Mechanism of increased serum cytokeratin 19 fragment levels in patients with diabetic nephropathy as a model of chronic renal failure

We examined serum and urinary cytokeratin 19 fragment (CYFRA 21-1) levels in patients with diabetic nephropathy as a model of chronic renal failure, to investigate the mechanism of increased serum CYFRA 21-1 levels in chronic renal failure. Serum and urinary CYFRA 21-1 levels in non-insulin-dependent diabetes mellitus (NIDDM) patients with abnormal urinary immunoglobulin G (IgG) levels (>1.1 mg/g x Cr, n=126) were higher than those with normal urinary IgG levels. In NIDDM patients with normal urinary IgG levels (n=81); the urinary albumin or transferrin levels were not related to serum or urinary CYFRA 21-1 levels. We speculate that the increased serum CYFRA 21-1 levels contribute to metabolic abnormality in the kidney itself rather than the decreased urinary excretion per se, and that increased urinary CYFRA 21-1 levels are found in advanced cases of diabetic nephropathy with destruction of the size barrier.     

The diabetes mellitus regimen

Some patients with essential hypertension manifest increased urinary albumin excretion (UAE). Hypertensive patients with microalbuminuria manifest abnormal circadian variation of blood pressure, increased serum levels of LDL-cholesterol and lipoprotein(a), a greater rise of serum insulin in response to an oral glucose tolerance test, and greater thickness of the carotid artery than patients without microalbuminuria. A 7 year follow-up of 141 hypertensive patients, 54 with microalbuminuria and 87 without microalbuminuria, we observed 12 cardiovascular events in patients with microalbuminuria and only 2 events in the patients with normal urine albumin excretion (P < 0.0002). Creatinine clearance decreased more in patients with microalbuminuria than in those with normal UAE. In conclusion, hypertensive individuals with microalbuminuria manifest a greater incidence of cardiovascular events and more decline in renal function than patients with normal UAE. We propose that measurements of UAE may be a useful marker for cardiovascular risk in patients with essential hypertension.     

Specific fluorescence assay for advanced glycation end products in blood and urine of diabetic patients

Late rearrangement products that accumulate by glycation of proteins, known as advanced glycation end products (AGEs), have been implicated in the pathogenesis of complications related to diabetes. Circulating AGEs, especially in the form of a small peptide (AGE-peptide) of less than 10 kd, increase in the blood of diabetic patients with end-stage renal disease (ESRD). The aim of the study was to evaluate AGE-peptide levels by measuring AGE-specific fluorescence (excitation at 370 nm and emission at 440 nm) and to examine the relationship between AGE-peptide and diabetic nephropathy. AGE-specific fluorescence in serum and urine were examined in diabetic subjects with various levels of renal complications of varying severity: normoalbuminuria (N), microalbuminuria (Mi), macroalbuminuria (Ma), chronic renal failure (C), and hemodialysis (HD). We also assessed correlations among the AGE-peptide level and age, duration of diabetes, hemoglobin A1c (HbA1c), serum creatinine, and creatinine clearance. Serum and urine AGE-peptide levels in C and HD were significantly higher than in N, Mi, and Ma. Serum AGE-peptide levels were significantly correlated with serum creatinine (r=.866, P < .0001) and creatinine clearance (r=-.720, P < .0001) but not with duration of diabetes or age. There was a significant correlation between AGE-peptide levels measured by enzyme-linked immunosorbent assay (ELISA) and levels determined from the specific fluorescence intensity (r=.688, P < .0001). These findings suggest that renal function may play a greater role in the accumulation of AGEs than persistent hyperglycemia in diabetic patients. Measurement of AGE-specific fluorescence (ie, AGE-peptide) may serve as a simple and useful test to assess circulating AGE levels and monitor AGE excretion.     

Urinary excretion and clearance of insulin in diabetic and normal children and adolescents

Seventy-two diabetic (38 males) and 86 normal (41 males) children provided timed overnight urine collections. Fourteen of the diabetic and 33 of the normal children had concurrent overnight plasma insulin profiles. Urinary insulin clearance in the diabetic subjects was compared with excretion of albumin, growth hormone, retinol-binding protein, and N-acetyl-beta-D-glucosaminidase. In the normal subjects, urinary insulin excretion correlated with mean overnight plasma levels in the boys (r = 0.82, p < 0.001) but not in the girls (r = 0.32), and varied with puberty stage in the boys. Insulin clearance was greater in boys than girls during puberty, and fell in both sexes with advancing puberty. Insulin excretion was greater in diabetic than normal children in both sexes at all puberty stages. Insulin clearance was also greater in diabetic than normal subjects (1.05 +/- 0.1 ml min-1 1.73 m-2 vs 0.48 +/- 0.05 ml min-1 1.73 m-2, p < 0.001). Insulin excretion as a percentage of the filtered load was also greater in diabetic than normal subjects (1.9 +/- 0.27% vs 0.85 +/- 0.09%, p < 0.01). In the diabetic children, there was a correlation between urinary insulin and growth hormone excretion (r = 0.52, p < 0.02), and retinol-binding protein in those (n = 10) with higher retinol binding protein excretion (r = 0.76, p = 0.01). The value of urinary insulin excretion as a measure of free plasma insulin levels in normal and diabetic children may be limited by sex differences in renal insulin clearance, and by proximal renal tubular dysfunction in children with diabetes.     

The impact of a national impregnated bed net programme on the outcome of pregnancy in primigravidae in The Gambia

The effect of the non-ionic contrast medium iohexol (Omnipaque) on renal function was investigated in diabetic patients with signs of peripheral ischaemia. Forty-six patients, 70 +/- 11 years (mean +/- SD) old, age at diabetes diagnosis 53 +/- 17 years, and with varying degrees of diabetic nephropathy were studied before 1, 2, and 30 days after aortobifemoral arteriography. Serum creatinine, creatinine clearance, urinary excretion of immunoglobulin G, albumin collagen IV (NC1), kappa and lambda chains, alpha-1 microglobulin and Tamm-Horsfall protein were evaluated. Within 1 month before and 30 days after arteriography, the glomerular filtration rate was measured by clearance of iohexol. The acute effect of the radiocontrast medium was an increase in the serum creatinine level in 41 (89%) patients, with a more than 25% increase in 12 (26%) patients. The excretion rates of immunoglobulin G and albumin decreased, whereas the proximal and distal tubular function and the excretion of collagen IV did not change. The increment in serum creatinine was associated with the preangiographic renal function (p < 0.05), a history of heart failure (p < 0.01), but not with age, duration and type of diabetes, gender, systolic or diastolic blood pressure, glycated haemoglobin (HbAlc) or blood glucose levels. The increase of serum creatinine was associated with a pre-existing proximal tubular dysfunction and a worsening of distal tubular function. No changes in the parameters measured persisted 30 days after angiography. In summary, a transient increment in serum creatinine level after arteriography occurred in 89% of diabetic patients. It was associated with the preangiographic renal function, a history of heart failure and signs of preexisting proximal tubular dysfunction and worsening of distal tubular function. However, these changes were reversible.     

Urinary excretion of apo(a) fragments in NIDDM patients

Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA1c or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM.     

A longitudinal study of seroreactivity against Mycoplasma penetrans in HIV-infected homosexual men: association with disease progression

The soluble form of the vascular cell adhesion molecule-1 (VCAM-1) is detectable in human sera and is elevated in diabetic patients, with unknown clinical significance. In the present study, the relationship between serum soluble VCAM-1 and diabetic microvascular complications (retinopathy, nephropathy, and neuropathy) was evaluated in 95 Japanese patients with Type 2 diabetes mellitus (DM). Serum soluble VCAM-1 concentration was higher in patients with more advanced stages of retinopathy as well as nephropathy. There was a significant correlation between soluble VCAM-1 and log10 (urinary albumin excretion) in 69 patients with normal serum creatinine levels (r = 0.51, p < 0.0001) and a significant correlation between soluble VCAM-1 and log10 (serum creatinine) in all the patients (r = 0.83, p < 0.0001). Soluble VCAM-1 concentration was also elevated in patients with neuropathy. There was a significant correlation between soluble VCAM-1 concentration and the number of microvascular complications (r = 0.59, p < 0.0001). However, multivariate regression analysis revealed that only diabetic nephropathy, was associated with the soluble VCAM-1 concentration. The elevation of circulating VCAM-1 level in diabetic nephropathy may result from underlying systemic endothelial dysfunction, increased VCAM-1 production in damaged renal tubular or glomerular epithelial cells and/or decreased renal clearance of this molecule, depending on the stage of nephropathy.     

Urinary fibrin-fibrinogen degradation products in nephrotic syndrome

The urinary concentration of fibrin-fibrinogen degradation products (F.D.P.) was measured in 90 patients with proteinuria above 2 g/1 and correlated with proteinuria, differential protein clearances, serum urea and creatinine, and renal biopsy findings. There was a linear correlation (r equals 0-7; P less than 0-001) between the urinary F.D.P. excretion and the selectivity of the proteinuria such that patients with highly selective proteinuria excreted only small amounts of F.D.P. whereas those with non-selective proteinuria excreted much higher levels. There was a significant correlation between the urinary F.D.P. excretion and the urine:serum (U:S) ratio of IgG excretion but not with the U:S ratio or urinary excretion of albumin or transferrin. Sephadex G200 column chromatography of the concentrated urine in 26 cases showed that patients with highly selective proteinuria excreted predominantly F.D.P. of low molecular weight in the urine whereas those with non-selective proteinuria excreted mainly fibrinogen and products of high molecular weight. Hence the type and quantity of F.D.P. in the urine are determined primarily by the differential filtration of fibrinogen and the various degradation products from the plasma through the glomerular basement membrane, which in turn is determined by the "pore size" of the basement membrane. In clinical nephrology measurement of the urinary F.D.P. level provides a rapid and convenient means of estimating the differential protein clearance.     

Renal structural-functional relationships in early diabetes mellitus

To define the earliest renal morphological changes in patients with type I diabetes, we studied renal function and morphometric analysis of renal biopsies in 59 patients with diabetes for 5-12 years and normal blood pressure, normal creatinine clearance (CCr), and negative dipstick urinary protein. Arteriolar hyalinization and intimal fibrous thickening were noted in 43%. Glomerular basement membrane thickness and fractional mesangial volume were increased in 51% and 56%, respectively. The pre-pubertal and post-pubertal years of diabetes were associated with similar degrees of renal structural changes, but during the pre-pubertal years normal urinary albumin excretion (UAE) was seen. Principal factor analysis of morphometric structural parameters yielded four clusters of variables: "glomerular size" correlated with patient age, CCr, and UAE; "peripheral capillary decrease" correlated with glycosylated hemoglobin, diastolic blood pressure, glomerular filtration rate, and UAE; "mesangial increase" correlated with UAE; and "interstitial scarring" correlated with diastolic blood pressure. This study provides unique documentation of renal structural abnormalities which precede clinically evident renal functional abnormalities and documents that these early structural abnormalities are present in the pre-pubertal years of diabetes as well as postpuberty, and are associated with each other in constellations that correspond to postulated mechanisms in diabetic nephropathy.     

Relationship of thyroid states and serum thrombomodulin (TM) levels in patients with Graves' disease: TM, a possible new marker of the peripheral activity of thyroid hormones

Thrombomodulin (TM) is a thrombin receptor glycoprotein that functions as an anticoagulant on the surface of endothelial cells. Serum TM is regarded as a new marker of generalized endothelial cell damage. Serum TM concentrations were measured in 75 patients with Graves' disease and 75 age- and sex-matched healthy subjects. Serum TM levels in patients in the hyperthyroid state were significantly increased, while those in patients in the hypothyroid state due to treatment were significantly decreased compared with levels in control subjects. All patients with untreated Graves' disease had markedly elevated TM levels. Serum TM levels correlated closely with thyroid hormone concentration (TM vs. free T4, r = 0.858; P = 0.001). Serial measurement of individual patients revealed that serum TM levels paralleled thyroid hormone concentration, reaching normal control values upon attainment of euthyroidism. On the other hand, there was no significant correlation between serum TM concentration and titer of antithyroglobulin antibodies, titer of antimicrosomal antibodies, serum thyroglobulin level, or goiter size, and serum TM was not directly influenced by TSH receptor antibodies or resting pulse rates. The close correlation between serum TM and thyroid hormone concentration suggests that thyroid hormones might influence the synthesis or metabolism of TM on the surface of endothelial cells in patients with Graves' disease.     

Guiding dialogue in the transformation of teacher-student relationships

We evaluated the role of tissue inhibitors of metalloproteinase-1 (TIMP-1) in patients with diabetic nephropathy by comparing the serum and urine TIMP-1 levels with those of renal biopsy specimens. A total of 35 diabetic patients were divided into four groups, D0, DI, DII and DIII-IV, according to the severity of diffuse glomerular lesions using Gellman's criteria. Using serum and 24-hour urine specimens, TIMP-1 was measured by a sandwich enzyme immunoassay. Serum and urinary TIMP-1 showed significant increases in association with the progress of glomerular diffuse lesions. There was no correlation between serum TIMP-1 and serum creatinine, creatinine clearance, serum and urinary beta 2-microglobulin, urinary NAG, HbA1c, or urinary TIMP-1. There was a significant correlation between urinary TIMP-1 and urinary albumin, and was a significant correlation between urinary TIMP-1 and urinary NAG. We conclude that TIMP-1 has a potential role in the regulation of glomerular matrix accumulation in diabetic nephropathy.     

Endoscopic endonasal dacryocystorhinostomy: indications, technique and results

To understand the changes of urinary endothelin-1 (ET-1) concentrations in acute renal failure (ARF) and to investigate the origin of human urinary ET-1, we studied urinary ET-1 excretion in 70 normal children and 12 children with ARF caused by tubular dysfunction. Urinary ET-1 excretion was expressed as a ratio of urinary ET-1 to urinary creatinine (ET-1/Cr). Among healthy children, the highest urinary ET-1/Cr values were found during infancy. In patients with ARF, there was a positive correlation between urinary ET-1/Cr values and daily total urinary ET-1 (r = 0.42, n = 26, p < 0.05). Plasma ET-1 concentrations were elevated in children with ARF during the period of peak serum creatinine concentration. During the course of ARF, the lowest urinary ET-1/Cr value occurred during the period of peak serum creatinine, whereas the plasma ET-1 concentration declined after the peak. These results provide insight into the developmental changes of urinary ET-1 values in normal children, and illustrate the pattern of changes in plasma and urinary ET-1 concentrations during the course of ARF in children. The results suggest that renal production, rather than clearance from the circulation by glomerular filtration, may be the source of urinary ET-1.     

Prorenin and renal function in NIDDM patients with normo- and microalbuminuria

OBJECTIVES: To assess whether prorenin is elevated and perhaps a predictor of deteriorations in albuminuria and/or renal function in NIDDM patients with normo- and microalbuminuria. DESIGN: A cross-sectional and a longitudinal study. SETTING: Outpatient diabetic clinic. SUBJECTS: Twenty-eight NIDDM patients (16 with normoalbuminuria, 12 with microalbuminuric) and 16 healthy subjects, matched for sex, age and BMI. Fifteen patients were reinvestigated after (mean [range]) 3.1 (2.1-4.3) years. MAIN OUTCOME MEASURES: Serum prorenin and renin, urinary albumin excretion rate, and glomerular filtration rate. RESULTS: Serum prorenin was similar in both normoalbuminuric (116x/divided by) 1.9 microU ml-1 (geometric meanx/divided by antilog SD) and microalbuminuric (124x/divided by) 1.7 microU ml-1) as well as in healthy control subjects (90x/divided by) 1.7 microU ml-1). Prorenin did not correlate to either urinary albumin excretion rate or glomerular filtration rate. No difference between baseline and follow-up levels of albuminuria, glomerular filtration rate or prorenin were observed. The annual changes in albuminuria, glomerular filtration rate and prorenin were not correlated, and no correlation was found between baseline prorenin levels and annual changes in albuminuria or glomerular filtration rate. CONCLUSIONS: Serum prorenin levels are not elevated in either normoalbuminuric or microalbuminuric NIDDM patients, and serum prorenin is not a valid predictor of long-term changes in albuminuria in this patient group.     

Increasing required neural response to expose abnormal brain function in mild versus moderate or severe Alzheimer''s disease: PET study using parametric visual stimulation

OBJECTIVES: Glycaemic control often deteriorates during puberty in girls with insulin dependent diabetes mellitus (IDDM). This may be due in part to the normal psychosocial changes associated with adolescence. Puberty is, however, also characterized by rapid somatic development, orchestrated by hormonal changes. Some of these hormones play a major role in glucose homeostasis. We have examined the insulin-GH-IGF-I axis in 11 adolescent girls with poorly controlled insulin dependent diabetes and compared the data with those of 10 non-diabetic girls matched for age, pubertal stage and body mass index (BMI). METHODS: Serum profiles of glucose, insulin, GH and IGF binding protein 1 (IGFBP1) were analysed in addition to IGF-I in serum and nocturnal urinary excretion of GH. MEASUREMENTS: Serum glucose, insulin and IGFBP1 were measured every hour for 24 h, whereas GH in serum was measured every 30 minutes during the same period. Nocturnal urinary GH was analysed as a mean of three consecutive nights. RESULTS: The insulin profiles of the IDDM patients were flat with low post-prandial peaks, corresponding to only one-third of the peaks of the non-diabetic girls. The integrated insulin levels, both during 24-h sampling and during daytime, were significantly lower in the diabetic group. There were no differences during night-time. The diabetic patients had elevated mean baseline levels of serum GH (IDDM 2.8 +/- 0.5 mU/l, controls 0.7 +/- 0.2; P < 0.001), a higher 24-h mean serum GH level (9.8 +/- 1.7 mU/l vs. 4.4 +/- 0.7; P < 0.001), significantly more peaks and a urinary GH excretion twice as high as in the non-diabetic group. An interesting observation was the finding of marked differences in daytime GH concentrations between the groups, both regarding overall integrated levels (GH AUC 103 +/- 15.8 and 35.9 +/- 7.1 mU/l x 12 h, respectively; P < 0.005) as well as baseline levels (3.8 +/- 0.6 mU/l vs. 0.7 +/- 0.2; P < 0.001). In contrast, during night-time only the mean basal levels of GH differed. The level of IGF-I was reduced in the diabetic group compared with the healthy controls (IDDM 233 +/- 19 micrograms/l vs. controls 327 +/- 21; P < 0.005). In addition, the IDDM patients had significantly increased concentrations of IGFBP 1, but kept a normal diurnal rhythm with a pronounced night peak. CONCLUSION: Hypoinsulinaemia in adolescent IDDM patients, particularly in the portal hepatic circulation, results in decreased IGF-I and increased IGFBP 1 production in the liver. High levels of IGFBP 1 may, in turn, reduce the bioactivity of IGF-I even further. Low levels of IGF-I will lead to increased GH secretion. Earlier studies on the relationship between GH and diabetic control have focused on elevated GH levels during the night. In this study we have observed markedly elevated levels of GH also during daytime in adolescent IDDM patients. This indicates increased insulin resistance and insulin demand also during the day in diabetic subjects. The increased insulin resistance may result in hyperglycaemia leading to additional insulin resistance. A vicious circle may thus be induced, accelerating metabolic impairment in poorly controlled adolescent IDDM girls.     

Clinical evaluation of serum 1,5AG levels in patients with liver cirrhosis

We measured serum 1,5 anhydroglucitol (1,5AG) levels by HPLC in 32 patients with liver cirrhosis, 32 with diabetes mellitus and 61 normal subjects. Serum 1,5AG was significantly lower in patients with diabetes mellitus and liver cirrhosis compared with that in normal subjects. Serum levels of type IV collagen were higher in patients with liver cirrhosis than in those without liver cirrhosis. A negative correlation was observed between serum 1,5AG and type IV collagen in patients with liver cirrhosis (r = -0.37, p < 0.05), but not in patients with diabetes mellitus. These data suggest that serum 1,5AG levels reflect the degree of liver cirrhosis.     

Free and total insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and IGFBP-3 and their relationships to the presence of diabetic retinopathy and glomerular hyperfiltration in insulin-dependent diabetes mellitus

The existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. Free IGF-I may have greater physiological and clinical relevance than total IGF-I. Recently, a validated method has been developed to measure free IGF-I levels in the circulation. Serum free and total IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in 56 insulin-treated IDDM patients and 52 healthy sex- and age-matched controls. Diabetic retinopathy was established by direct fundoscopy. In 54 IDDM patients, the glomerular filtration rate (GFR) and effective renal plasma flow were calculated from the clearance rate of [125I]iothalamate and [131I]iodohippurate sodium. Fasting free IGF-I, total IGF-I, and IGFBP-3 levels were significantly lower in IDDM patients than in age- and sex-matched healthy controls (free IGF-I, P < 0.005; total IGF-I, P < 0.001; IGFBP-3, P = 0.001), whereas IGFBP-1 levels were higher (P < 0.001). In IDDM subjects, decreases in free IGF-I, total IGF-I, and IGFBP-3 levels with age were observed (free IGF-I, r = -0.27 and P = 0.05; total IGF-I, r = -0.52 and P < 0.001; IGFBP-3, r = -0.37 and P = 0.005). Free IGF-I was inversely related to fasting glucose in IDDM subjects (r = -0.35; P = 0.01), whereas the relationship between total IGF-I and fasting glucose did not reach significance (r = -0.27; P = 0.06). Age-adjusted free IGF-I levels were significantly higher (P < 0.05) in IDDM subjects with retinopathy than in subjects without retinopathy after adjustment for age. Total IGF-I and IGFBP-3 levels were positively related to GFR (total IGF-I, r = 0.35 and P < 0.05; IGFBP-3, r = 0.28 and P < 0.05). Both of these differences lost significance after adjustment for age. Free IGF-I, total IGF-I, and IGFBP-3 levels were lower and IGFBP-1 levels were higher in insulin-treated IDDM subjects compared to those in age- and sex-matched controls. Free IGF-I, total IGF-I, and IGFBP-3 levels decreased significantly with age in IDDM subjects. Age-adjusted free IGF-I levels in subjects with diabetic retinopathy were higher than those in subjects without diabetic retinopathy. Total IGF-I and IGFBP-3 levels were positively related to GFR in IDDM subjects, but these relations were lost after adjustment for age. Measurement of serum free IGF-I levels in IDDM subjects did not have clear advantages compared to that of total IGF-I, IGFBP-1, and IGFBP-3 levels. Serum IGF-I and IGFBPs reflect their tissue concentrations to a various degree. Consequently, extrapolations concerning the pathogenetic role of the IGF/IGFBP system in the development of diabetic complications at the tissue level remain speculative.     

Renal and cardiovascular predictors of 9-year total and sudden cardiac mortality in non-insulin-dependent diabetic subjects

BACKGROUND: The objective was to evaluate the impact of urinary albumin excretion rate (UAER), glomerular filtration rate (GFR) and subclinical autonomic neuropathy (SANP) on 9-year total (TM) and sudden cardiac mortality (SCM) in recently diagnosed (< 1 year; RD; n = 150) and known (mean duration 11 years; KD; n = 146) NIDDM subjects. METHODS: The study was prospective and controlled (n = 150). Mortality predictors were analysed by logistic regression analysis. The dependent variables were TM and SCM, the predictors were UAER, GFR, SANP, age, gender, BMI, mean arterial pressure (MAP), fasting serum cholesterol, HDL-cholesterol, triglycerides, insulin, haemoglobin A1c, diabetes duration, QTc-interval (ECG), coronary heart disease (CHD), peripheral vascular disease (PVD), cerebrovascular disease (CVD), congestive heart failure (CHF), antihypertensive therapy, and smoking habits. RESULTS: CHD predicted TM and SCM in both RD (P = 0.041 and 0.029) and KD (P = 0.034 and 0.006). PVD predicted TM and SCM in KD only (P = 0.001 and 0.003). CVD predicted TM and SCM in RD only (P = 0.001 and 0.017). In RD male gender (P = 0.049), fasting serum cholesterol (P = 0.007) and CHF (P = 0.001) predicted TM and in kDa haemoglobin A1c (P = 0.004), age (P = 0.001) and MAP (P = 0.014) predicted TM. Serum triglycerides predicted SCM in both RD and kDa (P = 0.001 and 0.003). SANP predicted TM (P = 0.009) and SCM (P = 0.044) in KD only. GFR (inverse value) predicted TM and SCM (P = 0.04 and 0.027) in kDa only. The UAER did not predict mortality in the diabetic subjects. CONCLUSION: SANP and a slightly reduced GFR still in the normal range predicted mortality in KD. Microalbuminuria (30 < UAER < 300 mg/24 h) did not independently predict 9-year mortality in the NIDDM subjects studied.     

The significance of urinary N-acetyl-beta-D-glucosaminidase for predicting early stage diabetic nephropathy

We studied urinary N-acetyl-beta-D-glucosaminidase (NAG) in the early stage of diabetic nephropathy in 27 non-insulin-dependent diabetes mellitus (NIDDM) patients with a microalbumin level below 20 mg on 24-hour urine sample. Microalbumin and NAG excretion were measured in 24-hour urine samples collected on three separate occasions within seven days of admission. Creatinine clearance was determined simultaneously. There was a significant negative correlation between the creatinine clearance and 24-hour urinary NAG (r = -0.38, p < 0.05). Elevation of urinary NAG may indicate decreased renal function during early stage NIDDM nephropathy.     

Striving to prevent falls in an acute care setting--action to enhance quality

Endothelial damage is thought to be a contributing factor in the pathogenesis of Thrombotic Thrombocytopenic Purpura/Hemolytic Uremic Syndromes (TTP/HUS). The present studies measured two markers of endothelial cell stimulation and/or activation [von Willebrand Factor (vWF:Ag) and thrombomodulin (TM)] in patients with TTP/HUS disorders and compared them to controls. The patient groups consisted of adults with TTP/HUS, with (n = 13) and without (n = 14) peak Cr levels >2.0 mg/dl. Additionally, 52 patients with Bone Marrow Transplant-associated Thrombotic Microangiopathy (BMT-TM) following allogeneic BMT were evaluated. Both vWF:Ag and TM were elevated in all patient groups compared to controls. TTP/HUS patients with peak Cr >2.0 mg/dl had higher TM levels (P < 0.001) than did those with peak Cr levels below 2 mg/dl. However, thrombomodulin/ creatinine (TM/Cr) ratios did not differ in these two groups nor did they differ from controls. BMT-TM pts had higher vWF:Ag levels and higher TM/Cr ratios than controls and TTP/ HUS, P < 0.001. The median TM/Cr ratio in BMT-TM was 91 (range = 34-229) compared to 38 (range = 29-50) in controls, P < 0.001 and 38 (range = 6 to 156) in TTP/HUS, P < 0.001. Additionally both TM (P < 0.001) and TM/Cr (P < 0.02) were higher in patients with Grades 3 and 4 BMT-TM compared to those with Grade 2 BMT-TM. These results suggest that endothelial cell activation occurs in TTP/HUS and BMT-TM. Since TM/Cr ratios were higher in BMT-TM compared to TTP/HUS, these findings suggest that the mechanism of elevated TM in BMT-TM cannot be explained solely by altered renal excretion. Taken together, these findings strongly indicate a role of endothelial cell damage in BMT-TM.     

Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions

The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers.