Evaluation of the Losartan in Hemodialysis (ELHE) Study.

Angiotensin converting enzyme inhibitors (ACEIs) have been shown to be effective in the treatment of dialysis patients with high blood pressure, however, they also have been associated with anaphylactoid reactions at the start of dialysis, when they have been used concomitantly with AN69 membranes. A multicenter, open six-month study was designed to test the tolerability and efficacy of losartan as antihypertensive in patients under hemodialysis (HD), with particular emphasis on the appearance of anaphylactoid reactions. HD patients with systolic blood pressure (SBP) levels > or = 140 and/or diastolic blood pressure (DBP) > or = 90 mm Hg, previously nontreated, treated but uncontrolled, or treated with a poor tolerability, were included. The study performed three controls: baseline, at month 3, and at study completion. DBP and SBP levels were measured on the six HD sessions previous to the three visits in addition to biochemical and hematology measurements. Four hundred and six patients were included. The mean age was 55 years, 42% were women, and 23.6% of the patients were dialyzed with AN69 membranes. There was a significant reduction in pre- and postdialysis SBP and DBP at three and six months. Fifteen patients discontinued the study due to adverse reactions related to losartan, and in seven of them the adverse reaction was hypotension. Only two patients have reported a possible anaphylactoid reaction on treatment with AN69, in one of them the HD session had to be stopped and losartan was discontinued. On the contrary, nine patients with a history of previous anaphylactoid reaction, with ACEIs and AN69, have not shown this complication with losartan and AN69. We conclude that losartan is a well tolerated antihypertensive by HD patients, with a very low incidence of adverse reactions, and a lower prevalence of anaphylactoid reactions than those detected with ACEIs and AN69.

Fluconazole treatment of candida peritonitis with delayed removal of the peritoneal dialysis catheter.

Candida peritonitis was treated with fluconazole in ten continuous ambulatory peritoneal dialysis (CAPD) patients without immediate removal of the peritoneal catheter. Shortly prior to diagnosis, six patients (60%) had received broad-spectrum antibiotics. Gram stain of peritoneal fluid detected yeast in 70% of cases. In eight patients the peritoneal dialysis catheter was removed within one week of diagnosis because of clinical deterioration. In the majority of cases (90%), candida peritonitis resolved only after catheter removal in spite of ongoing fluconazole therapy. Fluconazole was well tolerated by all patients.

Factors influencing serum aluminum in CAPD patients.

The aim of this study was to find out the relationship between body iron stores and serum aluminum levels among 82 stable CAPD patients. The influence of other factors such as time on CAPD and residual renal function was also considered. Thirty-three patients received aluminum hydroxide as a phosphate binder, and they had significantly higher aluminum levels (36.45 microg/l) than the patients who were not taking aluminum preparations (17.2 microg/l, p = 0.001). A statistically-significant correlation between serum aluminum levels and residual renal function and time on CAPD was also observed (p <0.05). However, there was no relationship between serum aluminum levels and serum iron, ferritin and transferrin saturation, neither between body iron stores and total excretion of aluminum (p >0.05). In previous reports, low serum iron levels were associated with high serum aluminum concentration among hemodialysis patients. However, this effect was not observed in the CAPD population under study. The highest risk of hyperaluminemia was found in the patients who were taking aluminum hydroxide, had worse residual renal function and had been longer on CAPD.

Reversibility of parathyroid gland suppression in CAPD patients with low i-PTH levels.

The i-PTH response to changes in the peritoneal calcium balance was studied prospectively in a group of 13 stable CAPD patients, who presumably had adynamic bone disease, with low or normal i-PTH values and low aluminum in plasma. Five days after the reduction of dialysate calcium concentration from 1.75 mmol/l to 1 mmol/l, there was a significant elevation in the serum i-PTH. These increased PTH levels returned to baseline values when patients were changed to the 1.75 mmol/l Ca solution (p = 0.004). The changes in i-PTH mirrored the changes in peritoneal calcium balances. These results support the notion that the low or normal levels of i-PTH frequently seen in peritoneal dialysis patients are due to the hypercalcemic effects of the standard peritoneal dialysis solutions; in these patients, the parathyroid hormone production is normal since negative peritoneal balances of calcium are associated with an increase in serum i-PTH.

Exit-site care with ciprofloxacin otologic solution prevents polyurethane catheter infection in peritoneal dialysis patients.

OBJECTIVE: Mupirocin ointment and antiseptics are standard cleansing agents in routine exit-site care of peritoneal dialysis (PD) catheters, but these agents have a deleterious effect on polyurethane devices. We assessed the effectiveness of topical use of ciprofloxacin otologic solution for preventing exit-site infection (ESI) in PD patients with polyurethane catheters. DESIGN: Prospective study. SETTING: Service of Nephrology of an acute-care teaching hospital in Galdácano, Bizkaia, Spain. PATIENTS: A total of 164 patients with polyurethane catheters inserted was studied from start of continuous ambulatory PD to the end of a 24-month period. Patients were divided into two groups according to exit-site treatment protocols. INTERVENTION: Patients in group 1 (n = 86) were instructed on daily exit-site care with soap and water only; whereas patients in group 2 (n = 78) cleansed with soap and water, followed by application of a single-dose vial of 0.5 mL ciprofloxacin (1 mg) for application around the insertion site. MAIN OUTCOME MEASURES: Episodes of ESI and peritonitis. RESULTS: There were 67 episodes of ESI among patients in group 1 versus 9 episodes among patients in group 2 (p < 0.05), resulting in a rate of 0.41 and 0.06 episodes per patient-year of exposure, respectively (p < 0.001). Staphylococcus aureus ESI rate was 0.34 in group 1 versus 0.06 in group 2 (p = 0.001). Infections caused by Pseudomonas aeruginosa and other pathogens occurred in 11 patients in group 1 and in no patients in group 2 (p = 0.05). Peritonitis due to S. aureus ESI was significantly less frequent among patients treated with ciprofloxacin (1 vs 9 cases, p = 0.001). Removal of the catheter was necessary in 5 patients in group 1 and in no patients in group 2 (p < 0.05). CONCLUSION: Daily application of ciprofloxacin otologic solution at the exit site of PD patients with polyurethane catheters inserted significantly reduces the rate of ESI caused by S. aureus and other organisms, particularly P. aeruginosa.

Beta 2 microglobulin in CAPD.

The peritoneal clearance (Kp) and renal clearance (Kr) of beta 2 microglobulin (beta 2 m) were studied prospectively on 50 ESRD patients treated with CAPD, in order to determine the effect of the number of daily exchanges on Kp and to investigate the factors which influence the serum levels of beta 2m. Kr and Kp of beta 2m and creatinine (Cr) were calculated using standard formulae at the initiation of study and again at 6, 12, 18 and 24 months by collecting 24 hour urinary output and dialysate effluent. Kp of beta 2m of patients on 3 exchanges/day was .94 +/- .08 ml/min at the initiation of study and 1.1 +/- .08 at the end. For patients on 4 exchanges/day it was .99 +/- .14 ml/min and 1.1 +/- .12 respectively. There was no significant difference. Serum levels of beta 2m were lower on patients with significant residual renal function (RRF) (17 +/- .9 mg/L) than on patients without RRF (38 +/- 2 mg/L. p = .001). Serum levels of beta 2m correlated inversely with Kr of Cr and beta 2m at the initiation of study and at the end (r = .67 and .77 respectively, p = .0001). We conclude that serum levels of beta 2m correlate inversely with Kr of Cr and are expected to rise as RRF decreases. The combined peritoneal and renal excretion of beta 2m is less than its daily production. The number of dialysis exchanges does not influence Kp of beta 2m.

High flow peritoneal dialysis.

We have developed a catheter extension/continuous ambulatory peritoneal dialysis (CAPD) set (ANDY high flow set) of larger lumen (minimum internal diameter 3.25 mm), and compared peritoneal dialysate flow rates in two groups of 6 stable CAPD patients of comparable age, sex distribution, and time on dialysis according to type of catheter. Both groups were studied with two different extension/sets, standard ANDY and ANDY high flow set. The shortest infusion time was observed with the combination Cruz catheter/ANDY high flow set. The switch to a high flow set decreased significantly the inflow time of both types of catheter, and the infusion time of the Tenckhoff catheter/ANDY high flow combination approximated that of the Cruz/ANDY combination. Likewise, the dialysate outflow rates were highest with the Cruz catheter/ANDY high flow set than with any other catheter/set combination (p = 0.005). This was apparent, not only in the total outflow time, but also in the vol/min during the first 4 min (p = 0.005). None of the patients experienced discomfort during the dialysis exchanges with the high flow system. This combination of Cruz catheter/high flow set effectively reduces the dialysis exchange time and is very much appreciated by the patients.

Testing the safety of non-disconnect disposable Y sets for peritoneal dialysis.

In order to test the efficacy of the Del Clamp as a contamination barrier, the following protocol was carried out. Sixty bags of dialysate (1.5 L, 1.5% Dextrose) were connected to matching disposable Y sets and 100 mL of dialysate allowed to flow into each drain bag, after which the clamps were closed. The bags were arranged in groups of 10 and each group was inoculated with 1 mL of a standard suspension of S. aureus, S. epidermidis, E. coli, E. faecalis, P. aeruginosa and C. albicans, respectively. 3 bags were inoculated and left with the clamp open as controls. After 6 hr, incubation at 37 degrees C, 20 mL duplicate samples from each drain bag were centrifugated and processed for anaerobic and aerobic culture. None of the specimens taken from the sets grew bacteria or fungi. All the drain bags of the control sets grew the inoculated organism. We conclude that the Del Clamp makes CAPD safer by working as an effective contamination barrier and eliminating a potential for combination during the dialysis exchange.

[Role of diet in the management of osteodystrophy during progressive renal insufficiency]. / Papel de la dieta en el manejo de la osteodistrofia en la insuficiencia renal progresiva.

Secondary hyperparathyrodism (SH) is an early manifestation of chronic renal failure (CRF), which has serious complications. Moreover, treating SH is not a risk-free process. Once in its advanced state, it is extremely difficult to reverse and therefore it is critical an early intervention and prevention. An excess of phosphorus and a deficit of calcium and calcitriol are key factors in the evolution of SH. Despite the fact that plasma phosphorus levels remain normal until an extremely advanced stage of CRF, and even apparent hyperphosphatemia in mild CRF, it has been shown that restricting dietary levels of protein and phosphorus impedes the progression of SH. A decrease of protein in the diet also decreases the amount of calcium, thus the calcium levels must be supplemented in order to prevent their deficit. In addition to that slightly diminished levels of calcitriol can be observed in the early stages of CRF, thus it is logical to provide this hormone. However, administering calcitriol may induce hypercalcemia and hyperphosphatemia, which in turn risks the onset of cardiovascular calcifications and complications. Therefore, the calcitriol dosage should be small and then adjusted according to the degree of SH. Neither the PTH levels nor alterations in the phospho-calcium metabolism follow a linear increase appropriate to the decrease in renal function, therefore we propose a treatment strategy which adapts to the different degrees of renal failure.

[Doxazosin, of modified liberation, in hemodialyzed patients]. / Doxazosina, de liberación modificada, en pacientes de hemodiálisis.

INTRODUCTION: Valuation of doxazosin, system formulation modified, in the hypertension in the hemodialysis population. METHOD: Arterial Hypertension (AHT) has been studied in 77 patients (p) subjected to hemodialysis (HD). Mean age (mag) was 61 years (y), range 84y-25y; 66% were males. The underlying etiology was glomerular in 19%, tubulo-interstitial in 18%, congenital in 18%, vascular in 19% and diabetic in 26%. RESULTS: Doxazosin (system formulation modified, single daily dose (4 mg), treatment follow-up was completed in 16 patients subjected to HD for 24 weeks (wk). CONCLUSION: It is concluded that AHT is of great importance in HD, and can be adequately controlled with the new antihypertensive drugs. In this context, doxazosin affords excellent therapeutic control, efficiency and good pharmacological tolerance.

Calcium mass transfer in CAPD: the role of convective transport.

One hundred and fifty calcium (Ca) balance studies were performed in 50 patients treated with CAPD using dialysate with a 1.75 mmol/l (7 mg/dl) Ca content, in order to calculate the peritoneal balance of Ca by measuring the Ca in all the effluent for a 24-h period, and looking at the influence of serum ionized Ca and the ultrafiltration rate in the calcium balance. Of the 150 balance studies, 77 were made using four exchanges of dialysate per day and 73 using three exchanges per day. The serum ionized Ca was 1.17 +/- 0.09 mmol/l, the ultrafiltration 844 +/- 723 ml/day and the peritoneal Ca transfer 39 +/- 46 m/day. The net Ca abortion with four exchanges was less than that with three exchanges per day. There was a strong negative correlation between the peritoneal Ca absorption and the ultrafiltration (r = -0.7, P < 0.00001) and with the ionized Ca (r = -0.49, P < 0.0001). Thirty-three peritoneal balance studies showed a negative Ca balance and in all 33 cases ultrafiltration was greater than 350 ml/day. We conclude that the peritoneal balance of Ca depends not only on the serum ionized Ca, but also on ultrafiltration. The lesser Ca gain observed with four dialysis exchanges per day is due to greater ultrafiltration rates present in this setting.

The importance of dietary calcium and phosphorous in the secondary hyperparathyroidism of patients with early renal failure.

Secondary hyperparathyroidism (HPT) was evaluated in 157 patients with chronic renal failure (CRF). It was noted that HPT developed early in CRF at a time when plasma calcium and phosphorous were within normal limits. As creatinine clearance decreased below 80 mL/m, there was a significant decrease in plasma calcitriol and a slow and progressive significant increment in plasma parathyroid hormone (PTH). The effect of dietary intake of calcium and phosphorous was evaluated in these patients with early renal failure (ERF). They were divided into two groups. Group A was placed on a protein- and phosphorous-restricted diet (10 days) followed by a daily phosphorous-load diet (10 days). Group B had similar sequential diets plus a calcium supplement throughout the study. Dietary protein and phosphorous restriction resulted in an amelioration of the HPT only in the group of patients receiving calcium supplementation. The phosphate-load diet resulted in worsening of HPT in both groups. In summary, a deficit of calcitriol occurs early in CRF, which in turn leads to a significant increase in PTH. Phosphorous restriction, together with calcium supplementation, ameliorated the HPT of patients with ERF.

A deficit of calcitriol synthesis may not be the initial factor in the pathogenesis of secondary hyperparathyroidism.

Secondary hyperparathyroidism (HPT) develops early in chronic renal failure (CRF) at a time when plasma calcitriol levels are normal. At this time, PTH are higher than normal controls and serum phosphorous levels are lower. A decrement in total serum Ca is noted, after an oral phosphate load, only in patients with ERF. These data suggest that factors, other than a decrease in calcitriol synthesis, may be involved in the pathogenesis of HPT. A hypothesis is forwarded suggesting that an alteration in the newly cloned calcium sensor receptor may be the earliest abnormality in the HPT, preceding a decrease in plasma calcitriol levels.

Is there a lesser hyperparathyroidism in diabetic patients with chronic renal failure?

Diabetic patients on dialysis have lower levels of parathyroid hormone (PTH); however, there is no data regarding PTH levels with different degrees of chronic renal failure (CRF). We compared 58 diabetic patients with different degrees of CRF with 268 non-diabetic patients with CRF (serum creatinine >1.2 mg/dl). In both groups, we investigated the main biochemical parameters together with plasma calcium, phosphorus, magnesium, PTH and calcitriol. Diabetic patients showed lower levels of PTH than non-diabetics (P=0.003). The differences were observed in patients with creatinine clearance <70ml/min. We also observed differences in phosphorus, magnesium and tubular resorption of phosphate. In the group of diabetic patients, serum glucose correlated inversely with PTH. Our study suggests that poor control of diabetes (hyperglycaemia) may play a role in the pathogenesis of the hypoparathyroidism observed in patients with diabetes and CRF.