Shigeko Hara

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.

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.

Slower Decline of Glomerular Filtration Rate in the Japanese General Population: A Longitudinal 10-Year Follow-Up Study

The prevalence of stage 3 to 5 chronic kidney disease (CKD) in Japan (18.7%) is considerably higher than that in the United States (4.5%). This study investigated in the Japanese general population whether this higher prevalence of CKD might reflect to a progressive decline of renal function, and in turn to the increased risk of end-stage renal disease. A decline in renal function over 10 years was examined in 120,727 individuals aged 40 years or older who participated in the annual health examination program of the two periods over 10 years, 1988–1993 and 1998–2003. Renal function was assessed with estimated glomerular filtration rate (GFR) using the abbreviated Modification of Diet in Renal Disease (MDRD) Study equation modified by a Japanese coefficient. The rate of GFR decline in the participants was 0.36 mL/min/1.73 m2/year on average. In the male population aged 50–79, the mean rate of GFR decline was significantly higher in the presence of hypertension than in its absence. The rate of GFR decline was more than two times higher in participants with proteinuria than in those without proteinuria in both sexes. The rate was significantly higher in participants with an initial GFR <50 mL/min/1.73 m2 among the groups younger than age 70 and in participants with an initial GFR <40 mL/min/1.73 m2 in the group with age 70–79. Based on the slow rate of GFR decline, we concluded that the decline in renal function progresses slowly in the Japanese general population. Hypertension, proteinuria and lower GFR were found to be significant risk factors for a faster decline of GFR.

HbA1c 5·7–6·4% and impaired fasting plasma glucose for diagnosis of prediabetes and risk of progression to diabetes in Japan (TOPICS 3): a longitudinal cohort study

BACKGROUND The clinical relevance of the diagnostic criteria for prediabetes to prediction of progression to diabetes has been little studied. We aimed to compare the prevalence of prediabetes when assessed by the new glycated haemoglobin A(1c) (HbA(1c)) 5·7-6·4% criterion or by impaired fasting glucose, and assessed differences in progression rate to diabetes between these two criteria for prediabetes in a Japanese population. METHODS Our longitudinal cohort study included 4670 men and 1571 women aged 24-82 years without diabetes at baseline (diabetes was defined as fasting plasma glucose ≥7·0 mmol/L, self-reported clinician-diagnosed diabetes, or HbA(1c) ≥6·5%) who attended Toranomon Hospital (Tokyo, Japan) for a routine health check between 1997 and 2003. Participants with a baseline diagnosis of prediabetes according to impaired fasting glucose (fasting plasma glucose 5·6-6·9 mmol/L) or HbA(1c) 5·7-6·4%, or both, were divided into four groups on the basis of baseline diagnosis of prediabetes. Rate of progression to diabetes was assessed annually. FINDINGS Mean follow-up was 4·7 (SD 0·7) years. 412 (7%) of 6241 participants were diagnosed with prediabetes on the basis of the HbA(1c) 5·7-6·4% criterion. Screening by HbA(1c) alone missed 1270 (61%) of the 2092 prediabetic individuals diagnosed by a combination of impaired fasting glucose and HbA(1c) 5·7-6·4%. Overall cumulative probability of progression to diabetes did not differ significantly between participants with prediabetes discordantly diagnosed by either HbA(1c) or impaired fasting glucose alone (incidence was 7% for HbA(1c) alone [n=412 individuals and 30 incident cases] and 9% for impaired fasting glucose alone [n=1270, 108 cases]; log-rank test, p=0·3317). Multivariate-adjusted hazard ratios for incident diabetes were 6·16 (95% CI 4·33-8·77) for those diagnosed with prediabetes by impaired fasting glucose alone and 6·00 (3·76-9·56) for diagnosis by HbA(1c) alone, and were substantially increased to 31·9 (22·6-45·0) for diagnosis by both impaired fasting glucose and HbA(1c) compared with normoglycaemic individuals. INTERPRETATION Diagnosis of prediabetes by both the new HbA(1c) criterion and impaired fasting glucose identified individuals with an increased risk of progression to diabetes. Although the new HbA(1c) criterion identified fewer individuals at high risk than did impaired fasting glucose, the predictive value for progression to diabetes assessed by HbA(1c) 5·7-6·4% was similar to that assessed by impaired fasting glucose alone. The two tests used together could efficiently target people who are most likely to develop diabetes and allow for early intervention. FUNDING Japan Society for the Promotion of Science; Ministry of Health Labor and Welfare, Japan.

Effect of Orally Administered Shao-Yao-Gan-Cao-Tang (Shakuyaku-kanzo-to) on Muscle Cramps in Maintenance Hemodialysis Patients: A Preliminary Study

Muscle cramps are one of the most common complications of hemodialysis (HD), and often are a source of great pain in spite of various clinical measures. The traditional herbal medicine, shao-yao-gan-cao-tang (Japanese name: Shakuyaku-kanzo-to), consists of equal amounts of paeony and licorice roots, and has been used in Japan and China for muscle pain or skeletal muscle tremors. To determine whether this medicine is able to prevent frequent and unendurable muscle cramps in patients undergoing HD, Shakuyaku-kanzo-to at 6 g per day was prospectively administered for 4 weeks to five patients on HD who were suffering from frequent muscle cramps. The frequency and severity of cramping before and after the treatment treatment were carefully observed and compared. Skeletal muscle cramps completely disappeared in two of the treated patients after the start of oral administration of Shakuyaku-kanzo-to. Moreover, the frequency of cramping was significantly decreased in two of the remaining three patients after persistent administration. The severity of muscle cramps was also decreased by this treatment in the responsive patients. No serious side effects were detected during the treatment period. The inhibitory effect of Shakuyaku-kanzo-to on muscle contraction was also experimentally examined by using phrenic nerve-diaphragm preparations from male Wistar rats. Differences between the twitch responses were determined when the diaphragms and the nerves were stimulated in the presence and absence of the extract of Shakuyaku-kanzo-to. The results demonstrated that extracts of paeony and licorice roots inhibit contraction of skeletal muscles in rats. Taken together, we suggest that administration of Shakuyaku-kanzo-to is a safe, effective treatment for preventing muscle cramps in patients undergoing HD.

Metabolically Healthy Obesity, Presence or Absence of Fatty Liver, and Risk of Type 2 Diabetes in Japanese Individuals: Toranomon Hospital Health Management Center Study 20 (TOPICS 20)

OBJECTIVE We investigated whether the metabolically healthy obese (MHO) phenotype was associated with an increased risk of the development of diabetes. If so, we aimed to determine what factors could explain this finding. DESIGN, SETTING, AND PARTICIPANTS Studied were 8090 Japanese individuals without diabetes. Metabolic health status was assessed by common clinical markers: blood pressure, triglycerides, high-density lipoprotein-cholesterol, and fasting glucose concentrations. The cutoff value for obesity or normal weight (NW) was a body mass index of 25.0 kg/m(2). RESULTS The 5-year incidence rate of diabetes was 1.2% (n = 58 of 4749) in metabolically healthy NW (MHNW) individuals, 2.8% (n = 20 of 719) in MHO individuals, 6.0% (n = 102 of 1709) in metabolically abnormal NW individuals, and 10.3% (n = 94 of 913) in metabolically abnormal obese individuals. Although MHO individuals had no or one metabolic factor, 47.8% had ultrasonographic fatty liver (FL). The MHO group had a significantly increased risk of diabetes compared with the MHNW group [multivariate adjusted odds ratio (OR) 2.23 (95% confidence interval [CI] 1.33, 3.75)], but this risk was attenuated after adjustment for FL. Compared with the MHNW/non-FL group, the risk of diabetes in the MHO/non-FL group was not significantly elevated [OR 1.01 (95% CI 0.35, 2.88)]. However, the MHO/FL and MHNW/FL groups had similarly elevated risks of diabetes [OR 4.09 (95% CI 2.20, 7.60) and 3.16 (1.78, 5.62), respectively]. CONCLUSIONS Almost half of the MHO participants had FL, which partially explained the increased risk of diabetes among the obese phenotypes. The presence of FL should be evaluated to assess whether an individual was actually in a metabolically benign state for the prediction of diabetes.

High serum uric acid level and low urine pH as predictors of metabolic syndrome: a retrospective cohort study in a Japanese urban population

The objective of this study was to evaluate whether hyperuricemia, acidic urine, or their combination predicts metabolic syndrome (MetS). In study 1, 69,094 subjects who received a general health checkup between 1985 and 2005 were included in a cross-sectional study of serum uric acid (SUA) and urine pH in relation to MetS. In study 2, the association of SUA and urine pH with MetS development over a 5-year period was evaluated in 5617 subjects with body mass index less than 25 kg/m(2) at the first examination. In study 1, higher SUA and lower urine pH were both positively correlated to MetS status (P < .001). The combination of high SUA and low urine pH was significantly associated with higher MetS prevalence compared with the combination of low SUA and high urine pH (odds ratio, 3.383; 95% confidence interval [CI], 3.034-3.784 in men; odds ratio, 4.000; 95% CI, 2.992-5.452 in women). In study 2, the top quartile of SUA levels was associated with higher MetS development compared with the bottom quartile during the 5-year period in men (hazard ratio [HR], 1.793; 95% CI, 1.084-2.966; P = .023). In women, the HR was 3.732 (95% CI, 0.391-35.62; P = .252) for the upper vs the lower half of SUA levels. For urine pH, the HR was 1.955 (95% CI, 1.089-3.509; P = .025) for the bottom vs the top quartile in men. A likelihood ratio test confirmed that high SUA and low urine pH act synergistically in the development of MetS. High SUA, low urine pH, and their combination are predictive risk factors for MetS development.

B-cell lymphoma of mucosa-associated lymphoid tissue of the thymus: A report of two cases with a background of sjogren's syndrome and monoclonal gammopathy☆

Two rare cases of low-grade B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) arising in the thymus are reported. Both patients (a 61-year-old man and a 75-year-old woman) were suffering from Sjögrens syndrome and immunoglobulin (Ig)A kappa monoclonal gammopathy. Mixed IgA-IgG cryoglobulinemia was also present in the male case. Tumor cells expressed IgA and kappa antibody reactive proteins identical with serum IgA kappa M. Moreover, we could demonstrate rearrangements of the immunoglobulin heavy and light chain genes, which supported the monoclonal origin of tumor cells. Immunological abnormalities improved after thymectomy in one case in which the tumor cells were confined to the thymus, but not the other with regional lymph node involvement, suggesting a causal role for the tumor. MALT lymphomas of the thymus thus appear to be associated with immunological disorders such as Sjögrens syndrome or monoclonal gammopathy.

Experimental IgA Nephropathy Induced by a Low-Dose Environmental Mycotoxin, Nivalenol

Based on the hypothesis that IgA nephropathy (IgAN) is triggered by some exogenous antigen(s) which induces dysregulation of the mucosal immune system, we developed an experimental model of orally induced IgAN by an environmental mycotoxin, nivalenol (NIV), which often contaminates agricultural products in Southeast Asia and Japan. In the present study, low doses of oral NIV reproducibly induced significant IgA deposits in the glomerular mesangium and elevated serum IgA levels in mice irrespective of the strain; the degree of immunopathological changes analogous to human IgAN was associated with the dose and duration of NIV treatment. Furthermore, a competitive enzyme-linked immunosorbent assay with an NIV analogue-protein conjugate disclosed that the IgA antibody in the sera from the NIV model mice had a higher affinity to the mycotoxin. Conclusively, these findings suggest that NIV induces some pathological changes in mice which resemble those in human IgAN, and that this mycotoxin is associated with pathogenesis in some types of glomerulonephritis.

Transcatheter renal arterial embolization therapy on a patient with polycystic kidney disease on hemodialysis

We report a patient with autosomal dominant polycystic kidney disease (ADPKD) undergoing long-term hemodialysis who underwent transcatheter arterial embolization (TAE) of the renal arteries to shrink enlarged kidneys. In 1983, the patient started hemodialysis because of chronic renal failure secondary to ADPKD. However, renal size continued to increase. In January 1997, he was admitted to our hospital with abdominal distension and anorexia, in addition to progression of anemia. Upper gastroendoscopy showed an esophageal ulcer and severe external compression of the stomach. Renal angiography using the Seldinger technique showed stretched and deformed segmental renal arteries with massive enlargement of the kidneys. TAE with stainless steel coils was performed on both renal arteries. With a rapid and progressive decrease in kidney size, anorexia and anemia were improved, and the gastrointestinal compression was eliminated. In some patients with ADPKD, renal size continues to increase even after the initiation of dialysis. In about 10 years, patients develop gastrointestinal complications, such as dysphagia, ileus, severe constipation, and intestinal perforation. Surgical procedures such as nephrectomy are not satisfactory. This report shows that TAE is a safe and effective therapy for patients with ADPKD with massively enlarged kidneys.