[Preliminary results of the Spanish Society of Nephrology multicenter study of quality performance measures: hemodialysis outcomes can be improved]. / Resultados del proyecto de mejora de la calidad de la asistencia en hemodiálisis: estudio multicéntrico de indicadores de calidad de la Sociedad Española de Nefrología (SEN).

INTRODUCTION: The Spanish Society of Nephrology "Quality in Nephrology Working Group" (QNWG) was created in 2002. The aims of this group are the identification, diffusion, implementation and consolidation of a systematic, objective and comprehensive set of quality performance measures (QPMs) to help along the improvement of patient care and outcomes on hemodialysis, by means of strategies of feedback and benchmarking, and the design of quality improvement projects. The objective of this study is to present the preliminary results of a set of quality performance measures obtained in a group of Spanish hemodialysis centers, as well as to evaluate the repercussion of the application of the aforementioned thecniques on the observed results. METHODS: During 2007 a total of 28 hemodialysis units participated in the study; 2516 patients were evaluated. A specific software was designed and used to facilitate the calculation of CPMs in each unit. The clinical indicators used refered to dialysis adequacy; anemia; mineral metabolisme; nutrition; viral infections; vascular access; mortality, morbidity (number and days of hospital admissions); and renal transplant. Every three months each center received its own data and its comparison with the rest of the group. RESULTS: Except for hemoglobin levels we observed a global improvement. The percentage of centers reaching the stablished standards defined by the QNWG passed from 65% to 90,9% for Kt/V Daugirdas II (> 1,3 in > that 80% of the patients); from 71,4 % to 77,2 % for PTH (> 30 % of patients with serum PTH between 150 and 300 pg/ml); and from 42,8 % to 63,5 % for phosphate (> 75 % of patients with a serum phsphate < 5,5 mg/dl). More than 50% of centers showed an improvement in their final results as compared with their own initial results in all analyzed CPMs. Those centers that did not obtained an improvement in their results started the study with better percentages of acomplishment than those that showed a significant improvement in QPMs. (80,6+/-15,4 versus 71,8+/-16,6 respectively; p<0,001) CONCLUSIONS: We are starting to make progresses in our knowledge of clinical results in our hemodialysis units, although there is still a long way to go over. To monitor and share CPMs results within hemodialysis centers might help to improve their results as well as to reduce intecenters variability.

Effects of long-term treatment with indomethacin on renal function.

The prolonged effects (42 days) of indomethacin treatment on the renin-angiotensin-aldosterone axis, renal hemodynamics, and renal excretory function in humans were studied. Indomethacin produced a 41% sustained depression in the 24-hour excretion of prostaglandin E2 and a mild (7%) decrease in inulin clearance but did not affect the clearance of p-aminohippurate, the 24-hour excretion of sodium and potassium, or the basal values of plasma aldosterone; however, it decreased the basal values of renin and prevented the stimulated (3 hours of walking) responses of plasma renin activity and plasma aldosterone. Indomethacin also produced a decrease in both the diuretic and saluretic response to furosemide and in the renal ability to concentrate urine. The indomethacin-induced hyporeninism and hypoaldosteronism were more pronounced when the subjects were receiving a sodium-restricted diet. This finding indicates that prolonged administration of anti-inflammatory drugs induces chronic hyporeninism and hypoaldosteronism. Prolonged treatment with indomethacin also produced some of the symptoms of a syndrome of hypoprostaglandinism, such as decreased plasma renin activity, plasma aldosterone, and urinary prostaglandin E2 in association with increases in plasma potassium levels and diastolic pressure.

Immunogenicity of a yeast-derived hepatitis B vaccine in hemodialysis patients.

In a multicenter study of hemodialysis patients in Spain, the immunogenicity of a yeast-derived recombinant deoxyribonucleic acid hepatitis B vaccine was evaluated. Two different vaccination schedules were examined: zero, one, two, six months and zero, one, two, 12 months. Two different dose levels (20 micrograms and 40 micrograms) were also compared. No serious adverse effects were reported by any of the vaccinees; the most frequently reported reaction was soreness at the injection site. This study also indicated that higher concentrations of antibodies are attained when more frequent doses of vaccine are administered. The yeast-derived vaccine produced an immune response similar to that of the plasma-derived vaccines.

Does an adequate control of blood pressure protect the kidney in essential hypertension?

We analyzed the clinical course of 120 patients who were diagnosed as having primary hypertension and subsequently given standard stepped-care therapy (diuretic, beta-blocker and vasodilator) for 9 years. At the end of the follow-up period, 21 patients (17.5%) had developed overt proteinuria. The initial study showed no difference in systolic blood pressure, age, sex, serum creatinine and its clearance, glucose, cholesterol and triglycerides between these patients and those who had not become proteinuric, but uric acid levels and diastolic blood pressure were higher (both P less than 0.01). An adequate control of blood pressure was obtained and maintained in all patients, who had similar therapeutic needs. During the follow-up period, uric acid levels remained significantly elevated (P less than 0.01) in the proteinuric patients, while changes in serum glucose, cholesterol and triglycerides were similar in all patients. These results indicate that long-term treatment of primary hypertensives does not fully protect kidney function and that initially elevated uric acid levels could be a predictor of a poor prognosis.

Renal effects of fenoldopam in refractory hypertension.

Fenoldopam, a dopamine-1 (D1) agonist, was administered by a 6-h intravenous infusion to patients with refractory hypertension [diastolic blood pressure (DBP) greater than 115 mmHg while on triple therapy] in order to achieve a fall in DBP of 30 mmHg. The evolution of blood pressure, heart rate, glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, renal excretion of sodium, potassium, chloride, calcium, uric acid, phosphate, plasma renin activity (PRA), aldosterone and prolactin were evaluated. A significant fall in blood pressure (P less than 0.01) accompanied by an increase in heart rate (P less than 0.01) was attained after 30 min. GFR and RPF increased significantly (P less than 0.01) but the filtration fraction fell. Urine volume and urinary output of sodium, potassium, chloride, calcium, uric acid and phosphate increased markedly (P less than 0.01). Meanwhile, plasma potassium fell (P less than 0.01) and the hormonal parameters showed no significant change. We concluded that in refractory hypertension fenoldopam has potent renal and systemic vasodilatory properties through which blood pressure falls. The hypotensive effect of fenoldopam is also facilitated by its marked diuretic and natriuretic properties. The absence of variations of plasma prolactin confirm the D1 selectivity of fenoldopam and the lack of increase in PRA indicates that fenoldopam blocks the renin-angiotensin-aldosterone system.

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)

Sodium intake does not influence the effect of verapamil in hypertensive patients with mild renal insufficiency.

Information is limited regarding the efficacy of antihypertensive drugs in patients with hypertension associated with renal insufficiency. To address this question, a group of 14 outpatients with essential hypertension and mild renal insufficiency received slow release verapamil 240 mg/day for 14 days after a 4-week washout period. Patients were randomly assigned to a low (4 g/day) or high (11 g/day) salt diet, and crossed over to the alternative diet after 7 days. 24-Hour blood pressure monitoring was performed at the end of the washout period and after 7 and 14 days during verapamil treatment. Verapamil induced a significant fall in mean 24-hour blood pressure that was similar for patients on both diets (p < 0.01). As expected, natriuresis increased significantly during high sodium intake (p < 0.01), and bodyweight fell significantly when sodium intake was reduced (p < 0.05). Meanwhile, serum creatinine and creatinine clearance remained stable. These results indicate that the antihypertensive effect of verapamil is independent of sodium intake even in the presence of mild renal insufficiency.

Ischemic nephropathy: clinical characteristics and treatment.

Ischemic nephropathy is a long-term cause of hypertension and renal failure. Although its real incidence is unknown, ischemic nephropathy is growing because of the increased mean age of the population and the greater prevalence of hypertensive and diabetic populations. This review describes the clinical profile of afflicted patients. Atherosclerosis in different vascular beds is common in these patients. The evolution of ischemic nephropathy is generally progressive, although some patients present with acute renal failure, either secondary to the administration of angiotensin-converting enzyme inhibitors or caused by thrombosis of the renal arteries. Revascularizing surgery may stabilize or improve renal function, even in patients with nonfunctioning kidneys. The results obtained with intraluminal angioplasty are worse, with a high percentage of restenosis. Placement of an endoprothesis is recommended when the lesions affect the ostium or proximal third of the artery. This complex disease typically affects multiple organs, thus making individual assessment essential.

Induction of microalbuminuria by l-arginine infusion in healthy individuals: an insight into the mechanisms of proteinuria.

Despite evidence from individuals with diabetes mellitus or reduced renal mass, the actual relationship between protein- or amino acid-induced changes in renal function and urinary albumin excretion (UAE) is largely unknown in subjects without renal disease. In humans, infusions of l-arginine have been used recently in vascular and renal pathophysiological studies. The present study was undertaken to analyze the mechanisms involved in a particular effect; namely, the behavior of UAE during amino acid loading. A prospective interventional protocol was performed on 10 healthy adults by means of an intravenous infusion of l-arginine. The main results show that l-arginine induced a significant increase in UAE from 13.1 +/- 3.8 before to 53.3 +/- 11.1 microgram/min after the infusion (P < 0.005). This increment was simultaneous to an increase in glomerular filtration rate (GFR) and renal plasma flow (RPF). Furthermore, l-arginine markedly increased the urinary excretion of beta2-microglobulin. UAE correlated significantly with GFR (r = 0. 738; P = 0.014) and RPF (r = 0.942; P < 0.0001), but not with urinary beta2-microglobulin (r = 0.05; P = not significant). Furthermore, marked differences (P = 0.001) were found between the percentage of increase in UAE (306.8% +/- 163.2%) with respect to either albumin filtered load (FLAlb; 57.9% +/- 16.3%) and beta2-microglobulin excretion (1,088.5% +/- 424.6%). No changes were found in vehicle-infused individuals. In conclusion, the present study shows, in controlled conditions, that l-arginine infusion induces a relevant increase in UAE in healthy individuals that significantly exceeds that expected from the increase in GFR alone. The intense and simultaneous increment in beta2-microglobulin excretion strongly suggests that the effect of l-arginine on UAE is, in a relevant part, mediated through a blockade in the tubular protein reabsorption pathways. However, the profound differences observed in the changes induced by l-arginine on UAE and beta2-microglobulin excretion and the differences in the correlation of UAE and beta2-microglobulin with respect to GFR suggest that substantial diversity exists in the mechanisms by which l-arginine affects the renal management of albumin and beta2-microglobulin. These findings are relevant for understanding the renal response to l-arginine and protein/amino acid loads.

Aging abolishes the renal response to L-arginine infusion in essential hypertension.

A defect in the endothelium-dependent vasorelaxation could contribute to the development of arterial hypertension through the facilitation of renal vasoconstriction and sodium retention. In this study, we tested the hypothesis that aging impairs kidney function in essential hypertension through a derangement of nitric oxide-dependent renal mechanisms. To this end, we compared the renal response to an intravenous infusion of the precursor of nitric oxide synthesis, L-arginine, in young and aged essential hypertensives. In young hypertensives, L-arginine induced a significant increase in renal plasma flow, glomerular filtration rate, natriuresis and kaliuresis, without changes in filtration fraction. These effects were not observed in aged hypertensives. Neither PRA nor PA were affected by L-arginine infusion in any group. These results indicate that aging produces a derangement of endothelial function in essential hypertension.

A fixed combination of hydrochlorothiazide and amiloride for the treatment of essential hypertension.

The combination of hydrochlorothiazide and amiloride has been used in a group of patients diagnosed as having essential hypertension. Sixty-five percent of the patients for whom dietary restrictions did not achieve a reduction in blood pressure were initially controlled with this combination; the addition of a second or third drug was required by the remaining patients. During the six-month follow-up, the control of blood pressure was satisfactory with increased drug requirements, but the diuretic had to be discontinued in 12 patients because of side effects.

The antihypertensive effect of verapamil in patients with chronic renal failure.

The calcium antagonist verapamil has been demonstrated to be effective in reducing hypertension in patients in whom sodium intake was not restricted. The present study evaluated the effect of verapamil in reducing hypertension in patients with chronic renal failure on low or high sodium diets. Also, the present study evaluated the effect of verapamil on proteinuria in chronic renal failure patients who were administered a normal and low protein diet. The results reveal that verapamil-SR 240 mg daily is effective in reducing hypertension in patients with chronic renal failure and the effect of verapamil is equal in patients on a high or low sodium intake. In addition, verapamil-SR 240 mg daily is effective in maintaining reduced proteinuria in chronic renal failure patients on low protein diet and may prevent proteinuria in such patients on a normal protein diet. Therefore, verapamil-SR 240 mg daily appears to be an excellent choice for the treatment of hypertensive chronic renal failure patients.

Vaccination against hepatitis B in renal dialysis units: short or normal vaccination schedule?

Three I.M. injections of hepatitis B vaccine (Merck Sharp & Dohme) were administered, according to the recommended schedule (0, 1, 6 mos), to seronegative individuals of one renal dialysis unit (33 patients, 58 health care personnel) and, according to a shorter regimen (0, 1, 3 mos), in another unit of similar characteristics (30 patients, 53 health care personnel). Staff members and renal patients received, respectively, 20 y 40 mcg of vaccine per injection. In the early vaccination phase, the two regimens did not lead to a difference in seroconversion rates nor in anti-HBs titers. After a 9-month surveillance, lower seroconversion rates, although not significant, were observed with the accelerated regimen among staff members (84.2%) and renal patients (79.2%) as compared with 93% and 87.5%, respectively, following the normal schedule. At the same time, anti-HBs titers were significantly lower (p less than 0.001) in the staff (316 RIA U) and patients (93 U) vaccinated according to the short regimen than in their respective counterparts (4196 and 1047 U) assigned to the normal schedule. A fourth dose of vaccine given to subjects with low and no anti-HBs titers significantly increased seroconversion and anti-HBs levels, although with little success among the former non-responders.

Fractional excretion of sodium represents an index of cyclosporine nephrotoxicity in the early post-transplant period.

We reviewed the evolution of FENa in the EPP (first 4 weeks) in a group of CyA-treated patients as well as Aza-treated patients who did not present with acute rejection during this period of time. The CyA-treated patients showed lower values of FENa than did Aza-treated patients. Values of FENa below 1% were found in 51% of CyA- and 0% Aza-treated patients (P less than .01) before RFR. The finding of low FENa values was accompanied by more prolonged oliguric and RFR phases. Furthermore, the lower the level of FENa, the higher the prolongation of renal failure. We concluded that FENa values could probably be an index of CyA nephrotoxicity in the EPP.

[Treatment of arterial hypertension in the aged]. / Tratamiento de la hipertensión arterial en la tercera edad.

The response to different therapeutic schedules in arterial hypertension in the elderly is studied and compared with response to treatment in younger patients. Blood pressure in the elderly was best controlled with non pharmacologic measures and low doses of diuretics; there were no differences between both groups with respect to complications and side effects. The response to angiotensin-converting enzyme inhibitors is also evaluated, presenting good results on blood pressure control without side effects in the elderly, although efficaciousness was higher in younger patients. The possible therapeutic schedules in arterial hypertension in the aged are discussed.

[Hypertensive crisis. Clinical and therapeutic study of 130 cases (author's transl)]. / Crisis hipertensivas. Estudio clínico y terapéutico de 130 casos.

The clinical aspects and response to therapy of 130 hypertensive emergencies are reviewed in this report. According to the main features of the clinical picture, the patients were divided into neurologic, cardiac or mixed emergencies. The patients were evaluated with clinical examination, fundoscopy, routine biochemistry, ECG, and chest radiograms. According to the response of the blood pressure to the administration of hypotensive drugs, the patients were divided into two groups: group I, with good response to a single drug associated to frusemide, and group II, with good response to two or more drugs associated to frusemide. Neurologic emergencies appeared in 55 patients (42% of total), and cardiac emergencies in 45 (34%), the initial blood pressure beeing higher in the first group (p less than 0.005). The fundus showed hypertensive retinopathy degrees III-IV in 55% of the patients. Patients in group I had less elevation of the initial blood pressure, showed a better response to therapy, and had only mild side effects from the administered drugs. Group II had a mortality of 11% and, as expected, showed more complications due to side effects. The frequency of appearance of toxic side effects from the drugs given is reviewed, and a therapeutic schedule is proposed.

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.

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.

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, beta-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/24 h (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.

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.