Jose M. Alcazar

Occult Hepatitis C Virus Infection among Hemodialysis Patients

Occult hepatitis C virus (HCV) infection (i.e., detectable HCV-RNA in the liver or peripheral blood mononuclear cells) in the absence of both serum HCV-RNA and anti-HCV antibodies has not been investigated in hemodialysis patients. In this study, real-time PCR and in situ hybridization was used to test for the presence of genomic and antigenomic HCV-RNA in peripheral blood mononuclear cells of 109 hemodialysis patients with abnormal levels of liver enzymes. Occult HCV infection, determined by the presence of genomic HCV-RNA, was found in 45% of the patients; 53% of these patients had ongoing HCV replication, indicated by the presence of antigenomic HCV-RNA. Patients with occult HCV infection had spent a significantly longer time on hemodialysis and had significantly higher mean alanine aminotransferase levels during the 6 mo before study entry. Logistic regression analysis revealed that mortality was associated with age >60 yr (odds ratio 3.30; 95% confidence interval 1.05 to 10.33) and the presence of occult HCV infection (odds ratio 3.84; 95% confidence interval 1.29 to 11.43). In conclusion, the prevalence of occult HCV infection is high among hemodialysis patients with persistently abnormal values of liver enzymes of unknown cause. The clinical significance of occult HCV infection in these patients requires further study.

Calcium antagonists and renal protection

Aim: To review the renal benefits of calcium antagonists. Methods: Review of published studies. Results: Both experimental and clinical studies have indicated that, apart from being highly potent antihypertensive agents, calcium antagonists may also provide tissue protection and preservation. In three well defined clinical situations, the use of calcium antagonists has proved to be of value. First, in acute renal failure we and others have shown that the administration of dihydropyridine or diltiazem can, by preventing an intracellular calcium overload, avoid the renal damage induced by the use of a radiographic contrast agent. Second, in chronic renal failure, the administration of a calcium antagonist has been shown to be safe and at least similar in efficacy to other commonly used antihypertensive drug classes. Third, in renal transplant patients, calcium antagonists have been shown to prevent both acute and chronic cyclosporin nephrotoxicity. Calcium antagonists have a clear advantage in the case of acute toxicity because they allow faster renal function recovery and a shorter hospitalization time. The mechanisms by which this class reduces cyclosporin toxicity may be related to a reduction in the calcium influx into cells during ischaemic and reperfusion periods, which would reduce the generation of oxygen-free radicals and perhaps reduce thromboxane production. Conclusions: Calcium antagonists have potential renal protective effects that favour their use in many clinical situations where renal function is impaired.

Renal consequences of arterial hypertension.

AIM To seek ways of improving the prognosis for renal function in the presence of arterial hypertension. BACKGROUND Nephrosclerosis is a term used to define the renal damage induced by arterial hypertension. The renal vasculature can participate in the genesis of essential hypertension and can suffer the consequences of elevated blood pressure. There is no doubt that antihypertensive therapy has dramatically improved the prognosis for renal function in the presence of arterial hypertension. RESULTS OF LITERATURE REVIEW There appears to be a need for a further improvement in the prognosis for renal hypertension. At present, the prevalence of nephrosclerosis as a cause of terminal renal failure may be increasing and a progressive fall in renal function in treated hypertensive patients compared to normotensives has been described. CONCLUSIONS It is not yet clear whether improvements in renal hypertension depend merely on the effectiveness of antihypertensive therapy in reducing arterial blood pressure or whether it will be necessary to improve the metabolic disturbances that accompany hypertension or the renal hemodynamic effects of different drugs before the prognosis for nephrosclerosis can be improved.

Blood pressure control in patients with chronic renal insufficiency in Spain: a cross-sectional study.

Objective Despite therapeutic advances, strict control of hypertension remains elusive in patients with chronic renal insufficiency (CRI). The present study was designed for assessment of control rates of blood pressure in patients with CRI. Secondary objectives included evaluation of the control rates of proteinuria and cardiovascular comorbidities. Methods A multicenter and cross-sectional survey of unselected patients with CRI attending outpatient nephrology clinics in Spain between April and September 2003 was performed. Results Fifty-two centers recruited 2501 patients with a mean age 64.8 years (65.7% men). The prevalence of previous cardiovascular disease was 55%. The two most prevalent renal diseases were vascular (38.9%) and diabetic nephropathy (20.1%). Blood pressure below 130/80 mmHg was observed in 435 patients (17.4%). A poor blood pressure control was associated with older age, greater proteinuria and higher low-density lipoprotein cholesterol levels. Proteinuria less than 0.5 g/day was observed in 1209 cases (48.3%). A total of 1899 patients (75.9%) were receiving drugs suppressing the activity of the renin–angiotensin system and 1048 patients (41.9%) were being treated with three or more antihypertensive drugs. Lipid-lowering agents and antiplatelet therapy were used in 49.3 and 38.1% of patients, respectively. Conclusions The control rate of blood pressure in patients with CRI is inadequate despite frequent use of combination therapy that most commonly included an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Greater emphasis should be made to increase the number and dose of antihypertensive drugs and the need for using a statin as well as antiplatelet therapy in order to improve renal and cardiovascular outcomes.

Endoluminal colonization as a risk factor for coagulase-negative staphylococcal catheter-related bloodstream infections in haemodialysis patients

BACKGROUND Approximately 25% of haemodialysis (HD) patients use catheters as vascular access. Catheter-related bloodstream infections (CRBSI) are a major risk in this population. The objective of our study was to determine whether endoluminal catheter colonization (ECC) predicts CRBSI. METHODS We followed up a cohort of HD patients in our institution who underwent HD with tunnelled cuffed central venous catheters (TCC) between December 2006 and June 2008. Colonization of the inner catheter lumen was assessed every 15 days immediately before HD by culture of blood-heparin mixture and the time to positivity (TTP) was recorded by the BacT/Alert automated system. CRBSI was confirmed by differential TTP (> 2 h) between TCC and peripheral blood cultures. RESULTS We studied 51 patients who required 64 TCC. The incidence of CRBSI was 1.65 episodes per 1000 catheter-days, with Staphylococcus epidermidis being the most common cause of infection (76.2%). ECC was more frequent in the CRSBI group than in the non-CRBSI group (100 vs 5.4%, P < 0.001). For S. epidermidis CRBSIs, the median time from ECC to CRBSI was 31.5 days (interquartile range, 27.0-79.0). The sensitivity, specificity and negative and positive predictive values of arterial lumen cultures for S. epidermidis CRBSIs were 100, 96.3, 92.3 and 100%, respectively, while for venous culture, these values were 92.3, 96.3, 92.3 and 96.3%, respectively. For predicting S. epidermidis CRBSI, endoluminal cultures with a TTP of ≤ 14 h had sensitivity and specificity of 52.1 and 97.7%, respectively. CONCLUSIONS This study shows that ECC may predict the risk of developing CRSBI. Surveillance cultures could, therefore, be used to triage individual HD patients who might benefit from specific intervention measures.

Renal effects of calcium entry blockers

SummaryCalcium entry blockers exert several characteristic effects on renal function that contribute to their blood-pressure lowering capacity. They are able to dilate renal vasculature and, in certain circumstances, can increase the glomerular filtration rate, both effects being dependent on the preexisting vascular tone. Calcium blockers are also able to increase renal sodium excretion, mainly through a direct tubular effect that remains during the chronic administration of these drugs. These effects clearly differentiate calcium entry blockers from nonspecific vasodilators and contribute to their effectiveness when they are used as first-step drugs in the therapy of arterial hypertension.

Doxazosin GITS versus hydrochlorothiazide as add-on therapy in patients with uncontrolled hypertension.

The objective of this prospective, randomized, open‐label, parallel‐arm comparative study, with a 4‐month follow‐up, was to assess the antihypertensive efficacy, tolerability and metabolic safety of doxazosin GITS (gastrointestinal therapeutic system) 4–8 mg/day vs hydrochlorothiazide (HCTZ) 12.5–25 mg/day as add‐on therapy in patients not controlled with monotherapy with other drugs. Ninety‐eight patients completed the study (mean age 57.4 ± 15 years, 53% female). Mean systolic/diastolic blood pressure reduction was 8.2/4.5 mmHg in the HCTZ group and 8.9/5.0 mmHg in the doxazosin GITS group, and a strict blood pressure control was achieved in 79% and 83% of the patients, respectively. The incidence rates of adverse events were low and similar in both groups. However, metabolic differences were seen between the groups, doxazosin GITS vs HCTZ, respectively: total cholesterol (mg/dl) 210 ± 53 vs 231 ± 62 (p < 0.05), low‐density lipoprotein (LDL) cholesterol (mg/dl) 139 ± 40 vs 161 ± 57 (p < 0.01), high‐density lipoprotein (HDL) cholesterol (mg/dl) 58 ± 16 vs 48 ± 13 (p < 0.01), HDL/total cholesterol ratio 27.6 ± 8 vs 21.2 ± 7 (p < 0.001), plasma uric acid (mg/dl) 5.3 ± 2.6 vs 6.8 ± 3.1 (p < 0.05) and serum potassium (mEq/l) 4.1 ± 1.3 vs. 3.7 ± 1.2 (p < 0.01). In conclusion, doxazosin GITS has a tolerability and efficacy profile similar to low doses of thiazide diuretics, with a better evolution of metabolic and electrolyte parameters. Therefore, in patients not controlled with monotherapy, doxazosin GITS can be considered an alternative to the addition of thiazide diuretics.

Randomly allocated study of the effects of standard therapy versus ACE inhibition on micro-albuminuria in essential hypertension

Objective To compare the effects of standard therapy (diuretic, β-blocker or both) with those of angiotensin converting enzyme (ACE) inhibition with quinapril on renal function and urinary albumin excretion in patients with essential hypertension. Methods A 1-year, placebo-controlled, randomly allocated study was conducted in a group of 40 patients with essential hypertension. Before beginning the active treatment phase, all patients were given a matched placebo for quinapril for at least 14 days. At baseline and after 1, 3, 6 and 12 months of treatment, blood pressure, heart rate, body weight, renal plasma flow, glomerular filtration rate, plasma renin activity, plasma aldosterone and urinary albumin excretion were measured. Results Both the standard therapy and quinapril produced similar decreases in blood pressure, but only quinapril produced a significant decrease in micro-albuminuria, from 68.5 ± 16.7 to 47.2 ± 14.9 mg/24h (P < 0.05). The renal plasma flow remained constant in both study groups while the glomerular filtration rate and filtration fraction decreased significantly (P < 0.05) in the quinapril group. Conclusions The results of this study indicate that long-term therapy for essential hypertension with ACE inhibition has a more favorable effect on micro-albuminuria than standard therapy for an equal level of blood pressure control.

Long-term diuretic therapy and renal function in essential arterial hypertension.

One of the main objectives of antihypertensive therapy is to preserve renal function from the deleterious effects of elevated blood pressure. Diuretics alone or in combination are effective for the treatment of arterial hypertension. Nevertheless, their use is accompanied by unwanted biochemical side effects, which have been attributed to their renal effects. During the last 10 years a group of 211 patients, diagnosed as having essential hypertension, were followed up. During the follow-up, they received a stepped-care therapeutic regimen consisting of nonpharmacologic measures (group 1), hydrochlorothiazide and amiloride (group 2), propranolol (group 3) and, if necessary, hydralazine (group 4). During the study, blood pressure remained within comparable, well-controlled levels in the 4 groups of patients. A progressive elevation of the levels of total serum cholesterol and glucose was observed in every group. The elevation attained statistical significance (p less than 0.01) after 4 years of therapy in those groups receiving the diuretic alone or in combination. Nevertheless, after 8 years of follow-up, the increment observed in these 2 parameters did not differ when patients in group 1 were compared with those in the remaining groups, indicating that thiazide diuretics could contribute to the earlier appearance of forthcoming events. Serum potassium levels were significantly lower (p less than 0.01) in groups 2 and 3 than in group 1. At the same time, we have observed the progressive appearance of clinically relevant proteinuria in 15.2% of patients, and the range of protein excretion ranged from 350 to 3,700 mg/24 hours. The appearance of proteinuria did not depend on the lack of control of blood pressure, nor on the different therapeutic requirements but was accompanied by a progressive decrease in creatinine clearance. The consequences of the renal effects of diuretics are of great importance during long-term therapy. The present results indicate that diuretics preempt the appearance of a forthcoming increase in serum glucose and cholesterol, and lessen the clinical relevance of these events.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of angiotensin converting enzyme inhibitors on the progression of renal failure and proteinuria in humans

We studied the long-term effect of an angiotensin converting enzyme (ACE) inhibitor, captopril, on the progression of chronic renal failure and on the rate of urinary protein excretion. When compared with standard triple therapy, captopril slowed the progression of renal failure. Captopril was also able to reduce the proteinuria of non-diabetic glomerular origin. This reduction was not dependent on the presence or absence of arterial hypertension but was limited by the presence of low serum albumin levels, and only occurred in patients with proteinuria in excess of 3 g/24 h.