Diagnosis and prevalence of protein-energy wasting and its association with mortality in Japanese haemodialysis patients.

AIM: The International Society of Renal Nutrition and Metabolism (ISRNM) has proposed the diagnostic criteria for protein-energy wasting (PEW). We studied Japanese haemodialysis (HD) patients to verify the diagnostic method, especially with respect to the body mass index (BMI) criterion, as well as the prevalence of PEW and its association with mortality. METHODS: Japanese patients receiving maintenance HD at three outpatient clinics in Tokyo (n = 210) were enrolled, and prospectively followed-up for 3 years. PEW was diagnosed at baseline, according to the four categories (serum chemistry, body mass, muscle mass and dietary intake) recommended by the ISRNM. For the category of body mass, we select a body mass index (BMI) and set up three thresholds, <18.5, <20.0 and <23.0 kg/m2 , as the diagnostic criterion. The patients who satisfied at least three out of the four categories were diagnosed as PEW. RESULTS: Protein-energy wasting, when the threshold of a BMI among the diagnostic criteria was defined as <18.5 kg/m2 , was recognized as an independent risk factor for mortality. However, PEW was not recognized as a risk factor when the BMI diagnostic criterion was set at <20.0 or <23.0 kg/m2 . Overall, 14.8% of the patients had PEW. The survival rate of PEW patients was significantly lower than that of non-PEW patients (log rank, P < 0.001). CONCLUSIONS: The diagnosis algorithm of PEW proposed by an expert panel of the ISRNM strongly associates with mortality. However, given differences in body size in Japan, we suggest to revise the BMI criterion from <23.0 kg/m2 to <18.5 kg/m2 .

Relationship between dietary protein intake and the changes in creatinine clearance and glomerular cross-sectional area in patients with IgA nephropathy.

BACKGROUND: Dietary protein intake (PI) induces glomerular hyperfiltration and reduced dietary PI can be effective in preserving kidney function. However, there is limited information regarding the relationship between dietary PI and glomerular histological changes in chronic kidney disease. We investigated the relationship between changes in dietary PI and both the changes in creatinine clearance and glomerular histomorphometry in adult patients with IgA nephropathy (IgAN). METHODS: A total of 24 consecutive adult patients with biopsy-confirmed IgAN were enrolled and glomerular histomorphometric variables and clinical variables were investigated. The main clinical variables were differences in creatinine clearance (Ccr) (dCcr) and in PI (dPI) which were calculated by subtracting PI and Ccr values in patients on a controlled diet during hospitalization for kidney biopsy from the respective values in patients on daily diets as outpatients. These values of PI were estimated from urinary urea excretion measured by 24-h urine collection. The main renal histomorphometric variable was glomerular tuft area (GTA) (µm(2)). RESULTS: dCcr positively correlated with dPI (r = 0.726, P < 0.001). GTA correlated positively with dPI (r = 0.556, P = 0.013). Multiple regression analysis showed that dPI was independently associated with both dCcr and GTA. Additionally, GTA positively correlated with dietary PI as outpatients (r = 0.457, P = 0.043). CONCLUSION: Changes in dietary PI were associated with the changes in glomerular filtration rate. Furthermore, histomorphometric findings suggested that a greater dietary PI can affect the glomerular size at the time of the initial diagnostic biopsy for IgAN.

Association between visit-to-visit clinic blood pressure variability and home blood pressure variability in patients with chronic kidney disease.

Although both clinic blood pressure (BP) variability and home BP variability are associated with the risk of cardiovascular disease, the relationship between both BP variabilities remain unclear. We evaluated the association between visit-to-visit variability of clinic BP (VVV) and day-by-day home BP variability (HBPV) in patients with chronic kidney disease (CKD). We recruited 143 CKD patients in whom we performed HBP measurements every morning and evening over seven consecutive days. We obtained clinic BP data during 9.6 ± 1.0 consecutive visits within 24 months. The associations between the variables of VVV and HPBV were examined. The CV values of clinic systolic BP (CSBP) was significantly correlated with the mean values of morning systolic BP (MSBP) and those of evening systolic BP (ESBP) (r = 0.23, 0.20; p = 0.007, 0.02, respectively). The CV values of CSBP was significantly correlated with the CV values of MSBP and those of ESBP (r = 0.19, 0.31; p = 0.02, <0.001, respectively). On the multivariate regression analysis, the CV values of CSBP was significantly correlated with the CV values of MSBP and those of ESBP [standardized regression coefficient (ß) = 0.19, 0.34; p = 0.03, <0.001, respectively]. In conclusion, VVV showed a weak but significant association with HBPV, especially the CV values of ESBP in CKD patients. Further studies are necessary to clarify whether these different BPV elements will be alternative marker of BPV.

Glycated hemoglobin and risk of death in diabetic patients treated with hemodialysis: a meta-analysis.

BACKGROUND: Studies investigating the association between glycated hemoglobin (HbA1c) level and mortality risk in diabetic patients receiving hemodialysis have shown conflicting results. STUDY DESIGN: We conducted a systematic review and meta-analysis using MEDLINE, EMBASE, Web of Science, and the Cochrane Library. SETTING & POPULATION: Diabetic patients on maintenance hemodialysis therapy. SELECTION CRITERIA FOR STUDIES: Observational studies or randomized controlled trials investigating the association between HbA1c values and mortality risk. Study authors were asked to provide anonymized individual patient data or reanalyze results according to a standard template. PREDICTOR: Single measurement or mean HbA1c values. Mean HbA1c values were calculated using all individual-patient HbA1c values during the follow-up period of contributing studies. OUTCOME: HR for mortality risk. RESULTS: 10 studies (83,684 participants) were included: 9 observational studies and one secondary analysis of a randomized trial. After adjustment for confounders, patients with baseline HbA1c levels ≥ 8.5% (≥ 69 mmol/mol) had increased mortality (7 studies; HR, 1.14; 95% CI, 1.09-1.19) compared with patients with HbA1c levels of 6.5%-7.4% (48-57mmol/mol). Likewise, patients with a mean HbA1c value ≥ 8.5% also had a higher adjusted risk of mortality (6 studies; HR,1.29; 95% CI, 1.23-1.35). There was a small but nonsignificant increase in mortality associated with mean HbA1c levels ≤ 5.4% (≤ 36 mmol/mol; 6 studies; HR, 1.09; 95% CI, 0.89-1.34). Sensitivity analyses in incident (≤ 90 days of hemodialysis) and prevalent patients (>90 days of hemodialysis) showed a similar pattern. In incident patients, mean HbA1c levels ≤ 5.4% also were associated with increased mortality risk (4 studies; HR, 1.29; 95% CI, 1.23-1.35). LIMITATIONS: Observational study data and inability to adjust for diabetes type in all studies. CONCLUSIONS: Despite concerns about the utility of HbA1c measurement in hemodialysis patients, high levels (≥ 8.5%) are associated with increased mortality risk. Very low HbA1c levels (≤ 5.4%) also may be associated with increased mortality risk.

Phosphate handling by end-stage kidneys and benefits of residual renal function on phosphate removal in patients on haemodialysis.

AIM: We investigated the handling of phosphate by end-stage kidneys and the contribution of residual renal function (RRF) to phosphate homeostasis in haemodialysis patients. METHODS: Blood and 24 h urinary specimens were obtained from 79 consecutive chronic haemodialysis patients with a urinary output greater than 100 mL/day. Thirty-five patients with a glomerular filtration rate (GFR) ≥ 3.0 mL/min were included as group A, and 44 patients with GFR < 3.0 mL/min as group B. Additionally, the whole dialysed fluids during a session of haemodialysis were collected from another nine patients. Concentrations of phosphate, creatinine, urea nitrogen, intact parathyroid hormone (iPTH) and fibroblast growth factor 23 (FGF-23) were measured. RESULTS: Twenty-four hour urinary phosphate excretion (UPE) was 283 ± 115 and 139 ± 57 mg/day (9.1 ± 3.5 and 4.5 ± 1.8 mmol/day) in groups A and B, respectively. Tubular reabsorption of phosphate (TRP) was 39.2 ± 13.3 and 31.7 ± 13.6% in groups A and B, respectively (P = 0.02). UPE significantly correlated with GFR (r = 0.85, P < 0.001) and PTH (r = 0.44, P < 0.001), but not with FGF-23, in the entire patient population. The correlation between UPE and intact PTH levels was absent in group B. Weekly UPE in group A was significantly greater (P < 0.001), while that in group B was similar to the amount of phosphate removed by a haemodialysis session. CONCLUSIONS: Urinary phosphate excretion by end-stage kidneys depends more on GFR than diminishing TRP. The action of PTH on the kidneys remains until GFR decreases to as low as 3 mL/min. Residual renal function plays a significant role in phosphate elimination, and it is possible that FGF-23 no longer acts effectively to excrete phosphate in the urine in these patients.

Clinical significance of microscopic haematuria in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

AIM: Although some patients with diabetic nephropathy with overt proteinuria have microscopic haematuria, the pathological characteristics and clinical significance related to microscopic haematuria have not yet been clarified. The aim of the present study was to clarify the pathological characteristics and clinical significance of microscopic haematuria. METHODS: Eighty-four type 2 diabetes patients with overt proteinuria and biopsy-confirmed diabetic nephropathy were enrolled. The clinical and histological findings were compated between the patients with persistent haematuria (group 1, n=25) and those with persistent non-haematuria (group 2, n=23) after renal biopsy. The association between persistent haematuria and renal outcome at 5 years was examined. Histological scoring was made according to the original system and that of Tervaert et al. RESULTS: Thirty-six patients (43%) had microscopic haematuria at the time of renal biopsy. Age was significantly smaller and blood pressure was significantly greater in group 1 than in group 2 (age: group 1, 56 ± 10 years; group 2, 62 ± 9 years; P=0.03, systolic blood pressure: group 1, 152 ± 16 mm Hg; group 2, 140 ± 16 mm Hg; P=0.01). There were no significant differences in histological parameters between the two groups. A logistic regression model demonstrated that arteriolar hyalinosis was significantly associated with persistent haematuria (OR=2.81; P=0.04). There were no significant differences in changes in reciprocal serum creatinine and rates of doubling of serum creatinine after renal biopsy between the two groups. CONCLUSION: Although arteriolar hyalinosis was associated with persistent haematuria, the clinical significance of microscopic haematuria was minor in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

[Validity of the assessment of urinary protein excretion by spot urine in patients with chronic kidney disease].

AIM: We investigate the validity of the assessment of urinary protein excretion by spot urine samples collected by different methods in outpatients with chronic kidney disease (CKD). SUBJECTS AND METHODS We obtained 24-hour urine and two spot urine samples, including the first morning urine and daytime urine in 159 CKD patients. Urinary protein excretion was assessed by the protein/creatinine ratio from spot urine samples (morning: m-UP (g/gCr), daytime: d-UP (g/gCr) ]. We examined the correlations and the differences among m-UP, d-UP and the actual urinary protein excretion obtained by 24-hour urine (a-UP(g/day) . RESULTS: Significant correlations were found between m-UP and a-UP, and between d-UP and a-UP (r = 0.88, 0.85; p < 0.001). Correlations between m-UP and a-UP were greater relative to those between d-UP and a-UP in patients with less than 3.5 g/day of a-UP and in patients with CKD stages 1 to approximately 3. The percent difference between m-UP and a-UP was--16.0 +/- 40.5%, and that between d-UP and a-UP was 27.1 +/- 72.9%. The absolute value of the percent difference between d-UP and a-UP tended to be greater than that between m-UP and a-UP (34.9 +/- 25.9% vs. 49.9 +/- 59.9%, p = 0.06). CONCLUSION: Urinary protein/creatinie ratio of the first morning urine is better approximate the urinary protein excretion obtained by 24-hour urine compared with that of spot urine in the daytime.

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. METHODS: We enrolled 69 diabetes mellitus type 2 patients with overt proteinuria and biopsy-confirmed diabetic nephropathy with mesangial expansion, and retrospectively examined the association of histological and clinical findings with renal outcome. The median follow-up duration was 52 months. Histological scoring was made according to that of Tervaert et al. Patients were divided into four groups according to glomerular classification (class 2a, mild mesangial expansion, n=11; class 2b, severe mesangial expansion without nodular sclerosis, n=15; class 3, nodular sclerosis, n=36; class 4, global glomerulosclerosis observed in more than 50% of glomeruli, n=7). Interstitial and vascular lesions were scored for each patient. A renal event was defined as a condition requiring the initiation of chronic dialysis or doubling of the serum creatinine level. RESULTS: Cox proportional hazard analysis showed that the glomerular classes were not significant variables, while interstitial fibrosis, tubular atrophy and interstitial inflammation were independent variables associated with renal end-point (HR: 3.36 (95% confidence interval: 1.21-9.32), 4.74 (1.26-17.91)). There were no significant differences in the renal survival rates between the glomerular classes 2a and 2b combined group and the glomerular class 3 group (P=0.17, log-rank test). CONCLUSION: Interstitial lesions but not glomerular lesions were a significant predictor for renal prognosis in diabetic nephropathy in type 2 diabetes patients with overt proteinuria.

Clinical evaluation of chronic nephrotoxicity of long-term cyclosporine A treatment in adult patients with steroid-dependent nephrotic syndrome.

AIM: Chronic nephrotoxicity of long-term cyclosporine A (CsA) treatment is a matter of concern in patients with steroid-dependent nephrotic syndrome (SDNS). METHODS: Twenty-eight adult NS patients (25, minimal-change nephrotic syndrome (NS); three, focal-segmental glomerulosclerosis) were divided into three groups. Group A was continuously treated with CsA for more than 5 years (143 ± 40 months, 1.3 ± 0.4 mg/kg per day at final analysis, n = 12); group B had been previously treated with CsA (70 ± 27 months, n = 6); and group C had been treated with corticosteroids alone (n = 10). The clinical variables related to chronic CsA nephrotoxicity were examined. RESULTS: In groups A and B, estimated glomerular filtration rate decreased from 86 ± 22 and 107 ± 17 to 83 ± 23 and 88 ± 13 mL/min per 1.73 m(2) , respectively, at final analysis (both P < 0.05). Serum magnesium levels in group A were significantly lower than those in group B or C (A, 1.78 ± 0.16 mg/dL; B, 2.00 ± 0.14 mg/dL; C, 2.03 ± 0.10 mg/dL; A vs B, C, P < 0.01), and a significant correlation between these and the duration of CsA treatment was found (r = -0.68, P < 0.001). There was a trend towards a correlation between the duration of CsA administration and urinary α1-microglobulin (r = 0.38, P = 0.07). CONCLUSION: Mild decrease in renal function and hypomagnesemia were found in adult SDNS patients with long-term CsA treatment. Careful monitoring of renal function, blood pressure and serum magnesium levels is necessary.

Benefits of first-half intensive haemodiafiltration for the removal of uraemic solutes.

AIM: Haemodiafiltration (HDF) is the most efficient blood purification method and can remove a wide spectrum of solutes of different molecular weights (MW). The purpose of this study was to investigate whether the removed amounts of solutes, especially the larger molecules, could be increased by changing the HDF filtration procedure. METHODS: A new first-half intensive HDF treatment (F-HDF) was designed, whereby convective clearance is intensively forced during the first half of a HDF session. We compared the removed amounts of solutes in the same group of nine patients treated by F-HDF, constant rate-replacing HDF (C-HDF) and a high-flux haemodialysis (HD). RESULTS: F-HDF can remove significantly larger amounts of α(1) -microglobulin (MG), molecular weight (MW) 33,000, compared with HD and C-HDF (30.1 ± 15.1 vs 12.4 ± 0.3, 15.0 ± 3.1 mg, P < 0.01). Regarding the removal amounts and clear space of ß(2) MG, MW 11,800, there were no significant differences between the three treatment modalities. Regarding amounts of creatinine, urea nitrogen and phosphorus, there were no significant differences between the three treatment modalities. CONCLUSION: In post-replacement HDF with a high-flux membrane dialyzer, the method used in the present study in which replacement is completed during the first half of the process, is associated with a greater rate of larger molecule removal than the conventional uniform replacement method.

Benefits of staple food restriction for Japanese obese patients with chronic kidney disease: a pilot study.

OBJECTIVE: We conducted a pilot study to assess the effects of dietary intervention on metabolic risk factors and renal parameters in obese patients with chronic kidney disease (CKD). METHODS: We studied 19 obese patients with CKD at our outpatient clinic. The diet selected for this study restricted only their staple food intake, with no change in the side dish component of their meals. We studied neither the lifestyles of the patients nor the activities that they were involved in. We examined changes in clinical and laboratory parameters at baseline and after consumption of the diet. RESULTS: After 2 and 6 months of staple food restriction, changes in body weight were found to be -3.6% ± 3.9% and -3.4% ± 4.7%, respectively. Of the 19 patients, the body weights of 9 decreased by >3% (range: 3.4% to 17.1%) from baseline to follow-up at 6 months. After 6 months of following the diet, these 9 patients showed marked reductions in blood pressure, homeostasis model assessment insulin resistance, and triglycerides, when compared with the remaining 10 patients with stable body weights; however, for proteinuria and estimated glomerular filtration rate they reported having values similar to the 10 patients with stable body weights. CONCLUSIONS: Weight reduction associated with a lowered insulin resistance was reported in obese patients with CKD after 6 months of staple food restriction; however, further studies need to be conducted to confirm the presence of other possible renal benefits.

Structural changes in renal arterioles are closely associated with central hemodynamic parameters in patients with renal disease.

Although central hemodynamics are known to be closely associated with microvascular damage, their association with lesions in the small renal arteries has not yet been fully clarified. We focused on arterioles in renal biopsy specimens and analyzed whether their structural changes were associated with noninvasive vascular function parameters, including central blood pressure (BP) and brachial-ankle pulse wave velocity (baPWV). Forty-four nondiabetic patients (18-50 years of age) with preserved renal function underwent renal biopsy. Wall thickening of arterioles was analyzed based on the media/diameter ratio, and hyalinosis was analyzed by semiquantitative grading. Associations of these indexes (arteriolar wall remodeling grade index (RG index) and arteriolar hyalinosis index (Hyl index)) with clinical variables were analyzed. Multiple regression analyses demonstrated that the RG index was significantly associated with central systolic BP (ß = 0.97, p = 0.009), serum cystatin C-based estimated glomerular filtration rate (ß = -0.36, p = 0.04), and high-density lipoprotein cholesterol levels (ß = -0.37, p = 0.02). The Hyl index was significantly associated with baPWV (ß = 0.75, p = 0.01). Our results indicate that aortic stiffness and abnormal central hemodynamics are closely associated with renal microvascular damage in young to middle-aged, nondiabetic kidney disease patients with preserved renal function.

Method for the quantitative evaluation of ecosystem services in coastal regions.

Wetlands, tidal flats, seaweed beds, and coral reefs are valuable not only as habitats for many species, but also as places where people interact with the sea. Unfortunately, these areas have declined in recent years, so environmental improvement projects to conserve and restore them are being carried out across the world. In this study, we propose a method for quantifying ecosystem services, that is, useful for the proper maintenance and management of artificial tidal flats, a type of environmental improvement project. With this method, a conceptual model of the relationship between each service and related environmental factors in natural and social systems was created, and the relationships between services and environmental factors were clarified. The state of the environmental factors affecting each service was quantified, and the state of those factors was reflected in the evaluation value of the service. As a result, the method can identify which environmental factors need to be improved and if the goal is to increase the value of the targeted tidal flat. The method demonstrates an effective approach in environmental conservation for the restoration and preservation of coastal areas.

Value of morning home blood pressure as a predictor of decline in renal function in patients with chronic kidney disease.

BACKGROUND: Although blood pressure (BP) control is significantly associated with progression of chronic kidney disease (CKD), the influence of BP control based on home BP (HBP) measurement on the change in renal function in CKD patients is not fully defined. METHODS: We recruited 137 patients with stage 3-5 CKD, who performed daily HBP measurements continuously. HBP was measured every morning and evening and data were obtained every 6 months in each patient with a follow-up of 32 +/- 5 months. The associations between BP data, other clinical variables and the change in estimated glomerular filtration rate (eGFR) were examined. RESULTS: Mean morning BP, evening BP and clinic BP were 132.9/76.2, 128.5/72.5 and 129.4/69.1 mm Hg, respectively. There were significant correlations between mean morning systolic BP (SBP), mean evening SBP, mean clinic SBP and the change in eGFR (r = -0.318, -0.215, -0.174, p < 0.0001, <0.05, <0.05). Stepwise multivariate regression analysis demonstrated mean morning SBP and mean urinary protein excretion as independent predictors of the change in eGFR. CONCLUSION: Morning SBP is a more significant predictor of decline in renal function than evening SBP or clinic SBP.

[Day-by-day variability of home blood pressure in patients with chronic kidney disease].

PURPOSE: We examined the characteristics of the day-by-day variability of home blood pressure (HBP) in patients with chronic kidney disease (CKD). METHODS: We obtained HBP recordings from 368 CKD patients (63+/-13 years, eGFR 34+/-23 mL/min/1.73 m2, males 253). The day-by-day variability of HBP was defined as the coefficient of variation (CV) values of BP measurements every morning after waking and every evening before sleeping on 7 consecutive days. In a portion of the patients, the CV values of HBP were collected every 6 months during a 2-year period and the association with a decline in GFR was examined. RESULTS: CV values of morning/evening systolic BP (SBP) were 5.4+/-2.4%, 6.1+/-2.9 % (p<0.01). The CV values of morning SBP in females or patients with diabetic nephropathy (DN) were significantly greater than those in males or patients without DN, respectively (females 5.9+/-2.3%, males 5.2+/-2.4%, p< 0.01, DN 6.1+/-2.8 %, non DN 5.2+/-2.2 %, p<0.05). Multivariate linear regression analysis showed that female gender, DN, the number of antihypertensive drugs, higher heart rate and higher CV values of heart rate were associated with higher CV values of the morning SBP. CV values of the morning SBP showed no significant change during the 2-year period (0; 5.4+/-2.6%, 1 year; 5.3+/-2.9%, 2 years 5.6+/-3.1%, n=200). There was no significant difference in the change in eGFR between a group with high CV values (greater than 5 %) and a group with low CV values (lower than 5 %) during the 2-year period. CONCLUSIONS: In CKD patients, the day-by-day variability of HBP tended to be greater in the evening, in female and DN patients. There was no significant association between the day-by-day variability of HBP and decline rate in eGFR. Further studies are needed to clarify the clinical significance of the day-by-day variability of HBP in CKD patients.

Bilateral TKA for Charcot arthropathy associated with multiple levels of spinal canal stenoses: A case report and review of literature.

We report a case of an 84-year-old male with multiple levels of canal stenoses who are diagnosed as Charcot arthropathy of bilateral knees. Although he did not feel any pain, recurrence of joint fluid collection and severe instability prevented him from standing and walking. Deficit in superficial sensation and bathyesthesia below the level of Th10, and tendon reflexes of extremities were seen. Romberg test was positive. Laboratory data showed no abnormal findings. We performed bilateral TKA based on the diagnosis of Charcot arthropathy. At 3-year follow-up, there is no complaint about joint instability and collection of joint fluid.

Discrimination of Mediterranean mussel (Mytilus galloprovincialis) feces in deposited materials by fecal morphology.

In the present study, we determined the common morphological characteristics of the feces of Mytilus galloprovincialis to develop a method for visually discriminating the feces of this mussel in deposited materials. This method can be used to assess the effect of mussel feces on benthic environments. The accuracy of visual morphology-based discrimination of mussel feces in deposited materials was confirmed by DNA analysis. Eighty-nine percent of mussel feces shared five common morphological characteristics. Of the 372 animal species investigated, only four species shared all five of these characteristics. More than 96% of the samples were visually identified as M. galloprovincialis feces on the basis of morphology of the particles containing the appropriate mitochondrial DNA. These results suggest that mussel feces can be discriminated with high accuracy on the basis of their morphological characteristics. Thus, our method can be used to quantitatively assess the effect of mussel feces on local benthic environments.