Evaluation of i-STAT creatinine assay.

BACKGROUND: We evaluated a new, 2-min blood creatinine method using the hand-held i-STAT analyzer. Good results have already been reported using this analyzer for 10 methods including electrolytes, TCO2, pH, PCO2, bicarbonate, glucose, hemoglobin and urea for uremic blood, hemodialysate and peritoneal effluent. METHODS: Evaluation included study of imprecision and accuracy. RESULTS: Imprecision studies gave excellent results, including those for reproducibility of 6 solutions with a mean of 10 repeats and coefficients of variation (CVs) of 0.4-3.4%, and also the mean of the differences between 33 duplicate blood specimens which was 2.2% of the specimen mean. To assess accuracy, we compared results of 149 tests by i-STAT and Beckman Synchron CX7 methods. The difference between the two means was 2.6% and the mean of all differences was 10.9% with i-STAT results higher, especially when blood creatinine values were < 100 micromol/l (1.1 mg/dl) indicating the need for a slightly higher upper limit of the normal range. The correlation coefficient between the two methods was 0.99, the slope 1.0 and the intercept -5.0 micromol/l (-0.06 mg/dl). We assessed the recommended creatinine correction for variation in PCO2 above and below 40 mm Hg, but our results did not suggest the need for such a correction in our range of 27-64 mm Hg; omission would remove a major method disadvantage. Assays of hemodialysate and peritoneal effluent were also satisfactory. CONCLUSIONS: The i-STAT creatinine method is simple and rapid and our evaluation showed satisfactory accuracy and precision. However, results were on average slightly higher than for the Beckman Synchron CX7 method.

Relationship of frequency, age, sex, stone weight and composition in 15,624 stones: comparison of resutls for 1980 to 1983 and 1995 to 1998.

PURPOSE: We studied the relationship of stone frequency and composition to age, sex and stone weight. MATERIALS AND METHODS: A retrospective study was performed of all 15,624 stones submitted for analysis with infrared and wet chemical methods in Newfoundland and Labrador from 1979 to 1998. RESULTS: There were 1,067 bladder stones of which 216 contained magnesium ammonium phosphate. The remaining 14,557 stones were from the kidney and ureter, and 11,707 were composed only of calcium oxalate and/or phosphate. Of the remaining 2,850 kidney and ureter stones magnesium ammonium phosphate was present in 573, uric acid/urate without magnesium ammonium phosphate in 1,109 and other compounds in 1,168. The 11,707 oxalate phosphate group was subdivided by infrared peak analysis based on oxalate-to-phosphate ratio into phosphate-ratio 1 or less, intermediate-1 to 10 and oxalate-10+. Oxalate comprised 65% of the 11,707 stones compared to 16% for phosphate. Women submitted 52% of phosphate stones compared with 28% of oxalate stones. From the first (1980 to 1983) to the last (1995 to 1998) complete 4-year study periods, there was a relative increase in oxalate and decrease in phosphate stones, associated with increasing age from decades 5 to 6 for oxalate and phosphate stones, except that the age peak for phosphate stones in women remained in decade 3. Median weight of 1, 828 phosphate stones was 43 mg. (mean 234) compared with 25 mg. (mean 98) for 7,634 oxalate stones. Male-to-female ratio was 0.91 for phosphate stones compared with 2.62 for oxalate stones. CONCLUSIONS: Phosphate stones were on average heavier and relatively more common in women, had an earlier age peak frequency in women than oxalate stones and became less frequent during our last 4-year study period. In contrast, oxalate stones were much more common, of lighter weight and became more frequent with time.

i-STAT hand-held point-of-care analyzer for dialysis units.

The i-STAT hand-held analyzer assays ten tests including electrolytes, gases, urea, glucose, ionized calcium, and hematocrit. Eight different cartridges assay one to eight tests. We have previously confirmed or demonstrated that accuracy and precision for blood assays are comparable to accepted laboratory methods. We now report similar results for hemodialysis dialysate and peritoneal dialysis effluent. The i-STAT analyzer is simple to use, and dialysis nurses produced accurate results with 20 min training. The results are viewed digitally on the analyzer and automatically on a small attachable printer. i-STAT blood analysis is most valuable when results are desired immediately, anywhere, including before, during and after dialysis in hemodialysis units. Hemodialysate analysis using i-STAT can be most valuable for rapidly checking dialysis machine function such as dialysate mixing and conductivity and ramping results and dialysate concentrations prepared in the unit. Peritoneal effluent analysis is useful for rapid evaluation of membrane function.

Analgesic nephropathy.

Many questions about analgesic nephropathy (AN) lack clear-cut answers. We present available evidence for and against proposed answers to many of these questions. These include: (1) Is acetaminophen (AC) nephrotoxic when taken as the sole analgesic? (2) Is the combination of acetylsalicylic acid (ASA) and AC more nephrotoxic than AC taken alone, and if so, why? (3) What are the minimum doses and durations of ingestion required to produce analgesic nephrotoxicity? (4) Is the combination of ASA and AC (a major metabolite of phenacetin) less nephrotoxic than that of phenacetin and ASA combined? (5) Does caffeine in combination with analgesics contribute to nephrotoxicity? (6) What is the incidence of end-stage renal disease (ESRD) due to AN? (7) What uniform diagnostic criteria should be established for AN? (8) What are the earliest anatomic and biochemical abnormalities? (9) What are the mechanisms of renal injury? (10) Does AC cause uroepithelial neoplasia? (11) What research might be most beneficial? Based mainly on associations, some strong, we suggest that AN still exists as a cause of ESRD in the United States, where AC/ASA combinations are available over the counter, and in Canada, where they are not. We also suggest that the evidence needed to recommend that the AC/ASA combination be excluded from over-the-counter analgesic preparations still has limitations. A prospective multicenter study comparing incidence related to AC/ASA in the United States and to AC in Canada and the United States may be needed to answer this question. For such a study to be worthwhile, an adequate incidence in both countries is required.

Evaluation of i-STAT portable clinical analyzer in a hemodialysis unit.

OBJECTIVE: To evaluate a hand held portable i-STAT analyzer used for point-of-care testing in a hemodialysis unit. DESIGN AND METHODS: Imprecision and comparison studies. Assays by nonlaboratory personnel. RESULTS: Study of both quality control solutions and hemodialysis patients' duplicate blood specimens with 6+, E3+, EC6+, and EC8+ cartridges both gave CVs for sodium, potassium, chloride, pH, and ionized calcium of 0 to 2.2%. CVs for hematocrit, glucose and pCO2 for whole blood duplicates were 4.6, 3.5, and 4.0%. The mean differences between i-STAT and central laboratory values for the above compounds and urea, when expressed as a % of mean central laboratory values were 0.2 and 3.1%, except for an ionized calcium value of 4.3% (for which there is an explanation) and for glucose (11%) that were both higher for i-STAT. Preliminary data suggest that sodium, potassium, ionized calcium, and pH can be assayed in the aqueous dialysate fluid used for hemodialysis. CONCLUSIONS: We confirm previous reports that i-STAT cartridges give simple, rapid, and reliable values for sodium, potassium, chloride, urea, glucose, and hematocrit that are clinically acceptable when performed by nonlaboratorians, but also suggest the same conclusions apply to ionized calcium, pH, and pCO2. The hemodialysis unit may prove to be one of several hospital units where the analyzer has considerable value.

Stable renal function in insulin-dependent diabetes mellitus 10 years after nephrotic range proteinuria.

It has been considered unlikely that patients with insulin-dependent diabetes and diabetic nephropathy with nephrotic range proteinuria can substantially reduce proteinuria and continue for many years without further loss of renal function. We present a patient who had the diagnosis of insulin-dependent diabetes made at age 15, had his first of 6 laser treatments for proliferative and hemorrhagic retinopathy at age 27 and was found to have nephrotic range proteinuria and edema with hypertension at age 29, when results of a renal biopsy were typical of diabetic nephropathy. Ten years later, with the last 5.5 years on ACE inhibitors, proteinuria has been < 0.65 g/24 h for 2 years and recently 0.22 g, serum creatinine is unchanged at 90 to 102 mu mol/l, DTPA GFR is 104 ml/min and retinopathy has remained stable without laser therapy for 7 years. Blood pressure on clinic visits has averaged 126/74 for the last 8 years. This duration of stable renal function and the major decrease in proteinuria after being in the neprotic range is very rare in reports, if not unique.

Bacteriology of urinary tract stones.

It has been reported that up to half of renal stones and associated urine specimens have been positive on culture, and that up to 50% of such stones contain magnesium ammonium phosphate. In a prospective study using infrared and wet chemical analysis, we found positive cultures in only 7 of 132 renal, 5 of 105 ureteral and 6 of 21 bladder stones obtained surgically and handled with sterility. Of the culture positive calculi only 43% from the kidney, none from the ureter and 50% from the bladder contained detectable magnesium ammonium phosphate. However, magnesium ammonium phosphate was detectable in 20% of renal, 2% of ureteral and 27% of bladder stones with negative cultures. Of the culture positive renal and ureteral calculi 42% were predominantly calcium phosphate and 17% were predominantly calcium oxalate. For culture negative stones 25% and 51% from the kidney, and 15% and 82% from the ureter were composed of predominantly calcium phosphate and calcium oxalate, respectively. Among the culture positive stones, related positive urine cultures were noted in 100% of the renal, 20% of the ureteral and 50% of the bladder cases, compared to 26%, 10% and 27%, respectively, of culture negative calculi. The same organism was found in the stone and urine in only 38% of the cases. The lower frequency of positive urine cultures, of stones with magnesium ammonium phosphate, and especially of culture positive renal and ureteral stones (5%) than in previous reports suggests that stone culture may be of less value than indicated previously, except for bladder calculi and large renal stones, such as the branched type.

Prediction of reduction in predialysis concentrations due to interdialysis weight gain.

There is little quantitative information about the influence of weight change before and during hemodialysis on the concentration of proteins, lipoproteins, lipids, enzymes and other dialysis-resistant compounds in blood. We studied the concentration of 12 such compounds before and at the end of high-flux hemodialyses, 1.5 h after the start and 1, 2 and 3 h postdialysis and have developed formulae for roughly predicting the near steady-state 2-3 h postdialysis concentration. For hemoglobin, albumin, total protein and total cholesterol, the relationship of mean change in concentration to weight loss in groups was linear, and the % increase in concentration correlation correlated with % weight reduction (r = 0.64-0.81 and p = 0.002-0.0002). Correlations with ultrafiltration rate were comparable. By 3 h postdialysis values were relatively stable; the average fall in concentration for theses 4 compounds was 25% from end dialysis. The simplest formula we found which roughly predicts the % increase in concentration from predialysis to 3 h postdialysis is to multiply the % loss in body weight in kg during dialysis by 3.3. More accurate formulae were developed using combined and specific regression equations relating % weight loss during dialysis to % concentration rise. Mean values for alkaline phosphatase, triglycerides, lipoprotein (a), high-density lipoprotein cholesterol, calcium, apolipoprotein B, bilirubin and aspartate aminotransferase also rose appreciably during dialysis with significant increases for the first five. With major interdialytic weight gain, the reduction in predialysis concentrations of hemoglobin and cholesterol may be enough to inappropriately modify treatment decisions about anemia (e.g. erythropoietin) or hypercholesterolemia, and to cause false concern about the concentration of albumin for nutrition and prognosis. Major weight gain may also contribute to concentration changes in numerous other compounds resistant to dialysis.

Comparison of Lp(a) concentrations and some potential effects in hemodialysis, CAPD, transplantation, and control groups, and review of the literature.

Apolipoprotein (a)-Lp(a)-is reported to be an independent risk factor for coronary artery disease and for hemodialysis (HD) access occlusion. Homology with plasminogen may predispose to thrombosis. High concentrations usually have been reported in patients on HD and on continuous ambulatory peritoneal dialysis (CAPD), but near-normal values in many kidney transplants (TP). We used Pharmacia immunoradiometric assay in 52 patients on HD, 58 on CAPD, 94 after TP, and 56 controls. The Lp(a) mean levels for CAPD, HD, TP, and control groups were 738, 647, 348, and 368 U/l and the medians were 542, 537, 96 and 143 U/l, respectively. The means and medians for CAPD and HD were significantly greater than those for TP and controls (p < 0.003 for means and < 0.005 for medians). We found no significant difference between: (1) Lp(a) means or medians comparing HD and CAPD or TP and controls; (2) Lp(a) means for the 33 patients with insulin-dependent diabetes mellitus and the 171 without; (3) number of occlusions of HD fistulae or grafts in patients with high Lp(a) values and without; (4) mean Lp(a) for CAPD patients on gemfibrozil and also for TP patients on 3-hydroxy-methylglutaryl coenzyme 1 reductase inhibitors, or diet alone, before and after treatment, and (5) mean Lp(a) values for HD and CAPD patients with and without myocardial infarction. Lp(a) did not correlate significantly with fractional shortening or left ventricular end systolic or diastolic diameter by echocardiogram or with ejection fraction. For TP patients, Lp(a) and serum creatinine correlated (p = 0.004), and mean Lp(a) for 71 TP on ciclosporin A exceeded that for the other 23 patients (p < 0.03). Lp(a) fell in 13 of 14 patients after TP (mean fall 77%). The dominant Apo(a) isoform in 10 of 13 patients on CAPD or HD with high Lp(a) values was the equivalent of S2 (Utermann). Lp(a) in HD or CAPD is often elevated and regulated by both genetic and renal failure factors, but falls after TP with return of renal function and mainly genetic regulation. Lp(a) was not a risk factor for coronary artery disease in HD or CAPD patients and did not fall significantly with two drugs or diet.

First morning urine pH in the diagnosis of renal tubular acidosis with nephrolithiasis.

Few reports of patients with renal stones compare fasting first morning urine pH with the lowest urine pH after a single oral dose of 0.1 g/kg ammonium chloride. We studied these values in 110 individuals, including 96 stone formers and 14 non-stone forming controls. We hypothesized that fasting first morning urine pH > or = 6.10 is abnormal. Nine of ten patients who had urine pH > or = 5.25 after NH4Cl, had pH > or = 6.10 for both a single and a second first morning urine, giving a sensitivity of 90%. In contrast, a single fasting first morning urine pH > or = 6.10 was found in 19 of 100 individuals with pH < 5.25 after ammonium chloride. However, only 4 of these 100 individuals had abnormal fasting first morning pH > or = 6.10 on two occasions, giving a specificity of 96% for the two urines. Useful prediction of urine pH > or = 5.25 after ammonium chloride occurs when two fasting first morning urines have pH > or = 6.10.

Mid-menstrual cycle decline in creatinine and urea clearances.

In 6 pre-menopausal and 6 post-menopausal women we compared urine volume and excretion of creatinine and urea daily from day 2 of the 1st period of menstruation to day 1 of the 2nd, along with clearances of creatinine (CCr) and urea (C-urea). Clearances were based on 7 serum samples which were taken on day 2 of the 1st menstruation and on days 8, 14, 15, 16, 21, and day 1 of the next menstruation, when 4 cycling hormones were also assayed. Mean group ages were 35 and 59 years for pre- and post-menopausal women. CCr cycled only in the pre-menopausal group, with a nadir around the time of ovulation. The mean CCr combining days 14 and 15 was lower than that for the average of the 5 other days by 22% (p < 0.003) in the pre-menopausal but not in the post-menopausal group (p = 0.99). Average CCr values fell from the peak mean of 129 ml/min on day 8 in the follicular phase to the mean nadir of 93 ml/min for days 14 and 15 and recovered to 117 ml/min by day 1 of the 2nd menstruation; the percent fall in CCr ranged from 9 to 39%. A mid-cycle nadir was also present for C-urea (p = 0.03), also found only in the pre-menopausal group. We conclude that, in pre-menopausal women, there is generally a fall in CCr and C-urea from a peak in the follicular phase to a nadir around ovulation.

Digoxin-like factors in herbal teas.

Forty-six commercially packaged teas and 78 teas prepared from purchased herbs were assayed for digoxin-like factors (DLF) by their crossreactivity with digoxin antibody (immuno-crossreactive DLF) and by their inhibition of ouabain binding to membrane Na,K-ATPase (NKA inhibitory DLF). Three packaged teas and 3 herbs gave NKA inhibitory DLF values > 30 micrograms digoxin equivalents/cup. Two packaged teas and 3 herbs gave immuno-crossreactive DLF values > .050 micrograms digoxin equivalent/cup. One herb, pleurisy root, had a crossreactive DLF value of 187 micrograms/cup and NKA inhibitory DLF equivalent to 3658 micrograms/cup. Plasma digoxin-like factors were measured after ingestion of the 3 commercially packaged herbal teas with highest values for NKA inhibitory DLF. After ingestion of each of the 3 teas, plasma NKA inhibitory DLF increase, in one case more than 100-fold. Two teas produced a measurable increase in plasma immuno-crossreactive DLF after ingestion. Some digoxin-like factors in human plasma may have a dietary source.

Calcium and calcium magnesium carbonate specimens submitted as urinary tract stones.

Of 8,129 specimens submitted as urinary stones from 6,095 patients, 67 from 15 patients were predominantly calcium carbonate or calcium magnesium carbonate (dolomite) by infrared analysis. Detailed study of 1 man and 4 women who submitted 3 or more such specimens showed that all were of aragonite calcium carbonate crystal form in 2 women and all calcite in the man. All 3 patients had a long history of nephrolithiasis preceding submission of calcium carbonate stones. There was frequent and often painful spontaneous passage of many small stones. Medullary sponge kidney was reported in 2 patients. Specimens submitted by the other 2 women included dolomite and quartz artifacts. Of the other 10 patients 4 had calcite and 1 had aragonite (possibly true stones). Five patients had artifacts with dolomite in 3 and mixed specimens in 2. True calcium carbonate kidney stones and calcium carbonate artifacts may be difficult to distinguish, and dolomite and quartz artifacts may require x-ray diffraction for clear-cut diagnosis.

Pharmacoeconomic comparison of cyclosporine oral solution and capsules after kidney transplantation.

We studied 20 kidney transplant recipients who had received Sandimmune cyclosporine A (CSA) capsules for an average of 7.9 months at a mean dose of 312 mg/day. They were switched to CSA liquid in the same dosage for an average of 15.5 months. There was no significant difference between the means for the monthly values of either serum creatinine or whole blood CSA when the periods on capsules and liquid were compared. Fourteen bottles from 4 batches with volume stated as 50 ml CSA actually contained an average of 53.7 ml. Comparison of the amount of capsules and liquid CSA prescribed and the amount dispensed by the pharmacy showed that the amount neglected (prescribed > dispensed) was similar for patients on liquid and capsules. Wastage (prescribed < dispensed) was about 5% greater when on liquid, and as our cost for liquid was 18% less than for capsules, we saved about 13% by use of the liquid.

In search of sterile, endotoxin-free dialysate.

Sterile dialysate, free of endotoxin (ET) and other cytokine inducing factors, will probably become a future standard. High-flux dialysis with bicarbonate and reuse has the membrane, the pressures, and bacteriologic potential for ET fragments to pass from dialysate to the blood side of the membrane with activation of monocytes and production of cytokines. Ultrafiltration through polysulfone filters has been shown to remove bacteria, ET, and its fragments and other cytotoxic inducing factors. The authors found that in spite of sterile, ET-free, reverse osmosis (RO) water, ET was usually present at the dialyzer inlet and arose from the RO storage tank water with bacteria < 30 CFU/ml, in spite of repeated disinfection. The authors now remove bacteria, ET, and fragments from RO tank water with a 5 mu cellulose filter followed by ultrafiltration with a Fresenius F-80 polysulfone dialyzer inserted between the wall RO delivery port and each delivery system. At the dialyzer inlet, monthly bacterial counts were < 30 cfu/ml, and ET values (n = 38) were not detectable in 89% and < 0.5 EU/ml in 11%. The F-80 filters were used for 180+ dialyses along with the 5 mu filters, which replaced the frequently endotoxin contaminated 10 mu filters in the Monitral-S delivery systems. The costs did not increase.