Hideki Hirakata

Estimation of glomerular filtration rate by the MDRD study equation modified for Japanese patients with chronic kidney disease

BackgroundAccurate estimation of the glomerular filtration rate (GFR) is crucial for the detection of chronic kidney disease (CKD). In clinical practice, GFR is estimated from serum creatinine using the Modification of Diet in Renal Disease (MDRD) study equation or the Cockcroft-Gault (CG) equation instead of the time-consuming method of measured clearance for exogenous markers such as inulin. In the present study, the equations originally developed for a Caucasian population were tested in Japanese CKD patients, and modified with the Japanese coefficient determined by the data.MethodsThe abbreviated MDRD study and CG equations were tested in 248 Japanese CKD patients and compared with measured inulin clearance (Cin) and estimated GFR (eGFR). The Japanese coefficient was determined by minimizing the sum of squared errors between eGFR and Cin. Serum creatinine values of the enzyme method in the present study were calibrated to values of the noncompensated Jaffé method by adding 0.207 mg/dl, because the original MDRD study equation was determined by the data for serum creatinine values measured by the noncompensated Jaffé method. The abbreviated MDRD study equation modified with the Japanese coefficient was validated in another set of 269 CKD patients.ResultsThere was a significant discrepancy between measured Cin and eGFR by the 1.0 × MDRD or CG equations. The MDRD study equation modified with the Japanese coefficient (0.881 × MDRD) determined for Japanese CKD patients yielded lower mean difference and higher accuracy for GFR estimation. In particular, in Cin 30–59 ml/min per 1.73 m2, the mean difference was significantly smaller with the 0.881 × MDRD equation than that with the 1.0 × MDRD study equation (1.9 vs 7.9 ml/min per 1.73 m2; P <?0.01), and the accuracy was significantly higher, with 60% vs 39% of the points deviating within 15%, and 97% vs 87% of points within 50%, respectively (both P <?0.01). Validation with the different data set showed the correlation between eGFR and Cin was better with the 0.881 × MDRD equation than with the 1.0 × MDRD study equation. In Cin less than 60 ml/min per 1.73 m2, the accuracy was significantly higher, with 85% vs 69% of the points deviating within 50% (P <?0.01), respectively. The mean difference was also significantly smaller (P <?0.01). However, GFR values calculated by the 0.881 × MDRD equation were still underestimated in the range of Cin over 60 ml/min per 1.73 m2.ConclusionsAlthough the Japanese coefficient improves the accuracy of GFR estimation of the original MDRD study equation, a new equation is needed for more accurate estimation of GFR in Japanese patients with CKD stages 3 and 4.

Th1/Th2 balance of peripheral T helper cells in systemic lupus erythematosus

OBJECTIVE To analyze the Th1/Th2 balance of peripheral Th cells in patients with systemic lupus erythematosus (SLE). METHODS The Th1:Th2 ratio was analyzed in 3 groups: SLE without proteinuria (group I; n = 23), SLE with proteinuria (group II; n = 31), and normal controls (group III; n = 24). Group II patients who had undergone renal biopsy were classified into 3 subgroups based on their renal histopathologic findings. The intracellular cytokine detection method with flow cytometry was used to quantitate Th1 and Th2 cells. RESULTS There was no difference in the mean Th1:Th2 ratio between SLE patients (groups I and II) and healthy controls (group III). However, the mean value in group II was significantly higher than those in groups I and III. Moreover, within group II, the mean value in SLE patients who had diffuse proliferative lupus nephritis (World Health Organization class IV) was especially high. CONCLUSION Although SLE has been considered to be a disease in which Th2 cells predominate, the Th1/Th2 balance of peripheral Th cells in SLE patients in the present study did not show a predominance of these cells. In contrast, among SLE patients with WHO class IV lupus nephritis, there was a strong predominance of Th1.

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.

Predominance of Th1 Immune Response in Diffuse Proliferative Lupus Nephritis

OBJECTIVE Lupus nephritis, which shows various histologic patterns, is a serious complication of systemic lupus erythematosus (SLE). We previously demonstrated the importance of Thl cell-mediated immune response in patients with diffuse proliferative lupus nephritis (DPLN). The aim of this study was to examine the relationship between the peripheral blood Th1/Th2 balance and the intrarenal immune response. METHODS The Th1:Th2 ratio in peripheral blood was measured by intracellular staining for cytokines with flow cytometry. Immunohistochemical analysis of renal biopsy specimens was performed to clarify the characterization of local infiltrating cells in 3 groups of subjects: SLE patients with World Health Organization (WHO) class IV nephritis (DPLN) (group I; n = 13), SLE patients with WHO class V nephritis (group II; n = 9), and patients with minor glomerular lesions (group III; n = 7). In addition, the histologic activity index and chronicity index were evaluated and correlated with the Th1:Th2 ratio. RESULTS Immunohistochemical studies showed higher numbers of CD68+ macrophages, CD3 + T cells, and interferon-gamma-positive cells in group I than in groups II or III. Renal tissues from patients in group I also showed up-regulation of expression of osteopontin and CD40, with a small number of infiltrating T cells expressing interleukin-4. Overall, the Thl:Th2 ratio in group I patients (SLE with DPLN) was high and correlated significantly with the histologic activity index, but not with the chronicity index. CONCLUSION We have identified a predominance of Thl-type response in both peripheral and renal tissues of patients with DPLN, suggesting that the peripheral blood Thl:Th2 ratio directly reflects the local histopathologic findings. In patients with lupus nephritis, the peripheral blood Th1:Th2 ratio could be useful as a parameter that reflects the renal histologic activity or the strength of the local Thl response.

2008 Japanese Society for Dialysis Therapy: guidelines for renal anemia in chronic kidney disease.

The Japanese Society for Dialysis Therapy (JSDT) guideline committee, chaired by Dr Y. Tsubakihara, presents the Japanese guidelines entitled “Guidelines for Renal Anemia in Chronic Kidney Disease.” These guidelines replace the “2004 JSDT Guidelines for Renal Anemia in Chronic Hemodialysis Patients,” and contain new, additional guidelines for peritoneal dialysis (PD), non‐dialysis (ND), and pediatric chronic kidney disease (CKD) patients.

Clinical practice guideline for the management of chronic kidney disease-mineral and bone disorder

Masafumi Fukagawa, Keitaro Yokoyama, Fumihiko Koiwa, Masatomo Taniguchi, Tetsuo Shoji, Junichiro James Kazama, Hirotaka Komaba, Ryoichi Ando, Takatoshi Kakuta, Hideki Fujii, Msasaaki Nakayama, Yugo Shibagaki, Seiji Fukumoto, Naohiko Fujii, Motoshi Hattori, Akira Ashida, Kunitoshi Iseki, Takashi Shigematsu, Yusuke Tsukamoto, Yoshiharu Tsubakihara, Tadashi Tomo, Hideki Hirakata, and Tadao Akizawa for CKD-MBD Guideline Working Group, Japanese Society for Dialysis Therapy

Association of Kidney Function With Coronary Atherosclerosis and Calcification in Autopsy Samples From Japanese Elders: The Hisayama Study

BACKGROUND Chronic kidney disease (CKD) is associated with increased risk of coronary heart disease. However, information regarding the histopathologic characteristics of coronary atherosclerosis in individuals with CKD is scarce. This study investigated the relationship between CKD and severity of coronary atherosclerosis in population-based autopsy samples. STUDY DESIGN Cross-sectional study. SETTING & PARTICIPANTS 126 individuals randomly selected from 844 consecutive population-based autopsy samples. PREDICTOR Estimated glomerular filtration rate (eGFR) calculated using the 6-variable Modification of Diet in Renal Disease (MDRD) Study equation. OUTCOMES Severity of atherosclerosis in 3 main coronary arteries, including atherosclerotic lesion types defined using the American Heart Association classification; stenosis rates; and coronary calcified lesions. MEASUREMENTS The relationship between CKD and severity of coronary atherosclerosis was evaluated using generalized estimating equation methods. RESULTS Frequencies of advanced atherosclerotic lesions increased gradually as eGFR decreased (33.6%, 41.7%, 52.3%, and 52.8% for eGFRs > or = 60, 45-59, 30-44, and <30 mL/min/1.73 m(2), respectively; P for trend = 0.006). This relationship was substantially unchanged even after adjustment for potential confounding factors (ORs, 1.40 [95% CI, 0.76-2.55], 2.02 [95% CI, 0.99-4.15], and 3.02 [95% CI, 1.22-7.49] for eGFRs of 45-59, 30-44, and <30 mL/min/1.73 m(2), respectively). Frequencies of calcified lesions of coronary arteries also increased gradually with lower eGFRs (P for trend = 0.02). Hypertension and diabetes were associated with increased risk of advanced coronary atherosclerosis and calcification of coronary arteries in individuals with decreased eGFR. LIMITATIONS Cross-sectional study, absence of data for proteinuria, and extremely high proportion of aged people. CONCLUSIONS The autopsy findings presented here suggest that CKD is associated significantly with severity of coronary atherosclerosis. Patients with CKD should be considered a high-risk population for advanced coronary atherosclerosis.

Increased renal resistive index in atherosclerosis and diabetic nephropathy assessed by Doppler sonography

Objective The renal resistive index (RI) and pulsatility index (PI), measured using Doppler ultrasonography, reflect intrarenal vascular resistance. We evaluated the relationship between these indices and pulse wave velocity (PWV), a measure of arterial stiffness, which reflects atherosclerosis, and determined whether renal RI and PI differ depending on the underlying renal disease. Methods A total of 245 inpatients with or without renal impairment who underwent ultrasonographic assessment of the renal artery were enrolled in the study. Patients with renal artery stenosis or severe renal failure (serum creatinine ≥ 6 mg/dl) were excluded from the study. Results In univariate analysis, the RI and PI of the main renal arteries and the interlobar arteries were significantly correlated with PWV. Multivariate analyses showed that PWV was independently associated with the RI of the main renal arteries (P < 0.01, R2 = 0.256). Patients with a creatinine level less than 3 mg/dl were divided into a control group without renal diseases and three groups with different underlying renal diseases: diabetic nephropathy, chronic glomerulonephritis, and nephrosclerosis. The RI and PI of the main renal arteries and the interlobar arteries were significantly higher in patients with diabetic nephropathy than in the other three groups, even after adjusting for multiple variables, including creatinine clearance. Conclusion These results suggest that the increased RI of the renal arteries is associated with the severity of systemic atherosclerosis. Furthermore, the intrarenal vascular resistance differs depending on the underlying renal disease, and appears to increase to a greater extent in diabetic nephropathy.

Membranous Glomerulonephritis Development with Th2-Type Immune Deviations in MRL/lpr Mice Deficient for IL-27 Receptor (WSX-1)

MRL/lpr mice develop spontaneous glomerulonephritis that is essentially identical with diffuse proliferative glomerulonephritis (World Health Organization class IV) in human lupus nephritis. Lupus nephritis is one of the most serious complications of systemic lupus erythematosus. Diffuse proliferative glomerulonephritis is associated with autoimmune responses dominated by Th1 cells producing high levels of IFN-γ. The initial mounting of Th1 responses depends on the function of the WSX-1 gene, which encodes a subunit of the IL-27R with homology to IL-12R. In mice deficient for the WSX-1 gene, proper Th1 differentiation was impaired and abnormal Th2 skewing was observed during infection with some intracellular pathogens. Disruption of the WSX-1 gene dramatically changed the pathophysiology of glomerulonephritis developing in MRL/lpr mice. WSX-1−/− MRL/lpr mice developed disease resembling human membranous glomerulonephritis (World Health Organization class V) with a predominance of IgG1 in glomerular deposits, accompanied by increased IgG1 and IgE in the sera. T cells in WSX-1−/− MRL/lpr mice displayed significantly reduced IFN-γ production along with elevated IL-4 expression. Loss of WSX-1 thus favors Th2-type autoimmune responses, suggesting that the Th1/Th2 balance may be a pivotal determinant of human lupus nephritis development.

2011 update Japanese Society for Dialysis Therapy Guidelines of Vascular Access Construction and Repair for Chronic Hemodialysis

Abstract:  The guideline committee of Japanese Society for Dialysis Therapy (JSDT), chaired by Dr Ohira, has published an original Japanese guideline, ‘Guidelines for Vascular Access Construction and Repair for Chronic Hemodialysis’. The guideline was created mainly because of the existence of numerous factors characteristic of Japanese hemodialysis therapy, which are described in this report, and because we recognized the necessity for standardization in vascular access‐related surgeries. This guideline consists of 10 chapters, each of which includes guidelines, explanations or comments and references. The first chapter discusses informed consent of vascular access (VA)‐related surgeries, which often resulted in trouble between dialysis staff and patients. The second chapter describes the fundamentals of VA construction and timing of the introduction of hemodialysis with emphasis on the avoidance of catheter indwelling if at all possible. In the third chapter, arteriovenous fistula (AVF) construction and management are discussed from the viewpoint of the most preferable type of VA. The fourth chapter deals with arteriovenous grafts (AVG) which has recently increased in clinical applications. The factors which improve the AVG patency rate are discussed and postoperative management methods are emphasized to avoid possible complications. The fifth chapter deals with short and long‐term vascular catheters. It is emphasized that these methods are definitely effective but, at the same time, are apt to be associated with several serious complications and might result in vascular damage. In the sixth chapter, superficialization of an artery is explained. This was originally for emergency use or backup but has been used permanently in 2–3% of Japanese hemodialysis patients. In the seventh chapter, methods for the use of VA are described and the buttonhole method is referred to as one of the options for patients who complain of intense pain at every cannulation. In the eighth chapter, the importance of continuous monitoring is stressed for maintaining appropriate function of VA. As a rule, the internal shunt type VA (AVF, AVG) places a burden on cardiac function. Thus, in the ninth chapter, it is stressed that VA construction, maintenance and repair should always be carried out with consideration of cardiac function which is not constant but variable. The 10th chapter forms one of the cores of this guideline and deals with repair and timing of VA. It is shown how to select a surgical or interventional repair method. In the final 11th chapter, VA types and resultant morbidity and mortality of hemodialysis patients are reviewed.