therapy Clinical Guideline for “Hemodialysis Initiation for Maintenance Hemodialysis”

Yuzo Watanabe, Kunihiro Yamagata, Shinichi Nishi, Hideki Hirakata, Norio Hanafusa, Chie Saito, Motoshi Hattori, Noritomo Itami, Yasuhiro Komatsu, Yoshindo Kawaguchi, Kazuhiko Tsuruya, Yoshiharu Tsubakihara, Kazuyuki Suzuki, Ken Sakai, Hideki Kawanishi, Daijo Inaguma, Hiroyasu Yamamoto, Yoshiaki Takemoto, Noriko Mori, Kazuyoshi Okada, Hiroshi Hataya, Takashi Akiba, Kunitoshi Iseki, Tadashi Tomo, Ikuto Masakane, Tadao Akizawa, and Jun Minakuchi, for “Hemodialysis Initiation for Maintenance Hemodialysis” Guideline Working Group, Japanese Society for Dialysis Therapy

Significance of Serum Magnesium as an Independent Correlative Factor on the Parathyroid Hormone Level in Uremic Patients

CONTEXT PTH is a critical factor in mineral homeostasis, and chronic kidney disease mineral and bone metabolism disorder is a very important problem in patients with renal failure. Abnormal levels of PTH, serum phosphate, and calcium influence chronic kidney disease mineral and bone metabolism disorder, but there is little information about the influence of magnesium (Mg) on PTH. OBJECTIVE The aim of this study was to elucidate the correlation between magnesium and PTH levels in uremic patients just prior to beginning hemodialysis (HD) for the first time. PATIENTS We enrolled 1231 patients in nine Japanese facilities who had begun HD for end-stage renal disease. We investigated their serum Mg levels and the correlation between intact PTH (iPTH) and the serum Mg levels and other clinical parameters and medications. RESULTS The mean serum Mg was 2.2 ± 0.5 mg/dL, and hypermagnesemia was found in 663 patients (53.9%). Divided into two groups according to median iPTH level, the serum Mg levels were significantly higher in patients with low iPTH (2.3 ± 0.5 vs 2.1 ± 0.5, P < .01). Furthermore, divided into two groups according to the Mg level, iPTH levels were lower in patients with high Mg than in patients with normal serum Mg levels (277.9 ± 195.9 pg/mL vs 321.9 ± 203.7 pg/mL, P < .01). In the multiple regression analysis according to the effect of iPTH level, the serum Mg level was an independent variable after adjustment for other factors. CONCLUSIONS A high serum level of Mg is frequent in uremic patients with end-stage renal disease just prior to beginning HD. In the present set of patients, there was a significant correlation between the serum Mg and iPTH levels. Furthermore, the serum Mg level was an independent factor apart from the other factors regulating iPTH. These results suggest that serum Mg may be one of the factors regulating the serum PTH level in uremic patients.

Association between the Hemoglobin Level and Cardiothoracic Ratio in Patients on Incident Dialysis

Background/Aim: The present study explores associations between hemoglobin (Hb) levels and patients with cardiac enlargement in end-stage kidney disease (ESKD) to help prevent cardiac remodeling during the predialysis phase of chronic kidney disease (CKD). Methods: This cross-sectional study included 2,249 patients with ESKD (age, 67 w 13 years; male, 67%; diabetic kidney disease, 41%) who started hemodialysis (HD) between January 2006 and October 2013 at eight participating hospitals. We examined associations between Hb levels immediately before the first HD session and cardiothoracic ratios (CTRs). Clinical factors associated with the CTR were also assessed. Results: The mean Hb level was 8.7 w 1.6 g/dl, and the mean and median CTRs were 55.0 and 54.7%, respectively. The correlation between the Hb level and the CTR was linear and negative (r = -0.129, p < 0.001). The mean CTR and the prevalence of patients with a CTR >50% obviously decreased with increasing Hb levels (both p < 0.001 for trend). Univariate logistic regression analysis revealed an approximately 20% reduction in the odds ratio for complicating CTRs >50% per 1 g/dl increase in Hb. Hb levels of <9 g/dl were significantly associated with CTRs >50%. Numerical and categorical Hb remained significantly associated with CTRs >50% after adjusting for confounding variables. Conclusions: Lower Hb levels participate in progressive CTR enlargement in patients with ESKD, and maintaining Hb levels of >9 g/dl might help prevent cardiac remodeling during the predialysis phase of CKD. i 2014 S. Karger AG, Basel

Relationship between renal function at the time of percutaneous coronary intervention and prognosis in ischemic heart disease patients

BackgroundAs hypertension and diabetes mellitus increase, the number of patients developing complications of cardiovascular disease (CVD) associated with conventional risk factors is increasing. In addition to these risk factors for CVD, chronic kidney disease (CKD) has also been reported to play an important role. We investigated the association of representative ischemic heart disease and CKD.MethodsBetween July 1, 2000, and June 30, 2005, a total of 790 patients who underwent percutaneous coronary intervention (PCI) for angina pectoris or myocardial infarction in our division of cardiovascular disease were reviewed. Serum markers at the implementation of PCI were compared in patients classified according to renal function. For prognosis, in-hospital mortality, 1-year survival rate, overall mortality, and CVD death were investigated. Changes in renal function were also monitored during the follow-up period. The glomerular filtration rate (GFR) was calculated by the Modification of Diet in Renal Disease Study Group (MDRD) formula.ResultsThe mean estimated GFR (eGFR) at PCI implementation was 66.2 ± 21.0 ml/min/1.73 m2. Stage 2 CKD was shown in 51.5% of all the patients. During the overall follow-up period, 126 patients died. With the progression of CKD stage, all-cause, CVD, and in-hospital mortality increased, and the 1-year survival rate decreased. It was proved that a medical history of hypertension, hyperlipidemia, and diabetes, multiple vessel lesions, hypoalbuminemia, C-reactive protein (CRP), and estimated GFR were independent risk factors for all-cause death. In CVD death, in addition to the above risk factors, anemia and total cholesterol were also an independent risk factor. Renal function deteriorated significantly during the follow-up period.ConclusionsPatients with ischemic heart disease requiring PCI often develop renal dysfunction, which may considerably affect prognosis.

Effect of erythropoietin-stimulating agent on uremic inflammation

BackgroundThe goal of the present study was to explore the effect of medications that are commonly prescribed for CKD patients on uremic state.MethodsThis was a cross-sectional study. From January 2006 to October 2009, 1,623 patients with end-stage kidney disease (ESKD) commenced hemodialysis (HD) at the 9 participating hospitals. The criteria for exclusion from the database were 1) serum C-reactive protein (CRP) > 3 mg/dL, 2) WBC count > 9,000/mm3 or <4,000/mm3, and 3) patients with cancer, immune complex disease, or vasculitis. A total of 900 patients were entered into the final database. We explored the association of serum CRP just before the first HD session with clinical characteristics, laboratory data, and medications for CKD in the predialysis period.ResultsOn univariate analysis, age, CTR, eGFR, and WBC were significantly correlated with CRP. Systolic and diastolic blood pressure, serum albumin, LDL-C, HDL-C, Hb, Cr, and Ca were inversely associated with CRP. Use of erythropoietin-stimulating agents (ESA) using (r = −0.111, p = 0.0015), renin-angiotensin-aldosterone system inhibitors (r = −0.083, p = 0.0154), and calcium channel blockers (r = −0.1, p = 0.0039) was also negatively correlated with CRP. However, only use of ESA showed a significant negative correlation with CRP that was independent of other clinical factors and CKD medications on multiple regression analysis.ConclusionESA may strongly reduce uremic inflammation in addition to improving anemia. To confirm this potential effect, a large-scale longitudinal study would be required.

Significance of C4d deposition in antibody‐mediated rejection

The C4d staining as a special tissue marker for humoral immunity has served criteria of pathological diagnosis for antibody‐mediated rejection (ABMR) in Banff classification since 2003. However, the sensitivity and specificity of C4d staining have been questioned, and recently, C4d‐negative ABMR has been more focused in renal allograft pathology. The aim of this study was to make certain of C4d staining for ABMR that was diagnosed by clinical and morphological findings. C4d staining was employed by immunofluorescence. This study included 14 patients with acute ABMR and 16 with chronic active ABMR. Eight of acute ABMR were ABO‐blood‐type‐incompatible renal transplantation (ABOinRTx) pre‐treated by DFPP and splenectomy or rituximub. In acute ABMR after ABOinRTx, C4d staining along peritubular capillary (PTC) was positive in five of them (62.5%). Only one graft biopsy of five acute ABMR with donor‐specific antibody (DSA) showed C4d positive. We assembled 16 graft biopsies showing typical transplant glomerulopathy and thickened PTC basement membrane with peritubular capillaritis as a suspicious pathological chronic active ABMR. Four of eight DSA‐positive patients were C4d negative in PTC; however, three of four DSA‐positive and C4d‐negative patients in PTC chronic active ABMR were C4d positive in only glomerular capillaries. C4d positivity could not come to a specific marker of ABMR diagnosing based on clinically and ordinary morphological findings.

Presence of Atrial Fibrillation at the Time of Dialysis Initiation Is Associated with Mortality and Cardiovascular Events

Background: Death in dialysis patients results mainly from cardiovascular and cerebrovascular diseases. To our knowledge, no prospective study has compared the rates of mortality or cardiovascular events between patients with and without atrial fibrillation (AF) at the time of dialysis initiation. Methods: This study included 1,516 patients who were initiated into dialysis between October 2011 and August 2013. Rates of mortality and cardiovascular events were compared between patients with and without AF, and between AF patients with and without warfarin (WF) treatment. Results: The study comprised 1,025 men and 491 women with a mean age of 67.5 ± 13.1. Of these patients, 93 had AF, while 1,423 did not; 22.6% of the former group and 9.7% of the latter group died by March 2014 (p < 0.01). Cardiovascular events occurred in 34.4% of patients with AF and 15.1% of patients without (p < 0.01). Even after adjustments for various factors, AF remained an independent risk factor for mortality (hazard ratio (HR) 1.873, 95% CI 1.168-3.002, p < 0.01). It was also an independent risk factor for cardiovascular events (HR 1.872, 95% CI 1.262-2.778, p < 0.01). No difference in any parameter was noted between the groups that did and did not receive WF treatment. Conclusion: Patients with AF at the time of dialysis initiation show a poor prognosis and are at high risk of cardiovascular events. Therefore, AF should be taken into consideration in dialysis patients.