Guanidino compounds in serum and urine of nondialyzed patients with chronic renal insufficiency.

Levels of 15 guanidino compounds and urea were determined in serum and urine of nondialyzed patients with chronic renal insufficiency subdivided according to etiology and creatinine clearances. No significantly different guanidino compound levels in serum and urine were found for the interstitial nephritis, glomerulonephritis, nephrangiosclerosis, and diabetic nephropathy subgroups. Subdividing the patients according to creatinine clearance yields the following results: (1) Serum guanidinosuccinic acid (GSA) and methylguanidine levels of patients with end-stage renal failure (creatinine clearance < 10 mL/min) are up to 100 and 35 times higher than control levels, while guanidine, creatinine, and symmetrical dimethylarginine (SDMA) are increased about 10 times. Serum levels of asymmetrical dimethylarginine (ADMA) are only doubled in end-stage renal failure. Serum levels of guanidinoacetic acid (GAA) and homoarginine are significantly decreased. (2) Urinary excretion levels of most guanidino compounds decrease with decreasing creatinine clearance except for GSA and methylguanidine. (3) Greater than 90% of patients with creatinine clearance ranging from subnormal to 40 mL/min have serum SDMA levels higher than the upper-normal limit; up to 80% have increased GSA levels. (4) The clearance rates of some of the guanidino compounds could be calculated: with the exception of arginine, they decrease with decreasing creatinine clearance. This study shows specific abnormal guanidino compound levels in serum and urine of nondialyzed patients with chronic renal insufficiency that can be used as complementary diagnostic parameters. The best correlation between serum guanidino compound levels and the degree of renal insufficiency is found for GSA, SDMA, methylguanidine, and guanidine. Urinary excretion levels of ADMA correlate best with decreasing creatinine clearance. Serum levels of GSA and especially SDMA are candidate indicators for the onset of renal failure.

Guanidino compounds in uraemic dialysed patients.

The concentrations of guanidino compounds in blood are raised in uraemic patients and may have toxic effects. The concentrations of 13 guanidino compounds in serum were measured in 29 patients with chronic renal failure treated by chronic intermittent haemodialysis using liquid cation exchange chromatography with a highly sensitive fluorescence detection method. For taurocyamine we used another column system. Substantial increases in guanidinosuccinic acid, creatine, N-alpha-acetylarginine, creatinine, guanidine and methylguanidine were found. The values obtained for taurocyamine and beta-guanidinoproprionic acid were much lower than those reported by others: a much smaller increase was observed for beta-guanidinoproprionic acid and taurocyamine was only doubled in 4 of 29 uraemic patients. The concentrations of other guanidino compounds such as arginine and guanidinoacetic acid were normal. No differences were found between the polycystic renal disease, the chronic glomerulonephritis and the interstitial nephritis subgroups.

Shunt nephritis.

A case of nephritis occurring in a 40-year old patient with a ventriculojugular shung infected with staphylococcus albus is described. Circulating antistaphylococcal antibodies could be demonstrated. Renal manifestations disappeared after treatment with systemic antibiotics and surgical removal of the shunt.

Intermittent venovenous haemodiafiltration in critically ill patients with acute renal failure.

Various renal replacement therapies have been used for the treatment of acute renal failure in critically ill patients in the last decade. Due to the slower rate of solute and fluid removal, the continuous renal replacement therapies are generally better tolerated than conventional therapy. There is no consensus whether different treatment strategies effect the outcome of critically ill patients and no clear definition of adequacy of renal support in the severely ill patient. Despite their possible benefits, the continuous renal replacement therapies place major demands on the organisation and workload in the dialysis unit. Having taken this into consideration our unit has opted for a ten hours daytime intermittent venovenous haemodiafiltration technique as an alternative for patients in severe conditions of haemodynamic instability, the so-called "go slow" dialysis.

Remarkable removal of beta-2-microglobulin by on-line hemodiafiltration.

UNLABELLED: Eight chronic, anuric hemodialysis patients were randomly treated with a high-flux polysulphone dialyzer (F80), using 6 different modes: conventional bicarbonate hemodialysis (HD), hemodiafiltration (HDF) with a replacement solution at 40, 60, 80 or 100 ml/min in postdilution and 80 ml/min in predilution. The differences in beta 2-microglobulin (beta 2M) reduction ratio and clearance were evaluated statistically by analysis of variance (ANOVA). Both studies revealed no significant difference between HD and HDF40 in postdilution, but an increasing significant difference from HDF60 to HDF100 in postdilution and with HDF80 in predilution. The mean reduction ratio ranged from 49.7 (HD) to 72.7% (HDF 100 ml/min), showing an overall statistically significant difference (p = 0.0000). For the clearance, the range was between 63.8 (HD) and 116.8 ml/min (HDF 100 ml/min) (p = 0.0000). beta 2M in the effluent dialysate with HDF 100 ml/min reached up to a mean of 258 mg/session. Concerning small molecules (BUN, creatinine and P), there was a statistically significant different clearance for creatinine and especially for P with HDF 100 ml/min. CONCLUSION: HDF with an on-line replacement solution at 100 ml/min and a high-flux and biocompatible polysulphone membrane represents a new tool for enhanced removal of beta 2M. Besides a significant increase in creatinine and especially in phosphorus clearance is noted.

Serum guanidino compound levels and the influence of a single hemodialysis in uremic patients undergoing maintenance hemodialysis.

Guanidino compounds are increased in uremia and are highly suspected to be uremic toxins. The serum levels of 11 guanidino compounds and the influence of a single hemodialysis were evaluated in 30 steady-state uremic patients undergoing maintenance hemodialysis. Guanidino compound levels were detected using liquid cation exchange chromatography with a highly sensitive fluorescence detection method. Highly standardized dialysis procedures were performed. Before hemodialysis, high levels were found for guanidinosuccinic acid, N-alpha-acetylarginine, argininic acid, creatinine, gamma-guanidinobutyric acid, guanidine and methylguanidine. Guanidinosuccinic acid reached levels associated with toxic effects in vitro. After hemodialysis, although lowered, guanidinosuccinic acid, creatinine, guanidine and methylguanidine were still markedly increased. No differences in the percent decrease, during a single hemodialysis, of the studied compounds were found using different membranes such as cellulose acetate, cuprophane and polyacrylonitrile membranes. Substantial differences, however, in the percent decrease of the different guanidino compounds were found, ranging from 25 +/- 13% for arginine to 74 +/- 7.5% for guanidinosuccinic acid. Data reported here show that guanidino compounds are raised in serum of uremic patients undergoing maintenance hemodialysis, before as well as after a single hemodialysis, while substantial differences in the percent decrease of the different guanidino compounds are found.

On-line haemodiafiltration. Remarkable removal of beta2-microglobulin. Long-term clinical observations.

BACKGROUND: The accumulation of beta2-microglobulin (beta2-M) in long-term dialysis patients may lead to dialysis amyloidosis. In this respect, the removal with different modes of on-line haemodiafiltration (HDF) of beta2-M was studied. Long-term clinical observations in patients with more than 10 years of dialysis, treated mainly with biocompatible and highly permeable membranes and in the last years with on-line HDF are also reported. METHODS: In the first part of this report, the reduction ratios and clearances of beta2-M, blood urea nitrogen, creatinine and phosphorus (P) of on-line HDF with 40 to 120 ml/min replacement fluid are compared with bicarbonate haemodialysis (HD). In the second part, we investigated 16 patients with more than 10 years of dialysis treatment. The prevalence of dialysis amyloidosis and the mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol and parathyroid hormone are reported, as well as the mean dose of erythropoietin. RESULTS: In the first part with on-line HDF, starting from HDF 60 ml/min a significantly higher beta2-M reduction ratio and clearance vs HD is noted. In HDF100 (i.e. with 241 replacement volume per 4-h treatment) vs HD, a beta2-M reduction ratio of 72.7% vs 49.7% (P= 0.0000) and a beta2-M clearance of 116.8 vs 63.8 ml/min (P=0.0000) was obtained. Comparing HDF120 with HDF100, there is a significantly higher beta2-M clearance with the former (P<0.005), although the beta2-M reduction ratio was not significantly better. In the HDF120 session the amount of beta2-M in the total dialysate was 292 mg per session. If one adds the known 17% adsorption on the polysulfone membrane, a total of 341.6 mg beta2-M per session is removed, which adds up to 1024.8 mg a week. Concerning the small molecules, our results with HDF100 also show a higher creatinine and especially P clearance vs HD. In the second part with 16 patients with more than 10 years of dialysis treatment (mean 14 years 1 month), the mean time on HDF amounted to 39.5% of the total treatment time. In four patients only biocompatible and highly permeable membranes were used, AN69 and mainly polysulfone, and in four other patients these membranes were used for more than 95% of the treatment time. Therefore, it is not surprising that the prevalence of carpal tunnel syndrome was only 12.5% in the patients after 10 years of dialysis. Twenty-five percent of these patients met the criteria for diagnosis of beta2-M bone-amyloidosis, proposed by van Ypersele de Strihou et al., but without a retrospective X-ray analysis. The mean predialysis beta2-M value was 29.6 mg/l. The mean values for serum albumin, serum total cholesterol, HDL and LDL cholesterol were within normal limits. For the parathyroid hormone a mean of 287.5 pg/ml was found. Subtotal parathyroidectomy was performed in five patients. The mean dose of 43 U erythropoietin/kg per session is comparable with those reported in the literature. Conclusions. Like Canaud, in our renal unit, treatment with on-line HDF with a highly permeable and biocompatible membrane has proven to be an efficient, well-tolerated and safe technique. Furthermore it leads to a low prevalence of dialysis amyloidosis and a superior P clearance. However, continuous attention must be paid to an on-line sterile and apyrogenic dialysate. Although on-line HDF is undoubtedly a more optimal approach of chronic dialytic treatment, it also carries a higher cost, which is currently evaluated to be nearly US$11 per session.

Autogenous saphenous vein AV fistulae for haemodialysis: eight years experience with 30 patients.

Since 1973, 41 autogenous saphenous vein (ASV) fistulae in the arm or the leg have been constructed in 30 chronic haemodialysis patients. The mean patency rate for the arm fistulae was 36.8 months and 21.9 months for leg fistulae. Eight patients received a leg fistula, after their arm fistula thrombosed: in this group the mean patency rate for the arm and leg fistulae was 15.4 and 20 months respectively. If a conventional fistula is not feasible, an ASV fistula is the method of choice for some patients.

Pharmacokinetics of aluminoxamine and ferrioxamine and dose finding of desferrioxamine in haemodialysis patients.

We investigated the pharmacokinetics of desferrioxamine and its chelated compounds aluminoxamine and ferrioxamine in normal volunteers and haemodialysis patients with and without iron overload. Desferrioxamine was administered in a single dose of 30 mg per kg body-weight was a 30-min infusion to five healthy volunteers and to 20 haemodialysis patients (five patients without haemosiderosis and 15 patients with haemosiderosis). The interdialytic half-life of ferrioxamine was 2.2 h in normal volunteers, 13.3 h in dialysis patients without haemosiderosis, and 24.6 h in patients with haemosiderosis. There was no interdialytic elimination of aluminoxamine. In a second study, seven dialysis patients received 5, 10, and 20 mg per kg body-weight desferrioxamine in a random order with a time interval of 2 weeks. The peak serum concentrations after these doses were 4.1 +/- 2.9, 6.4 +/- 2.9, and 10.7 +/- 7.1 mumol/l for ferrioxamine and 2.8 +/- 1.5, 3.1 +/- 1.5, and 4.2 +/- 1.7 mumol/l for aluminoxamine. Thus, a 4-fold increase in desferrioxamine dosage resulted in a 2.7-fold increase in peak ferrioxamine levels and in only a 1.5-fold increase in peak aluminoxamine levels. We conclude that dialysis patients, especially those with haemosiderosis, are exposed to persistently elevated ferrioxamine levels. Weekly doses of 5-10 mg/kg of desferrioxamine would be sufficient for aluminium chelation therapy.