Pharmacokinetics of netilmicin in hypertonic hemodiafiltration and standard hemodialysis.

Recently, we developed a peculiar model of hemodiafiltration (HDF), in which a conventional acetate hemodialysis (HD) is combined with a high flux dialyzer, a high ultrafiltration flow rate and a postdilution hypertonic reinfusion (H HDF). The pharmacokinetics of netilmicin (N), a relatively new aminoglycoside, were evaluated during 5 sessions of H HDF of 180 min and 2 sessions of HD of 270 min in the same 8 patients with a comparable blood (approximately 400 ml/min) and dialysate flow rate (approximately 520 ml/min). Additional studies were performed in 7 out of the 8 patients after 2 sessions of H HDF and one session of HD. N clearance, calculated both as plasma water and total body clearance, was so exceedingly higher during H HDF than during HD, that the amount of drug removed by H HDF in 180 min was still significantly higher than that removed by HD in 270 min. Consequently, the N half-life during HD was about 5 h, whereas during H HDF it was less than 2.5 h, approaching that reported in normal subjects. N half-life out of dialysis treatments was about 55 h. In conclusion, N pharmacokinetics are strikingly different between H HDF and HD, with N clearance during H HDF about the double of that during HD. The implications of this study are: a different dosage adjustment of aminoglycosides is needed for patients routinely treated by HDF; HDF may be a very effective treatment for the overdose of many drugs.

Effects of omeprazole therapy on peptic disease and serum gastrin levels in hemodialysis patients. A preliminary study.

Hemodialysis patients are frequently affected by peptic disease, and in many cases they have high serum levels of gastrin. The aim of this study was to evaluate the effects of omeprazole, an inhibitor of gastric parietal cells hydrogen pump, on peptic disease and gastric secretion of 16 selected dialysis patients. H2-receptors blocking drugs or gastric acidity buffers were withdrawn for 2 weeks, then omeprazole was administered for 4 weeks at a daily dosage of 20 mg. Before and after the omeprazole therapy, registration of subjective peptic symptoms, baseline serum gastrin dosage and endoscopy of upper digestive tract were performed. Before starting omeprazole, the serum gastrin value was 515 +/- 180 pg/l, all the patients complained of peptic symptoms, and endoscopy showed: 8 cases of duodenal ulcer, 3 cases of pyloric ulcer and 5 cases of antral erosive gastritis. At the end of the omeprazole treatment period, a slight but statistically not significant increase of serum gastrin level (537 +/- 198 pg/l) was observed. Twelve patients reported the total disappearance of symptoms of peptic disease, 3 patients a partial reduction, and 1 patient had no improvement. Control endoscopy showed the healing (white scar) of all the ulcers, and the disappearance of all the erosive lesions. In conclusion, our results show that a 20 mg/day omeprazole short-term therapy can be given safely to uremic patients undergoing hemodialysis and is effective for a quick healing of active peptic lesions.

Plasma volume changes induced by sequential ultrafiltration-hemodialysis and sequential hemodialysis-ultrafiltration.

Isolated ultrafiltration (UF) has been shown to preserve plasma volume (PV) by means of a high plasma refilling rate, mediated by a rapid rise in oncotic pressure. This mechanism contributes to the good tolerance of sequential ultrafiltration-hemodialysis (SUH). This study compared PV changes induced by SUH and sequential hemodialysis-ultrafiltration (SHU). Seven dialysis patients underwent two sets of SUH and SHU, in which 2 h of UF (approximately equal to 3L) respectively preceded or followed 2 h of no-weight-change hemodialysis (ISO HD). VEM (volume of extravascular mobilization), VEM/VUF (percent of plasma refilling rate) and delta PV were calculated by mathematical formulas. Results showed: 1) a high VEM/VUF during the UF period, either before or after ISO HD: 80 and 77% respectively; 2) a significant increase in PV during ISO HD after UF, compared to ISO HD before UF: + 229 ml and + 43 ml, P less than 0.05; 3) VEM/VUF significantly higher during SUH than during SHU: 87 and 80%, P less than 0.01. In conclusion, the decrease in PV was lower in SUH than in SHU (11 vs. 19%, P less than 0.001) because the plasma refilling persisted through the ISO HD period.

A hemostasis study in CAPD patients during fibrinolytic intraperitoneal therapy with urokinase (UK).

Catheter obstruction due to fibrin deposits during CAPD can cause poor outflow of peritoneal fluid and recurrent peritonitis. In order to treat this complication, 75,000 IU of diluted Urokinase (UK) were infused into catheters obstructed by fibrin in 10 CAPD patients (4 of which had peritonitis), without adverse reactions. After 60 minutes, a 2 liter exchange of peritoneal fluid was performed. In all the cases a normal outflow was restored. Hemostasis parameters (PT, PTT, TT, Fibrinogen, FDP, Fibrin monomers, BT, AT III) and blood cells count (RBC, HGB, HCT, WBC, PTL), were assayed before and two hours after the UK infusion, and did not show any significant variation, except for a decrease of white blood cells, which remained, however, within the normal range. No peritonitis episode occurred in the follow-up period. UK fibrinolytic therapy is safe and effective in treating fibrin obstruction of CAPD catheters without catheter removal and prevents recurrent peritonitis.

First exchange neutrophilia is not always an index of peritonitis during CAPD.

To date, the medical literature suggests that CAPD patients with peritonitis have an increase in the dialysate white cell count (greater than 100 cells mL) with neutrophilia (greater than 50%). In order to explore the differential composition of the peritoneal fluid cells (P.F.C.), we have followed 21 patients (PTS) twice a month over a 30-month period. Nine hundred and fifty samples obtained either from the 24 hours (hrs) drained CAPD fluid, or from the "First Morning Exchange" (F.M.E.) during the same day, when possible, were estimated with the "Millipore Filter" (5-8 Micron (lw) pore size), stained by the Papanicolau method. The results can be so summarized: (1) 13 PTS (62%) showed constantly a low polynuclear count (3-32%); (2) 8 non-infected PTS (38%) showed constantly a higher neutrophilia (40-80%); and (3) from time to time the PTS of the two groups showed a higher neutrophilia and an increased cellularity during clinical infection. In all the samples, the differential P.F.C. count was not affected by the dialysate composition and no difference was observed between the 24 hrs samples and the F.M.E. samples made on the same day. Differential peritoneal cell count may be useful when there are important changes in the stable individual composition.

[Severe hyperparathyroidism in 2 uremic patients. Diagnostic and therapeutic difficulties]. / Iperparatiroidismo grave in due pazienti uremici. Difficoltà diagnostiche e terapeutiche.

We report here the unusually difficult cases of two patients with end-stage renal failure who suffered from severe hyperparathyroidism requiring surgical correction. The first patient had previously undiagnosed primary hyperparathyroidism. A first surgical neck exploration led to the discovery of four glands, paradoxically normal in size and aspect, which were removed. Subsequently, a supernumerary gland was localized in the mediastinum by computerized tomography and removed via sternotomy. After confirming the hypoparathyroid state, parathyroid autotransplantation was performed using cryopreserved tissue. The second patient had five hyperplastic parathyroid glands removed during the first neck exploration, followed by immediate parathyroid autografting. Because of the persistence of severe hyperparathyroidism, forearm autografts were subsequently removed and a sternotomy performed. Both failed to improve parathyroid hyperfunction. Numerous localization procedures remained negative. A repeat surgical neck exploration was performed because of positive double isotope scanning but was of no success in preventing fatal outcome, as were all medical treatments. These observations of two patients illustrate the difficulties in localizing and removing ectopic parathyroid lesions. Even when relying on the presently available powerful diagnostic means, correction of severe hyperparathyroidism may be extremely difficult.

Acute renal failure due to tubular necrosis caused by wildfowl-mediated hemlock poisoning.

We report the clinical and histological findings in patients with acute renal failure caused by the ingestion of wildfowl who had eaten hemlock buds. Neurotoxic effects were accompanied by rhabdomyolysis, myoglobinuria, and acute tubular necrosis. Histological studies showed diffuse degeneration of the tubular epithelium. Immunohistological studies demonstrated the presence of myoglobin and actin in renal tubular cells.

Solute kinetics in hypertonic hemodiafiltration and standard hemodialysis.

Hemodiafiltration (HDF) is a new dialysis treatment that combines convective and diffusive forces. In order to assess the efficiency of a peculiar model of hypertonic HDF (H HDF), we studied eight uremic patients when they were undergoing five sessions of H HDF of 180 minutes duration and two sessions of standard hemodialysis (HD) of 270 minutes duration with a comparable blood (approximately 400 mL/min) and dialysate flow rate (approximately 520 mL/min). The plasma water clearances (Kw) of small [urea (U), creatinine (C), uric acid (UA), and phosphorus (P)] and middle molecules [netilmicin (N) and inulin (I)] were exceedingly higher in H HDF than in HD; however, because of the different treatment times, U and C removal (R) in HD overcame and UA and P R in HD equalized that in H HDF. The factor time was not sufficient to HD to compensate for the large difference in Kw in the case of I. Additional studies were performed in seven out of the eight patients after two sessions of H HDF and one session of HD. Two significantly higher rebounds were observed when comparing both treatments: for U after HD and for parathyroid hormone (PTH) after H HDF; however, PTH Cx/Cs ratios (ratios of the plasma water concentration of PTH at any postdialysis time to the plasma water concentration of PTH at the start of the run) were not different in both treatments, meaning that there was an increased PTH secretion in the early post H HDF hours in order to compensate for the larger PTH R with H HDF.(ABSTRACT TRUNCATED AT 250 WORDS)

One-hour and half, high-surface-area haemodiafiltration: a feasibility study.

In order to explore the limitations of further shortening of dialysis time, six uraemic patients underwent three different dialysis treatments: haemodiafiltration (HDF) of 180 min with a polyacrylonitrile membrane (1 m2); standard haemodialysis (SH) of 270 min with a cuprophan membrane (1 m2); 90 min, 2 m2 haemodiafiltration (H HDF) with two RP6 in series, dialysate coursed through the two dialysers in parallel and postdilution reinjection of 220 mEq/L of Na+ and 100 mEq/L of bicarbonate after each dialyser. Clearances were extremely more elevated in H HDF than in SH; urea extraction index was significantly higher in SH, but inulin extraction index was significantly lesser in SH than in H HDF.

[Electrophysiologic follow-up (brainstem acoustic evoked potentials and visual evoked potentials) in chronic uremic patients treated with various therapeutic protocols]. / Follow-up elettrofisiologico (Potenziali Evocati Acustici Troncoencefalici e Potenziali Evocati Visivi) in uremici cronici trattati con diversi protocolli terapeutici.

The aim of our study was to evaluate the possibility of recording also sub-clinical alterations of the Central Nervous System during chronic uremia by means of the study of Pattern-Reversal Visual Evoked Potentials (P-R V.E.Ps) and Brainstem Acoustic Evoked Potentials (B.A.E.Ps), to study their behaviour in answer to different kinds of treatment and follow their possible modifications during the time. With this purpose the uremic patients were divided into therapeutic groups: only dietetic and pharmacological treatment, conventional hemodialysis, hemodiafiltration, peritoneal dialysis and well functioning kidney transplant. A first record of Evoked Potentials was made in 1985 and the values were compared with those obtained by an homogeneous control group. The same patients were evaluated 3 years later and the two records results were compared. In both cases the most important percentage of altered values were found in the group under only dietetic and pharmacological treatment, the less important in the transplanted patients and these data were stable at the follow-up. So that Evoked Potentials are a good test in chronic uremia and the best therapy able to hinder the alterations of Central Nervous System arising during chronic renal failure would seen to be kidney transplant.

Acute renal failure due to rifampicin (R-ARF).

Five episodes of acute renal failure due to rifampicin (R-ARF) were observed in four patients and the clinical and histological data were compared with the records of 52 episodes reported in the literature. The bulk of data supports the assumption that the by far most frequent renal injury responsible for R-ARF is acute tubular necrosis produced by a vasomotor mechanism. Nevertheless a few data, above all immunohistological findings, suggest the local presence of allergic process. It may be, that the development of an immunological renal lesion is prevented or blunted by the consequences of vasomotor effects.

Combined dialysis and plasma-exchange in acute renal failure.

Combined use of plasma-exchange and dialysis therapy in 3 different cases of acute renal failure is presented. The first is a case of acute renal failure due to rhabdomyolysis caused by hemlock poisoning. Plasma-exchange was effective in improving the signs of rhabdomyolysis and renal failure. The second is a case of acute renal failure in an IgG-kappa myeloma. After 9 sessions of plasma-exchange, performed simultaneously with CAPD, a significant fall in the plasma and urine light chains levels was obtained. After the recovery of normal renal function, CAPD was prosecuted to remove light chains. The last is a case of acute renal failure in a patient with a mesangiocapillary nephritis and a high level of circulating immune complexes (CIC). He underwent steroid therapy and daily sessions of hemodialysis, followed by plasma-exchange, which permitted a fall of the CIC level, until a normal renal function was achieved. In conclusion, plasma-exchange combined with dialysis, is an useful tool for the management of acute renal failure caused by toxic proteins.

Clinical spectrum of accidental hemlock poisoning: neurotoxic manifestations, rhabdomyolysis and acute tubular necrosis.

In the past, hemlock poisoning was only known for its neurotoxic effects; quite recently non-neurological features, consisting of rhabdomyolysis and acute renal failure, have been also described. Here we report our experience with these clinical findings, which we frequently observe in accidental hemlock poisoning. Between 1972 and 1990 we studied 18 patients: 17 of them were poisoned by conline (an alkaloid of Conium maculatim) in Apulia (Italy), and one by cicutoxin (the active principle of water hemlock) in New Mexico (USA). In the non-rapidly-fatal cases we tested myoglobinuria, serum muscle enzymes, and renal function. In the patients with acute renal failure we performed microscopical examination of kidney specimens; immunohistochemistry was carried out to identify myoglobin and actin in tubules. Coniine was detected in urine, serum, or tissues. Neurological features were present in all of our cases: coniine had a curare-like effect on the neuromuscular junction, whereas cicutoxin was convulsant on the central nervous system. In addition rhabdomyolysis was noted in the 17 subjects poisoned by coniine. Acute renal failure was observed in five patients; it was confirmed by histological evidence of tubular necrosis with intratubular deposition of myoglobin and actin released by rhabdomyolysis. Our cases seem to be the first with histopathologically proven acute tubular necrosis in coniine intoxication. In conclusion, in hemlock poisoning neurotoxic manifestations may be accompanied by rhabdomyolysis and acute tubular necrosis; increased awareness of these clinical features is recommended in order to improve the diagnostic and therapeutic procedure.

Netilmicin pharmacokinetics in uremic patients undergoing hemodialysis.

The pharmacokinetics of netilmicin after i.v. administration were studied in 10 adult hemodialyzed patients during and after a dialysis session. The mean interdialysis half-life was 49.6 h, whereas during dialysis this value was reduced to 5.02 h. The mean volume of distribution of netilmicin was about 20% of the total body weight. The dialyzer clearance of netilmicin, measured at 60 and 150 min after the beginning of the session, was about 50 ml/min; this means that 60-65% of the drug may be lost during the 4.5 h standard dialysis. The total body clearance of netilmicin was similar to the dialyzer clearance values, suggesting that the drug is eliminated almost entirely by hemodialysis and that its renal elimination in our patients is negligible. In conclusion, in uremic hemodialyzed patients netilmicin behaves like other aminoglycosides.

Confirmation of high prevalence of hepatitis C antibodies in hemodialysis patients by second generation immunoblot assay.

Sera from 209 dialysis patients were tested for antibodies to hepatitis C virus (anti-HCV) by a 2nd generation enzyme-linked immunoassay (ELISA 2) using nonstructural and core antigens. Confirmation of reactivity was obtained by a 2nd generation immunoblot assay (RIBA 2) for antibodies to 4 separate antigens (5-1-1, c100-3, c33c, c22-3). ELISA 2 was positive in 99 sera, 95 of which were confirmed by RIBA 2, thus accounting for an anti-HCV prevalence of 45.5%. Anti-HCV positivity was correlated to longer duration of dialysis therapy (p less than 0.001), higher number of transfusions (p less than 0.001), history of kidney transplant (p less than 0.001) and of serum alanine/aspartate aminotransferase (AST/ALT; p less than 0.001) or gamma-glutamyltransferase (GGT) (p less than 0.001) increments. The most frequent RIBA 2 patterns were: reactivity to all 4 antigens (34 patients) and to c33c and c22-3 (45 patients). The former patients, compared to the latter, had higher values of AST (p less than 0.08), ALT (p less than 0.02), GGT (p less than 0.005), IgG (p less than 0.05). It is possible that the reactivity to all 4 antigens of RIBA 2 is a clue of a greater activity of viral hepatic disease.