Early and late effects of low-dose aspirin on renal function in elderly patients

Background

Although low-dose aspirin is used by many elderly patients, monitoring of renal function is currently not recommended. We recently reported transient retention of uric acid and creatinine caused by aspirin in doses of 75 to 325 mg/d. We therefore evaluated the renal effects of aspirin (100 mg/d), including post-treatment effects.

Methods

We studied 83 stable geriatric patients in long-term care (aged 56 to 98 years) who were treated with low-dose aspirin (100 mg/d) for 2 weeks and 40 control patients. Other medications and diet were kept constant. Biochemical monitoring including blood samples and 24-hour urinary collections for creatinine and uric acid at baseline and weekly for a total of 5 weeks.

Results

After 2 weeks on aspirin, urinary excretion of creatinine decreased in 60 (72%) and excretion of uric acid decreased in 54 (65%) of the 83 patients, and their mean clearances decreased; during the same period, serum blood urea nitrogen, creatinine, and uric acid levels increased (P <0.05 for all). Deterioration from baseline levels was significantly greater (and more prevalent) in the aspirin-treated group than in the 40 control patients (P = 0.001 to 0.09). After withdrawal of aspirin these parameters improved. However, 3 weeks after stopping aspirin, 48% (35 of the 73 in whom this measurement was available) had a persistent decline in creatinine clearance from baseline, as compared with only 8% (3/36) controls (P <0.001).

Conclusion

Short-term low-dose aspirin treatment may affect renal function in elderly patients. These effects persist 3 weeks after cessation of the drug in some of these patients.     

Effect of intermittent administration of 200 IU intranasal salmon calcitonin and low doses of 1α(OH) vitamin D3 on bone mineral density of the lumbar spine and hip region and biochemical bone markers in women with postmenopausal osteoporosis: a pilot study

A 1-year prospective, open, randomized, controlled trial was conducted as a pilot study to examine the effect of intermittent administration of 200 IU intranasal salmon calcitonin and 1(OH) vitamin D₃ [1(OH)D₃] on bone mineral density (BMD) of the lumbar spine and hip as well as on the markers of bone metabolism in women with postmenopausal osteoporosis. A total of 102 randomly recruited women received either 200 IU intranasal salmon calcitonin (Miacalcic nasal 200, Novartis, Basel, Switzerland) daily, 1 month on–1 month off, 0.25 g 1(OH)D₃, and 500 mg elemental calcium continuously (n=57 women) or only 0.25 g 1(OH)D₃ and 500 mg calcium (n=45 women) for a period of 1 year. BMD of the lumbar spine and hip plus biochemical markers reflecting calcium (Ca) metabolism and bone turnover [serum Ca, serum phosphorus, intact parathormone (iPTH), total and bone-specific alkaline phosphatase, osteocalcin levels, 24-h urinary Ca, morning fasting urinary Ca/creatinine, and Pyrilinks-D/creatinine ratio] were measured at the beginning of the study before treatment and after 6 and 12 months of treatment. Baseline characteristics of participants, including age, body mass index, lumbar and hip BMD, and biochemical markers were similar between the two groups. A total of 91 patients completed the study (50 in the salmon calcitonin nasal spray group and 41 in the other group). Lumbar BMD increased significantly in the salmon calcitonin group from baseline (3.0%, p=0.005) and in comparison to the non-calcitonin-treated group (p=0.009). The salmon calcitonin group also had a significant increase in femoral neck BMD compared with baseline values (3.1%, p=0.0005) and in comparison to the non-calcitonin-treated group (p=0.0005) in Wards triangle BMD (2.9% from baseline values, p=0.009) and in comparison to the non-calcitonin-treated group (p=0.005) in trochanteric BMD (3.4% from baseline values, p=0.007) and in comparison to the non-calcitonin-treated group (P=0.01). Urinary Ca/creatinine and Pyrilinks-D/creatinine levels were significantly decreased from baseline in the salmon calcitonin-treated group (–6.1 and –6.3%, respectively, p=0.001). Bone-specific alkaline phosphatase levels were also significantly decreased from baseline in the salmon calcitonin-treated group (–3.6%, p=0.003). In the same group, a significant decrease in iPTH serum levels compared to baseline values (–2.5%, p=0.005) and in comparison to the non-calcitonin-treated group (p=0.005) was noted. In conclusion, in this pilot study, 1-year intermittent treatment with 200 IU intranasal salmon calcitonin and low doses of 1(OH)D₃ produced a significant effect on bone turnover and BMD in postmenopausal women with osteoporosis.     

Ticlopidine and Aspirin Fail to Suppress the Increased Platelet Aggregability That Follows Percutaneous Coronary Interventions

Previous studies indicate that percutaneous transluminal coronary angioplasty (PTCA) is associated with platelet activation. It is not well-established whether enhanced platelet aggregability after PTCA is prevented by the association of ticlopidine with aspirin. The aim of this study was to evaluate whole blood platelet aggregability before and after elective PTCA in patients with chronic stable angina receiving ticlopidine and aspirin. We studied 16 patients referred for elective PTCA, treated for72 hours with oral aspirin and ticlopidine (group 1), and 10 patients referred for diagnostic coronary angiography, treated with oral aspirin alone (group 2). An intravenous bolus of heparin was administered at the start of PTCA. In both groups, platelet aggregability was assessed at baseline and 24 hours after the procedure, using the PFA 100® system. This method measures the time required for flowing whole blood to occlude a collagen and adenosine diphosphate (ADP)–coated ring, shorter times indicating greater aggregability. In both groups, platelet aggregability after the procedure was significantly increased compared with baseline: 104±30 seconds before versus 88±24 seconds at 24 hours in group 1 (p=0.03) and 84±16 seconds before versus 69±14 seconds at 24hours in group 2 (p=0.004). Group 1 patients, compared with group 2, showed a trend toward reduced aggregability at baseline (p=0.06) and significantly lower aggregability 24 hours after the procedure (p=0.03). Ticlopidine and aspirin reduce whole-blood platelet aggregability compared with aspirin alone but fail to suppress the increased aggregability that occurs 24 hours after PTCA.     

Impact of renal function on morbidity and mortality after percutaneous aortocoronary saphenous vein graft intervention

Background Percutaneous coronary intervention in patients with chronic renal insufficiency (CRI) and native coronary artery disease is often problematic, marred by increased morbidity and mortality rates and a high incidence of restenosis and revascularization. However, little is known about the effect of CRI in patients who have undergone prior coronary artery bypass graft surgery and then undergo saphenous vein graft (SVG) intervention. Methods We analyzed the inhospital and 1-year outcomes of 1265 consecutive patients with normal renal function and varying degrees of renal insufficiency who underwent percutaneous SVG intervention and divided them into 4 groups on the basis of the calculated creatinine clearance (CrCl): group 1, CrCl ≥70 mL per minute (n = 626); group 2, CrCl 50 to 69 mL per minute (n = 357); group 3, CrCl 30 to 49 mL per minute (n = 228); and group 4, CrCl <30 mL per minute (n = 54). Patients undergoing dialysis replacement therapy were excluded from the study. Results Patients with lower CrCl more often were older, female, had diabetes mellitus, and had worse left ventricular function. Angiographic baseline characteristics were comparable among the 4 groups. Overall immediate procedural success was similar for all groups. Patients with a low CrCl had significantly higher inhospital overall and cardiac mortality rates (P < .001), including a significantly higher incidence of myocardial infarction, vascular complications, pulmonary edema, and renal function deterioration. At 1-year follow-up, the overall mortality rates remained significantly higher in patients with decreased CrCl, with an incremental rise in overall mortality rate associated with lower renal function (P < .001). Conclusions This study suggests that renal function is a primary determinate of short- and long-term survival in patients undergoing percutaneous SVG intervention and that there is a clear relationship between CrCl and cardiovascular outcome. (Am Heart J 2003;145:529-34.)     

Impact of initial treatment on renal function in newly-diagnosed Type 2 (non-insulin-dependent) diabetes mellitus

Summary The impact of improved glycaemic control on renal function in newly-presenting Type 2 (non-insulin-dependent) diabetic patients has not been adequately researched. Consequently, glomerular filtration rate and effective renal plasma flow and urinary albumin excretion rates were determined in 76 subjects (age (mean (SD)): 54 (9.5) years; 50 male) of an original cohort of 110 newly-presenting normotensive non-proteinuric Type 2 diabetic patients following 6 months treatment with diet alone (n=42) or with oral hypoglycaemic agents (n=34). Significant reductions were observed in (presentation vs 6 months): body mass index (p<0.01); fasting plasma glucose (p<0.001); glycated haemoglobin (HbA₁) (p<0.001); systolic blood pressure (p<0.01); and diastolic blood pressure (p<0.001). Glomerular filtration rate declined from 117 (22) to 112 (21) ml·min^–1 (p<0.01), with unchanged effective renal plasma flow (534 (123) vs 523 (113) ml·min^–1) and filtration fraction (22.4 (3.0) vs 21.8 (3.4)%). Albumin excretion rate (median (range)) declined from 1.1 (0.1–34.7) to 0.5 (0.1–29.9) g·min^–1 (p<0.01). Changes in glomerular filtration rate ( values) were inversely correlated with presentation values (p<0.001), and positive relationships were observed with effective renal plasma flow (p<0.01), and glycated haemoglobin (p<0.05). Type 2 diabetic patients with glomerular filtration rate values at presentation over 120 ml·min^–1 demonstrated significant reduction in glomerular filtration rate (n=31; p<0.001), whilst those with original values less than 120 ml·min^–1 remained unchanged (n=45). Glomerular filtration rate, effective renal plasma flow and filtration fraction for the Type 2 diabetic patients remained elevated compared with age-controlled normal subjects (p<0.01-0.001). Albumin excretion rate at presentation and 6 months were positively correlated with fasting plasma glucose levels (p<0.05) but not renal haemodynamics. Thus, glomerular filtration rate and albumin excretion rate in newly-presenting Type 2 diabetic patients are influenced by metabolic control. Improved glycaemia for 6 months produces a reduction in glomerular filtration rate, mainly in the younger patients with values greater than 120 ml·min^–1 at diagnosis of diabetes. Despite these changes, renal haemodynamic parameters remain elevated compared with age-matched normal subjects.     

The Effects of Chronic Administration of Indomethacin and Misoprostol on Renal Function in Cirrhotic Patients with and without Ascites

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) often cause renal dysfunction in cirrhotic patients with ascites through inhibition of prostaglandin synthesis. However, their renal effects in cirrhotic patients without ascites are controversial. In addition, the role of prostaglandins in cirrhotic patients with ascites and in non-ascitic cirrhotic patients receiving NSAIDs also remains elusive. Thus we evaluated the chronic renal effects of indomethacin and misoprostol in 9 cirrhotic patients with ascites (protocol 1) and 21 cirrhotic patients without ascites (protocol 2).

Methods: The patients of protocol I received 200 μg of misoprostol every 6 h for 7 consecutive days. In protocol 2, 11 patients received 25 mg indomethacin three times a day for 7 consecutive days. The other 10 patients received 25 mg indomethacin three times a day plus 200 μg misoprostol every 6 h for 7 consecutive days. Renal function tests, plasma renin activity, and plasma aldosterone concentration were measured before and after treatment.

Results: In protocol 1, misoprostol tended to reduce the urinary sodium excretion (p = 0.08). In protocol 2, indomethacin alone greatly impaired renal plasma flow (p < 0.05), creatinine clearance (p < 0.05), blood urea nitrogen (p < 0.05), and serum creatinine (p = 0.06) in 11 patients. Similar magnitudes of renal dysfunction were observed in the other 10 patients despite the concomitant misoprostol treatment.

Conclusion: Chronic administration of misoprostol may have caused a negative natriuretic effect in cirrhotic patients with ascites. In cirrhotic patients without ascites chronic administration of indomethacin may induce a renal dysfunction that cannot be reversed by misoprostol.     

Safety and efficacy of sitagliptin in patients with type 2 diabetes and chronic renal insufficiency

Objective: To assess the safety of sitagliptin in patients with type 2 diabetes and moderate [creatinine clearance (CrCl) ≥30 to <50 ml/min] or severe renal insufficiency [CrCl <30 ml/min including patients with end‐stage renal disease (ESRD) on dialysis]. The efficacy of sitagliptin in this patient population was also assessed. Methods: In a 54‐week, randomized, double‐blind, parallel‐group study, patients with baseline glycosylated haemoglobin A_1c (HbA_1c) values of 6.5–10% were allocated (2:1) to sitagliptin (for 54 weeks) or the sequence of placebo (for 12 weeks) followed by active treatment with glipizide (for 42 weeks). To achieve plasma concentrations similar to those observed in patients with normal renal function treated with 100 mg sitagliptin once daily, patients with moderate renal insufficiency were allocated to receive sitagliptin 50 mg once daily and patients with severe renal insufficiency to receive 25 mg once daily. Glipizide treatment was initiated at 2.5 or 5 mg/day and uptitrated to a maximum of 20 mg/day. Results: Patients (N = 91) with a mean baseline HbA_1c value of 7.7% (range: 6.2–10.3%) were randomized to sitagliptin (n = 65) or placebo (n = 26). After 12 weeks, the mean change [95% confidence interval (CI)] from baseline in HbA_1c was ?0.6% (?0.8, ?0.4) in the sitagliptin group compared with ?0.2% (?0.4, 0.1) in the placebo group [between‐group difference (95% CI) = ?0.4% (?0.7, ?0.1)]. At 54 weeks, patients continuously treated with sitagliptin had a mean change (95% CI) from baseline in HbA_1c of ?0.7% (?0.9, ?0.4). The overall incidence of adverse experiences was generally similar between groups. Between‐group differences in incidences of specific clinical adverse experiences were generally small; however, the proportion of patients for whom hypoglycaemia was reported was lower in the sitagliptin group (4.6%) compared with the placebo/glipizide group (23.1%). Consistent with the high mortality risk in this patient population, there were six deaths during this 54‐week study [5 of 65 patients (7.7%) in the sitagliptin group and 1 of 26 patients (3.8%) in the placebo/glipizide group]; no death was considered by the investigator to be drug related. The overall incidences of drug‐related and serious adverse experiences and discontinuations because of adverse experiences were generally similar between groups. Conclusions: In this study, sitagliptin was generally well tolerated and provided effective glycaemic control in patients with type 2 diabetes and moderate to severe renal insufficiency, including patients with ESRD on dialysis.     

Effect of low‐carbohydrate diet on markers of renal function in patients with type 2 diabetes: A meta‐analysis

Meta‐analysis was conducted to clarify the effect of low‐carbohydrate diet (LCD) on renal function in patients with type 2 diabetes. An extensive literature search was conducted on scientific databases including PubMed, Scopus, and Cochrane Library until September 2017. Only controlled trials on human subjects written in English were included in this meta‐analysis. Several markers of renal function were compared between subjects who adopted an LCD or control diet, including estimated glomerular filtration rate, creatinine clearance, urinary albumin, serum creatinine, and serum uric acid. Random effect model was used in the analysis of each marker. In this meta‐analysis, 12 controlled trials were selected, which involved 942 participants (500 received LCD and 442 received a control diet). The pooled standardized mean difference (SMD) of estimated glomerular filtration rate from LCD vs control diet was not different (pooled SMD: 0.26; 95% CI, ?0.03 to 0.55; P = .08). Investigation on creatinine clearance also showed no significant difference (pooled SMD: 0.51; 95% CI, ?0.38 to 1.40; P = .26). Other comparisons from urinary albumin (pooled SMD: ?0.04; 95% CI, ?0.75 to 0.67; P = .90), serum creatinine (pooled SMD: ?0.57; 95% CI, ?1.51 to 0.38; P = .24), and serum uric acid (pooled SMD: ?0.86; 95% CI, ?4.00 to 2.28; P = .59) also showed no significant difference in the results. In the present meta‐analysis, no effect on markers of renal function was found after provision of a LCD compared with a control diet in patients with type 2 diabetes.     

The efficacy and tolerability of fosinopril in Chinese type 2 diabetic patients with moderate renal insufficiency

BACKGROUND: The renoprotective effect of angiotensin II antagonists has been demonstrated in type 2 diabetic patients with nephropathy but similar data on angiotensin-converting enzyme (ACE) inhibitors are limited. We examined the efficacy and tolerability of fosinopril, an ACE inhibitor with dual hepatic and renal clearance, in 38 type 2 diabetic patients with moderate renal impairment (plasma creatinine 130-300 micromol/l) over a 2-year period. METHODS: This was a single-centre, randomized, double-blinded, placebo-controlled trial comparing fosinopril 20 mg daily vs. placebo in addition to conventional antihypertensive treatment over a 2-year period. The primary endpoints were the rate of change and the percentage change in both 24-h urinary albumin excretion (UAE) and creatinine clearance (CrCl). RESULTS: The mean age of the patients was 65 +/- 6 years (range 47-76 years, median 66 years) and plasma creatinine 190 +/- 49 micromol/l. For similar blood pressure control, the percentage change of UAE in patients with microalbuminuria was greater in the fosinopril than the placebo group (-24.2 +/- 28.8 vs. 11.6 +/- 42.1%, p = 0.003 after adjustment for baseline covariates). In the fosinopril group, the rate of change of endogenous CrCl was slower than the placebo group (-0.07 +/- 0.19 vs. -0.24 +/- 0.35 ml/min/week, p = 0.026). The incidence of adverse events was similar between the two groups. CONCLUSIONS: Fosinopril treatment reduced albuminuria and rate of decline in renal function in type 2 diabetic patients with moderate renal insufficiency and did not increase the incidence of adverse events.     

Assessment of renal function in patients with multiple myeloma: the role of urinary proteins

 Renal failure (RF) in multiple myeloma (MM) is considered an ominous complication even though, when timely therapy is started in patients with minimal damage, a high percentage of cases can achieve a regression. The evaluation of renal involvement usually relies on serum creatinine or its clearance, but these parameters have proved to be inadequate to identify initial damage. The aim of this study was to assess the role of the following urinary proteins in diagnosing renal impairment at an early stage: high-molecular-mass proteins (transferrin, IgG, albumin) as markers of glomerular damage, and low-molecular-weight proteins and parenchymal enzymes [α₁-acid glycoprotein (AGP), α₁-microglobulin (α₁M), retinol-binding protein (RBP), β₂-microglobulin (β₂M), lysozyme (LZ), and N-acetyl-β-d-glucosaminidase (NAG)] as indicators of tubular disorder. Thirty MM patients (nine at disease onset and 21 previously treated) were included in the study. No correlation was found between the urinary proteins and the phase or the stage of the disease. By the Spearman test, Bence Jones proteinuria correlated significantly with the 24 h proteinuria (p=0.01) and β₂M (p=0.02), and weakly with the α₁M. Serum creatinine concentrations and urea correlated with most of the analytes evaluated: RBP correlated well with urea (p=0.004) and creatinine (p=0.004); IgG (p=0.006) albumin (p=0.009), AGP (p=0.04), and NAG (p=0.02) correlated with serum creatinine. Significant statistical correlation was found between all the analytes except LZ and the creatinine clearance. Twelve of the 30 MM patients (40%) showed abnormal values of urinary proteins. Four of these patients showed overt renal failure with significant modification of the serum parameters and of creatinine clearance, three showed an isolated decrease of creatinine clearance, and five did not present any alteration of serum or urinary parameters. This testifies to the utility of urinary proteins in highlighting renal damage even in cases where the customary serum indicators of renal disorder are normal. In conclusion, our results demonstrate that AGP, RBP, NAG, transferrin, and IgG are good indicators of renal damage. They do not correlate with the severity of the disease, but they seem to be helpful in identifying a subset of patients with initial renal dysfunction. Received: November 9, 1998 / Accepted: March 5, 1999     

Safe Contrast Volumes for Preventing Contrast-Induced Nephropathy in Elderly Patients With Relatively Normal Renal Function During Percutaneous Coronary Intervention

The aim of this study was to evaluate contrast media volume to creatinine clearance (V/CrCl) ratio for predicting contrast-induced nephropathy (CIN) and to determine a safe V/CrCl cut off value to avoid CIN in elderly patients with relatively normal renal function during percutaneous coronary intervention (PCI).We prospectively enrolled 1020 consecutive elderly patients (age ≥65 years) with relative normal renal function (baseline serum creatinine <1.5 mg/dL) undergoing PCI. Receiver operating characteristic (ROC) curves were used to identify the optimal cut off value of V/CrCl for detecting CIN. The predictive value of V/CrCl for CIN was assessed with a multivariate logistic regression.Thirty-nine patients (3.8%) developed CIN. There was a significant association between a higher V/CrCl ratio and CIN risk (P < 0.001). ROC curve analysis indicated that a V/CrCl ratio of 2.74 was a fair discriminator for CIN (C statistic = 0.68). After adjusting for other known CIN risk factors, V/CrCl ratios >2.74 remained significantly associated with CIN (odds ratio = 3.21, 95% confidence interval [CI] 1.45–7.09, P = 0.004) and worse long-term mortality (hazard ratio = 1.96, 95% CI 1.14–3.38, P = 0.016).A V/CrCl ratio >2.74 was a significant independent predictor of CIN and was independently associated with long-term mortality in elderly patients with relatively normal renal function.     

Deferasirox effect on renal haemodynamic parameters in patients with transfusion‐dependent β thalassaemia

Some patients with β thalassaemia experience non‐progressive creatinine increases with deferasirox, mostly within normal limits; the mechanisms involved are not fully elucidated. The effects of deferasirox on renal haemodynamics, including glomerular filtration rate (GFR) and renal plasma flow (RPF), were investigated in a Phase I, open‐label study in β thalassaemia major patients with iron overload. Patients received deferasirox 30 mg/kg/d up to Week 8, followed by a 2‐week washout period, and extended treatment up to Week 104 with a 4‐week washout period. In the short‐term study (n = 11), mean GFR and RPF declined from baseline to Week 8 (mean [%] change:?9·2 [?9·5%] and ?105·7 ml/min [?17·8%], respectively). A similar pattern was observed during the long‐term study (n = 5); mean GFR and RPF decreased up to Week 52 (?19·1 [?17·7%] and ?155·6 ml/min [?26·1%]), with similar change at Week 104 (?18·4 [?17·2%] and ?115·9 ml/min [?19·6%]). Measures returned to baseline values after each washout. Serum creatinine and creatinine clearance followed a similar pattern. Effects of deferasirox on renal haemodynamics were mild and reversible for up to 2 years of treatment, with no progressive worsening of renal function over time. www.clinicaltrials.gov : NCT00560820.     

Adverse effects of left ventricular hypertrophy in the reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL) study

Aims/hypothesis We explored the impact of baseline left ventricular hypertrophy (LVH) and losartan treatment on renal and cardiovascular (CV) events in 1,513 patients from the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) trial, which studied the effects of losartan on the progression of renal disease and/or death in patients with type 2 diabetes and nephropathy.Materials and methods LVH was assessed using ECG criteria (Cornell product and/or Sokolow–Lyon voltage). The risk of renal or CV events was determined by a proportional hazards model fit with treatment allocation and presence of LVH. Covariates at baseline included age, sex, systolic BP, mean arterial pressure, pulse, proteinuria, serum creatinine, albumin and haemoglobin.Results A total of 187 subjects (12%) had LVH at baseline. Treatment with losartan resulted in a significant decrease in the Cornell product (–6.2%) and Sokolow–Lyon voltage (–6.3%). LVH was shown to be significantly associated with the primary endpoint, which was a composite of doubling of serum creatinine (DSCR), endstage renal disease (ESRD) or death (hazard ratio [HR]=1.44, p=0.011), as well as with the composite renal endpoint of DSCR/ESRD (HR=1.42, p=0.031) and CV events (HR=1.68, p=0.001). Losartan treatment of patients with LVH decreased the CV as well as renal risk to a level similar to that of patients without LVH.Conclusions/interpretation In patients with type 2 diabetes and nephropathy, LVH is associated with significantly increased risk of CV events and the progression of kidney disease. Importantly, in patients with LVH, losartan reduced the CV as well as the renal risk to a level similar to that seen in subjects without LVH.     

Early subcortical ischemic infarction and delayed leucoencephalopathy after carbon monoxide poisoning

Controversy still exists about uric acid as a potential prognosticrisk factor for outcomes in patients with acute myocardial infarction. We prospectively assessed, in 856 patients with ST-elevation myocardial infarction (STMI) consecutively admitted to our Intensive Cardiac Care Unit after primary percutaneous coronary intervention (PCI) whether uric acid (UA) levels are associated with in-hospital mortality and complications. Killip classes III-–IV were more frequent in the 3° UA tertile that was associated with the highest values of peak Tn I (p = 0.005), NT-proBNP (p < 0.001), and fibrinogen (p = 0.036). Uric acid was associated with mortality (crude OR: 1.24; 95% CI 1.03–1.51; p = 0.025), but, when adjusted for Tn I and renal failure (as inferred by eGFR <60 ml/min/1.73 m²), uric acid lost its statistical significance, while Tn I (100 pg/ml step OR: 1.002; 95% CI 1.000–1.003; p = 0.007) and renal failure (OR 9.16; 95% CI 3.60–23.32; p < 0.001) were independent predictors for in-ICCU mortality. Uric acid remained as independent predictor for in-ICCU complications (1 mg/dl step OR: 1.11; 95% CI 1.01–1.21; p = 0.030) together with admission glycemia (1 g/dl step OR: 1.50; 95% CI 1.19–1.91; p < 0.001) and renal failure (OR: 1.46; 95% CI 0.99–2.16; p < 0.001). In STEMI patients submitted to PCI, increased uric acid levels identify a subgroup more prone to in-ICCU complications, probably because hyperuricemia stems from several complex mechanisms ranging from pre-existing risk factors to the degree of myocardial ischemia (as indicated by Killip class, ejection fraction) and to the acute metabolic response (as inferred by glucose levels). Hyperuricemia is not independently associated with early mortality when adjusted for renal function and the degree of myocardial damage.     

Effect of Recent Alcohol Intake on Parathyroid Hormone and Mineral Metabolism in Men

The mechanisms by which alcohol intake, particularly moderate alcoho1 intake, effects bone metabolism are poorly defined. We have examined the relationship between mineral metabolism and recent self-reported alcohol intake (SRAI) across a wide range of such intakes in a series of 104 men aged 32 to 78 years of age in an outpatient setting. A morning nonfasting urine, serum specimen and recent SRAI were obtained from each subject. SRAI was reported as between 0 and 45 oz/week. SRAI correlated positively with her function tests, including serum bilirubin (r= 0.30, p= 0.002), alkaline phosphatase (r= 0.30, p= 0.004), and aspartate aminotransferase (SGOT) (r= 0.29, p= 0.006). SRAI correlated with serum calcium corrected for albumin (r= -0.39, p < 0.001), estradiol (r= 0.43, p < 0.001), and immunoreactive parathyroid hormone (iPTH) (r= -0.51, p < 0.001), as well as urinary calcium (per 100 mg of creatinine) (r= 0.55, p < 0.001). We have arbitrarily divided the participants into two groups on the basis of their reported alcohol intake. Individuals in the first group had intakes ranging from none to moderate intake (drank 8.4 oz or less of ethanol per week, equivalent to an average of two drinks daily or less). Those in the second group had moderate or heavier intake, with >8.4 oz of ethanol intake/week. Mean serum iPTH was significantly greater in those in the first group (none to moderate), compared with the second group (moderate or heavier) (56.0 ± 3.4 and 39.9 ± 2.0 pM/liter, respectively). Calcium corrected for serum albumin was significantly greater in individuals in the first, compared with the second, group (9.23 ± 0.05 vs. 8.88 ± 0.07 mg/dl, respectively). In addition, urinary calcium (cod per 100 mg of creatinine) was significantly lower in the former, compared with the latter (3.1 ± 0.4 vs. 8.4 ± 1.1 mg/100 mg of creatinine, respectively). Similarly, urinary excretion of collagen crosslinks (corrected per 100 mg of creatinine) was significantly less in men in the second group, compared with the first group (316 ± 38 vs. 530 ± 78 nM/100 mg of creatinine, respectively). Not surprisingly, a series of correlations between iPTH and age, 250-hydroxyvitamin D, and testosterone were significant in individuals with none to moderate SRAI, but not moderate or heavier SRAI. Significant independent predictors of serum iPTH in the entire group of men were age (β= 0.215, p= 0.025), SRAI (β= -0.281, p= 0.003), 250-hydroxyvitamin D (β= -0.309, p= 0.002), and testosterone (β=?184, p= 0.048). We have concluded that, in free-living men, alcohol intake >8.4 oz/week was associated with decreased serum iPTH concentrations.     

Endoscopic Ulcer Rates in Healthy Subjects Associated with Use of Aspirin (81 mg q.d.) Alone or Coadministered with Celecoxib or Naproxen: A randomized, 1-Week Trial

Aim: To determine the rate of endoscopic gastric/duodenal ulcers (GDUs) associated with use of aspirin (81 mg q.d.) alone or coadministered with celecoxib or naproxen. Methods: In this multicenter, double-blind study, healthy subjects were randomized to receive daily aspirin (81 mg q.d.) plus celecoxib 200 mg q.d., naproxen 500 mg b.i.d., or placebo. Upper endoscopy was performed at baseline and day 7. The primary end point was incidence of GDUs ≥3 mm diameter. Results: Incidence of GDUs was significantly lower in subjects receiving celecoxib plus aspirin (7%) compared with naproxen plus aspirin (25.3%; relative risk [RR], 0.28 [95% confidence interval (CI), 0.17–0.45]; P < 0.001), but significantly higher than placebo plus aspirin (1.6%; RR, 4.78 [95% CI, 1.12–20.32]; P = 0.016). Conclusion: In a healthy population taking aspirin (81 mg q.d.), coadministration of celecoxib resulted in fewer GDUs than naproxen, but significantly more mucosal damage than aspirin alone.     

Long-term progression of retinopathy after initiation of insulin therapy in Type 2 diabetes: an observational study

Aims/hypothesis Universal worsening of retinopathy after starting insulin therapy in Type 2 diabetes has been suggested in previous work.Methods We studied 294 such patients for up to 5 years to evaluate retinal changes and define the factors affecting progression of retinopathy. Yearly retinal photographs were graded using the EURODIAB system.Results Prior to insulin therapy, 26.2% (77/294) of the patients had minimal non-proliferative diabetic retinopathy (NPDR), 3.7% (n=11) had moderate NPDR and 1% (n=3) had severe NPDR. Over the first 3 years of insulin therapy, significant progression occurred in 36 subjects (12.6%). This comprised 5/193 (2.6%) without any retinopathy at baseline, 22/77 (28.5%) with minimal NPDR and 6/11 with moderate NPDR (54.5%) (²=56.1, p<0.001). In a control group of 70 patients who remained on oral hypoglycaemic agents, nine patients had significant worsening of retinopathy over 3 years. Over 5 years, 22/127 (17.3%) of patients (9/95 without and 13/32 with retinopathy at baseline [²=16.2, p<0.001]) had significant progression of retinopathy. Higher baseline HbA₁c (p=0.002) and lower initial decrease in HbA₁c (p=0.007) were each independent predictors of greater retinopathy progression over this period. There was no significant worsening of visual acuity in patients whose retinopathy progressed.Conclusions/interpretation After initiation of insulin treatment in Type 2 diabetes, clinically significant worsening of retinopathy over a 3-year period was uncommon in those with no retinopathy (2.6%) but occurred in 31.8% of patients with any retinopathy at baseline. The risk of serious worsening of retinopathy after insulin therapy is started in all patients with Type 2 diabetes may have been previously overestimated.Abbreviations ACR albumin creatinine ratio - DCCT Diabetes Control and Complications Trial - NPDR non-proliferative diabetic retinopathy - UKPDS United Kingdom Prospective Diabetic Study     

Urinary proteins in multiple myeloma: correlation with clinical parameters and diagnostic implications

Renal failure is one of the worst complications occurring in multiple myeloma (MM) patients. It does not affect survival if reverted by a prompt chemotherapy before the damage becomes irreversible; therefore, the early diagnosis of renal dysfunction is crucial. High and low molecular weight urinary proteins have proved to be helpful in diagnosing initial renal damage since they are more sensitive than urea and creatinine serum levels or creatinine clearance. We studied the renal function of 111 MM patients through serum creatinine, urea, urinary IgG, ₁-microglobulin (₁-M), and albumin (Alb). Two successive controls were made in a subset of 30 patients, categorized in three groups (improved, stable, worsened) according to the behavior of tumor burden markers (bone marrow plasmacytosis, monoclonal component, and ₂-microglobulin). In every group, we evaluated the behavior of urinary proteins. Renal dysfunction evaluated with serum parameters was present in 19 patients (17%), while if studied with urinary proteins was revealed in 71 patients (64.5%). Urinary proteins statistically correlated with each other. They correlated with creatinine, IgG, and ₁-M also with urea. By contrast, they showed a variable correlation with clinical parameters: ₁-M correlated with bone marrow plasmacytosis (BMPC) (p=0.02) and ₂-M (p=0.000001), IgG with all three disease parameters (MC p=0.0005, BMPC p=0.009, ₂-M p=0.007), and Alb only with ₂-M (p=0.0004). In the subset of 30 patients followed with two successive controls, urinary proteins showed a parallel behavior with the indices of tumor burden. In conclusion, IgG, ₁-microglobulin, and albumin are reliable and sensitive to precociously reveal renal damage, and we recommend their routine use for the definition and monitoring of renal function in multiple myeloma patients, mainly those in early stage, to better identify initial signs of progression.     

Prevalence and impact of renal insufficiency on clinical outcomes of patients undergoing coronary revascularization.

BACKGROUND: Patients with renal insufficiency are more likely to die after coronary revascularization, but mild renal insufficiency is neglected and little is known about its clinical effects. METHODS AND RESULTS: In the present study 3,025 patients grouped by estimated creatinine clearance (CrCl) were analyzed to evaluate the association between CrCl and clinical outcome. The mean serum creatinine was 1.0+/-0.4 mg/dl, with 4.3% above normal; in 65.8% CrCl was <90 ml/min. During hospitalization, there were significant differences in mortality among the groups stratified by CrCl (p<0.0001). During follow-up after hospital discharge, there were significant differences in mortality (p<0.0001), new-onset myocardial infarction (p=0.007), and stroke (p=0.032). In patients with severe renal insufficiency, the in-hospital and follow-up mortality reached 15.4% and 31.3%, respectively. The independent risk factors for all-cause death after revascularization were the mode of revascularization, age and the CrCl level. In patients with mild renal insufficiency or normal renal function, the all-cause mortality after percutaneous coronary intervention was significantly lower than that after CABG. CONCLUSIONS: Renal insufficiency is not rare in patients undergoing coronary revascularization and in the present study even mild renal insufficiency correlated with adverse clinical outcomes after revascularization. In patients with normal renal function or mild renal insufficiency, the mode of revascularization might lead to a prognostic difference.