Cell Excretion Rates Research Articles

Increased renal tubular cell excretion by patients receiving chronic therapy with gold and with nonsteroidal anti-inflammatory drugs

Using rheumatoid arthritis patients who were receiving gold as models, we evaluated the renal effects of the chronic administration of very low doses of a nephrotoxic drug. The heavy metal gold has been shown to increase urinary enzyme excretion when it is given in usual doses for the treatment of rheumatoid arthritis. It is not clear whether the increased urine enzyme excretion caused by long-term drug therapy represents injury to the kidney or whether it is merely an effect of the drug. Urinary N-acetyl-beta-glucosaminidase and renal tubular cell excretion rates were measured in 19 patients who were receiving chronic treatment with gold and with nonsteroidal anti-inflammatory drugs for rheumatoid arthritis, in 10 patients who were receiving nonsteroidal anti-inflammatory drugs, and in 8 healthy control subjects. No subjects showed evidence of kidney disease. Both renal tubular cell and enzyme excretion rates were elevated in the gold-treated group. This showed that there was increased renal tubular cell turnover in this group, which suggests low level renal tubular injury and not merely an effect of the usual dose of gold.

Faecal and Introital Bacteria and Urinary Tract Infection

The faecal, introital, and urinary bacterial flora have been studied in 3 normal women and 5 women with recurrent urinary infection. In the normal women urinary abnormalities were uncommon, but the patients regularly had episodes of bacteriuria and pyuria, only a quarter of which were symptomatic. Symptoms tended to be associated with high white cell excretion rates and with the longer episodes. Introital colonisation was heavier and more frequent in the patients than in the control subjects. Organisms recovered from the urine had previously colonised the introitus in most cases. It appears that symptomatic episodes constitute only a small part of the disease process in patients with recurrent urinary tract infection.

Short-term oral toxicity study of diethyl phthalate in the rat

Groups of 15 male and 15 female rats were given diets containing 0 (control), 0·2, 1·0 or 5·O% diethyl phthalate (DEP) for 16 wk. Consumption of diet containing 5% DEP was associated with a reduction in food intake and in the rate of body-weight gain, and similar effects were seen in the females given 1% DEP. No statistically significant effects on water intake or on the results of the haematological examinations, serum-enzyme levels, urinary cell-excretion rate, renal concentration tests or histological examination were seen in the treated animals. However, there were increases at wk 16 in the relative liver weight of females at all treatment levels and of males fed the highest level. There were also increases in the absolute and relative weights of stomach and small intestine in rats of both sexes; in the females these were statistically significant at all dietary levels at wk 16.

ANALGESICS AND THE KIDNEY A COMMUNITY‐BASED STUDY

The adult population of a small Victorian town was interviewed for current analgesic consumption and the replies were validated by urine testing. One thousand four hundred and fifty-six subjects were ranked by stated analgesic consumption, and the 50 highest consumers matched for age and sex with non-consumers. Early morning urine specimens were collected and no significant difference in osmolality or white cell excretion rates was found between the two groups. It was concluded that the absolute risk of renal impairment on chronic analgesic consumers is low, and that patients on therapeutic regimens, including analgesics, may be reassured that any risk is minimal.

Comprehensive one-day renal function testing in man.

A comprehensive one-day renal function test consisting of a single outpatient visit lasting nine hours, with a minimum of time off work or away from home, is described in detail. Although a large number of laboratory tests are performed in one day, patients usually appreciate thoroughness, and the cost is more than offset by the saving in occupancy of hospital beds and by the early and precise diagnosis of reversible aspects of renal disease. Some aspects of improved methodology, such as the sequential determination of minimum urinary pH, bicarbonate, titratable acid, ammonium, and total acid on a single sample using an automatic titrator, are given in detail. Clinical application of the comprehensive nine-hour renal function testing system is illustrated by the result sheet of a patient with analgesic nephropathy, who was shown in one day to have secondary severe renal failure (glomerular filtration rate 20% of normal for age and surface area), renal tubular acidosis of the distal gradient type (minimum urinary pH 6.20), increased urinary white cell excretion rate, hyaline casts, and absence of red cell casts, consistent with a diagnosis of analgesic nephropathy and urinary tract inflammation. Normal values with 95% range for this laboratory are also given. This testing system has been found to be very useful in investigating patients with analgesic nephropathy, renal tubular acidosis, and after renal transplantation.

Use of metolazone, a new diuretic, in patients with renal disease.

Metolazone, a new diuretic/saluretic/anti-hypertensive agent related to quinethazone, was used to treat 20 patients with impaired renal function. Among eight water loaded hospitalized patients given metolazone 5 mg intra venously, glomerular filtration rate rose in four and diminished slightly in four while urine flow and sodium excretion in creased significantly. In 12 out-patients given long-term oral metolazone (usually 5–10 mg in single daily doses) treatment effectively removed oedema and induced weight loss; in the seven initially hypertensive patients blood pressure decreased also. Plasma renin activity was measured in seven patients before and after several weeks’ metolazone therapy. Activity fell in two patients and rose in five, but the upper limit of normal was exceeded in one only. Renal epithelial cell excretion rates indicated that drug nephrotoxicity was absent. Mean creatinine clearances rose, serum potassium levels fell, and ten patients received oral potassium supplements. Small transient increases in liver enzymes were seen in three patients. Metolazone tended to maintain glomerular filtration rate and renal plasma flow while increasing salt and water losses. A proximal as well as a distal site of action was suggested for the drug, and its anti-hypertensive effect was confirmed.

Renal function in chronic intravascular haemolysis associated with prosthetic cardiac valves.

1. Glomerular nitration, wate rconcentration and acid load tests, measurement of urinary protein and cell excretion rates, bacteriological examination of the urine, and analysis of the urinary amino acid content were carried out in eight patients with chronic intravascular haemolysis due to aortic valve replacement. 2. All results were normal except for a slight reduction in creatinine clearance rate in two patients and a slight elevation of urinary protein in a third; these abnormalities were considered of doubtful significance. 3. It is concluded that chronic intravascular haemolysis with its consequent renal haemosiderosis appears not to interfere with renal function.

A blue catalase screening test for pyuria and haematuria.

The blue catalase test is easy to perform and economical of materials. In a series of 529 adult female hospital patients it appeared to be a good screening test for pyuria and haematuria, detecting all but one of the specimens examined with more than 20 red and white cells combined per cubic millimetre of urine and 95.2% of those with more than 10 cells. It indicates a raised leucocyte or red cell excretion rate but is not a test for bacteriuria.

The value of leucocyte excretion rates in determining "at risk" patient with asymptomatic bacilluria.

SummaryWomen with asymptomatic bacilluria in pregnancy were investigated for the presence of elevated urinary white cell excretion rates. One hundred and twenty‐five women were observed throughout pregnancy with monthly recordings of their urinary leucocyte values; 64 were treated with chemotherapeutic agents and 61 were not treated.Women with asymptomatic bacilluria had a higher incidence of small babies than women who had their bacteria eliminated by chemotherapy. When the leucocyte rate was elevated above 8 × 105 per hour during the last four weeks of gestation the incidence of prematurity rose to 21 per cent, and the perinatal mortality to 8 per cent. Of the 61 women who were not treated when bacilluria was present, 39 (64 per cent) had elevated levels of white cells in urine and these were found to be the women at risk during pregnancy.If four chemotherapeutic agents were given in a continuous rotation throughout pregnancy the organisms were eliminated from urine and the leucocyte excretion rate and the fetal morbidity were reduced.

The hypocalcaemic effect of intravenous phosphate administration.

1. Sodium phosphate was infused intravenously over approximately 2½ h and produced a mean linear rise in plasma phosphorus levels of 9·1 mg/100 ml. Twenty-one infusions were performed in twelve control subjects and thirty-eight were carried out in thirty-two patients with disorders of calcium and phosphorus metabolism. 2. The fall in plasma calcium under these conditions was related to: a. The initial height of plasma calcium. b. The rate of rise of plasma phosphorus. c. The initial level of plasma phosphorus and the theoretical renal phosphorus threshold. d. The presence of metabolic bone disease. The fall in plasma calcium levels per mg rise in plasma phosphorus was greater in patients with hyperparathyroidism, osteomalacia, osteoporosis, Paget's disease and certain other rarer conditions than in the control group or in patients with hypoparathyroidism, whose plasma calcium levels changed least of all. 3. It was concluded that pre-existing increased bone resorption or osteoblastic activity may determine the degree of hypocalcaemia which occurs under these conditions. 4. Phosphate was also infused at a constant rate over 10 h in five tests on five patients with moderately severe hypercalcaemia (plasma calcium 14·0–17·3 mg/100 ml). Plasma calcium levels fell steadily, and small or negligible changes were seen in serial determinations of glomerular filtration, urine protein and cell excretion rate.

USE OF DIAZEPAM IN TREATMENT OF SEVERE CONVULSIVE STATUS EPILEPTICUS

Semi-quantitative urinary white cell counts were performed in 198 patients before and after surgery. A significant rise in white cell excretion rates was found in 61% of the females but in only 11% of the males. The results were confirmed in a further group of patients by means of fully quantitative cell counts, and bacterial counting showed that this pyuria was often associated with significant bacteriuria. The possible significance of these findings is discussed.

Observations on urinary white cell excretion before and after surgery.

Quantitative determination of the cells excreted in the urine has until recently been regarded as a cumbersome and time consuming procedure {Lancet, 1961). Houghton and Pears (1957) attempted to simplify the technique, and McGeachie and Kennedy (1963) described a method of semi-quantitative cell counting which was suitable for routine use yet was much more accurate than the ordinary wet-film technique. In the course of a recent study of renal function after surgery (Lindsay et al., 1965) it was observed that there was a considerable difference between urinary white cell excretion rates before and after surgery in many patients, so further investigation of this was undertaken.

Use of diazepam in treatment of severe convulsive status epilepticus.

Semi-quantitative urinary white cell counts were performed in 198 patients before and after surgery. A significant rise in white cell excretion rates was found in 61% of the females but in only 11% of the males. The results were confirmed in a further group of patients by means of fully quantitative cell counts, and bacterial counting showed that this pyuria was often associated with significant bacteriuria. The possible significance of these findings is discussed.

Course of the renal excretion of cells after necrosis of the proximal convoluted tubule by mercuric chloride

Twenty-three rats were given mercuric chloride intramuscularly in doses ranging from 0.5 mg/kg to 4 mg/kg. The renal cell excretion rates were then observed. With large doses an abnormal cell excretion rate was evident within 24 hours. With smaller doses cell excretion usually remained normal until 48 hours had elapsed. If the cell excretion rate was normal at 48 hours, it never became abnormal subsequently. The peak excretion rate was observed at 48 hours. Peak values of similar magnitude were observed in animals given doses which varied considerably. In the animals given the largest doses, cell excretion remained abnormal for 8–10 days, whereas with the smaller doses it became normal within a week. When the renal cell excretion rate was normal for 3 days the animals were killed and the kidneys were examined histologically. No abnormality was found in any of them. We conclude that the duration of abnormal cell excretion rate is a more reliable index of the severity of renal damage than the peak excretion rate. Also, if the cell excretion rate remains normal for 3 days, this indicates that the appearance of the kidney is normal.

Diagnosis of latent urinary tract infections in pregnancy: Study of the iron sorbitol citric acid provocative test

Urinary white cell excretion rates were measured in a random sample of 30 women in the third trimester of pregnancy and in 50 cases diagnosed as anemia or toxemia of pregnancy. Seven per cent of the healthy women, 29 per cent with toxemia, and 18 per cent with anemia were found to have overt infection as shown by urinary white cell excretion rates of more than 190,000. A positive response to a provocative test with 50 mg. of iron sorbitol citric acid complex was obtained in 13 per cent of the patients with normal third trimester pregnancies, 27 per cent with toxemia, and 33 per cent with anemia. One third of the patients with positive cell excretion tests had positive cultures.

URINARY CELL EXCRETION IN THE DIAGNOSIS OF PYELONEPHRITIS.

SUMMARY The error involved in estimating the excretion rates of white cells in urine has been shown to vary grossly. Estimations of urinary cell excretion rates may be particularly misleading when close to the limits of normality. Cell excretion rates have been correlated with the presence of pyelonephritis in eighty-three randomly selected patients. Rates below the accepted limit of 400,000 W.B.C. per hour do not exclude the presence of bacteriuria or renal damage, but a C.E.R. above this level is presumptive evidence of urinary tract pathology. Since the patient's symptoms themselves require further investigation, casual estimations of C.E.R. alone are valueless. Prednisolone by mouth in a dose of 40 mg. is effective in producing positive steroid provocation tests in patients with chronic pyelonephritis. Where other tests are inconclusive a steroid provocation test may aid in the diagnosis of chronic pyelonephritis. We are grateful to the Faculty of Medicine of the University of Edinburgh for a grant from the Gunning Medical Bursaries Fund to one of us (N. W. H. O.) to enable this work to be performed.

A comparison of quantitative methods in the investigation of urinary infections

Bacterial colony counts and urinary white and non-squamous epithelial cell excretion rates have been compared in successive urine samples from 51 hospital patients. In all 19 cases with a colony count greater than 100,000/ml. the cell excretion rate was over 200,000/hour. Urinary cell concentrations correlate poorly with both colony counts and the cell excretion rate. It is concluded that simple culture of a properly taken urine sample combined with a measurement of the urinary cell excretion rate is adequate for the detection of most urinary infections. In the few instances where these methods do not provide a clear-cut result, colony counting techniques may be of value.