Randomized comparison of pitavastatin and pravastatin treatment on the reduction of urinary albumin in patients with type 2 diabetic nephropathy

The effect of pitavastatin and pravastatin treatment on renal function was compared in type 2 diabetic patients with nephropathy in a randomized, controlled, open-label, parallel and multi-centre study. Type 2 diabetic patients with modest renal impairment (serum creatinine level <1.4 mg/dl) accompanied by albuminuria (30-600 mg/g creatinine) were randomly assigned to receive 2 mg of pitavastatin (n = 44) or 10 mg of pravastatin (n = 43) for 12 months. At 12 months, pitavastatin significantly reduced urinary albumin-to-creatinine ratio than pravastatin in subjects with macroalbuminuria (-67.2% vs. +14.5%, p = 0.0040), but not in subjects with microalbuminuria. There was no significant difference in the change in estimated glomerular filtration rate between the two groups. Pitavastatin is more effective than pravastatin for the reduction of albuminuria in type 2 diabetic patients with early stage of diabetic nephropathy.     

Remission and regression of diabetic nephropathy

Diabetic kidney disease is considered to be an irreversible and inexorable progressive disease. Therefore, prevention of development of ESRD is extremely important. Animal studies have demonstrated that regression of existing renal morphologic lesions is feasible. In a sizable fraction of type 1 diabetic patients with overt nephropathy, remission (decrease in albuminuria to < 300 mg/24 h) was obtained (31%), and regression of diabetic nephropathy (rate of decline in GFR≤mL/min/y), achieved (22%) by aggressive antihypertensive treatment. Furthermore, remission of nephrotic-range albuminuria (from > 2500 mg/24 h to < 600 mg/24 h) have been demonstrated to be achievable in one fifth of patients with nephrotic-range albuminuria. Remission of nephrotic-range albuminuria was associated with a reduction in decline in GFR and improved survival free of ESRD. However, to prevent development of ESRD in diabetic patients, an aggressive multifactorial approach, aiming at lowering blood pressure and albuminuria, and improving glycemic control, must be applied.     

Significance of hyperuricemia on the early detection of renal failure in a cohort of screened subjects.

A high level of serum creatinine (S-Cr) is a predictor of end-stage renal disease (ESRD), but only a few studies have investigated the prevalence of high S-Cr and its correlates in a large population. We analyzed the data collected from 6,403 subjects (4,222 men and 2,181 women) who participated in the Okinawa General Health Maintenance Association (OGHMA) screening both at 1997 and 1999. The computer-saved data included sex, age, blood chemistries, blood pressure, medical histories, and lifestyles. Multivariate Cox proportional hazard analyses were performed to identify the correlates of developing high S-Cr levels: > or = 1.4 mg/dl in men and > or = 1.2 mg/dl in women. The prevalence of high S-Cr was 3.0% (N=193), which was 4.1% in men (N=175) and 0.8% in women (N=18), and increased with age in both sexes at the 1997 screening. Among those who showed normal levels of S-Cr in 1997 (N=6,210), 241 subjects (223 men and 18 women) developed high S-Cr. The 2-year cumulative incidence of high S-Cr was 5.5% in men and 0.8% in women. Other than sex, serum uric acid was the most significant correlate for developing high S-Cr. The adjusted relative risk (95% confidence interval) of those with serum uric acid 8.0 mg/dl and over was 2.91 (1.79-4.75) in men and 10.39 (1.91-56.62) in women when compared to those with serum uric acid less than 5.0 mg/dl. Prevalence of high levels of S-Cr was relatively high in men. Other than gender, serum uric acid was a significant positive correlate of developing high S-Cr in this sample of the Japanese population.     

Utility of non-high-density lipoprotein cholesterol in hemodialyzed patients

Non-high-density lipoprotein-cholesterol (HDL-C) is proposed as a strong predictor of cardiovascular disease (CVD). Measuring non-HDL-C, as total cholesterol minus HDL-C, is convenient for routine practice because, among other advantages, fasting is not required. There are limited data of non-HDL-C in end-stage renal disease patients. We applied non-HDL-C calculation to 50 chronic renal patients receiving maintenance hemodialysis (HD) and 20 healthy subjects, apart from measurement of low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL) HDL, intermediate-density lipoprotein-cholesterol (IDL-C), apoprotein (apo) B, and triglycerides. HD patients presented higher plasma triglycerides and IDL-C and lower HDL-C than the control group, even after adjustment for age (P < .05). VLDL-C increased in HD patients (P < .001) while differences in non-HDL-C did not reach significance (P = .08). To detect which parameter constitutes a better marker of CVD risk among HD patients, a receiver-operating characteristic (ROC) analysis was performed considering HD patients in the highest risk group for CVD. In the ROC graphic, the plots of VLDL and IDL-C exhibited the greater observed accuracy and the best performance, while non-HDL-C showed a curve close to the 45 degrees line indicating that this parameter is a poor discriminator for evaluating CVD risk among HD patients. Non-HDL-C calculation, expressing all apo B-containing lipoproteins, may miss the significant contribution of each atherogenic lipoprotein, such as increase in IDL. This observation would not be in agreement with the currently proposed application of non-HDL-C a useful tool for risk assessment among HD patients.     

Protective effect of an oral adsorbent on renal function in chronic renal failure: determinants of its efficacy in diabetic nephropathy

Large-scale clinical trials have shown that the oral adsorbent AST-120 improves renal function and delays the initiation of dialysis in chronic renal failure (CRF) secondary to chronic glomerulonephritis. If renal failure progresses via common mechanisms, then the same effects can be expected in diabetic nephropathy. However, no study on diabetic nephropathy has been reported. Thus, we enrolled patients with statistically significant progression of CRF secondary to diabetic nephropathy, and analyzed the changes in renal function after AST-120 therapy, and the clinical factors associated with response to therapy. We enrolled 276 patients with diabetic nephropathy, whose serum creatinine (Scr) had increased from 3.4 to 4.5 mg/dL during the 4.5 +/- 3.7 months prior to the study. These patients took AST-120 at a dose of 5.0 +/- 1.4 g/day for 6 months. The clinical data were analyzed by dividing the patients into three groups based on the changes in Scr after AST-120 therapy, with responders showing a decrease (N = 82), partial responders showing <1.5-fold increase (N = 144), and non-responders showing >/=1.5-fold increase (N = 50). AST-120 significantly lowered the slope of 1/Scr-time line, suggesting that AST-120 suppressed the progression of renal impairment. No responders required dialysis, whereas 24.3% of the partial responders and 36.0% of the non-responders started dialysis therapy. In responders, the 1/Scr-time slope showed a negative-to-positive shift and serum urea nitrogen decreased significantly, whereas the improvement was moderate in partial responders and minimal in non-responders. Among responders, AST-120 therapy significantly improved renal function despite the presence of hypoproteinemia, hyperlipidemia, anemia or hypertension in many patients. The beneficial effect of AST-120 was significantly more marked in patients with blood pressure controlled within the normal ranges and hematocrit maintained at 30% or above. AST-120 reversed renal dysfunction or delayed the initiation of dialysis therapy in patients with progressive aggravation of CRF secondary to diabetic nephropathy, independent of hypoproteinemia, hyperlipidemia, anemia and hypertension. Active use of AST-120 may be recommended in patients with good control of blood pressure and hematocrit above 30%.     

Renal handling of glycated albumin in non-insulin-dependent diabetes mellitus with nephropathy

Renal handling of glycated albumin in diabetic nephropathy was examined by studies on renal selectivity for glycated albumin in 23 normal controls and 52 patients with non-insulin-dependent diabetes mellitus (NIDDM) with various degrees of nephropathy. The serum and urinary levels of glycated albumin were measured by enzyme-immunoassay with monoclonal antibody to glucitol-lysine residues in human glycated albumin. The diabetic patients were divided into 3 groups according to the albumin index (AI): patients with normoalbuminuria [AI less than or equal to 30 mg/g creatinine(Cr)], with microalbuminuria (30 less than AI less than or equal to 270 mg/g Cr), and with macroalbuminuria (AI greater than 270 mg/g Cr). The renal selectivity for glycated albumin was calculated from the ratio of the urinary to serum level of glycated albumin. In the controls, the renal selectivity was as high as 4.40 +/- 0.48, and significantly higher than those in patients with normo- (2.87 +/- 0.29), micro- (1.72 +/- 0.20) and macroalbuminuria (1.26 +/- 0.23). The renal selectivity was inversely correlated with the AI in diabetic patients (r = -0.58, P less than 0.01). These data indicate that glycated albumin was selectively excreted in the urine and that the renal selectivity in diabetic patients gradually decreased to a value of 1 with increase in albuminuria. When the patients with normoalbuminuria were divided into two subgroups with high and low albumin excretion, the renal selectivities for glycated albumin in both subgroups were still significantly lower than that in controls. These results suggested that early diabetic nephropathy which cannot be detected clinically by albuminuria can be diagnosed by measurement of renal selectivity for glycated albumin.     

The association between end-stage diabetic nephropathy and methylenetetrahydrofolate reductase genotype with macroangiopathy in type 2 diabetes mellitus.

The T/T genotype of the methylenetetrahydrofolate reductase C677 T gene polymorphism is associated with elevated homocysteine levels and presumably with increased atherosclerotic risk. We evaluated the interaction between this gene polymorphism and end-stage diabetic nephropathy on the observed prevalence of macroangiopathy in type 2 diabetes mellitus. The methylenetetrahydrofolate reductase 677 C/T genotypes were determined in 174 type 2 diabetic patients: 80 with and 94 without renal failure due to diabetic nephropathy. In the patients with renal failure, the T/T genotype and T allele were significantly associated with macroangiopathy (T/T; 31 % vs. 2 %, P = 0.0001 T allele; 59 % vs. 29 %, P = 0.00014), whereas the associations were not significant in the patients without renal failure. In the multiple logistic regression analysis, age (10 years OR 4.05 [1.79 - 9.31], P < 0.0005) and 677 T allele (6.84 [2.12 - 22.05], P = 0.0013) were significantly associated with macroangiopathy in the patients with renal failure. In conclusion, this study demonstrated that the 677 T/T genotype and T allele of MTHFR were significantly associated with macroangiopathy in type 2 diabetic patients with renal failure. The MTHFR 677 T allele, together with renal dysfunction due to diabetic nephropathy, could be a strong risk factor for atherosclerotic disease.     

Cardiorenal syndrome in type 1 diabetes mellitus: the role of endothelial dysfunction

AIM: To elucidate the role of endothelial dysfunction in formation of cardiorenal syndrome in patients with type 1 diabetes and diabetic nephropathy. MATERIAL AND METHODS: Sixty patients with type 1 diabetes were divided according to severity of nephropathy into the following groups: with normal albuminuria (n=15), microalbuminuria (n=15), proteinuria (n=15), and chronic renal failure (n=15). Control group consisted of 15 healthy subjects of similar age and sex. Methods of investigation included assessment of brachial artery endothelium dependent dilation by duplex scanning during test with reactive hyperemia, measurement of levels of serum markers of endothelial dysfunction (endothelin-1, von-Willebrand factor), and inflammation (C-reactive protein), analysis of parameters of 24-hour blood pressure monitoring and echocardiography data. RESULTS: More severe diabetic nephropathy was associated with higher prevalence of cardiac pathology. Frequency of ischemic heart disease was 13 (2/15), 33 (5/15) and 53% (8/15), frequency of left ventricular concentric hypertrophy and remodeling - 33 (5/15), 40 (6/15) and 60% (9/15) among patients with microalbuminuria, proteinuria and chronic renal failure, respectively. Abnormalities of 24-hour blood pressure rhythm as well as signs of endothelial dysfunction were more pronounced in patients with more severe nephropathy. Correlation analysis revealed significant relationships between markers of endothelial dysfunction, parameters of renal function, blood pressure level and mass of left ventricular myocardium. CONCLUSION: In patients with type 1 diabetes: endothelial dysfunction represents a link integrating processes of progression of nephropathy and development of cardiovascular pathology; close relationship between these processes constitutes a basis of cardiorenal syndrome; active search for cardiac pathology should be initiated on the stage of microalbuminuria.     

Ambulatory blood pressure in type 2 diabetic patients with albuminuria: relation to the renal function and structural lesions

BACKGROUND/AIMS: To investigate possible relationships between ambulatory blood pressure (BP) and renal structure and function in type 2 diabetic patients. METHODS: Renal biopsies were performed on 39 patients with urine albumin concentrations above 100 mg/l. BP was investigated with a 24-h, automated, portable BP device. RESULTS: None of the patients in the study had signs of other renal disease than nephrosclerosis or diabetic nephropathy. Ten patients had slight, 13 intermediate, and 6 severe diabetic nephropathy on the renal biopsy. Among the remaining patients, 4 had normal microscopy findings and 6 had nephrosclerosis. The degree of albuminuria correlated to the systolic BP during the day (r = .43; P < .01) and night (r = .49; P < .01). The glomerular filtration rate (GFR) was associated with the systolic BP daytime (r = -.32; P < .05) and nighttime (r = -.47; P < .01). Neither degree of albuminuria nor GFR was associated with the diastolic BP levels. The degree of the glomerular pathology correlated to the systolic BP during daytime (P < .05), whereas the degree of interstitial fibrosis did not correlate to the BP levels. CONCLUSIONS: We have demonstrated that degree of albuminuria and GFR was significantly associated with daytime and nocturnal BP and glomerular structure with daytime BP. Furthermore, no renal disease other than diabetic nephropathy was found.     

老年2型糖尿病肾病病人血脂与肾功能指标的变化

目的 探讨老年2型糖尿病肾病病人血脂与肾功能指标变化的关系.方法 选取2018年1月至2019年12月在我科门诊及住院接受治疗的≥60岁的老年糖尿病病人100例.按照尿蛋白排泄率(UAER)不同,将其划分为正常蛋白尿组、微量蛋白尿组以及大量蛋白尿组,同时选取40例老年健康体检者作为对照组.检测各组的TC、TG、HDL-...     

Risk factors for non-ischaemic foot ulceration in diabetic nephropathy.

It is recognized that diabetic patients with nephropathy frequently have macrovascular disease leaving them at risk of ischaemic foot lesions. In order to assess non-vascular risk factors for foot ulceration 64 patients were stratified into four groups: microalbuminuria, albuminuria with creatinine clearance greater than 40 ml min-1, chronic renal failure (clearance less than 40 ml min-1), and a non-nephropathic diabetic control group. Vibration perception threshold was measured by biothesiometry, peroneal nerve conduction velocity by conventional methods, and dynamic foot pressure by pedobarography. Vibration perception threshold was elevated in all three groups when compared with age-matched normal and diabetic control groups. Mean vibration perception threshold was 20.8 +/- 8.6 (+/- SD) in the microalbuminuria group (p less than 0.001 compared with age-matched normal control group), 28.1 +/- 5.6 (p less than 0.001) in the albuminuria group, 38.9 +/- 9.4 (p less than 0.001) in the renal failure group, 14.8 +/- 5.2 in the diabetic control group and 12.3 +/- 2.9 in the normal control group. Peroneal motor conduction velocity was reduced in all three groups when compared with normal control subjects, microalbuminuria 38.6 +/- 4.2 m s-1 (p less than 0.001), albuminuria 38.0 +/- 6.1 m s-1 (p less than 0.01), renal failure 35.5 +/- 1.2 m s-1 (p less than 0.001), diabetic control 40.6 +/- 1.8 m s-1, and normal 43.1 +/- 2.3 m s-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Absolute level and rate of change of albuminuria over 1 year independently predict mortality and cardiovascular events in patients with diabetic nephropathy.

AIMS: To determine the nature of the association between baseline albuminuria and risk of all-cause mortality and cardiovascular disease, and to determine if the rate of change of albuminuria from baseline over 1 year predicts these endpoints in patients with diabetic nephropathy. METHODS: Cohort study of 427 patients (161 Type 1 and 266 Type 2) with diabetic nephropathy defined as urinary albumin excretion (UAE) > or = 30 mg/24 h at baseline (mean age 53.4 years). Patients were recruited at the time of referral to a diabetic nephropathy clinic and followed up annually for an average of 5 years. UAE rate was re-measured at 1 year and the rate of change from baseline calculated. RESULTS: All-cause mortality and cardiovascular disease increased significantly and continuously across quintiles of baseline UAE (P for linear trend < 0.001 in both outcomes). The rate of change of albuminuria over 1 year (log10) independently predicted all-cause mortality (hazard ratio (95% confidence interval) 1.76 (1.39, 3.11)) and cardiovascular mortality (1.57 (1.13, 5.22)). Taken as a categorical variable, a rate of change of albuminuria > or = 30% independently predicted mortality and cardiovascular events (2.07 (1.5, 4.30) and 1.89 (1.33, 4.06), respectively). CONCLUSIONS: The rate of change of albuminuria over 1 year independently predicts mortality and cardiovascular disease in diabetic nephropathy and may have clinical utility as a risk marker in identifying a subgroup of patients at particular risk. The risk of these outcomes is continuous across the range of baseline albuminuria in patients with diabetic nephropathy.     

Effect of insulin therapy on lipoproteins in non-insulin dependent diabetes mellitus (NIDDM)

Thirty patients with NIDDM and severe hyperglycemia (fasting plasma glucose greater than 200 mg/dl) were initiated on insulin therapy. Lipoprotein concentrations were measured by the Vertical Autoprofile procedure before insulin therapy and 1, 3, 6 and 26 weeks after insulin initiation. Patients were divided into 4 phenotypes based on their pretreatment lipoprotein profile: HyperVLDL (elevated VLDL), HyperLDL (elevated LDL), HyperVLDL-LDL (elevated VLDL and LDL), and non-hyperlipidemic. There were no differences in the initial fasting plasma glucose, Hgb Alc, or fasting free insulin concentrations between the groups. Both the HyperVLDL and HyperLDL groups had significantly lower HDL-C concentrations that the non-hyperlipidemic group and the HyperVLDL-LDL group had significantly higher IDL-C than any of the other groups. Insulin therapy resulted in similar decreases in fasting plasma glucose and increases in fasting free insulin concentrations in all 4 groups. HDL-C increased in all 4 groups. The most marked improvements in HDL-C were seen in the non-hyperlipidemic (+37%) and HyperLDL (+42%) groups while the HyperVLDL group had only an 18% increase. VLDL-C fell in all groups but in the HyperVLDL group it fell dramatically to almost normal levels within the first week, whereas it took 6 weeks for the HyperVLDL-LDL group to reach its VLDL-C nadir and this was still significantly higher than normal. LDL-C improved modestly in only the HyperLDL patients after 6 weeks of insulin therapy. There were no statistically significant changes in either the IDL-C or Lp(a)-C in any of the groups during insulin therapy. The changes in HDL-C and IDL-C were negatively correlated with the fasting plasma glucose and Hgb Alc but not with the free insulin concentration. We conclude that: 1) Insulin therapy can cause dramatic improvements in HDL-C and VLDL-C while it has only a mild suppressive effect on LDL-C and no statistically significant effect on IDL-C or Lp(a)-C. The degree of improvement in the lipid profiles varied considerably between the different lipid phenotypes. 2) The hyperlipidemic phenotypes seen in these patients appear to be determined primarily by factors other than the degree of hyperglycemia and hypoinsulinemia.     

Chronic kidney disease in the type 2 diabetic patients: prevalence and associated variables in a random sample of 2642 patients of a Mediterranean area

ABSTRACT: BACKGROUND: Kidney disease is associated with an increased total mortality and cardiovascular morbimortality in the general population and in patients with Type 2 diabetes. The aim of this study is to determine the prevalence of kidney disease and different types of renal disease in patients with type 2 diabetes (T2DM). METHODS: Cross-sectional study in a random sample of 2,642 T2DM patients cared for in primary care during 2007. Studied variables: demographic and clinical characteristics, pharmacological treatments and T2DM complications (diabetic foot, retinopathy, coronary heart disease and stroke). Variables of renal function were defined as follows: 1) Microalbuminuria: albumin excretion rate > 30 mg/g or 3.5 mg/mmol, 2) Macroalbuminuria: albumin excretion rate > 300 mg/g or 35 mg/mmol, 3) Kidney disease (KD): glomerular filtration rate according to Modification of Diet in Renal Disease < 60 ml/min/1.73 m2 and/or the presence of albuminuria, 4) Renal impairment (RI): glomerular filtration rate < 60 ml/min/1.73 m2, 5) Nonalbuminuric RI: glomerular filtration rate < 60 ml/min/1.73 m2 without albuminuria and, 5) Diabetic nephropathy (DN): macroalbuminuria or microalbuminuria plus diabetic retinopathy. RESULTS: The prevalence of different types of renal disease in patients was: 34.1% KD, 22.9% RI, 19.5% albuminuria and 16.4% diabetic nephropathy (DN). The prevalence of albuminuria without RI (13.5%) and nonalbuminuric RI (14.7%) was similar. After adjusting per age, BMI, cholesterol, blood pressure and macrovascular disease, RI was significantly associated with the female gender (OR 2.20;CI 95% 1.86-2.59), microvascular disease (OR 2.14; CI 95% 1.8-2.54) and insulin treatment (OR 1.82; CI 95% 1.39-2.38), and inversely associated with HbA1c (OR 0.85 for every 1% increase; CI 95% 0.80-0.91). Albuminuria without RI was inversely associated with the female gender (OR 0.27; CI 95% 0.21-0.35), duration of diabetes (OR 0.94 per year; CI 95% 0.91-0.97) and directly associated with HbA1c (OR 1.19 for every 1% increase; CI 95% 1.09-1.3). CONCLUSIONS: One-third of the sample population in this study has KD. The presence or absence of albuminuria identifies two subgroups with different characteristics related to gender, the duration of diabetes and metabolic status of the patient. It is important to determine both albuminuria and GFR estimation to diagnose KD.     

Prospective follow-up study of renal function in type 2 diabetes

Type 2 diabetes mellitus is the main cause of increase in patients suffering from end-stage renal failure in France. We performed an observational study of the change in renal function of type 2 diabetic patients, attending our diabetology clinic. Clinical and biological data were regularly entered in an informatic database (Pénélope, Poitiers University Hospital). We prospectively followed 351 type 2 diabetic patients (age at diagnosis: 40 to 75 years), for 32 months (extremes: 1-120). Renal function was graded in 4 stages according to plasma creatinine and urinary albumin excretion (UAE) determined by nephelometry on random urinary sample: absent (UAE < 20 mg/L et creatinine < 150 mumol/L), incipiens (UAE 20 to 200 mg/L and creatinine < 150 mumol/L), established (UAE = 200 mg/L et creatinine < 150 mumol/L) advanced (creatinine = 150 mumol/L). Glycated haemoglobin (HbA1c) was determined by HPLC. Systolic/Diastolic Blood Pressure (SBP/DBP) was measured with a mercury sphygmomanometer. We defined renal events as the change from one stage of nephropathy to a higher one. A total of 351 type 2 diabetic subjects were studied: 194 men/157 women mean age 63 +/- 11 years, mean diabetes duration 10 +/- 9 yr. At baseline, 206 patients had no nephropathy, 98 incipient nephropathy, 28 established nephropathy and 19-advanced nephropathy. Baseline stage of nephropathy was related to SBP (p < 0.0001), DBP (p = 0.0002), diabetes duration (p = 0.0064) but not HbA1c (p = 0.2182) or sex (p = 0.4794). Among those 332 subjects without baseline advanced nephropathy, 134 progressed in nephropathy. Progression of nephropathy was not related to the presence of hypertension (SBP/DBP > or = 160/95 mmHg) (log-rank = 0.22; p = 0.6377). Conversely, patients with a poor glycaemic control (HbA1c > or = 10%) had a worse renal-event free survival (log-rank = 4.89; p = 0.0269). Glycaemic control is a risk factor for the progression in nephropathy of type 2 diabetic patients.     

Brachial-ankle pulse wave velocity measured automatically by oscillometric method is elevated in diabetic patients with incipient nephropathy.

AIMS: To examine whether brachial-ankle pulse wave velocity (baPWV), a possible early marker of atherosclerotic vascular damage, is associated with albuminuria in patients with Type 2 diabetes. METHODS: BaPWV was measured by automatic oscillometric method in 346 Type 2 diabetic patients with normoalbuminuria (a mean level of three times measurements of albumin-to-creatinine (ACR)<30 microg/mg creatinine; n=200), incipient nephropathy (a mean level of ACR> or =30 and <300 microg/mg creatinine; n=119), and clinical nephropathy (a mean level of ACR> or =300 microg/mg creatinine; n=27), and without peripheral vascular disease. RESULTS: BaPWV (cm/s) was significantly higher in patients with incipient nephropathy (1722 +/- 382) and clinical nephropathy (1763 +/- 322) than in patients with normoalbuminuria (1559 +/- 343, P<0.0001, respectively). By univariate analysis it correlated significantly with age (r=0.44, P<0.0001), systolic blood pressure (r=0.55, P<0.0001), diastolic blood pressure (r=0.42, P<0.0001), albuminuria (r=0.24, P<0.0001) and HbA1C (r=0.11, P<0.05). Albuminuria revealed an independent significant association with baPWV (P<0.01) after adjustment for age, sex, smoking, BMI, HbA1C, hyperlipidemia, and hypertension. Multiple regression analysis showed age, diastolic blood pressure and albuminuria were independently associated with baPWV (adjusted R2=0.42, P<0.0001). CONCLUSIONS: The results might indicate a possible link between the pathogenesis of atherosclerosis and diabetic nephropathy. Future studies are needed to clarify the usefulness and its predictable value.     

Diabetes and Hypertension: Prognostic and Therapeutic Considerations

Hypertension and diabetes are common disorders which frequently co-exist. Both are risk factors for atherosclerotic vascular disease and their combination is associated with an increased incidence of nephropathy, ischaemic heart disease, peripheral vascular disease, and stroke. Several trials such as the HDFP and SHEP studies that included diabetic patients have demonstrated the beneficial effects of antihypertensive therapy in reducing mortality. In diabetes, studies have focussed predominantly on the efficacy of antihypertensive therapy in reducing the progression of diabetic kidney disease. Such therapy has been shown to decrease albuminuria in the setting of “normal” and elevated blood pressure in both type I and type II diabetic patients. This reduction in albuminuria has been observed in microalbuminuric diabetic patients and also in those with overt renal disease. Recent studies in type I diabetic patients with overt nephropathy indicate that these effects on urinary albumin excretion are associated with reduction in the rate of decline in renal function and development of end-stage renal failure. Indeed, several groups have shown that the initiation of antihypertensive therapy improves the prognosis of type I diabetic patients with nephropathy. While certain classes of drugs may reduce the rate of progression of complications such as nephropathy, others have side effect profiles that are disadvantageous in patients with diabetes.     

Plasma N-terminal pro-brain natriuretic peptide in Type 1 diabetic patients with and without diabetic nephropathy.

AIMS: Plasma N-terminal pro-brain natriuretic peptide (NT proBNP) is produced and released from cardiac ventricles; it is elevated in patients with heart failure, hypertension and chronic renal failure. This study aimed to examine the plasma levels of NT proBNP and their relationship in Type 1 diabetic patients with and without diabetic nephropathy. METHODS: We developed a non-competitive immunoluminometric assay with in-house antibodies to the N- and C-terminal domains of NT proBNP. We compared NT proBNP levels between 47 normoalbuminuric patients (group 1), 12 microalbuminuric patients (group 2) and 12 patients with macroalbuminuria (group 3). RESULTS: There were significant differences in 24-h systolic and diastolic blood pressure, diabetes duration, serum creatinine, LDL-cholesterol and HbA1c between the three groups; other parameters did not differ significantly. NT proBNP (median and range) levels were 5 (0.75-68), 22 (0.75-82) and 23 (0.75-374) fmol/ml for groups 1-3, respectively. Log-transformed data of NT proBNP were used to compare all three groups (P=0.016). The Pearson correlation between NT proBNP and albuminuria (R=0.27; P=0.02) was positive; HbA1c (R=0.25; P=0.03) and age (R=0.33; P=0.005) correlated significantly as well. On the basis of multiple regression analysis, the adjusted difference remained significant between the three groups. CONCLUSIONS: This is the first demonstration that NT proBNP levels are significantly higher in Type 1 diabetic patients with albuminuria. This may be caused by a down-regulation of A-type guanylate cyclase-coupled natriuretic peptide receptors in renal tubules or by elevated NT proBNP levels leading to higher glomerular hydraulic pressure or higher capillary permeability and possibly increased albumin excretion. Further studies are required to investigate the potential role of NT proBNP in patients with diabetic nephropathy and such other co-morbidities as cardiovascular disease.     

LDL apheresis for cholesterol embolism following coronary artery bypass graft surgery--a case report

A 76-year-old man without any prior history of abnormal urinalysis findings or renal insufficiency demonstrated mild renal dysfunction after coronary bypass graft surgery (CABG). Two months after CABG, pain and blueness in the toes (blue toe syndrome) appeared and, the serum creatinine level (S-Cr) increased from 1.2 to 2.0 mg/dL. On admission (3 months later), the urinary protein level was 0.5 g/day, white blood cell count 8,300/microL with eosinophils (Eo) 10.5%, S-Cr 2.1 mg/dL, and low-density lipoprotein (LDL) 106 mg/dL. Acute renal failure and blue toe syndrome due to a cholesterol embolism (CE) were diagnosed. Alprostadil 40 microg/day orally for 2 weeks and alprostadil 40 microg/day intravenously were used for 5 weeks, and Eo were 250/microL, S-Cr 2.5 mg/dL; however, blue toe syndrome gradually developed. At 8 weeks after admission, limaprost alfadex 30 microg/day orally was used for 3 weeks. However, the Eo gradually rose to 1,520/microL, S-Cr to 3.0 mg/dL, and LDL to 135 mg/dL, and LDL apheresis was therefore performed 20 times for CE. The data just after LDL apheresis was performed 10 times were as follows: Eo 1,120/microL, S-Cr 4.0 mg/dL, and LDL 89 mg/dL, and blue toe syndrome had disappeared. At 10 months after the first LDL apheresis, the Eo were 630/microL, S-Cr 2.9 mg/dL, and LDL 109 mg/dL. As a result, LDL apheresis was found to be beneficial for the treatment of CE with acute renal failure and blue toe syndrome after CABG.