Toshiyuki Nakao

International Differences in Dialysis Mortality Reflect Background General Population Atherosclerotic Cardiovascular Mortality

Existing national, racial, and ethnic differences in dialysis patient mortality rates largely are unexplained. This study aimed to test the hypothesis that mortality rates related to atherosclerotic cardiovascular disease (ASCVD) in dialysis populations (DP) and in the background general populations (GP) are correlated. In a cross-sectional, multinational study, all-cause and ASCVD mortality rates were compared between GP and DP using the most recent data from the World Health Organization mortality database (67 countries; 1,571,852,000 population) and from national renal registries (26 countries; 623,900 population). Across GP of 67 countries (14,082,146 deaths), all-cause mortality rates (median 8.88 per 1000 population; range 1.93 to 15.40) were strongly related to ASCVD mortality rates (median 3.21; range 0.53 to 8.69), with Eastern European countries clustering in the upper and Southeast and East Asian countries in the lower rate ranges. Across DP (103,432 deaths), mortality rates from all causes (median 166.20; range 54.47 to 268.80) and from ASCVD (median 63.39 per 1000 population; range 21.52 to 162.40) were higher and strongly correlated. ASCVD mortality rates in DP and in the GP were significantly correlated; the relationship became even stronger after adjustment for age (R(2) = 0.56, P < 0.0001). A substantial portion of the variability in mortality rates that were observed across DP worldwide is attributable to the variability in background ASCVD mortality rates in the respective GP. Genetic and environmental factors may underlie these differences.

Preservation of residual renal function and factors affecting its decline in patients on peritoneal dialysis

SUMMARY:   The decline of residual renal function (RRF) in peritoneal dialysis (PD) patients was analysed and assessed, and risk factors affecting its decline were identified. Residual glomerular filtration rate (GFR) was calculated from averaging the urea and creatinine clearance by 24‐h urine collection, and peritoneal solute removal was evaluated by creatinine clearance calculated from 24‐h effluent collection. Both GFR and peritoneal solute removal were chronologically examined in 34 PD patients from the time of initiation, and risk factors associated with rapid GFR decline were investigated. The RRF contributed to 43.1 ± 17.6% of total (peritoneal and renal) weekly creatinine clearance at 1 month after initiation of PD. Residual GFR, however, declined continuously with time (−0.19 ± 0.14 mL/min per month), and the reduction rate was high with a higher GFR, higher normalized dietary protein intake, higher urine volume and higher urine protein excretion at the initiation of PD. Other factors related to the rapid decline of GFR were: being older than 60 years of age, automated peritoneal dialysis (APD) rather than continuous ambulatory peritoneal dialysis, mean blood pressure higher than 110 mmHg, and serum human atrial natriuretic peptide level higher being than 60 pg/dL. These data suggest that while RRF plays an important role in the removal of uraemic solute in PD patients, they show a significant decrease over 2 years. The factors related to the rapid decline of GFR corresponded to older age, modality of PD (APD), higher GFR and higher amount of urine protein at initiation, higher dietary protein intake, and inadequate control of hypertension and body fluid volume.

Histological predictors for renal prognosis in diabetic nephropathy in diabetes mellitus type 2 patients with overt proteinuria.

Aim:  Although several clinical risk factors for end‐stage renal disease in diabetic nephropathy are known, the pathological findings that may help predict renal prognosis have not yet been defined.

Best Practice for Diabetic Patients on Hemodialysis 2012

1. Predialysis casual plasma glucose and glycated albumin (GA) levels are recommended as indicators for glycemic control. 2. The hemoglobin A1c (HbA1c) level might be used only as reference, because HbA1c level decreases in the presence of anemia or erythropoiesis-stimulating agents (ESAs) and may not accurately represent glycemic control in hemodialysis patients. 3. Tentative targets for glycemic control: predialysis casual plasma glucose levels (or 2-h postprandial plasma glucose levels) <180– 200 mg/dL and GA levels <20.0% are recommended for hemodialysis patients. GA levels <24.0% are suggested for hemodialysis patients with a history of cardiovascular events and who have hypoglycemic episodes.Further studies are required to definitively determine target values. 4. In glycemic control, multiple indicators, including predialysis casual plasma glucose and GA levels, should be comprehensively evaluated to reduce the risk of hypoglycemia and improve the prognosis of patients.

CKD Clinical Practice Guidebook. The essence of treatment for CKD patients.

1. Chronic kidney disease (CKD) is defined either as a kidney disorder (proteinuria, etc.) or as decreased kidney function with GFR (glomerular filtration rate) less than 60 mL/min/1.73 m lasting for 3 months or longer. 2. Estimated GFR (eGFR) is calculated using the following formula: eGFR (mL/min/1.73 m) = 194 9 Cr 9 Age (additional multiplication by 0.739 for women). 3. CKD is a critical risk factor for the development of CVD (cardiovascular disease) as well as ESKD (endstage kidney disease). 4. A CKD patient should be managed by a multidisciplinary approach in collaboration between primary care physicians and nephrologists. 5. It is desirable that the following cases are referred to nephrologists: (1) proteinuria of 0.5 g/g creatinine or greater, or 2? or greater; (2) eGFR less than 50 mL/min/1.73 m; (3) positive (1? or greater) for both proteinuria and hematuria. 6. The treatment goal of proteinuria is less than 0.5 g/g creatinine. 7. CKD management should be started with modification of lifestyle (smoking cessation, salt restriction, improvement of obesity, etc.). 8. The goal of blood pressure control is less than 130/80 mmHg and is gradually achieved. 9. Antihypertensive agents of first choice are ACE inhibitors or ARBs. A combination with other antihypertensive agents is applied as needed. 10. In the use of ACE inhibitors or ARBs, a physician should be aware of the risk of an elevation of serum creatinine level and hyperkalemia in CKD patients. 11. In diabetic nephropathy, the target level of hemoglobin A1C should be less than 6.5% in controlling the blood glucose level. 12. LDL cholesterol should be controlled below 120 mg/dL. 13. A physician should consult nephrologists when renal anemia is suspected. 14. A physician should consult nephrologists when prescription of erythropoiesis-stimulating agents or oral adsorbent is contemplated. 15. A physician should reduce the dosage or extend the administration interval depending on kidney function when administering drugs that are eliminated by the kidney. 16. Non-steroidal anti-inflammatory drugs (NSAIDs), contrast media, and dehydration are risk factors for decline in kidney function.

Prevalence and clinical characteristics of restless legs syndrome in chronic kidney disease patients

OBJECTIVE To clarify the prevalence of restless legs syndrome (RLS) in the chronic kidney disease (CKD) population and determine the relationship between severity of renal dysfunction and risk of RLS as well as the impact of the disorder on mood and sleep disturbance, we conducted a questionnaire survey followed by face-to-face interviews with Japanese CKD patients. METHODS We sent a questionnaire battery including demographics items, the National Institutes of Health/International RLS Study Group (IRLSSG) consensus questionnaire, the Center for Epidemiological Studies Depression Scale, and the Pittsburgh Sleep Quality Index to eligible CKD patients (n=514) and age- and sex-matched controls (n=535). Structured interviews were performed for the diagnosis of RLS. RESULTS The prevalence of positive RLS in the CKD subjects was significantly higher than that in the controls (3.5% vs. 1.5%, p=0.029). The proportion of renal failure (RF) in CKD subjects with RLS was significantly higher than in those without RLS, and multiple logistic regression analysis revealed that the presence of RLS symptoms was associated only with the existence of RF. In addition, the presence of both RLS and CKD was significantly associated with the presence of depression and sleep disturbance. CONCLUSIONS The risk of RLS in the CKD population was higher than that in the general population and increased with the progression of renal dysfunction. Additionally, the existence of RLS might play a role in an increased risk for developing depression and sleep disturbance in the CKD population.

Membranous glomerulonephritis with nephrotic syndrome associated with chronic lymphocytic leukemia.

A 66-year-old woman was admitted to our hospital for evaluation of edema of the extremities. Laboratory findings suggested that she had nephrotic syndrome and chronic lymphocytic leukemia (CLL). Renal biopsy (with PAM staining) showed a spike formation in the capillary wall. Immunofluorescent staining revealed deposition of immunoglobulin G (IgG) and the third component of complement in the glomerular basement membrane. Electron microscopy showed fibrillary deposits in the subepithelium. These findings indicated membranous glomerulonephritis (MGN). In addition, focal segmental sclerosis and interstitial lymphocytic infiltration were observed in the renal biopsy specimen. In CLL patients nephrotic syndrome occurs rarely. Even if the complication occurs, MGN is not frequent. Both diseases are suspected to occur in association with each other, and immunologic abnormality contributes to their coexistence. Although administration of prednisolone and endoxan improved leukocytosis, proteinuria was not sufficiently improved with combination therapy.

Association of home blood pressure variability with progression of chronic kidney disease.

ObjectiveHome blood pressure (HBP) has been found to be a predictor of the progression of chronic kidney disease (CKD). The objective of this study is to clarify the clinical significance of day-by-day HBP variability on the progression of CKD. MethodsWe recruited 135 patients with stage 3–5 CKD, who performed daily HBP measurements, every morning and evening over 7 consecutive days and recorded every 6 months, with a follow-up of 36 months. We examined the associations between the variables of blood pressure (BP) variability [SD, coefficient of variation (CV), average real variability (ARV)], and renal outcomes. ResultsNo significant correlations were found between the SD values, the CV values, the ARV values of each BP measurement, and the change in estimated glomerular filtration rate on multivariate regression analysis (&bgr; of SD, CV, and ARV of morning systolic BP: 0.04, 0.04, and 0.02; P=0.69, 0.63, and 0.20, respectively). None of these variables of each BP measurement showed a significant risk of renal events on multivariate Cox proportional hazards analysis (hazard ratios of SD, CV, and ARV of morning systolic BP: 0.99 (95% confidence intervals: 0.80–1.23), 0.97 (0.72–1.31), and 1.01 (0.83–1.24); P=0.94, 0.86, and 0.92, respectively). ConclusionDay-by-day BP variability as assessed by HBP measurements had no significant association with the progression of CKD.

Body Protein Index Based on Bioelectrical Impedance Analysis Is a Useful New Marker Assessing Nutritional Status: Applications to Patients with Chronic Renal Failure on Maintenance Dialysis

BACKGROUND Evaluation and monitoring of nutritional status is a fundamental concept in providing nutritional care to patients with end-stage renal failure. There have been, however, few practically available indices assessing whole body protein stores of patients. METHODS We enrolled 448 end-stage renal disease patients, 394 on maintenance hemodialysis (HD) and 54 on continuous ambulatory peritoneal dialysis (PD) in this study. 83 Age- and sex-matched subjects (controls) whose creatinine clearance was more than 70 ml/min and urinary protein excretion was less than 1.0 g/day were also recruited for comparison. To assess whole body somatic protein stores, we devised the body protein index (BPI). The volume of body protein mass was measured by multifrequency bioelectrical impedance analysis and then BPI was calculated as body protein mass (kg) divided by height in meters (m2). Based on BPI, we defined the nutritional status of the patients as normal if the value was within -10% of the mean value of control subjects, -10 to -14% as mild malnutrition, -15 to -19% as moderate malnutrition, and <-20% as severe malnutrition. RESULTS The required time for measurement was 5.2 +/- 1.3 min and coefficient of variation of measurements was 0.8 +/- 0.2%. Among men the mean BPI in both HD and PD patients was significantly lower than those of control subjects (4.25 +/- 0.37, 4.38 +/- 0.34 vs. 4.72 +/- 0.37 kg/m2, p < 0.001). In women, BPI was significantly lower in HD patients than in control subjects (3.65 +/- 0.34 vs. 4.00 +/- 0.34 kg/m2, p < 0.033), whereas only a nonsignificant lower tendency was found in PD patients (3.83 +/- 0.39 kg/m2, p = 0.067). There were no significant differences in BPI values between diabetic and non-diabetic subjects, both in men (4.26 +/- 0.41 vs. 4.25 +/- 0.36 kg/m2) and women (3.69 +/- 0.36 vs. 3.65 +/- 0.34 kg/m2). Based on BPI nutritional categories, 113 (28.7%) of all HD patients were classified as having mild malnutrition, 57 (14.5%) as having moderate malnutrition, 40 (10.1%) as having severe malnutrition, and 184 (46.7%) were classified as normal. The patients of longer dialysis history groups showed a tendency of lower BPI compared to those of shorter dialysis history groups (p < 0.05), although the ages of the patients of the two groups did not significantly differ. No correlations were found between BPI and serum albumin or transferrin concentrations. Only weak correlations were found with albumin in male and transferrin in female HD patients. CONCLUSION BPI calculated from measurement of multifrequency bioelectrical impedance analysis could evaluate whole body somatic protein stores, and is a potentially useful new marker assessing nutritional status in patients with chronic renal failure. Decreased body somatic protein stores, mainly due to muscle wasting, was prevalent in end-stage renal failure patients on maintenance dialysis.

Carpal Tunnel Syndrome in Patients Undergoing CAPD: A Collaborative Study in 143 Centers

Patients undergoing continuous ambulatory peritoneal dialysis (CAPD) who developed carpal tunnel syndrome (CTS) were retrospectively studied in 143 centers in Japan. Among the total 5,050 patients undergoing CAPD between 1980 and 1993 only 7 patients (0.14%) given CAPD developed CTS. Five of these 7 patients treated solely with CAPD developed CTS 12-108 months after starting CAPD. The remaining 2 patients who were initially treated with HD for 7-9 years and then switched to CAPD developed this complication 9 years after starting CAPD. All 7 patients were women, ranging in age from 32 to 70 (average 52) years. We detected the presence of amyloid deposits in 2 of 5 specimens and beta 2-microglobulin in 2 of 4 specimens from these patients. It was concluded that CAPD minimizes the emergence of CTS although constant surveillance is necessary to detect CTS in patients during CAPD.