Persistence of antibodies to pneumococcal vaccine in patients with chronic renal failure.

Antibody response to the 14-valent pneumococcal capsular polysaccharide vaccine was measured by the enzyme-linked immunosorbent assay (EIA) in 17 renal allograft recipients, 29 azotemic, 11 hemodialysis, and 33 control patients. The IgG, IgM, and IgA antibodies were measured against six pneumococcal antigen types 1, 3, 4, 6A, 8, and 19F. The control patients had the best antibody responses in the IgG and IgA antibody classes and the renal allograft recipients in the IgM class. The renal allograft recipients had significantly stronger antibody responses than the azotemic and hemodialysis patients. The hemodialysis patients had significantly weaker antibody responses than the control patients and the renal allograft recipients, and they also lost their antibodies most rapidly. Thus, the hemodialysis patients and probably some azotemic patients should be considered for revaccination.

Prevalence and incidence of moderate and severe chronic renal failure in south-western Finland, 1973-76.

In an area of south-western Finland with 195 000 inhibitants and a highly centralized health care system, all subjects with elevated serum creatinine (greater than or equal to 230 mumol/l) were registered on the basis of data collected from all hospitals and clinical laboratories of the region. The prevalence of chronic renal failure (S-creatinine greater than or equal to 230 mumol/l) was 67 per 100 000 inhabitants and that of severe chronic renal failure (S-creatinine greater than or equal to 500 mumol/l) 12.3/10(5). The annual incidence of chronic renal failure (S-creatinine greater than or equal to 230 mumol/l) was 31.7 per 100 000 inhabitants and that of severe chronic renal failure (S-creatinine greater than or equal to 500 mumol/l) 11.9/10(5). Age-specific prevalences and incidences rose progressively with age and were very high in the aged population. Chronic interstitial nephritis, in a broad sense, was the most common cause of chronic renal failure, and it was related to analgesic abuse in about half of the cases. Eleven of 68 subjects entering the study with a serum creatinine greater than or equal to 500 mumol/l had no previous knowledge of their chronic renal disease.

The use of clofibrate in patients with renal insufficiency.

Serum clofibrinic acid (CPIB) levels after single and multiple oral doses of clofibrate were studied in 28 patients with elevated serum creatinine values. The half-life of CPIB was prolonged in proportion to the serum creatinine level (r = 0.818 p less than 0.001). Peak CPIB concentrations in serum were not affected by azotemia, although CPIB levels 24 h after a single dose and under steady-state conditions correlated well with the serum creatinine level. The proportion of unbound CPIB was higher in patients with renal insufficiency than in controls (13.9% vs 4.3%), although this difference did not correlate with the serum creatinine level. Hypolipidemic medication is indicated in dyslipoproteinemias associated with renal insufficiency. If a reduced dose is given, clofibrate can be used safely in renal patients, although a CPIB concentration of 70 mg/l in serum should not be exceeded unless the unbound fraction has been measured and found not to exceed a safe level (i.e., 6 mg/l CPIB).

Trimethoprim alone in the treatment of urinary tract infections: eight years of experience in Finland.

In Finland the usage of trimethoprim (TMP) alone constitutes about 25% of all drug usage for urinary tract infections. Despite this widespread use the proportion of TMP-resistant strains is almost same as it is in countries where only the combination of trimethoprim-sulfamethoxazole (TMP-SMZ) has been used. In general, strains resistant to TMP were seldom found; only in closed wards did the use of trimethoprim result in an increase in the proportion of resistant strains. In the treatment of acute urinary tract infections, TMP alone (dose, 160 mg taken twice daily for seven days) gave a result as good as that of TMP-SMZ (94.5% vs. 90.6%) and a better result than cephalexin (98.3% vs. 82.1%). TMP proved suitable as a single agent in the treatment of urinary tract infections in outpatients. In a study of long-term treatment, TMP (dose, 100 mg taken once daily), was more effective than nitrofurantoin, methenamine hippurate, TMP-SMZ, or placebo. Fewer adverse effects were associated with TMP than with the other drugs.

Influenza vaccination in patients with chronic renal failure.

27 patients with chronic renal failure (CRF), 12 of whom were on maintenance hemodialysis, and 40 healthy control individuals were immunized with a split-type influenza vaccine containing A/Victoria/75 (H3N2), A/USSR/77 (H1N1), B/Hong Kong/73 antigens; 2 doses were given 4 weeks apart. Antibody responses were determined by the single radial hemolysis (SRH) technique. After immunization a significant rise (increase in SRH greater than or equal to 2 mm) was measured to A/Victoria in 11 (73%) azotemic and in 11 (92%) hemodialyzed patients and in 35 (88%) controls. To B/Hong Kong a significant antibody rise was observed in 10 (67%) azotemic, in 11 (92%) hemodialyzed and in 27 (68%) control individuals. The mean prevaccination and postvaccination antibody titers in patients with CRF, either azotemic or hemodialyzed, were significantly lower than in healthy control individuals to both A/Victoria and B/Hong Kong antigens (p less than 0.001). On the other hand the mean antibody rises after vaccination were of the same magnitude in all groups. The patients on maintenance hemodialysis had lower prevaccination antibody titers but the postvaccination mean titers were slightly higher than in the azotemic patients. No adverse reactions to the vaccination or deterioration of the renal function were observed; thus we recommend an annual vaccination of patients with CRF.

Changes of panorama in renal disease mortality in Finland after phenacetin restriction.

The purpose of the present study was to examine the effect of phenacetin consumption and its restriction on the mortality from nephropathy. Changes in this mortality in Finland during 1951-77 were investigated. The second part of the study was concerned with the frequency of papillary necrosis in cases autopsied in the Department of Medicine, Turku University Central Hospital, during 1952-79. These figures were studied in relation to increased phenacetin consumption after World War II, its restriction in 1962 and its complete banning in 1965. Both the epidemiologic survey of the mortality from nephropathy in Finland and the autopsies showed a clear and strong correlation both with increased phenacetin consumption and with its discontinuation. The banning of phenacetin led within 2-4 years to a decline in the mortality from nephropathy to its pre-phenacetin level.

Secondary prevention of recurrent urinary tract infections. Comparison of the effect of placebo, methenamine hippurate, nitrofurantoin and trimethoprim alone.

290 patients with recurrent urinary tract infection were treated with either placebo, methenamine hippurate, nitrofurantoin or trimethoprim. 38.9% of the patients had chronic pyelonephritis and 23.8% azotemia. During the follow-up period of 1 year 63.2% recurred in the placebo group, 34.2% in the methenamine hippurate group, 25.0% in the nitrofurantoin group and 10.4% in the trimethoprim group. 62.5% of the recurrences in the trimethoprim group were associated with trimethoprim-resistant strains. However, such strains appeared only in 6.5% of the patients treated with trimethoprim, compared with 16.2% in the placebo, 8.3% in the nitrofurantoin and 11.0% in the methenamine hippurate groups. Side-effects were mild and occurred most frequently in the nitrofurantoin group (13.9%).

Ceftazidime in the treatment of urinary tract infection.

Twenty-nine patients with urinary tract infection were treated with ceftazidime intramuscularly, at a dosage of 1000 mg twice daily for 7 days. The patient series was predominantly geriatric, with a mean age of 70.9 years and including 17 patients over 75 years. Nine had an in-dwelling catheter and azotaemia was found in 14 cases. In this clinically difficult group, a positive bacteriological response to treatment was obtained in 72.9% and, if patients with in-dwelling catheters are excluded, 90% were cured. Ceftazidime-resistant Streptococcus faecalis was cultured before treatment in 6 of the 8 unsuccessful cases. In the remaining 2 treatment failures, Streptococcus faecalis was isolated immediately after treatment. In terms of clinical response to therapy all patients were cured or improved. Treatment with ceftazidime was well tolerated. No subjective side-effects occurred. One patient developed a distinct but transient elevation of liver enzymes, and in 2 cases a negative direct Coombs test was temporarily positive.

Pharmacokinetics of naproxen in subjects with normal and impaired renal function.

The pharmacokinetics of naproxen after a single oral dose of 250 mg has been studied in 8 subjects with normal renal function and 16 patients with varying degrees of chronic renal insufficiency. Unchanged naproxen and its main unconjugated metabolite, 6-0-desmethylnaproxen, were determined fluorometrically in serum. In healthy subjects the elimination half-life of naproxen was 17.7 +/- 3.0 h (mean +/- SD) and it was not significantly prolonged in patients with renal failure (18.1 +/- 5.3) h. No accumulation of naproxen in serum occurred in uraemic patients. On the contrary, serum drug levels were slightly but significantly lower in patients with severe renal failure. The total body clearance and apparent volume of distribution of naproxen were significantly increased in this group of patients. Decreased binding of naproxen to serum proteins was observed in patients with renal failure. The apparent half-life of desmethylnaproxen was of the same order of magnitude as that of naproxen (18.6 +/- 4.4 h), and was also independent of renal function. A good correlation was found between the area under the curve (AUC), the peak concentration of the metabolite and the serum creatinine concentration. These observations suggest increased metabolism and an increased apparent volume of distribution of naproxen in severe renal failure, probably caused by decreased serum protein binding of the drug. However, it is proposed that in naproxen therapy no adjustment of the dosage regimen is necessary in patients with impaired renal function.

Renal accumulation of amikacin, tobramycin and gentamycin in the rat.

Free and total concentrations of amikacin, tobramycin and gentamycin were measured separately in the rat kidney after equal weight by weight doses. The accumulation of aminoglycosides followed the order amikacin less than tobramycin less than gentamycin. The ratio between free and total aminoglycosides was similar (about 0.6) in all 3 aminoglycosides and independent on the length of administration.

The nephrotoxicity and renal accumulation of amikacin, tobramycin and gentamycin in rats, rabbits and guinea pigs.

The nephrotoxicity and renal concentrations of amikacin, tobramycin and gentamycin were studied in rat, rabbit and guinea pig. The nephrotoxicity was estimated by histological examination and by measuring the relative weight of the kidneys (mg/100 mg body weight). These two systems had a significant correlation (r = 0.87; p less than 0.001). The concentrations of aminoglycosides were determined by the cylinder-plate method measuring free aminoglycosides. The renal toxicity of the aminoglycosides in equal doses weight by weight followed the order amikacin less than tobramycin less than gentamycin in the rat. The same order was observed in the renal accumulation of the aminoglycosides in rat, rabbit and guinea pig. The critical kidney damaging concentration of free aminoglycoside in the whole rat kidney was estimated to be 160--190 microgram/g.

Sulfadiazine-trimethoprim combination in the treatment of urinary tract infections.

In a clinical double-blind study on 198 patients with a urinary tract infection, no differences were found between comparable groups treated with either sulfadiazine (SD) 1,000 MG/trimethoprim (TM) 320 mg or sulfamethoxazole (SM) 1,600 mg/trimethoprim 320 g daily for 2 weeks. The favorable results were obtained according to the bacteriological control in 85 and 79%, respectively. Also the incidence of side effects was the same (22 and 24%, resp.). The number of cases within which the treatment had to be discontinued did not differ percentually, either (6.6 and 8.4%, resp.). Based on the bacteriological sensitivity tests and the clinical trial, the authors conclude that TM can be combined with SD as well as with SM. Pharmacokinetic advantages, like a lower protein-binding and a lesser metabolism, may even make SD more preferable.

Serum levels and half-life of sotalol in chronic renal failure.

The elimination of sotalol was studied in 25 patients with chronic renal failure. All patients were given a single 160 mg dose of sotalol orally and their sotalol serum levels were determined after 4, 6, 8, 10 and 12 hours. The elmination of sotalol was distinctly slower as the serum creatinine concentration rose. The half-lives, calculated graphically, were in lenear ratio to the serum creatinine values (r = 0,91; p less than 0.001). In accordance with the results, it is probable that sotalol accumulates in chronic renal insufficiency. Since beta-blockers may impair renal function, even in therapeutic concentrations, the dosage of sotalol, in particular, must be reduced in patient with kidney disease.