Urinary copper excretion in type 2 diabetic patients with nephropathy

BACKGROUND/AIMS: The aim of this study was to examine the relationship between the degree of urinary copper excretion and stages of diabetic nephropathy. METHODS: Copper, ceruloplasmin and albumin concentrations were measured in serum and urine samples from 41 type 2 diabetic outpatients with different stages of nephropathy and from 10 healthy controls. The copper/albumin and copper/ceruloplasmin ratios in serum and urine were determined. Furthermore, we examined whether free copper ions are dissociated from ceruloplasmin under various pH conditions. RESULTS: Urinary copper concentrations significantly increased only in macroalbuminuric patients. The copper/ceruloplasmin and copper/albumin ratios in urine were consistently greater than those in serum which were not different between patients and healthy controls except the copper/albumin ratio in macroalbuminuric patients. The ratios in urine decreased in parallel with the progression of nephropathy. Copper was found to be released from ceruloplasmin under acidic conditions. CONCLUSION: Urinary copper excretion in healthy controls may be the result of dissociation from the albumin-copper complex of serum during its passage through the kidney. In diabetic patients with advanced nephropathy, urinary copper excretion may be due to dissociations from both copper-albumin and ceruloplasmin-copper complexes filtered through the damaged glomerulus. Overloading of urinary copper to damaged renal tubules may play some roles in the progression of nephropathy in patients with advanced nephropathy.     

Lipid abnormalities associated with urinary albumin excretion rate in Taiwanese type 2 diabetic patients

BACKGROUND: The purpose of this study was to examine the lipid abnormalities associated with urinary albumin excretion rate (UAER) in type 2 diabetic patients. METHODS: A total of 275 (122 men and 153 women; aged 60.6 +/- 11.1 years) patients were selected with stringent criteria to prevent confounders. Normoalbuminuria (N= 152) and albuminuria (N= 123) were defined as urinary albumin-to-creatinine ratio (ACR) of <30 and > or =30 microg/mg, respectively. Total cholesterol, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and apolipoproteins A1 (ApoA1) and B (ApoB) were measured and non-HDL cholesterol calculated. The subjects were divided into four phenotypes based on triglycerides (<1.5 or > or =1.5 mmol/L) and ApoB (<1.2 or > or =1.2 g/L). RESULTS: Total cholesterol, ApoB, and non-HDL cholesterol were significantly (P < 0.05) higher in patients with albuminuria. For quartiles of the lipid parameters, prevalences of albuminuria showed significant association with ApoB and non-HDL cholesterol (P trend <0.05). After adjusting for age, systolic blood pressure and hemoglobin A(1c) (HbA(1c)) correlation coefficients between the natural logarithm (ln) ACR and lipid parameters, odds ratios for albuminuria, and standardized regression coefficients for ln ACR, were significant for total cholesterol, ApoB and non-HDL cholesterol in all subjects and in men, but only ApoB was significant in women. For patients with normoalbuminuria, frequencies of normotriglycerides/normo-ApoB, hypertriglycerides/normo-ApoB, normotriglycerides/hyper-ApoB, and hypertriglycerides/hyper-ApoB were 44.7%, 28.9%, 10.5%, and 15.8%, respectively; and were 30.1%, 19.5%, 15.4%, and 35.0% for patients with albuminuria (P < 0.001). The respective adjusted odds ratio for albuminuria for the four phenotypes was 1.00, 1.04 (0.54 to 2.00), 2.25 (1.02 to 5.00), and 3.38 (1.75 to 6.53). CONCLUSION: Increased UAER is associated with ApoB-containing lipoproteins and the phenotype of hypertriglycerides/hyper-ApoB is associated with the highest risk of albuminuria. The surrogate marker of non-HDL cholesterol for ApoB is more applicable to the diabetic men.     

Urinary albumin, transferrin and iron excretion in diabetic patients.

The present study was undertaken to determine urinary and serum iron, transferrin and albumin levels in diabetic patients with varying amounts of proteinuria. A highly significant correlation was found between urinary albumin and transferrin excretion over a wide range of urinary albumin excretion (0.005 to 18 g/g creatinine) (r = 0.972). The urine/serum ratio of transferrin and albumin were identical, documenting a similar glomerular leak and tubule handling for these two proteins. In contrast to the above correlation between transferrin and albumin, there was no correlation between iron and either of these proteins until nephrotic range proteinuria had occurred, and even at that time the correlation was much weaker than that found between the proteins (r = 0.680). Urinary iron excretion increased early in the course of diabetic renal disease, being increased in 3 of 11 patients without proteinuria and in 8 of 10 patients with mild proteinuria. All patients with nephrotic range proteinuria had markedly increased urinary iron excretion (150 +/- 166 micrograms/g creatinine vs. 6.4 +/- 0.7 micrograms/g creatinine in controls) and decreased serum iron levels (592 +/- 189 micrograms/liter vs. 979 +/- 394 micrograms/liter in the control group). The iron/transferrin ratio in urine was consistently greater than the iron/transferrin ratio in plasma at all stages of proteinuria. In patients with both subnephrotic and nephrotic range proteinuria, approximately 35 to 40 micrograms Fe/g creatinine was present in the urine with an excess of transferrin. In conclusion, urinary iron excretion is increased early in the course of diabetic renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary albumin as an indicator of diabetic nephropathy lesions in Japanese type 2 diabetic patients

Caucasian type 2 diabetic patients with microalbuminuria (MA) or overt nephropathy (ON) show greater heterogeneity of renal lesions than type 1 diabetic patients. We examined whether a similar situation exists in 30 Japanese type 2 diabetic patients [21 male, age 48 +/- (SD) 8 years, known duration 11 +/- (SD) 8 years] without definable renal disease other than diabetic nephropathy. Six patients were normoalbuminuric (NA), 11 MA, and 13 had ON. Normal controls were 9 age-matched Japanese living-related renal transplant donors. Electron microscopic morphometry was performed on renal biopsy specimens and related to renal function. Glomerular basement membrane width and mesangial fractional volume [Vv(Mes/glom)] were increased in all type 2 diabetic patients groups (NA, MA, ON) as compared with normal controls. The Vv(Mes/glom) correlated directly with urinary albumin/creatinine. However, Vv(Mes/glom) as well as glomerular basement membrane width overlapped among the three functional categories (NA, MA, ON) and normal controls. In conclusion: (1) similar to Caucasian type 2 diabetic patients, Japanese type 2 diabetic patients have greater heterogeneity of renal structure than Caucasian type 1 diabetic patients, and (2) urinary albumin is not a reliable indicator of underlying renal structure in Japanese type 2 diabetic patients.     

Urinary excretion of glycated albumin in insulin-dependent diabetic patients with micro- and macroalbuminuria.

Non-enzymatic glycosylation (glycation) involves both circulating proteins, such as albumin and structural proteins, such as the components of the glomerular basement membrane. Glycated albumin is more anionic than unmodified plasma albumin at physiologic pH. Preferential urinary excretion of glycated proteins has occasionally been reported in diabetes. We therefore investigated the selectivity index (renal clearance of non-glycated/glycated albumin) in 25 insulin-dependent diabetic patients (17 with microalbuminuria and 8 with macroalbuminuria), and 19 healthy subjects. The selectivity index was significantly higher (p less than 0.01) in the microalbuminuric patients than in the macroalbuminuric patients and the control subjects: 1.11 +/- 0.03 SEM vs 0.94 +/- 0.08 vs 0.98 +/- 0.02. These results are not consistent with preferential urinary excretion of glycated albumin in insulin-dependent diabetic patients with increased urinary albumin excretion.     

Course of renal function in type 2 diabetic patients with abnormalities of albumin excretion rate

Heterogeneity in renal structure has been described in type 2 diabetic patients with both microalbuminuria and proteinuria; in fact, only a subset of type 2 diabetic patients have the typical diabetic glomerulopathy. However, it is currently unknown whether abnormalities in albumin excretion rate (AER) have a different renal prognostic value depending on the underlying renal structure. Aims of this study were: 1) to study the course of renal function in type 2 diabetic patients with altered AER; 2) to evaluate the relationship between the course of glomerular filtration rate (GFR) and renal structure; and 3) to evaluate the relationship between the course of GFR and baseline AER levels, metabolic control, and blood pressure levels during a follow-up period of 4 years. A total of 108 type 2 diabetic patients, 74 with microalbuminuria (MA) and 34 with proteinuria (P), were recruited into a prospective study that encompassed: 1) a baseline kidney biopsy with morphometric measurements of glomerular parameters; 2) intensified antihypertensive treatment for an average 4-year period (blood pressure target <140/90 mmHg); and 3) determinations of GFR at baseline and every 6 months. Mean (+/- SD) GFR significantly decreased from baseline in both MA (-1.3+/-9.4 [95% CI -3.51 to +0.86], P < 0.05) and P (-3.0+/-13.0 ml x min(-1) x 1.73 m(-2) per year [-7.71 to +1.61], P < 0.01). However, the changes in GFR were quite heterogeneous. Thus, on the basis of percent GFR change per year from baseline (delta%GFR), both MA and P patients were defined as progressors or nonprogressors when they were below or above the median, respectively. Baseline parameters of glomerular structure had a strong influence on the course of GFR. Indeed, the odds ratios of being progressors significantly increased across the quartiles of baseline glomerular basement membrane (GBM) width and mesangial fractional volume [Vv(mes/glom)], being 2.71 and 2.85 higher, respectively, in the fourth quartile than in the first quartile (P < 0.01 for both). Conversely, nonprogressors outnumbered progressors in the first quartile of GBM width (odds ratio: 2.14, P < 0.05) and in the first quartile of Vv(mes/glom) (odds ratio: 2.28, P < 0.01). Baseline albumin excretion rate (AER) did not influence delta%GFR; in fact, the number of progressors did not increase across quartiles of baseline AER among either MA or P. Similarly, mean blood pressure levels during follow-up (and intensified antihypertensive therapy) did not affect the course of GFR: the number of progressors and nonprogressors did not change across quartiles of mean blood pressure. In contrast, HbA1c during follow-up had an impact on delta%GFR: the odds ratio for being a progressor increased across quartiles of HbA1c, particularly for the highest quartile (HbA1c >9.0%). In conclusion, the course of renal function is heterogeneous in type 2 diabetic patients with microalbuminuria or proteinuria. In fact, a subset of patients has a rapid decline in GFR over a 4-year follow-up period; these patients have more advanced diabetic glomerulopathy and worse metabolic control than the remaining patients, whose GFR remains stable. These two cohorts are otherwise undistinguishable as regards the degree of AER at baseline and tight blood pressure control. Kidney biopsy has an important prognostic role in these patients. Thus, tight blood pressure control, when not associated with satisfactory glycemic control, is unable to prevent rapid GFR decline in type 2 diabetic patients with typical diabetic glomerulopathy.     

Urinary albumin excretion in patients with diabetes after renal transplantation

BACKGROUND: Many studies support microalbuminuria screening as the cornerstone of early detection of nephropathy in patients with diabetes mellitus (DM), but there are no studies that address its utility in the follow-up of renal transplant recipients with DM. MATERIALS AND METHODS: We retrospectively studied 104 subjects with DM who had undergone renal transplantation. Sixty three had a history of preexisting DM and 41 developed posttransplant diabetes (PTDM). We collected data on random urine albumin/creatinine (A/C) ratio, systolic blood pressure (SBP), serum creatinine concentration (Cr), and HBA1C. RESULTS: Mean subject age was 58 +/- 9.8 years; 63% received cadaveric grafts while 37% received living donor grafts. Mean follow-up was 7 years (range 1.6 to 15.6). Seventy percentage developed proteinuria over time; of these 62% developed microalbuminuria (A/C ratio 30 to 300 microg albumin/mg creatinine) and 38% developed macroalbuminuria (A/C ratio >300 microg/mg). Subjects with preexisting DM were as likely to develop an elevated A/C ratio as those with PTDM. Higher A/C ratios correlated with higher SBP (P < .01), with higher HBA1C (P < .036), and with higher Cr (P < .01). Lower A/C ratios correlated with more stable Cr over time (P < .01). CONCLUSIONS: Strict SBP and glycemic control are associated with a significantly lower A/C ratio in patients with DM after renal transplantation. Annual monitoring of A/C ratio in patients with DM after renal transplantation can identify candidates for stricter glycemic and blood pressure control, similar to current recommendations for all other patients with DM.     

Urinary albumin excretion rate and its determinants after 6 years in non-insulin-dependent diabetic patients

BACKGROUND.: The present study was undertaken to clarify the progressionof urinary albumin excretion rate (UAER) in non-insulin-dependentdiabetic (NIDD) patients 6 years after diagnosis, and to elucidatethe risk factors of nephropathy. METHODS.: This is a population-based controlled (base-line) cohort study.The prospective evaluation utilized the diabetic patients asinternal controls. The setting was an urban primary health carecentre. Main outcome measures were the UAER-24 h and fractionalurinary albumin excretion rate (FAC) and their relation to meanblood pressure, haemoglobin A1c, fasting serum insulin and cholesteroland renal size. RESULTS.: UAER (mg/24 h) was increased (geometric mean, quartile 1 and3) in the diabetic patients at baseline, compared to the non-diabeticcontrol subjects; 21(10 and 33) versus 12 (8 and 15), P=0.0001(Wilcoxon's rank test). The UAER-24 h was not increased in diabeticsubjects at follow-up; 24 (7 and 49) P=0.3791 versus diabeticsubjects at baseline. Eighteen per cent of normoalbuminuric(UAER <30 mg/24 h) patients developed microalbuminuria (UAER=30–300mg/24 h) and 3% clinical nephropathy (UAER>300 mg/24 h).Of the microalbuminuric subjects 19% progressed to clinicalnephropathy, 46% remained microalbuminuric and 35% remittedto normoalbuminuria. Serum insulin concentration, after assessmentof confounding factors, measured at the baseline predicted theUAER for all diabetic subjects at follow-up in multiple linearregression analysis in an independent and significant way (P=0.01).Serum insulin concentration (P=0.034) and diuretic therapy (P=0.050)at baseline independently predicted the outcome of the categoricalvariable progressor/nonprogressor (n=22/86) based on the UAER-24h at baseline and at follow-up. CONCLUSIONS.: Progression of the UAER during the first 6 years is found amongapproximately every fifth NIDD subject who develops either microalbuminuria(from normoalbuminuria) or clinical nephropathy (from microalbuminuria).The role of serum insulin (insulin resistance) or some factorassociated with it, is suggestive in the genesis of kidney disease.     

Effects of imidazole-2-hydroxibenzoate on glycosaminoglycan and albumin urinary excretion in type 1 diabetic patients

The effect of imidazole-2-hydroxibenzoate on urinary excretion rates of glycosaminoglycans and albumin in 22 insulin-dependent diabetics with albumin excretion rates under 300 mg/day was evaluated in a 165-day double blind crossover study. Unlike placebo, the drug reduced glycosaminoglycan and albumin excretion rates significantly after 40 and 60 days of treatment, and the effects were significantly intercorrelated. Moreover, a parallel reduction in urinary excretion of N-acetyl-beta-D-glucosaminidase was also observed. These pharmacological effects may have a positive impact on the subsequent natural history of diabetic nephropathy.     

Estimated glomerular filtration rate and urinary albumin excretion are independently associated with greater arterial stiffness: the Hoorn Study

Mild renal insufficiency is a risk factor for cardiovascular disease (CVD). Both a decline in GFR and (micro)albuminuria are associated with greater cardiovascular mortality. In ESRD, arterial stiffness, an important cause of CVD, is known to be greater, but few data exist in individuals with mild renal insufficiency or microalbuminuria. This study investigated the association of impaired renal function expressed as lower GFR or greater urinary albumin excretion with arterial stiffness. In a population-based study in 806 individuals (402 men), mean age 68 yr (range 50 to 87), peripheral arterial stiffness (by compliance and distensibility of the carotid, brachial, and femoral arteries and by the carotid elastic modulus [E(inc)]) and central arterial stiffness (by total systemic arterial compliance, carotid-femoral transit time, and aortic augmentation index) were measured ultrasonically. GFR was estimated (eGFR) by the Modification of Diet in Renal Disease (MDRD) formula. Urinary albumin excretion was expressed as urinary albumin/creatinine ratio (UACR). eGFR was 60.6 +/- 11.1 ml/min per 1.73 m(2). Median UACR was 0.57 mg/mmol (range 0.1 to 26.6). After adjustment for age, mean arterial pressure (MAP), gender, and glucose tolerance status (GTS), each 5-ml/min per 1.73 m(2) lower eGFR was associated with a lower distensibility coefficient of the carotid (regression coefficient beta -0.20 10(-3)/kPa; 95% confidence interval [CI] -0.34 to -0.07 10(-3)/kPa) and brachial artery (-0.15 10(-3)/kPa; 95% CI -0.28 to -0.03 10(-3)/kPa) and a greater carotid E(inc) (0.02 kPa; 95% CI 0.0004 to 0.04 kPa). No statistically significant association was found of eGFR with other arterial stiffness indices. After adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was associated with a greater E(inc) (0.03 kPa; 95% CI 0.001 to 0.07 kPa) and a trend to a lower distensibility coefficient (-0.24 10(-3)/kPa; 95% CI -0.49 to 0.02 10(-3)/kPa) of the carotid artery. After adjustment for age, MAP, gender, and GTS, a greater UACR (per quartile) was in addition associated with a shorter carotid-femoral transit time (-1.67 ms; 95% CI -3.24 to -0.10 ms). These associations were not substantially changed by mutual adjustment for eGFR and UACR. In individuals with mild renal insufficiency, both a lower eGFR and a greater albumin excretion, even below levels that are considered to reflect microalbuminuria, are independently associated with greater arterial stiffness. Moreover, these associations were mutually independent. These findings may explain, in part, why eGFR and microalbuminuria are associated with greater risk for CVD and suggest that amelioration of arterial stiffness could be a target of intervention.     

Urinary excretion of podocytes in patients with diabetic nephropathy.

BACKGROUND: Detection of podocytes in the urinary sediments of children with glomerulonephritis has been shown to indicate severe injury to the podocytes. The aim of the present study was to determine whether podocytes are present in the urine sediments of adult patients with diabetes with and without nephropathy and whether trandolapril is effective for podocyte injury. METHODS: Fifty diabetic patients (10 with normoalbuminuria, 15 with microalbuminuria, 15 with macroalbuminuria and 10 with chronic renal failure) and 10 healthy controls were studied. Urinary podocytes were examined by immunofluorescence using monoclonal antibodies against podocalyxin, which is present on the surface of podocytes. In addition, we studied plasma metalloproteinase (MMP)-9 concentrations in all patients. RESULTS: Urinary podocytes were absent in healthy controls, diabetic patients with normoalbuminuria and diabetic patients with chronic renal failure. Podocytes were detected in the urine of eight diabetic patients with microalbuminuria (53%) and of 12 patients with macroalbuminuria (80%). The number of podocytes in the urine of patients with macroalbuminuria was significantly greater than in patients with microalbuminuria (P:<0.01). However, there was no relationship between urinary albumin excretion and urinary podocytes. In addition, plasma MMP-9 concentrations were significantly correlated with the number of urinary podocytes (P:<0.01). Twelve diabetic patients with macroalbuminuria and eight patients with microalbuminuria who had urinary podocytes were treated with the angiotensin-converting enzyme inhibitor trandolapril. Urinary albumin excretion, the number of podocytes and plasma MMP-9 concentrations were reduced by the trandolapril treatment. CONCLUSIONS: Podocytes in the urine may be a useful marker of disease activity in diabetic nephropathy. Trandolapril may be effective for podocyte injury.     

Urinary albumin excretion is associated with renal functional abnormalities in a nondiabetic population

Microalbuminuria (MA) is an important early sign of diabetic nephropathy. Hyperfiltration and impaired filtration in relation to albuminuria has been well investigated in diabetic subjects. This study tested the hypothesis that an increased urinary albumin excretion (UAE) is associated with renal functional abnormalities also in nondiabetic subjects. The relation between UAE and creatinine clearances (Ccr) in 7728 nondiabetic subjects was studied. Subjects were divided in four groups according to UAE (mg/24 h): 0 to 15 (control), 15 to 30 (high-normal albuminuria [HNA]), 30 to 300 (MA), >300 (macroalbuminuria). An elevated filtration and a diminished filtration were defined as a Ccr exceeding or below 2x the SD of the control group corrected for age and gender. Ccr followed a parabolic trend, with a higher Ccr in the HNA as compared with control and a lower Ccr in the MA and macroalbuminuria group as compared with HNA. With each increasing UAE level, male sex, age, body mass index, minimal waist circumference, systolic and diastolic BP, plasma glucose, and a positive family history for diabetes all followed a significant linear increasing trend (P < 0.001). After adjustment for age, gender, body mass index, plasma glucose, a positive family history for diabetes, systolic and diastolic BP, antihypertensive medication, and smoking in a multivariate analysis, HNA and MA were independently associated with an elevated filtration (RR 1.8 [95% confidence interval, 1.30 to 2.51] and 1.7 [1.17 to 2. 45]). Macroalbuminuria was independently associated with a diminished filtration (4.3 [range, 1.97 to 9.36]). In conclusion, an elevated UAE might be an important and early sign for progressive renal function loss in a nondiabetic population.     

Postprandial glucagon-like peptide 1 secretion is associated with urinary albumin excretion in newly diagnosed type 2 diabetes patients

BACKGROUND Microalbuminuria is an early and informative marker of diabetic nephropathy.Our study found that microalbuminuria developed in patients with newly diagnosed type 2 diabetes mellitus(T2DM).AIM To investigate the association between glucagon-like peptide 1(GLP-1) and microalbuminuria in newly diagnosed T2DM patients.METHODS In total, 760 patients were recruited for this cross-sectional study. The GLP-1levels during a standard meal test and urinary albumin-creatinine ratio(UACR)were dete...     

Urinary albumin excretion in Spanish children

We measured urinary albumin excretion in 2,224 school-children (1,168 boys, 1,056 girls) aged 2–18 years, between 1989 and 1990 to establish reference values. We recorded all pathological antecedents and findings from physical examination, including anthropometric parameters and arterial blood pressure. The analytical study included serum total protein, albumin and creatinine. The second-morning urine and the nightly (rest) 10-h urine sample were collected and we determined the concentration of albumin and creatinine. We found a positive statistically significant correlation between the urinary albumin excretion (g/10 h) and age, height, weight and body surface area. We suggest that it would be useful to relate the urinary albumin excretion to body surface area. The mean value for albumin excretion was 3.49 g/ml in boys and 3.63 g/ml in girls. The urinary albumin/creatinine ratio showed a high correlation with the albumin excretion (r=0.958).The following members are co-authors of this report: N. Caballo, M. A. Arias, C. Serna, M. Ramirez and A. Cornejo     

Urinary albumin excretion in families with type 2 diabetes is heritable and genetically correlated to blood pressure

Urinary albumin excretion in families with type 2 diabetes is heritable and genetically correlated to blood pressure. BACKGROUND: Levels of urinary albumin excretion (UAE) are used to define both the diagnosis of diabetic nephropathy and its progression. Predisposition to high blood pressure is also a risk factor for susceptibility to nephropathy, but its relationship with UAE in type 2 diabetes remains unclear. In this study, we have estimated heritabilities of UAE and blood pressure and their correlation attributable to genetic effects using 96 large families ascertained for type 2 diabetes. METHODS: In these families, 630 individuals with type 2 diabetes and 639 individuals with normoglycemia were examined. All of them had a determination of UAE as the urinary albumin creatinine ratio (ACR), a convenient index of UAE, together with blood pressure and other variables, such as age, sex, and body mass index. A variance components approach was used to estimate heritability and genetic correlations for ACR and systolic and diastolic blood pressures (SBP and DBP) after adjustment for relevant covariates. RESULTS: In the 96 pedigrees, 6481 usable pairs of relatives were identified. In the total collection of pairs, heritability for ACR (h2 = 0.27, P < 0.001) was similar to that for blood pressure. When only pairs of diabetic relatives were analyzed (N = 1732), the estimates of heritability increased slightly for ACR (h2 = 0.31), SBP (h2 = 0.33), and DBP (h2 = 0.23). A significant genetic correlation was found between ACR and SBP (rg 0.27) and DBP (rg 0.26) in all pairs of relatives (P < 0.001). In pairs of diabetic relatives, these values were higher for SBP and DBP, 0.38 and 0.52, respectively. CONCLUSION: In families with type 2 diabetes, UAE is a heritable trait, with a heritability similar to that for blood pressure. A significant genetic correlation between UAE and blood pressure, particularly in the presence of diabetes, indicates that these traits share common genetic determinants.     

Regional arterial stiffness in patients with type 2 diabetes and chronic kidney disease

Increased arterial stiffness is an independent predictor of death from cardiovascular disease, and aortic stiffness is more predictive than stiffness of other arterial regions. Because little is known about the effect of chronic kidney disease (CKD) on regional arterial stiffness, pulse wave velocity (PWV) of four different arterial segments was measured in patients who had type 2 diabetes with and without various stages of CKD. A total of 434 patients had type 2 diabetes, and there were 192 healthy control subjects who were comparable in age and gender. GFR was estimated by the abbreviated Modification of Diet in Renal Disease equation. The patients with diabetes were classified into CKD stages by the definition of the Kidney Disease Outcomes Quality Initiative guidelines. PWV was measured in the heart-femoral, heart-carotid, heart-brachial, and femoral-ankle segments simultaneously using an automatic pulse wave analyzer. PWV of each arterial region was increased in patients who had diabetes without kidney damage and was increased further in a stepwise manner with the advanced stages of CKD. The increase in PWV was greater in the heart-femoral and heart-carotid regions than in the heart-brachial and femoral-ankle segments. However, after adjustment for age, BP, and other confounding factors using a multiple regression model, decreased GFR was independently associated with increased PWV of the heart-femoral region but not with PWV of other arterial segments. In type 2 diabetes, CKD was associated with increased stiffness of arteries, particularly of the aorta. The cross-sectional result may explain the increased risk for cardiovascular disease in CKD, although longitudinal studies are needed to confirm it.     

Compromised arterial function in human type 2 diabetic patients

Diabetes is associated with a perturbation of signaling pathways in vascular tissue, which causes vasomotor dysfunction such as hypertension and accelerated atherosclerosis. In the present study, the mechanisms of vasomotor dysfunction, Akt (Thr308 and Ser473) phosphorylation and expression of endothelial NO (nitric oxide) synthase, and inducible NO synthase were investigated in human diabetic internal mammary arteries. The phospho-Akt (Thr308) level in arteries from diabetic patients was reduced to about one-half of the level in nondiabetic patients, suggesting impaired insulin signaling in human diabetic vascular tissue. Augmented vasoconstriction was observed in diabetic arteries, due in part to deficiency of basal and stimulated NO production. This correlated with decreased endothelial NO synthase expression and activity in diabetic vessels. The sensitivity of diabetic vessels to the NO donor, sodium nitroprusside, was reduced as well, suggesting that NO breakdown and/or decreased sensitivity of smooth muscle to NO are also responsible for abnormal vasoconstriction. In addition, the abnormal vasoconstriction in diabetic vessels was not completely abolished in the presence of Nomega-nitro-L-arginine methyl ester, revealing that NO-independent mechanisms also contribute to vasomotor dysfunction in diabetes. In conclusion, diabetes downregulates the Akt-signaling pathway and compromises human arterial function through a decrease in NO availability as well as through NO-independent mechanisms.     

Weight loss independently predicts urinary albumin excretion normalization in morbidly obese type 2 diabetic patients undergoing bariatric surgery

Background

Despite obesity being closely associated with two common risk factors for albuminuria, namely type 2 diabetes mellitus (T2DM) and hypertension, information on the impact of weight loss on albumin excretion rate in morbidly obese (MO) subjects is scarce.

Objective

To evaluate the independent contribution of weight loss following bariatric surgery (BS) to the improvement of the albumin-to-creatinine ratio (ACR) in MO subjects with T2DM.

Subjects and methods

Observational prospective study, including consecutive (n = 255) patients undergoing Roux-en-Y gastric bypass (GBP) or sleeve gastrectomy (SG) of whom 37.6 % (n = 96) presented with T2DM. Stepwise logistic regression analysis was used to assess the contribution of T2DM-related, hypertension-related, and weight loss-related variables, and type of surgery to normalization of ACR (<30 mg/g) at 12 and 24 months follow-up.

Results

In T2DM subjects, baseline ACR was 85.7 ± 171 mg/g with ACR ≥30 mg/g being present in 45.7 % of the cohort. At 12 months, the ACR significantly decreased in T2DM subjects (42.2 ± 142.8 mg/g; p < 0.005) with no further reduction at 24 months after surgery (44.4 ± 227.7; p = 0.862). Among T2DM subjects with ACR ≥30 mg/g at baseline, the ACR became <30 mg/g in 58.5 % and 76.9 % at 12 and 24 months, respectively (p < 0.001 relative to baseline). Body mass index (BMI) change from baseline was the only independent predictor of ACR normalization at 12 months [Exp(B) 1.373, 95 % confidence interval 1.075–1.703; p < 0.05]. None of the evaluated variables appeared as an independent predictor of ACR normalization at 24 months.

Conclusions

Our data suggest that, in MO subjects with T2DM, interventions aiming at slowing the progression of nephropathy should not only focus on optimization of glucose and blood pressure control but also include effective weight loss strategies.     

Urinary albumin excretion in renal transplant donors

Twenty-four hour urinary albumin excretion was measured using sensitive methods in 129 renal transplant donors 1 to 22 years (mean 7.3 years) after kidney donation. The 24 hour urinary albumin excretion values for the donor group was 6 +/- 9.9 mg (mean +/- standard deviation) (range of 0.1 to 65.2 mg) and was 7.7 +/- 4.5 mg for the control group. Five donors (3.9 percent) had 24 hour urinary albumin excretion levels of 25.5 to 65.2 mg 6 to 13 years after donation, values that were greater than a single value from any member of the control group. Elevated diastolic blood pressure (90 mm Hg or greater) was present in these five donors, and in three, labile or established hypertension was present at the time of donation. It is likely that more careful screening of potential donors with labile or fixed hypertension would further reduce the incidence of microalbuminuria in the renal transplant donor. We conclude that urinary albumin excretion values are within the normal range in most renal transplant donors studied several years after renal donation.