The pharmacokinetics of a single dose of calcitriol administered subcutaneously in continuous ambulatory peritoneal dialysis patients.

OBJECTIVES: To evaluate the kinetics of calcitriol (1,25(OH)2D3) administered subcutaneously. STUDY DESIGN: Calcitriol kinetics and efficacy after subcutaneous administration were studied in 13 CAPD patients with varying degrees of increased plasma levels of parathyroid hormone (i-PTH). A single dose of 2 micrograms of calcitriol was administered subcutaneously, and its serum levels at baseline and after 1, 2, 6, 12, and 24 hours were determined. Plasma ionized calcium and i-PTH were also determined at these periods. RESULTS: Serum calcitriol levels reached peak levels of 60 and 70 pg/mL at 1 and 2 hours after administration, respectively. These levels decreased thereafter, but remained above baseline values during 24 hours. The mean value of the area under the curve (AUC) was 809 +/- 226 pg/mL/hour. Plasma i-PTH levels showed a slight decrease after 1 and 2 hours, returning to baseline levels after this period. Plasma ionized calcium did not show significant changes during the study. A slight pain at the site of injection was mentioned by some patients. CONCLUSIONS: The subcutaneous route for calcitriol administration achieves theoretically adequate plasma levels in continuous ambulatory peritoneal dialysis (CAPD) patients. This is important when parenteral administration of calcitriol is considered in the treatment of secondary hyperparathyroidism.

Tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-I (PAI-I) levels in plasma and peritoneal effluent in patients on CAPD.

The formation of fibrin on peritoneal surface has been related to the appearance of adhesions both, in surgical and CAPD patients. It is known that mesothelial cells have fibrinolytic activity related with t-PA production. We studied plasma and overnight peritoneal effluent (OPE) from 20 CAPD stable patients. Antigenic PAI and t-PA were determined. These values and its correspondent peritoneal saturation indexes were compared to urea and creatinine MTCs, peritonitis incidence, UF capacity, protein losses, Pi, Ca, Na, CO2t, urea and creatinine OPE levels. Plasma t-PA 6.64 +/- 4.68 (2.4-20); Plasma PAI-I 24.8 +/- 17.1 (p < 0.001 in respect to controls) (4-62); OPEt-PA 1.46 +/- 0.95 (0.4-4.6); OPE PAI-I 7.3 +/- 5.6 (0-20.4). Peritoneal saturation ratios were for t-PA 29.6 +/- 21% (6-65) and for PAI-I 34 +/- 32% (7-132). In conclusion our data do not support strong relationship between peritoneal t-PA/PAI system and the functional characteristics of the peritoneal membrane although plasma PAI-I, after an increase in patients at early stages on CAPD, shows a tendency to decrease over time and frequent peritonitis. The values of peritoneal saturation ratios for t-PA/PAI are higher than expected for their molecular weight, which suggests local production. An elevated plasma t-PA levels has been found in older patients.

[The treatment of anemia in patients on hemodialysis with recombinant human erythropoietin]. / Tratamiento de la anemia de los pacientes en hemodiálisis con eritropoyetina humana recombinante.

BACKGROUND: Anaemia of chronic renal failure is primarily due to relative erythropoietin deficiency. This hormone has been recently cloned and it is now available for clinical use. METHODS: Sixteen patients maintained on haemodialysis with non-complicated anaemia and on stable clinical condition were selected for 12 months' treatment with r-HuEPO. Our aim was to analyse the factors influencing r-HuEPO response and the modifications on main haematological and biochemical parameters and adverse reactions occurrence. RESULTS: All patients responded with an increase of haemoglobin (from 78 +/- 9 to 103 +/- 18 g/dl at second month of therapy, p less than 0.001) and blood transfusions were eliminated. Time of response and doses were very different to one another. R-HuEPO requirements decreased slowly with time. Neither transfusion number, nor hyperparathyroidism, nor ferritin levels, nor diabetic condition influenced r-HuEPO response. Serum ferritin decreased significantly from 1,772 +/- 1,791 to 1,116 +/- 1,240 ng/ml (p less than 0.05), especially in patients without iron overload. Serum vitamin B12 levels did not decrease significantly. Both uric acid and phosporus increased significantly after the treatment period (5.25 +/- 1.18 to 6.29 +/- 0.99 mg/dl and 5.78 +/- 1.29 to 6.69 +/- 1.55 mg/dl respectively, p less than 0.01). Platelet counts did not modify. It was necessary to adjust antihypertensive therapy in a few patients because of a mild rise in blood pressure, although important adverse reactions did not occur. CONCLUSIONS: Anaemia of haemodialysis patients improves with r-HuEPO treatment and reduces blood transfusion requirement. Adverse effects are not very remarkable.

Characterisation of the mitogenic-induced capacity of peritoneal effluent on human and mice fibroblasts in culture.

During continuous ambulatory peritoneal dialysis, solutes capable of stimulating fibroblast activity could be transferred into dialysate; their significance and consequences remain to be established. Sixty-three stable non-selected patients on CAPD were included in this study. Peritoneal transport for water and small solutes was assessed. To explore the mitogenic-induced capacity of peritoneal nocturnal effluent, 50 microliters were added to culture plates of mice and human fibroblasts. Peritoneal effluent alone shows a mitogenic potency slightly greater than insulin and clearly less than bovine fetal serum. When coadjuvants are added, mitogenicity increases but in a variable manner among patients. No differences can be observed in relation to diabetes mellitus, time on CAPD, previous peritonitis, and losses of diffusion capacity. We noted significant inverse linear correlations between mitogenicity value and ultrafiltration, effluent calcium, and creatinine. Neither adrenergic nor calcium-channel blockers influenced these values. We conclude that the peritoneal effluent of CAPD patients has a variable effect on fibroblast growth. Some of the blood components seem to be implicated in this activity. Reduced peritoneal ultrafiltration capacity, probably by a concentration mechanism, is related to a greater mitogenic potency in peritoneal effluent. CAPD patients with impaired ultrafiltration may be at high risk for autoactivation of peritoneal fibroblasts, mainly in mesothelial denudate states.

Medium term response to H-R erythropoietin in CAPD patients: the influence of erythropoietin plasmatic levels and the effects on peritoneal transport capacity.

Anemia of CRF has been corrected by use of H-R-EPO both in hemodialysis and CAPD patients. Long term response to subcutaneous EPO and its relationship with serum EPO levels remain to be established. Twenty-five CAPD patients treated with CAPD during 30 +/- 28 (mean +/- SD) months were included in this study. The follow-up period was 6-24 months. All patients have been on CAPD at least 6 months and their Hemoglobin (Hb) level was lower than 8.5 g/dl. Twelve patients received EPO by subcutaneous route, at doses of 20 u./Kg daily and 13 other patients at doses of 2000 units twice a week. Thereafter, these doses were adjusted to obtain a Hemoglobin level ranging 10.5-13 g/dl. In conclusion, our results suggest that the subcutaneous route for H-R-Erythropoietin can be considered as the best choice for CAPD patients. Low doses twice a week seem to improve anemia in 2 months. Later, dose adjustment should be done according to the patient's response. The improvement in nutritional status we observed suggests a new positive aspect for EPO therapy. Our data did not show changes in peritoneal function.

Recombinant gamma-interferon as adjuvant to hepatitis B vaccine in hemodialysis patients.

Patients undergoing long-term hemodialysis are at high risk of acquiring hepatitis B yet tend to have poor rates of response to hepatitis B vaccine. The effect of recombinant human gamma-interferon (2 million units/m2) on the response to a recombinant hepatitis B vaccine was evaluated in a prospective, randomized controlled trial in 81 hemodialysis patients. A similar proportion of both groups of vaccinees ultimately developed antibody to HBsAg including 81% of the 41 recipients of vaccine alone (group I) and 89% of the 40 recipients of vaccine with gamma-interferon (group II). However, the antibody to HBsAg response occurred earlier in recipients of vaccine with gamma-interferon, so that at 4 mo 63% of group I and 88% of group II had antibody to HBsAg (p less than 0.025). Furthermore, titers of antibody to HBsAg tended to be higher in the vaccinees given interferon; the final geometric mean titers were 232 IU/L in group I and 330 IU/L in group II (p = not significant). Retrospective testing for antibody to hepatitis C virus revealed that 21 (26%) hemodialysis patients were seropositive at entry into this trial, but the presence of antibody to hepatitis C virus did not appear to affect the response rate to the hepatitis B vaccine. These results suggest that the effects of gamma-interferon as an adjuvant in increasing the response rate to hepatitis B vaccination deserve further evaluation perhaps most appropriately in persons who have not responded to an initial course of vaccine.

Treatment of the anemia with human recombinant erythropoietin in CAPD patients.

Three homogenous groups of CAPD patients, all of them with plasma hemoglobin levels lower than 8 g/dl were studied. Group 1 included 8 patients who received EPO by the subcutaneous route (s.c), at doses of 20 u./kg daily; this dose was reduced when a hemoglobin level higher than 10.5 g/dl was reached. Group 2 included 7 patients treated with EPO by subcutaneous route but at doses of 2000 units twice a week. Group 3 was constituted by 4 patients receiving EPO by intraperitoneal route (i.p.), at doses of 4000 u/day, three days a week. All patients showed an increase in hematocrit and Hb levels after three months of treatment, but the mean EPO dose was quite different comparing the groups, maintaining the reached levels at the 9th month; reticulocyte count increased only during the first month. The rest of clinical and biochemical parameters did not suffer any significant modifications. Our features showed a higher profit, that is, higher increase in Hb level with lower dose of EPO in the s.c. group in respect to i.p. group. Furthermore, we have registered a marked increase in the frequency of exogenous peritonitis in these particular patients while using i.p. EPO. In conclusion, we feel that subcutaneous route for H-R-Erythropoietin is an ideal way for this treatment, resulting in a more adequate profit ratio than that described in hemodialysis patients. The intraperitoneal route is more expensive and risky for the peritoneum, probably as a consequence of the increase of manipulations.

[Carbon tetrachloride poisoning: a report of 3 cases]. / Intoxicación por tetracloruro de carbono: presentación de tres casos.

Carbon tetrachloride is a toxic solvent easily obtained in our country. 3 cases of poisoning by accidental inhalation at place of work. The main clinical manifestations were acute renal failure and toxic hepatopathy. All patients, had a good evolution with dialysis therapy after a few weeks. We comment on some possible additional therapies to be used in treating patients with severe poisoning due to carbon tetrachloride.

Induced changes of the peritoneal diffusion capacity by smoking, intraabdominal hypertension and omentectomy.

UNLABELLED: Peritoneal membrane suffers in some CAPD patients changes which modify its functionalism. In order to know whether these changes could be expected or appropriate, it is necessary to explore the general and particular conditions which can alter peritoneal physiology. Three aspects, smoking, intraabdominal hyperpressure and and omentectomy are situations which have not been included in the studies of peritoneal physiology. PATIENTS: The control group was constituted by 23 patients. Diabetics were studied as a separate group, with their own 10 patient controls. Smokers (1-20 cigarettes per day): 15 were non-diabetic patients, 9 were females. Diabetic smokers: 7 patients. Intraabdominal hyperpressure was determined by two big polycycstic kidneys (PCKD) in 8 patients, none diabetic. Omentectomy was performed in 6 non-diabetic and 9 diabetic patients. In all cases the procedure was prescribed because of an early catheter entrapment. Smoker patients show significant higher MTCs values for urea and creatinine than controls, but the slightly lower ultrafiltration value did not reached significant difference. Polycystic kidney patients showed lower MTCs values in respect to controls. Ultrafiltration capacity was similar. Omentectomized patients did not show any differences in respect to controls. In the diabetic patients group, neither ultrafiltration nor MTCs values presented significant differences between the established subgroups. So, smoking did not seem to induce higher MTC values as in the non-diabetic group. In conclusion, and according to the present results, two more situations should be taken into account in the evaluation of the peritoneal membrane dialyzing capacities: smoking, which increases diffusion capacity except for diabetics and PCKD with tow big kidneys, which decreases this capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Hemolytic uremic syndrome in a patient with gastric adenocarcinoma: partial recovery of renal function after gastrectomy.

We report on a patient with gastric adenocarcinoma and severe renal failure caused by hemolytic uremic syndrome with predominantly vascular involvement. Evolution was favorable with partial recovery of renal function after tumor excision and administration of fresh plasma. Although microangiopathic hemolytic anemia is frequently associated with solid tumors, the appearance of a typical hemolytic uremic syndrome with carcinoma is exceptional.

Angiomyelolipoma associated with bilateral adrenocortical hyperplasia and hypertension.

We report a case of adrenal myelolipoma associated with adrenocortical hyperplasia and hypertension. Although several endocrine derangements have been described in association with myelolipomas, we have found no reports of its association with adrenocortical hyperplasia.

Magnesium excretion in idiopathic hypercalciuria.

Given the parallelism in calcium and magnesium metabolisms, we have studied urinary magnesium in normal subjects and in patients with idiopathic hypercalciuria under conditions of basal and restricted diet, fasting, and after oral calcium overload. Serum magnesium values showed no differences between groups. Urinary magnesium levels are increased in absorptive hypercalciuria under free and restricted diet and calcium overload, returning to normal during fasting. Renal hypercalciuria patients maintain a high magnesium excretion under all conditions. This suggests that in idiopathic hypercalciuria there is an impairment of renal magnesium management, dependent on that of calcium because it normalizes when urinary calcium is normal.