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.

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 .

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.

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.

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.

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.

Clinical Practice of Two Measurements of Home Blood Pressure on Each Occasion in Patients with Chronic Kidney Disease.

BACKGROUND/AIMS: Although several guidelines propose two or three measurements of home blood pressure (HBP) on each occasion, the actual status of multiple measurements is not clear in the practical management of hypertension. We surveyed the details regarding two measurements of HBP in patients with chronic kidney disease (CKD). METHODS: HBP was measured twice every morning and evening over 7 consecutive days in 175 CKD patients. The distribution of the differences between two BP values (2nd - 1st BP) and their association with BP parameters were evaluated. RESULTS: The 2nd - 1st morning systolic BP (SBP) and diastolic BP (DBP) differences were -2.3 ± 4.1 and -0.4 ± 2.6 mm Hg, respectively. The proportion of 2nd - 1st morning SBP differences >0 mm Hg was 31.7% in a total of 1,195 measurements. Eighty patients (45.7%) had days with a difference ≤-5 mm Hg and days with a difference ≥5 mm Hg in morning SBP during 7 days. The multivariate regression analysis of the SD values of 2nd - 1st morning SBP as a dependent variable showed that the SD value of the 1st morning SBP (ß = 0.65, p < 0.001) was a significant determinant. CONCLUSION: Although the 2nd SBP was 2-3 mm Hg lower than the 1st SBP in the population as a whole, various differences were found for each subject during 7 days. 2nd - 1st BP variability might be associated with day-by-day 1st BP variability.

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.

[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.

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.

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.

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.

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

OBJECTIVE: Home 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. METHODS: We 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. RESULTS: No 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 (ß 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). CONCLUSION: Day-by-day BP variability as assessed by HBP measurements had no significant association with the progression of CKD.

Triple therapy with single daily dose of cyclosporine in Japanese patients with idiopathic membranous nephropathy.

OBJECTIVE: The optimal therapeutic approach to patients with idiopathic membranous nephropathy (IMN) remains controversial. In this study, we assessed the efficacy of single daily dose cyclosporine (CsA) combined with low-dose prednisolone (PSL) and an angiotensin II receptor blocker (ARB) in patients with IMN. METHODS: We studied 13 nephrotic patients (8 men, 5 women) with IMN diagnosed on biopsy. An initial single daily dose of 2 mg/kg, but not exceeding 150 mg, CsA was given for 12 months, tapered by a 25 mg reduction every 2 months. An initial twice-daily dose of 0.5 mg/kg PSL was given for 2 months and was also tapered. An ARB was given to all patients and the same dosage was used throughout the study. Patients were followed up for 6 to 66 months. RESULTS: Nine patients achieved complete remission at 6.7±2.9 months, and incomplete remission was obtained in the remaining patients. After a follow-up period of 32.7±20.0 months, their serum creatinine and estimated glomerular filtration rate values were similar to baseline levels. The 9 patients who completed the treatment course have not relapsed. Moreover, there were no adverse effects requiring discontinuation of this triple therapy. CONCLUSION: A single daily dose of CsA combined with a low dose of PSL and an ARB in new-onset nephrotic patients with IMN induced a high remission rate of nephrotic syndrome, with a low incidence of relapse and a low risk of adverse effects. The triple therapy and prospective follow-up shows potential as a treatment approach for patients with IMN.

Ratio of urinary potassium to urinary sodium and the potassium and edema status in nephrotic syndrome.

OBJECTIVE: This study aimed to evaluate the relevance of ratios of urinary potassium to urinary sodium + potassium (U(K)/U(Na + K)) to edema status in minimal-change nephrotic syndrome (MCNS). METHODS: We retrospectively studied 26 adults with newly diagnosed MCNS with significant pitting edema. On the basis of mean value (0.46±0.21) of U(K)/U(Na + K) determined from spot urine samples on admission, patients were classified into 2 groups. RESULTS: On admission, 12 of 26 patients had U(K)/U(Na + K) >0.46 (0.65±0.16, Group H), 14 patients had U(K)/U(Na + K) <0.46 (0.29±0.08, Group L). The level of serum albumin was similarly decreased in these 2 groups. Noteworthy were lower urine volume, fractional excretion of sodium (FENa), serum sodium, and higher hematocrit in the group H as compared with the group L. The group H had a shorter mean time required from onset of edema to hospitalization, and tended to have a longer mean time to complete remission than group L. High U(K)/U(Na + K) levels in group H decreased significantly after remission, eventually becoming equal to those of group L (0.24±0.05 vs. 0.25±0.05). CONCLUSION: U(K)/U(Na + K) determined from spot urine sample on admission relates to laboratory or clinical indices to distinguish edema status in adult patients with MCNS.