Association between eosinophilia and renal prognosis in patients with pathologically proven cholesterol crystal embolism.

BACKGROUND: Approximately, 20-70% of patients with cholesterol crystal embolism (CCE) have eosinophilia. However, it remains unknown how eosinophilia influences renal prognosis in patients with CCE. In this study, we investigated the association between eosinophil count (Eo) and renal prognosis in CCE patients on steroid therapy. METHODS: The present study is a single-centered retrospective cohort study in patients with renal dysfunction and CCE from April 2007 to May 2018. This study included the patients who were treated with neither maintenance dialysis nor steroid before CCE diagnosis, and followed-up for kidney function until November 2019. We assessed whether eosinophilia at the time of CCE diagnosis was related to renal death after treating with steroid therapy. RESULTS: Thirty patients with pathologically diagnosed CCE were enrolled and followed-up for 11.0 (5.2-43.4) months. There were significant differences in the white blood cell count (p = 0.01), hemoglobin (p = 0.009), serum creatinine levels (p = 0.008), phosphate (p = 0.049), and Eo (p = 0.008) between the renal survival and renal death groups. Using the receiver operating characteristic curve analysis with Youden index, Eo of 810/µL showed 100% sensitivity and 69.6% specificity for detecting renal death (area under the curve: 0.839). Comparing the outcomes in patients having Eo ≥ and < 810/µL using the log-rank test, there is a significantly higher renal death rate in CCE patients with Eo ≥ 810/µL (p = 0.0016). CONCLUSION: Higher eosinophilia was a prognostic risk factor for renal death in the patients with CCE.

Intradialytic hypotension is an important risk factor for critical limb ischemia in patients on hemodialysis.

BACKGROUND: Critical limb ischemia (CLI) and intradialytic hypotension (IDH) are common complications in patients on hemodialysis (HD). However, limited data are available on whether IDH is related to CLI in these patients. The aim of this retrospective study was to evaluate whether IDH is a risk factor for CLI in HD patients. METHODS: We examined the frequency of IDH in 147 patients who received HD between January 1 and June 30, 2012. Blood pressure was measured during HD every 30 min and IDH was defined as a ≥ 20 mmHg fall in systolic blood pressure compared to 30 min before and a nadir intradialytic systolic blood pressure < 90 mmHg. The primary study outcome was newly developed CLI requiring revascularization treatment or CLI-related death. We assessed the association of IDH with outcome using a multivariable subdistribution hazard model with adjustment for male, age, smoking and history of cardiovascular disease. RESULTS: The median follow-up period was 24.5 months. Fifty patients (34%) had episodes of IDH in the study entry period. During follow-up, 14 patients received endovascular treatment and CLI-related death occurred in 1 patient. Factors associated with incident CLI in univariate analysis were age, smoking, diabetes mellitus, peripheral arterial disease, history of cardiovascular disease, and IDH. IDH was significantly associated with the outcome with the subdistribution hazard ratio of 3.13 [95% confidence interval, 1.05-9.37]. CONCLUSIONS: IDH was an independent risk factor for incident CLI in patients on HD.

Plasma neutrophil gelatinase-associated lipocalin (NGAL) is an indicator of interstitial damage and a predictor of kidney function worsening of chronic kidney disease in the early stage: a pilot study.

BACKGROUND: The aim of this study was to examine whether plasma neutrophil gelatinase-associated lipocalin (NGAL) levels predict the outcome of kidney function and correlate with the severity of tubulointerstitial damages in patients with chronic kidney disease (CKD). METHODS: In this prospective 18-month cohort study of 112 patients with CKD between 2010 and 2011, associations between plasma NGAL levels and estimated glomerular filtration ratio (eGFR), further worsening of kidney function and histological lesion on kidney biopsy were investigated. RESULTS: Serum levels of creatinine and eGFR before the study were 1.48 ± 0.65 mg/dl and 42.6 ± 22.0 ml/min/1.73 m2. Median plasma NGAL level was 148.5 (83.75-248.25) ng/ml and showed no correlation with eGFR or age. 87 out of 112 patients were able to follow up for 18 months. Patients with higher levels of NGAL (>107.8 ng/ml) showed significantly more decrease in eGFR in CKD stage 1 or 2 than those with lower levels of NGAL (≦107.8 ng/ml), while there was no difference in change in eGFR in CKD stage 3-5 between patients with higher and lower levels of NGAL. In the kidney biopsy of 27 patients out of enrolled patients, plasma NGAL levels correlated significantly with the degree of interstitial cell infiltration and fibrosis, but did not correlate with that of glomerular sclerosis. In ROC analysis, plasma NGAL levels predicted tubulointerstitial cell infiltrations more accurately [AUC = 0.8300 than eGFR (AUC = 0.716)]. CONCLUSION: Plasma NGAL is a useful marker of interstitial lesions in patients with CKD and a predictor of further kidney worsening in the early CKD stage.

Aliskiren, a direct renin inhibitor, improves vascular endothelial function in patients on hemodialysis independent of antihypertensive effect ∼ a pilot study∼.

AIMS: Aliskiren inhibits the first step in the renin-angiotensin system (RAS) and recently has been shown to modulate vascular diseases via RAS-dependent and independent pathways. This study aimed to determine the effect of aliskiren-associated direct renin inhibition on endothelial function in patients on hemodialysis via flow-mediated dilatation (FMD) and platelet-derived microparticles (PDMP), as biomarkers of atherosclerosis. METHODS: A 12-week prospective study was performed with 24 patients on hemodialysis who were administered 150 mg orally aliskiren once daily for 12 weeks. RESULTS: No significant difference were observed between pre-dialysis, home, and weekly averaged blood pressure at baseline and at 12 weeks (151.5 ± 8.5/80.9 ± 12.9 mmHg vs 150.3 ± 15.3/78.9 ± 21.2 mmHg, 151.4 ± 9.7/82.3 ± 14.7 mmHg vs 151.2 ± 17.7/81.4 ± 10.6 mmHg, and 156.0 ± 18.3/81.9 ± 9.4 mmHg vs 152.5 ± 18.9/81.7 ± 12.3 mmHg, respectively). FMD significantly increased from 2.54% ± 1.45% at baseline to 3.11% ± 1.37% at 12 weeks (P = 0.0267), and PDMP significantly decreased from 13.9 ± 5.8 U/mL at baseline to 10.9 ± 4.5 U/mL at 12 weeks (P = 0.0002). CONCLUSION: Aliskiren improved vascular endothelial function and platelet-endothelium activation in patients on hemodialysis independent of antihypertensive effect.

Sarpogrelate hydrochloride, a selective 5-HT(2A) receptor antagonist, improves skin perfusion pressure of the lower extremities in hemodialysis patients with peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) frequently occurs in patients on hemodialysis (HD); however, little is known about the effectiveness of drugs. We compare the effects of sarpogrelate and cilostazol in HD patients with PAD. METHODS: We conducted a prospective, randomized, open-label, and multicenter trial for 24 weeks in HD patients with PAD. Thirty-five patients were divided into two groups: sarpogrelate (n = 17) and cilostazol (n = 18). We analyzed changes in skin perfusion pressure (SPP), levels of oxidative stress biomarkers, and adverse events. RESULTS: At 24 weeks, SPP was increased in both groups (sarpogrelate, 43 ± 17 to 55 ± 15 mmHg; cilostazol, 49 ± 21 to 66 ± 29 mmHg; p < 0.05), and no difference was observed between the groups. Plasma pentosidine levels decreased in both groups (sarpogrelate, 0.65 ± 0.24 to 0.48 ± 0.12 mg/mL; cilostazol, 0.58 ± 0.22 to 0.47 ± 0.17 mg/mL; p < 0.05), and there were no differences between the groups. Serum malondialdehyde-modified low-density lipoprotein (MDA-LDL) levels significantly increased only in cilostazol group (p < 0.05). There were no clinically significant safety concerns linked to the both drugs. Although blood pressure did not differ in both groups, heart rate increased only in cilostazol group from 77 ± 13 to 83 ± 16 beats per minute (p < 0.05). CONCLUSION: Sarpogrelate improves SPP in HD patients with PAD without increasing heart rate and serum MDA-LDL levels. We demonstrated that sarpogrelate is an effective and safe drug for the treatment of HD patients with PAD.

Malnutrition and Insulin Resistance May Interact with Metabolic Syndrome in Prevalent Hemodialysis Patients.

BACKGROUND: We sought to determine the prevalence of metabolic syndrome (Mets) and whether 100 cm2 of visceral fatty area (VFA) measured by computed tomography (CT) validates the criteria of waist circumference (WC) in hemodialysis (HD) patients. METHODS: The study comprised 141 HD patients. Mets was defined according to the criteria of Adult Treatment Panel III (ATP III) and the modified criteria of National Cholesterol Education Program (NCEP) that defines abdominal obesity as a WC of >=85 cm in men and >=90 cm in women. RESULTS: The prevalence of Mets was 31.9% in men and 13.6% in women. However, the prevalence of patients with a body mass index over 25 in all HD patients was only 11.2%. The visceral fatty area (VFA) measured by CT showed a strong positive correlation with WC. The patients with Mets, comparing with those without Mets, have significantly shorter duration of HD, higher high-sensitive C-reactive protein, and higher Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). In the patients with Mets, there was a significant negative correlation between HOMA-IR and serum albumin levels. Multivariate logistic regression analysis showed that HOMA-IR and short duration of HD were chosen as independent risk factors for Mets. CONCLUSIONS: Mets is more prevalent in HD patients. In Japanese HD patients, 100 cm2 of VFA corresponded to a WC of 85 cm in men and 90 cm in women, thus confirming the validity of the modified criteria. HOMA-IR and serum albumin were significantly correlated in HD patients with Mets.

Transcranial Doppler Echography Measurement in Hemodialysis Patients: The Potential Role of Angiotensin II Receptor Blockades on Cerebrovascular Circulation.

BACKGROUND: Although hemodialysis (HD) patients have an elevated risk of strokes, there are few reports about transcranial doppler (TCD) echography measurements. It is well-known that angiotensin II receptor blockades (ARBs) protect against cardiovascular complications. In this study, we measured intracranial artery (ICA) velocity using TCD echography and studied the associated factors with its velocity in HD patients by a comparison with or without ARBs. METHODS: We conducted a cross-sectional study in a single hospital. We included 61 patients who had measurable ICA velocity by TCD echography. Among them, the ARB usage group consisted of 22 subjects, whilst the non-ARB usage group consisted of 39 subjects. RESULTS: Patients in the ARB (+) and ARB (-) groups did not show any difference in basic characteristics. ICA blood flow velocity in all intracranial arteries tended to show greater values in the ARB group than those in the non-ARB group. Particularly, blood velocity in the middle cerebral artery (MCA) (maximal flow velocity) statistically increased in the ARB group, respectively. In a univariate analysis, MCA maximum velocity was significantly associated with ARB usage (p = 0.011) and low hematocrit levels (p = 0.045). The multivariate analysis chose only ARB usage as an independent factor associated with left MCA maximum velocity (p = 0.022). CONCLUSIONS: We showed that dialysis patients with ARBs have significantly higher ICA blood velocity. ARBs might have a potential benefit for maintaining ICA blood flow in HD patients.

Impact of the 3% Oxygen Desaturation Index via Overnight Pulse Oximetry on Cardiovascular Events and Death in Patients Undergoing Hemodialysis: A Retrospective Cohort Study.

It is unclear whether the severity of sleep-disordered breathing (SDB) affects the risk of cardiovascular events and mortality in patients undergoing hemodialysis (HD). We determined the severity of SDB with the 3% oxygen desaturation index (ODI) via overnight pulse oximetry. This study was a retrospective cohort, observational study of 134 patients on maintenance HD at a single center. They were divided into four groups according to SDB severity (normal, mild, moderate, and severe), and were followed. The baseline characteristics of all patients were as follows: the median age was 67 (interquartile range, 59-75) years, 64.2% were men, 37.3% were diabetic, and the median duration of HD was 69 (29-132) months. During follow-up, major adverse cardiovascular events (MACEs) occurred in 71 patients and deaths in 60 (including 32 cardiovascular deaths). Severe SDB was an independent risk factor for MACEs (hazard ratio [HR] = 4.66, 95% confidence interval [CI] = 1.87-11.61, p = 0.001) and all-cause death (HR = 5.74, 95% CI = 1.92-16.70, p = 0.001). Severe SDB had a statistically significant impact on the risk of MACEs and mortality in patients undergoing HD. The severity of the 3% ODI via overnight pulse oximetry may be a useful marker as a risk factor for cardiovascular outcomes and mortality in these patients.

Association between zinc deficiency and aorta stiffness in non-diabetic hemodialysis patients.

OBJECTIVES: Zinc deficiency (Zn < 60 µg/dL) is known to play an important role for vascular calcification. However, little data is available regarding the association between zinc deficiency and aorta stiffness in dialysis patients. Thus, we studied the relationship between zinc deficiency and aorta stiffness in non-diabetic hemodialysis (HD) patients. METHODS: Of 150 patients receiving maintenance HD at our hospital, we included 79 non-diabetic HD patients (age: 70±11 years, 49 men) after excluding 71 diabetic HD patients. Zinc deficiency was defined as Zn <60 µg/dL during pre-HD blood sampling. The association between zinc deficiency and aorta stiffness was analyzed. Aorta stiffness was evaluated as brachial-ankle pulse wave velocity (baPWV). Other surrogate markers for cardiovascular complications were also measured. RESULTS: The zinc deficiency group (ZD group) included 45 patients (57.0%). Compared to the zinc non-deficiency group (ZND group), patients with ZD group were significantly older, higher levels of CRP and hypoalbuminemia. Moreover, they had significantly higher levels of baPWV, and lower levels of ankle-brachial pressure index (ABI) (p<0.05). After adjusting for hypoalbuminemia, and CRP, multivariate analysis showed that age and zinc level were independent predictors of baPWV. CONCLUSION: The study suggested that zinc deficiency may be an independent risk factor for aorta stiffness, even after adjusting for malnutrition and inflammation.

Impact of Arterial Calcification of the Lower Limbs on Long-Term Clinical Outcomes in Patients on Hemodialysis.

Lower limbs' arterial calcification is significantly associated with the clinical severity of lower extremity artery disease (LEAD) in patients undergoing hemodialysis (HD). However, the association between arterial calcification of the lower limbs and long-term clinical outcomes in patients on HD has not been elucidated. Calcification scores of the superficial femoral artery (SFACS) and below-knee arteries (BKACS) were quantitatively evaluated in 97 HD patients who were followed for 10 years. Clinical outcomes, including all-cause and cardiovascular mortality, cardiovascular events, and limb amputation were evaluated. Risk factors for clinical outcomes were evaluated using univariate and multivariate Cox proportional hazard analyses. Furthermore, SFACS and BKACS were divided into three groups (low, middle, and high), and their associations with clinical outcomes were evaluated using Kaplan-Meier analysis. SFACS, BKACS, C-reactive protein, serum albumin, age, diabetes, presence of ischemic heart disease, and critical limb-threatening ischemia were significantly associated with 3-year and 10-year clinical outcomes in the univariate analysis. Multivariate analysis showed that SFACS was an independent factor associated with 10-year cardiovascular events and limb amputations. Kaplan-Meier life table analysis showed that higher SFACS and BKACS levels were significantly associated with cardiovascular events and mortality. In conclusion, long-term clinical outcomes and the risk factors in patients undergoing HD were evaluated. Arterial calcification of the lower limbs was strongly associated with 10-year cardiovascular events and mortality in patients undergoing HD.

Impact of Contrast-Induced Nephropathy on Long-Term Renal Function after Coronary Angiography and Contrast-Enhanced Computed Tomography.

Background: It remains unclear whether contrast-induced nephropathy (CIN) has a prognostic impact on subsequent renal dysfunction and whether deteriorating renal function is a risk factor for CIN. This study aimed to evaluate the occurrence of CIN in patients with pre-existing renal dysfunction and investigate the long-term effects of worsening renal function after coronary angiography or contrast-enhanced computed tomography (CT). The prognostic factors of worsening renal dysfunction were also analyzed. Methods: This was a prospective cohort study of patients at risk for CIN, defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 on coronary angiography or eGFR <45 mL/min/1.73 m2 on contrast-enhanced CT. Serum creatinine levels and the 2-year prognosis were evaluated. CIN was defined as an increase in serum creatinine level by more than 0.5 mg/dL or a 25% increase from the previous value within 72 hours after contrast administration. The primary endpoint was the proportion of patients who had serum Cr doubling or induction of dialysis within 2 years according to CIN occurrence. Results: Of the 410 patients, 19 patients developed CIN (8/142 patients on coronary angiography and 11/268 patients on contrast-enhanced CT), and 38 patients had worsened renal function (21/142 patients on coronary angiography and 17/268 patients on contrast-enhanced CT). CIN was not associated with worsening renal function at 2 years. Analysis by renal function at the time of coronary angiography or contrast-enhanced CT (i.e., eGFR ≥30 ml/min/1.73 m2 and eGFR ≤1.73 m2) found no between-group difference in the occurrence of CIN. Conclusions: CIN is not a prognostic risk factor for the long-term of chronic kidney disease after coronary angiography or contrast-enhanced CT. Pre-existing renal dysfunction is also not a risk factor for CIN, even if the eGFR is <30 ml/min/1.73 m2.

Association between Anti-Erythropoietin Receptor Antibodies and Cardiac Function in Patients on Hemodialysis: A Multicenter Cross-Sectional Study.

Cardiac dysfunction is an important prognostic predictor of cardiovascular mortality in patients on hemodialysis (HD). Erythropoietin (EPO) has been reported to improve cardiac function by binding to the EPO receptor (EPOR) on cardiomyocytes. This study investigated whether anti-EPOR antibodies were associated with left ventricular cardiac function in patients undergoing HD. This multicenter, cross-sectional observational study included 377 patients (median age, 70 years; 267 (70.8%) males) with chronic kidney disease (CKD) undergoing stable maintenance HD. Serum levels of anti-EPOR antibodies were measured, and echocardiography was used to assess the left ventricular mass index (LVMI) and left ventricular ejection fraction (LVEF). Anti-EPOR antibodies were found in 17 patients (4.5%). LVMI was greater (median of 135 g/m2 vs. 115 g/m2, p = 0.042), and the prevalence of LVEF < 50% was higher (35.3% vs. 15.6%, p = 0.032) in patients with anti-EPOR antibodies than in those without. Multivariable linear regression and logistic regression analysis (after adjusting for known risk factors of heart failure) revealed that anti-EPOR antibodies were independently associated with LVMI (coefficient 16.2%; 95% confidence interval (CI) 1.0−35.0%, p = 0.043) and LVEF <50% (odds ratio 3.20; 95% CI 1.05−9.73, p = 0.041). Thus, anti-EPOR antibody positivity was associated with left ventricular dysfunction in patients undergoing HD.

Prevalence of mild cognitive impairment and its association with handgrip strength in patients on hemodialysis.

Dementia is associated with a high risk of death and hospitalization among patients on hemodialysis (HD). We retrospectively evaluated the prevalence of mild cognitive impairment (MCI) in 421 patients on maintenance HD across nine facilities and investigated whether decreased handgrip strength was associated with decreased cognitive function. The Montreal Cognitive Assessment-Japan (MoCA-J) score and handgrip strength were measured. The mean age was 69.8 ± 11.2 years, and the median dialysis vintage 74.5 (IQR 30-150) months. The median MoCA-J score was 25 (IQR 21-27), and MCI was confirmed in 245 (58.2%) patients. Both the MoCA-J score and MoCA-J executive score were associated with age, history of cerebrovascular disease (CVA), and handgrip strength after adjustments. We found, among patients on HD aged under 70 years with a history of CVA, a handgrip strength < 90% (25.2 kg in males and 16.2 kg in females) correlated with significantly lower MoCA-J scores. A high prevalence of MCI and decreased handgrip strength were observed in patients on HD. Handgrip strength may be useful for the easy detection of MCI. A decrease in handgrip strength would allow for the early detection of MCI, especially among patients on HD aged under 70 years with a history of CVA.

A novel mechanism in maggot debridement therapy: protease in excretion/secretion promotes hepatocyte growth factor production.

Maggot debridement therapy (MDT) is effective for treating intractable wounds, but its precise molecular mechanism, including the association between MDT and growth factors, remains unknown. We administered MDT to nine patients (66.3 ± 11.8 yr, 5 male and 4 female) with intractable wounds of lower extremities because they did not respond to conventional therapies. Significant increases of hepatocyte growth factor (HGF) levels were observed in femoral vein blood during 48 h of MDT (P < 0.05), but no significant change was found for vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), transforming growth factor-ß1 (TGF-ß1), or tumor necrosis factor-α (TNF-α). We conducted NIH-3T3 cell stimulation assay to evaluate the relation between HGF and protease activity in excretion/secretion (ES) derived from maggots. Compared with the control group, HGF was significantly higher in the 0.05 µg/ml ES group (P < 0.01). Furthermore, protease inhibitors suppressed the increase of HGF (P < 0.05). The HGF expression was increased in proportion to the ES protein concentration of 0.025 to 0.5 µg/ml. In fact, ES showed stronger capability of promoting HGF production and less cytotoxicity than chymotrypsin or bromelain. HGF is an important factor involved in cutaneous wound healing. Therefore, these results suggest that formation of healthy granulation tissue observed during MDT results from the increased HGF. Further investigation to identify molecules enhancing HGF expression by MDT will contribute greatly to drug target discovery for intractable wound healing therapy.

Impact of lower limbs' arterial calcification on the prevalence and severity of PAD in patients on hemodialysis.

BACKGROUND: Peripheral arterial disease (PAD) is one of the serious complications in patients on hemodialysis (HD) therapy. However, arterial calcification of lower limbs' arteries and its impact on the prevalence and severity of PAD has never been quantitatively evaluated in HD patients with PAD. METHODS: Ninety-seven HD patients were enrolled to evaluate calcification score in superficial femoral artery (SFACS) and below-knee arteries (BKACS) quantitatively by 64-row multidetector computed tomography as well as ankle-brachial pressure index (ABI), toe-brachial pressure index (TBI), and clinical and laboratory parameters. RESULTS: Forty-six patients (47.2%) had PAD, and 11 patients had critical limb ischemia (CLI). SFACS and BKACS were significantly associated with the prevalence and severity of PAD, and receiver-operating characteristic analysis showed that SFACS and BKACS well predicted the prevalence of PAD and CLI in HD patients. The independent associating factors for PAD were BKACS and low TBI (r(2) = 0.534; P < .0001). Low TBI was also an independent associating factor for CLI (r(2) = 0.245; P < .0001). Multivariate analysis indicated that the independent associating factors for TBI in HD patients were BKACS and C-reactive protein (CRP; r(2) = 0.358; P = .006). CONCLUSIONS: Present quantitative analysis clearly provided the first evidence that arterial calcification of lower limbs' arteries was closely associated with the prevalence and severity of PAD in HD patients. Furthermore, arterial calcification of below-knee arteries and micro-inflammation represented as CRP were the independent associating factors for low TBI, which was the independent associating factor for PAD and CLI in HD patients.

Serum biological antioxidant potential predicts the prognosis of hemodialysis patients.

BACKGROUND: It is well known that oxidative stress is enhanced in patients with end-stage renal disease. However, little is known about the relationship between serum antioxidant capacity and clinical outcome in hemodialysis (HD) patients. METHODS: We examined the relationship between serum biomarkers of oxidative stress and clinical outcomes including all-cause mortality, hospitalization rate and incidence of cardiovascular events in HD patients. As biomarkers of oxidative stress, we measured serum levels of coenzyme Q10 (CoQ10) and biological antioxidant potential (BAP). RESULTS: 108 patients were observed for 30 months as the follow-up periods. The survival group (n = 83) showed significantly higher BAP values compared with those in death groups (n = 25; p < 0.05). When serum BAP levels were divided into two groups by their median value, the group with higher BAP values had a better survival rate than that with lower BAP values on the Kaplan-Meier survival analysis (p = 0.05). Although serum levels of CoQ10 did not show any association with clinical outcomes, lower BAP was selected as an independent risk factor for all-cause mortality as well as the absence of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers therapy by age-adjusted Cox regression analysis. CONCLUSIONS: This study indicated that BAP could predict the prognosis of HD patients.

Pathological regression by angiotensin II type 1 receptor blockade in patients with mesangial proliferative glomerulonephritis.

Although angiotensin II type 1 receptor blocker (ARB) therapy reduces proteinuria and retards the progression of renal injury in patients with glomerulonephritis, whether these drugs actually ameliorate pathological damages in human glomerulonephritis has not been determined. Fifteen patients with biopsy-proven mild-to-moderate mesangial proliferative glomerulonephritis (10 with immunoglobulin A [IgA] nephropathy and 5 with non-IgA mesangial proliferative glomerulonephritis) received ARB monotherapy. In these patients, repeated renal biopsy was performed after a mean of 28.1 months, and pathological changes (including the mesangial matrix expansion ratio and interstitial fibrosis expansion ratio) were quantitatively examined using an image analyzer. Clinical markers were also evaluated, including the serum creatinine, serum IgA, creatinine clearance (Ccr), 24-h urinary protein excretion, urinary N-acetyl-beta-D-glucosaminidase (NAG), and blood pressure. ARB therapy significantly reduced urinary protein excretion (0.68+/-0.63 to 0.20+/-0.32 g/day, p=0.016) and the blood pressure (systolic: 133.3+/-18.2 to 123.4+/-10.5 mmHg, p=0.041; diastolic: 79.4+/-11.9 to 72.0+/-8.2 mmHg, p=0.038). Although the global glomerular sclerosis ratio was unchanged (6.3+/-8.5% to 10.7+/-16.1%, p=0.33), the mesangial matrix expansion ratio (33.1+/-10.8% to 22.7+/-7.8%, p=0.001) and the interstitial fibrosis ratio (19.9+/-5.8% to 13.8+/-4.4%, p=0.034) were significantly reduced by ARB treatment. The levels of pathological improvement were similar between patients with IgA nephropathy and those with non-IgA mesangial proliferative glomerulonephritis. The results of the present study strongly suggest that ARB monotherapy can significantly reverse pathological changes, including mesangial matrix expansion and interstitial fibrosis, in human glomerulonephritis.

Glucose metabolism, insulin resistance, and renal pathology in non-diabetic chronic kidney disease.

BACKGROUND: The relation between insulin resistance and atherosclerosis is widely recognized, but it remains unknown whether glucose metabolism/insulin resistance is related to renal pathology in humans. METHODS: We quantitatively evaluated pathological changes in the glomeruli, tubulointerstitium, and vessels in renal biopsy specimens from 23 patients with non-diabetic chronic kidney disease (CKD), all of whom took a 75-gram oral glucose tolerance test. We correlated the renal pathological changes with fasting plasma glucose (FPG), fasting plasma insulin, 2-hour plasma glucose (2-h PG), 2-hour plasma insulin (2-h PI), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index. RESULTS: HOMA-IR exceeded 1.73 in 11 patients (47.8%), and 2-h PI exceeded 64.0 microU/ml in 14 (60.9%). FPG significantly correlated with interstitial fibrosis (r = 0.532, p = 0.009). The significance was marginal in the correlation between FPG and tubular atrophy and arterio-arteriolosclerosis. Statistically significant correlation was also found between 2-h PG and arterio-arteriolosclerosis (r = 0.422, p = 0.04) and between HOMA-IR and interstitial fibrosis (r = 0.416, p = 0.04). CONCLUSION: Although precise mechanisms remain unknown, glucose metabolism/insulin resistance seem to play pathogenic roles in formation and progression of renal pathological changes, especially tubulointerstitial and vascular lesions, in non-diabetic CKD.

High-density lipoprotein cholesterol and left ventricular mass index in peritoneal dialysis.

OBJECTIVE: The prevalence of left ventricular hypertrophy (LVH) reaches 75% in patients with end-stage renal disease. In patients on peritoneal dialysis (PD), some factors, such as hypertension, volume overload, serum albumin, and residual renal function, have been reported to be related to LVH. Dyslipidemia often occurs in PD but it remains unclear whether dyslipidemia is related to LVH. We investigated the relationship between clinical parameters, including lipid profile, and left ventricular mass index (LVMI). METHODS: In this cross-sectional study, 34 patients undergoing PD for more than 1 year without combined therapy with hemodialysis were included. We recorded the patients' clinical data and related those parameters with LVMI as evaluated by echocardiography. RESULTS: The patients included 23 males and 11 females (age 62.2 +/- 12.1 years, duration on PD 31.6 +/- 15.6 months). Mean LVMI was 142 +/- 37 g/m2. In univariate analysis, urine volume (r = -0.493, p = 0.003), total cholesterol (r = -0.418, p = 0.01), high-density lipoprotein cholesterol (HDL-C; r = -0.374, p = 0.02), and human atrial natriuretic peptide (hANP; r = 0.600, p < 0.001) significantly correlated with LVMI. Stepwise multiple regression analysis showed that hANP (beta = 0.524, p = 0.001) and HDL-C (beta = -0.422, p = 0.007) were independently associated with LVMI (r2 = 0.32). CONCLUSION: Strict volume control and salt restriction is essential for prevention of LVH. The role of HDL-C in the development of LVH in PD patients remains to be determined.