The functional basis for nephrographic patterns in acute tubular necrosis.

There is considerable evidence that the principal functional abnormality in patients with acute reversible renal failure (ARF, or "acute tubular necrosis") is reduced cortical perfusion with diminished glomerular filtration. However, in such patients, high-dose intravenous urograms most commonly show an immediate obvious nephrogram. Since nephrographic density is believed to depend on the filtration of contrast medium into the tubular lumen, it is difficult to reconcile the early development of the nephrogram if glomerular filtration is reduced. Extensive experiments with both mercuric chloride and glycerol rat models of ARF have confirmed rapid intraluminal accumulation of contrast medium, albeit in reduced amounts. Studies using the normally filtered compound sodium nitroprusside and its precipitation as "prussian blue" suggest rapid transtubular diffusion from peritubular capillaries in kidneys with ARF. This, it is suggested, is also the mechanism for the rapid intraluminal ingress of contrast media and explains the early appearance of nephrogram. The less common intravenous urogram finding in ARF of a slowly developing and increasingly dense nephrogram may then represent cases with only slight tubular necrosis with predominant reduction in glomerular filtration.

Tamm-Horsfall glycoprotein excretion and aggregation during intravenous urography. Relevance to acute renal failure.

The effect of intravenous urography (IVU) on the excretion rate and precipitation of Tamm-Horsfall glycoprotein (THG) has been evaluated in 19 patients. Urine samples were collected immediately before the administration of contrast medium (U1) and then during the period of the excretion urogram (U2). The urinary THG: creatinine clearance ratio decreased in 15 patients by a mean of 28.2% (range 2.9-70.8) and increased in four by a mean of 22.8% (range 13.5-36.4). In 18 of 19 patients the amount of THG precipitated following the IVU decreased from an average of 75.6% of the total in U1 (range 2.2-100) to 19.5% (range 2.0-59) in U2. In the one exception the fraction precipitated was only 2.2% in U1 and 2.5% in U2. It is concluded that during routine IVU there is no marked increase in the excretion rate of THG. More importantly, the percentage of THG precipitated actually decreases.

Parathyroid carcinoma associated with chronic renal failure and previous radiotherapy to the neck.

Carcinoma of the larynx was treated by irradiation followed by laryngectomy in a man who had been receiving regular haemodialysis for two years. At least one, and probably two, parathyroid glands were removed at this time, and the remaining two were removed three years later for tertiary hyperparathyroidism. A portion of one gland was implanted into the forearm. The forearm implant was resected the following year for recurrent hypercalcaemia. Six years later, again with recurrent hypercalcaemia, he died of bronchopneumonia. Metastatic parathyroid carcinoma was found in the apex of the left lung. The source of this parathyroid tissue and the possible role of irradiation in the pathogenesis of parathyroid cancer in this patient were investigated.

Uropathogenic properties of Escherichia coli in recurrent urinary-tract infection.

Properties of Escherichia coli considered to be important in the pathogenesis of urinary-tract infection were investigated. The following properties were more common in E. coli strains isolated from urinary infections than in periurethral strains from healthy individuals: (i) O serogroups 2, 4, 6, 8, 18ab and 75; (ii) high K-antigen titre; (iii) production of haemolysin; (iv) production of fimbriae; (v) fermentation of salicin. The correlation between isolation of a strain from the urinary tract and possession of any single property was not strong; however, strains rich in a combination of these pathogenic properties were rarely isolated from the periurethral area of healthy subjects but were common in urinary infections. Nevertheless, a significant proportion of urinary strains had few pathogenic properties. Strains rich in pathogenic properties were more commonly isolated from upper urinary-tract infections than from lower-tract infections; this indicates that the properties of the invading organism may influence the localisation of infection.

Investigation and validation of the affinity chromatography method for measuring glycated albumin in serum and urine.

Affinity chromatography on m-aminophenyl boronate columns together with albumin measurement by radioimmunoassay has been validated as a method for determining glycated albumin in serum and urine. Optimisation of sample volume and of elution buffer composition and volume ensured reproducibility of results. Fructosamine assay confirmed the absence of glycated albumin species from the non-glycated fraction. It was possible to elute the glycated fraction from the affinity columns with Tris or glycine which do not contain 1,2 diols but have similar functional groups. Column affinity was, therefore, not specific for glycated protein moieties. Inhibition of binding by glucose, and other small molecules in urine, necessitated ultrafiltration or dialysis of samples before analysis. Reference ranges for glycated albumin in non-diabetic subjects were 0.6-1.8% in serum and 0.9-2.6% in urine. In patients with diabetes mellitus, glycated albumin ranged from 1.4-10.9% in serum and from 1.5-12.5% in urine.

The influence of geometrical factors in 131-I-hippuran renography.

Using a particular collimated NaI scintillation detector and a kidney phantom containing 131-I, the dependence of the resulting count rates on collimator-kidney geometry has been determined. These results have been used to calculate the geometrical contribution to the error in the measurement of relative effective renal plasma flow (REP) by 131-I-Hippuran renography. When radiographic and ultrasonic methods of localizing the kidneys are employed, this error has been found to follow a normal distribution with a SD of 2.6% in the case of equally divided function. Combination of this error with that from natural movement and statistical fluctuations, as observed using a dose of 10 muCi 131-I-Hippuran, has led to the estimation of a corresponding potential error 11%. Values of the potential error, which is defined as the 99% probability range, have been calculated covering the range of RFP.

The development of a fluoroimmunoassay for beta-2-microglobulin in serum.

A liquid-phase fluoroimmunoassay has been developed for the measurement of beta-2-microglobulin in undiluted serum or plasma. Protein labelled with fluorescein-isothiocyanate at a molar ratio of 1:2 respectively is employed as a tracer together with an antiserum to beta-2-microglobulin raised in a sheep. Separation is achieved by means of rabbit anti-sheep immunoglobulin G and, following precipitation of the bound fraction by centrifugation, the free fraction together with any potentially interfering factors is removed in the supernatant. Finally the precipitate is dissolved and the fluorescence measured. The assay is simple and rapid in that all reactants, including the second antibody, can be added at the start of the assay and equilibrium is attained within 60 min. The assay is reproducible and sufficiently sensitive to allow measurement of normal serum levels and has a wide range avoiding the need for sample dilution. Results correlated well with those of an established radioimmunoassay.

Serum Tamm-Horsfall glycoprotein levels in health and in renal disease.

Serum Tamm-Horsfall glycoprotein (THG) concentrations were measured by radioimmunoassay in a group of 95 people with normal renal function and lay in the range of 70 to 540 ng/ml. None was detectable in 6 anephric patients. Patients on hemodialysis but with both kidneys in situ had concentrations below the lower limit of normal, and in some cases THG was undetectable. Healthy kidney donors generally showed a decrease in serum levels following uninephrectomy although these remained within the normal range. In contrast, all transplant recipients showed a marked increase in serum THG concentration, the rates of rise being apparently dependent upon initial graft function. These findings support the view that THG is a normal constituent of human serum whose levels are related to the amount of renal functioning mass.

Assessment of arteriovenous fistulae from pressure and thermal dilution studies: clinical experience in forearm fistulae.

Knowledge of useful fistula flow (UFF), the maximum blood flow available using twin needles within acceptable pressure limits and without recirculation, is essential for the optimal management of patients receiving maintenance hemodialysis or hemofiltration. A technique for the measurement of UFF employing thermal dilution for the detection of recirculation has been developed. Using this technique, 94 studies were carried out in 69 forearm fistulae. UFF exceeded 400 ml/min in 45 fistulae. In these satisfactory fistulae a normal range was defined for basal intrafistula pressures (60 mmHg being the approximate upper limit of normal). Analysis of arterial and venous line pressure recordings with increasing extracorporeal blood flow and knowledge of the presence or absence of recirculation allowed us to define the functional problem in unsatisfactory fistulae. The functional diagnosis was supported in 16 of 24 fistulae by angiography or surgery or both. In all but two of the remainder, satisfactory UFF was obtained by repositioning the patients' needling sites. Fistulae were divided into different clinical groups. Of 35 fistulae which were thought to be clinically acceptable, 7 were found to be unsatisfactory. In 17 fistulae in patients with poor biochemical control, recirculation was detected in 8. Of 11 fistulae reported to produce poor flows on dialysis, 4 had UFF above 400 ml/min. Of 6 fistulae in patients experiencing needling difficulties, 5 had satisfactory UFF. These studies which take only a few minutes and can be carried out immediately preceding a routine dialysis session not only identify unsatisfactory fistulae, but yield valuable diagnostic information in these cases. This has reduced dependence on angiography and has led to more careful selection of patients for surgery.

The carriage of Escherichia coli on the peri-urethral area and in the feces in patients on long term low dose cotrimoxazole therapy.

Peri-urethral and fecal carriage of E. coli has been studied in 30 patients maintained on long term low dose cotrimoxazole and in abacteriuric subjects not receiving any antibiotic. Cotrimoxazole treatment is associated with a dramatic reduction in E. coli carriage both in the feces and especially on the peri-urethral area which persists over months or years. Recovery of trimethoprim-resistant E. coli from the feces was uncommon but when observed antedated subsequent relapse due to resistant organisms. Possible mechanisms for low peri-urethral carriage rates include reduction in fecal carriage, vaginal secretion of trimethoprim or low urinary concentrations of that drug.

Influence of intraperitoneal dialyzate on blood pressure during continuous ambulatory peritoneal dialysis.

Blood pressure (BP) of patients on continuous ambulatory peritoneal dialysis (CAPD) must be well controlled. The present study tests a clinical impression that BP recordings are higher with dialyzate within the peritoneal cavity than after it is drained out. 8 CAPD patients had systolic BP, diastolic BP and heart rate measured both with dialyzate in situ and after drainage. Paired t-tests showed systolic BP and diastolic BP but not heart rate to be significantly (P less than 0.05) higher with dialyzate in situ. To avoid a false impression of good BP control it is recommended patients on CAPD measure BP with dialyzate in situ.

Dialysis-induced change in erythrocyte volume: effect on change in blood volume calculated from packed cell volume.

Blood volume (BV) change during hemodialysis is often monitored by packed cell volume (PCV). This assumes erythrocyte volume is constant. We tested this by dialyzing 5 patients for 2 hours against high (154 mmol/l), normal (140 mmol/l) and low (126 mmol/l) dialysate sodium concentrations. Erythrocyte water content, calculated from measured blood and plasma water contents, decreased with high and increased with low dialysate sodium concentrations. Erythrocyte volume, calculated from mean corpuscular hemoglobin concentration (MCHC) decreased 3.8% with high concentration dialysate and increased 2.5% when dialysate concentration was low. These changes correlated significantly (r = 0.80, p less than 0.01) with alterations in plasma sodium. Mean corpuscular volume (MCV), measured with a Coulter-S Plus Counter did not alter because of a methodological artefact. BV change can be calculated from PCV when plasma concentrations of osmotically active substances are changed only if allowance is made for altered erythrocyte volume.

Hemosiderosis in a patient on regular hemodialysis: treatment by desferrioxamine.

Hemosiderosis following regular administration of parenteral iron was observed in a patient receiving maintenance hemodialysis. Infusions of desferrioxamine in doses of 2,3 and 4 g each resulted in the removal of approximately 45 mg of iron during dialysis. Desferrioxamine 2 g was infused thrice weekly during dialysis for twelve months. Body iron stores, as judged by liver iron and serum ferritin concentrations, fell by about half. This agrees well with the result calculated from the amount of iron administered and the amount removed during dialysis.

Bromocriptine improves reduced libido and potency in men receiving maintenance hemodialysis.

Twenty-five men on maintenance hemodialysis commenced a placebo-controlled, double-blind, crossover trial of bromocriptine for erectile impotence. Eight patients on bromocriptine and one on placebo failed to complete the trial due to side-effects and 2 were withdrawn following renal transplantation. Libido or the frequency and/or quality of erections or both improved in 11 of the remaining 14 patients during bromocriptine treatment. A significant (P less than 0.01) improvement in patients' perception of sexual performance occurred on bromocriptine compared with placebo. The 3 patients in whom potency failed to improve had the lowest serum testosterone concentrations. Bromocriptine is usually effective in the management of impotence in males receiving maintenance hemodialysis provided pretreatment serum testosterone is above the lower end of the normal range, but side-effects are relatively common.

Controlled trial of calcitriol in hemodialysis patients.

We report on a 5-year, prospective, double-blind trial of 1,25 dihydroxycholecalciferol (calcitriol) versus placebo in 76 hemodialysis patients without biochemical or radiological evidence of bone disease. Calcitriol, 1 microgram daily, regularly induced hypercalcemia. Doses of 0.25 microgram daily or less proved satisfactory in most patients. During calcitriol treatment, plasma calcium concentration was significantly higher and serum parathyroid hormone concentration significantly lower than on placebo. There was no difference in the rates of development or of progression of vascular calcification in the two groups. Significantly more patients on placebo (17 vs. 6, p less than 0.05) developed a sustained elevation of plasma alkaline phosphatase concentration. Calcitriol appeared to protect against the development of histological evidence of osteitis fibrosa but not of osteomalacia, but accumulation of aluminum in bone occurred during the study. We conclude that calcitriol delays and may prevent the development of osteitis fibrosa in patients receiving regular hemodialysis and may reasonably be prescribed routinely in hemodialysis patients without biochemical or radiological abnormality, unless there is a substantial prospect of early renal transplantation.

Kidney position and the measurement of relative uptake of 131-I Hippuran in renography.

The distribution of kidney position in the sitting posture has been determined in a series of patients presenting for renography, using radiographic and ultrasonic techniques. Both the craniocaudal distribution of kidney centre positions and the distribution of the differences in depth below the posterior skin surface of the two kidney centres have been found to have a significant standard deviation. The effect of these distributions on the measurement of relative effective renal plasma flow by 131-I Hippuran probe renography has been calculated for the situation in which no kidney localizing techniques are used. The resulting error distribution has an SD of 21.7 per cent in the case of equally divided function.

Renal function after high dose urography in patients with renal failure.

A retrospective study of 40 patients with moderate to severe renal failure who had high dose urography showed that none developed oliguric acute renal failure after the urogram. In 37 patients there was no worsening in renal function attributable to the urogram. This group included five patients in whom renal function was already deteriorating at the time of the urogram. In three patients a transient rise in serum creatinine without oliguria occurred in the week following urography. Differences between the British and North American experience are discussed.

The effect of DDAVP on intravenous urography.

The possible role of an antidiuretic hormone analogue, DDAVP (1 deamino-8-D-arginine vasopressin), in intravenous urography has been studied. The minimum effective dose of intravenous DDAVP in normal hydrated subjects was shown to be 2 ng/kg. During intravenous urography in fluid restricted subjects, a dose of 1 microgram DDAVP was necessary to reduce significantly the urine flow rate after contrast medium injection. Although the mean pyelographic score after DDAVP was increased, the differences observed were not statistically significant. The possible reasons for this finding are discussed.

The effect of osmotic diuresis on urinary iodine concentration using contrast media of differing osmolality.

The urinary iodine concentrations of a monomer (sodium iothalamate), a dimer (sodium iocarmate) and a non-ionic compound (metrizamide) have been compared in dogs with varying levels of solute excretion. All the animals were undergoing maximal antidiuresis. In dogs with normal solute excretion, metrizamide and iocarmate produced higher urinary iodine concentrations than iothalamate. There was no significant difference between metrizamide and iocarmate. With increasing levels of solute excretion, the differences between the compounds were reduced. These findings suggest that contrast media of reduced osmolality are unlikely to have a special place in advanced renal failure.

The assessment of arteriovenous fistulae created for haemodialysis from pressure and thermal dilution measurements.

A technique is described for the assessment of arteriovenous fistulae created for haemodialysis. This involves the measurement of intrafistula pressures and 'useful fistula flow' (UFF). The latter we define as the maximum blood flow available for twin needle haemodialysis without recirculation and without unacceptable pressures in the arterial ('A') and venous ('V') lines. The test circuit resembles that used for conventional haemodialysis except there is 'A' and 'V' line pressure and temperature monitoring and no dialyser. Intrafistula pressures are first measured at the time of insertion of the fistula needles. 'A' and 'V' line pressures are then recorded as the extracorporeal blood flow rate is increased in increments from zero to 500 ml/min. A check for recirculation is made at each flow rate. A bolus of cold saline injected into the 'V' line causes a momentary decrease in 'A' line temperature when recirculation is present; when there is no recirculation, 'A' line temperature remains constant. The blood flow rate at which recirculation is first detected will be above the useful fistula flow by definition. This technique allows identification of those patients who obtain high blood flows at the expense of recirculation and thus dialyse inefficiently. Combined pressure and thermal dilution measurements yield valuable information in the investigation of failing or problem fistulae.